The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters.

PubMed

Hu, Rujiu; Li, Jing; Soomro, Rab Nawaz; Wang, Fei; Feng, Yan; Yang, Xiaojun; Yao, Junhu

2017-01-01

This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.

The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters

PubMed Central

Hu, Rujiu; Li, Jing; Soomro, Rab Nawaz; Wang, Fei; Feng, Yan; Yang, Xiaojun

2017-01-01

This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients. PMID:29166671

Degradation kinetics of the antioxidant additive ascorbic acid in packed table olives during storage at different temperatures.

PubMed

Montaño, A; Casado, F J; Rejano, L; Sanchez, A H; de Castro, A

2006-03-22

The kinetics of ascorbic acid (AA) loss during storage of packed table olives with two different levels of added AA was investigated. Three selected storage temperatures were assayed: 10 degrees C, ambient (20-24 degrees C), and 40 degrees C. The study was carried out in both pasteurized and unpasteurized product. The effect of pasteurization treatment alone on added AA was not significant. In the pasteurized product, in general AA degraded following a first-order kinetics. The activation energy calculated by using the Arrhenius model averaged 9 kcal/mol. For each storage temperature, the increase in initial AA concentration significantly decreased the AA degradation rate. In the unpasteurized product, AA was not detected after 20 days in samples stored at room temperature and AA degradation followed zero-order kinetics at 10 degrees C, whereas at 40 degrees C a second-order reaction showed the best fit. In both pasteurized and unpasteurized product, the low level of initial dehydroascorbic acid disappeared during storage. Furfural appeared to be formed during storage, mainly at 40 degrees C, following zero-order kinetics.

Clinical implications of eicosapentaenoic acid/arachidonic acid ratio (EPA/AA) in adult patients with congenital heart disease.

PubMed

Kanoh, Miki; Inai, Kei; Shinohara, Tokuko; Tomimatsu, Hirofumi; Nakanishi, Toshio

2017-12-01

Recent studies showed that a low ratio between the levels of eicosapentaenoic acid and those of arachidonic acid (EPA/AA) is associated with higher incidence of coronary artery disease and poor prognosis of heart failure, arrhythmia, and cardiac sudden death. However, the clinical implications of EPA/AA in adult patients with congenital heart disease remain unclear. We aimed to assess the prognostic value of EPA/AA regarding cardiac events in adult patients with congenital heart disease. We measured the serum levels of eicosapentaenoic acid and arachidonic acid in 130 adult patients (median age, 31 years) stratified into two groups according to their EPA/AA (low, ≤0.22; high, >0.22). We prospectively analyzed the association between EPA/AA and incidence of cardiac events during a mean observation period of 15 months, expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI). In the subgroup of patients with biventricular circulation (2VC) (n = 76), we analyzed the same clinical endpoints. In our study population, EPA/AA was not associated with the incidence of arrhythmic events (HR, 1.52; 95% CI, 0.82-2.85; p = 0.19), but low EPA/AA was a predictor of heart failure hospitalization (HR, 2.83; 95% CI, 1.35-6.30; p < 0.01). Among patients with 2VC, an EPA/AA of ≤0.25 was associated with a significantly higher risk of arrhythmic events (HR, 2.55; 95% CI, 1.11-6.41; p = 0.03) and heart failure hospitalization (HR, 5.20; 95% CI, 1.78-18.1; p < 0.01). EPA/AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

Combined α-tocopherol and ascorbic acid protects against smoke-induced lung squamous metaplasia in ferrets.

PubMed

Kim, Yuri; Chongviriyaphan, Nalinee; Liu, Chun; Russell, Robert M; Wang, Xiang-Dong

2012-01-01

Many epidemiological studies show the benefit of fruits and vegetables on reducing risk of lung cancer, the leading cause of cancer death in the United States. Previously, we demonstrated that cigarette smoke exposure (SM)-induced lung lesions in ferrets were prevented by a combination of low dose of β-carotene, α-tocopherol (AT), and ascorbic acid (AA). However, the role of a combination of AT and AA alone in the protective effect on lung carcinogenesis remains to be examined. In the present study, we investigated whether the combined AT (equivalent to ∼100 mg/day in the human) and AA (equivalent to ∼210 mg/day) supplementation prevents against SM (equivalent to 1.5 packs of cigarettes/day) induced lung squamous metaplasia in ferrets. Ferrets were treated for 6 weeks in the following three groups (9 ferrets/group): (i) Control (no SM, no AT+AA), (ii) SM alone, and (iii) SM+AT+AA. Results showed that SM significantly decreased concentrations of retinoic acid, AT, and reduced form of AA, not total AA, retinol and retinyl palmitate, in the lungs of ferrets. Combined AT+AA treatment partially restored the lowered concentrations of AT, reduced AA and retinoic acid in the lungs of SM-exposed ferrets to the levels in the control group. Furthermore, the combined AT+AA supplementation prevented SM-induced squamous metaplasia [0 positive/9 total ferrets (0%) vs. 5/8 (62%); p<0.05] and cyclin D1 expression (p<0.05) in the ferret lungs, in which both were positively correlated with expression of c-Jun expression. Although there were no significant differences in lung microsomal malondialdehyde (MDA) levels among the three groups, we found a positive correlation between MDA levels and cyclin D1, as well as c-Jun expressions in the lungs of ferrets. These data indicate that the combination of antioxidant AT+AA alone exerts protective effects against SM-induced lung lesions through inhibiting cyclin D1 expression and partially restoring retinoic acid levels to normal. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Phospholipid sources for adrenic acid mobilization in RAW 264.7 macrophages. Comparison with arachidonic acid.

PubMed

Guijas, Carlos; Astudillo, Alma M; Gil-de-Gómez, Luis; Rubio, Julio M; Balboa, María A; Balsinde, Jesús

2012-11-01

Cells metabolize arachidonic acid (AA) to adrenic acid (AdA) via 2-carbon elongation reactions. Like AA, AdA can be converted into multiple oxygenated metabolites, with important roles in various physiological and pathophysiological processes. However, in contrast to AA, there is virtually no information on how the cells regulate the availability of free AdA for conversion into bioactive products. We have used a comparative lipidomic approach with both gas chromatography and liquid chromatography coupled to mass spectrometry to characterize changes in the levels of AA- and AdA-containing phospholipid species in RAW 264.7 macrophage-like cells. Incubation of the cells with AA results in an extensive conversion to AdA but both fatty acids do not compete with each other for esterification into phospholipids. AdA but not AA, shows preference for incorporation into phospholipids containing stearic acid at the sn-1 position. After stimulation of the cells with zymosan, both AA and AdA are released in large quantities, albeit AA is released to a greater extent. Finally, a variety of phosphatidylcholine and phosphatidylinositol molecular species contribute to AA; however, AdA is liberated exclusively from phosphatidylcholine species. Collectively, these results identify significant differences in the cellular utilization of AA and AdA by the macrophages, suggesting non-redundant biological actions for these two fatty acids. Copyright © 2012 Elsevier B.V. All rights reserved.

Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

PubMed

Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

2017-06-01

Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

Dietary arachidonic acid in perinatal nutrition: a commentary.

PubMed

Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo

2015-01-01

Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar levels in breast milk throughout the world, whereas the level of DHA is highly diet dependent. Autopsy studies show similar diet-dependent variation in brain DHA, whereas AA is little affected by intake. Early intake of DHA has been shown to affect visual development, but the effect of LCPUFA on neurodevelopment remains to be established. Few studies have found any functional difference between infants supplemented with DHA alone compared to DHA+AA, but some studies show neurodevelopmental advantages in breast-fed infants of mothers supplemented with n-3 LCPUFA alone. It also remains to be established whether the AA/DHA balance could affect allergic and inflammatory outcomes later in life. Disentangling effects of genetic variability and dietary intake on AA and DHA-status and on functional outcomes may be an important step in the process of determining whether AA-intake is of any physiological or clinical importance. However, based on the current evidence we hypothesize that dietary AA plays a minor role on growth and development relative to the impact of dietary DHA.

Relation of soya bean meal level to the concentration of plasma free amino acids and body growth in white rats.

PubMed

Mandal, Tapas K; Parvin, Nargish; Mondal, Santanu; Saxena, Vijaylaxmi; Saxena, Ashok K; Sarkar, Sabyasachi; Saha, Mitali

2012-04-01

Amino acid (AA) levels in plasma and body growth were determined in rats (n20) fed diets with different soya bean meal levels. Free AA in plasma was determined by reversed-phase high-pressure liquid chromatography. We have used four levels of protein diets like 8%, 15%, 23% and 35% in this trial. Rats which were fed the low-protein (8%) diet with low percentage of soya bean meal were found to be growth-retarded. The body weight gain of high protein group (35%) was lower than that of the 23% groups. In the rats fed with the low-soya bean meal diet, some nonessential AA (NEAA) in plasma like asparagine, aspartic acid, cysteine, glutamic acid and serine increased, whereas the essential AA (EAA), with the exception of arginine, methionine and valine decreased. Here, plasma EAA-to-NEAA ratios were not correlated to growth and experimental diet. We hypothesize that AA metabolism is associated to changes in growth in rats on different protein intake. This study has showed the sensitivity of body mass gain, feed intake, feed conversion rate of rats to four levels of protein in the diet under controlled experimental conditions. © 2011 Blackwell Verlag GmbH.

[Levels of serum ascorbate and its metabolites in hemodialysis patients].

PubMed

Hirano, Hiroko; Tone, Yoshinori; Otani, Haruhisa; Oya, Masaki; Kimura, Keigo; Saika, Yasushi; Fujii, Ryoichi; Mune, Masatoshi; Ichinose, Masakazu; Yukawa, Susumu

2004-07-01

The status of ascorbic acid (AA) in dialysis patients is the subject of debate. Some reports have found AA to be deficient in dialysis patients, while others have found that AA is not deficient. In an attempt to confirm AA serum concentrations in dialysis patients, we analyzed the concentrations of AA as well as its metabolites using the specific determination of AA with chemical derivatization and the HPLC method. We studied 131 patients under maintenance hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48 healthy controls (C). Serum concentrations of AA and the AA metabolites dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC. Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD patients not taking AA supplements exhibited deficient levels of AA (< 20 microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80 microM) group revealed that the DHA/AA ratio in HD patients was significantly higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%), whereas DKG was not detected in C. When compared to serum levels before the start of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD patients, serum levels of thiobarbituric reactive substances (TBARS) were significantly lower in the higher AA (> 80 microM) group than in the deficient and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum TBARS level declined when compared with levels before supplementation. In conclusion, the frequency of AA deficiency in dialysis patients is extremely high. AA deficiency in HD patients may result in high TBARS levels, which reflect increased oxidative stress. Adequate AA supplementation should therefore be considered in such patients.

Estimation of endogenous protein and amino acid ileal losses in weaned piglets by regression analysis using diets with graded levels of casein

PubMed Central

2013-01-01

Background Many studies have investigated endogenous loss of proteins and amino acids (AAs) at the ileal level in growing pigs. However, only a few studies have researched this subject in piglets. Knowledge regarding AA ileal digestibility in piglets would be helpful during the formulation of diets for weaning piglets, rather than just using coefficients obtained in growing pigs. Therefore, in this study, we sought to estimate endogenous protein and AA ileal losses in piglets. Furthermore, apparent and true ileal digestibility (AID and TID) of protein and AAs from casein were measured. Results The average flow of protein was 20.8 g/kg of dry matter intake (DMI). Basal protein loss, as estimated by regression, was 16.9 g/kg DMI. Glutamic acid, arginine, and aspartic acid (2.2, 1.4, and 1.2 g/kg DMI, respectively) were the AAs for which greater losses were seen. The AID of protein and AAs increased as the protein level in the diet increased. A higher increment in AID was observed between diets with 80 and160 g CP/kg of feed; this finding was mainly attributable to increases in glycine and arginine (46.1% and 18%, respectively). The TID of protein was 97.8, and the TID of AAs varied from 93.9 for histidine to 100.2 for phenylalanine. Conclusions The basal endogenous protein loss in piglets was 16.9 g/kg DMI. Endogenous protein was rich in glutamic acid, aspartic acid, and arginine, which represented 32.7% of endogenous protein loss in weaning piglets. The TID of casein was high and varied from 93.0 for histidine to 100.2 for phenylalanine. PMID:24053636

Differences in Arachidonic Acid Levels and Fatty Acid Desaturase (FADS) Gene Variants in African Americans and European Americans with Diabetes/Metabolic Syndrome

PubMed Central

Sergeant, Susan; Hugenschmidt, Christina E.; Rudock, Megan E.; Ziegler, Julie T.; Ivester, Priscilla; Ainsworth, Hannah C.; Vaidya, Dhananjay; Case, L. Douglas; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.; Mathias, Rasika A.; Chilton, Floyd H.

2012-01-01

Over the past 50 years, increases in dietary n-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, have been hypothesized to cause or exacerbate chronic inflammatory diseases. This study examines an individual’s innate capacity to synthesize n-6-long chain PUFAs (LC-PUFAs), with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes/metabolic syndrome. Compared to European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7.9±2.1; AfAm 9.8±1.9 % of total fatty acids, mean ± sd; p<2.29×10−9) and the AA to n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5.4±2.2, AfAm 6.9±2.2; p=1.44×10−5). Seven single nucleotide polymorphisms (SNP) mapping to the FADS locus revealed strong association with AA, eicosapentaenoic acid (EPA) and dihomogamma-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT: 6.3±1.0; GG: 8.5±2.1; p=3.0×10−5) and AA/DGLA ratios (TT: 3.4±0.8; GG: 6.5±2.3; p=2.2×10−7) but higher DGLA levels (TT: 1.9±0.4; GG: 1.4±0.4; p=3.3×10−7) compared to those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0.81) compared to EAm (0.46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are likely important differences in the capacity of different populations to synthesize LC-PUFAs. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent. PMID:21733300

Absence of a Causal Relationship between Auxin-Induced Growth and Changes in the Content of Ascorbic and Dehydroascorbic Acids in Excised Plant Tissues 12

PubMed Central

Lin, C. Y.; Key, Joe L.

1967-01-01

The data reported indicate that the oxidation-reduction balance of the ascorbic acid system is not causally related to the auxin-regulation of cell elongation. There was no shift in the ascorbic acid (AA) to dehydroascorbic acid (DHA) ratio with growth-promoting concentration of auxin in several plant tissues. The AA to DHA ratio was experimentally increased without altering the growth rate. Inhibition of growth by supra-optimal auxin was associated with a decrease in the AA to DHA ratio. Since the AA to DHA ratio was lowered by EDTA treatment without altering growth, it seems unlikely that the decrease in the AA to DHA ratio related to the inhibition of growth by high levels of auxin. PMID:16656564

Growth and clinical variables in nitrogen-restricted piglets fed an adjusted essential amino acid mix: Effects using partially intact protein-based diets

USDA-ARS?s Scientific Manuscript database

Current recommendations for protein levels in infant formula ensure that growth matches or exceeds growth of breast-fed infants, but may provide a surplus of amino acids (AA). Recent studies in infants using AA-based formulas support specific adjustment of the essential AA (EAA) composition allowing...

Metabolic cooperation of ascorbic acid and glutathione in normal and vitamin C-deficient ODS rats.

PubMed

Wang, Y; Kashiba, M; Kasahara, E; Tsuchiya, M; Sato, E F; Utsumi, K; Inoue, M

2001-01-01

Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato-renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased.

Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids.

PubMed

Lotrich, Francis E; Sears, Barry; McNamara, Robert K

2013-11-01

Anger worsens in some patients during interferon-alpha (IFN-α) therapy. Elevated anger has also been associated with lower long-chain omega-3 (LCn-3) fatty acid levels. We examined whether fatty acids could influence vulnerability to anger during IFN-α exposure. Plasma arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were determined prior to IFN-α therapy by mass spectroscopy. Repeated-measure analyses examined the relationship between AA/EPA+DHA and the subsequent development of labile anger and irritability in 82 subjects who prospectively completed the Anger, Irritability, and Assault Questionnaire (AIAQ) during the first eight weeks of IFN-α therapy. Prior to IFN-α therapy, AA/EPA+DHA did not correlate with either labile anger or irritability. Pre-treatment AA/EPA+DHA did correlate with the subsequent maximal increase in labile anger during IFN-α therapy (r=0.33; p=0.005). Over time, labile anger increased more in subjects with above median AA/EPA+DHA ratios (p<0.05). Of the 17 subjects ultimately requiring psychiatric intervention for anger, 14/17 had above-median AA/EPA+DHA ratios (p=0.009). There was also an interaction with the tumor necrosis factor-alpha (TNF-α) promoter polymorphism (A-308G), such that only those with both elevated AA/EPA+DHA and the A allele had increased labile anger (p=0.001). In an additional 18 subjects, we conversely observed that selective serotonin reuptake inhibitor treatment was associated with increased irritability during IFN-α therapy. LCn-3 fatty acid status may influence anger development during exposure to elevated inflammatory cytokines, and may interact with genetic risk for increased brain TNF-α. LCn-3 supplements may be one strategy for minimizing this adverse side effect of IFN-α. © 2013.

Amino acid supplementation alters bone metabolism during simulated weightlessness

NASA Technical Reports Server (NTRS)

Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

2005-01-01

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Decreased eicosapentaenoic acid levels in acne vulgaris reveals the presence of a proinflammatory state.

PubMed

Aslan, İbrahim; Özcan, Filiz; Karaarslan, Taner; Kıraç, Ebru; Aslan, Mutay

2017-01-01

This study aimed to determine circulating levels of polyunsaturated fatty acids (PUFAs), secretory phospholipase A2 (sPLA2), lipoprotein lipase (LPL) and measure circulating protein levels of angiopoietin-like protein 3 (ANGPTL3), ANGPTL4, cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with acne vulgaris. Serum from 21 control subjects and 31 acne vulgaris patients were evaluated for levels of arachidonic acid (AA, C20:4n- 6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3). PUFA levels were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods Serum EPA levels were significantly decreased while AA/EPA and DGLA/EPA ratio were significantly increased in acne vulgaris patients compared to controls. Serum levels of AA, DGLA and DHA showed no significant difference while activity of sPLA2 and LPL were significantly increased in acne vulgaris compared to controls. Results of this study reveal the presence of a proinflammatory state in acne vulgaris as shown by significantly decreased serum EPA levels and increased activity of sPLA2, AA/EPA and DGLA/EPA ratio. Increased LPL activity in the serum of acne vulgaris patients can be protective through its anti-dyslipidemic actions. This is the first study reporting altered EPA levels and increased sPLA2 activity in acne vulgaris and supports the use of omega-3 fatty acids as adjuvant treatment for acne patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

PubMed Central

Aquilani, Roberto; La Rovere, Maria Teresa; Corbellini, Daniela; Pasini, Evasio; Verri, Manuela; Barbieri, Annalisa; Condino, Anna Maria; Boschi, Federica

2017-01-01

The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF), and relate them to left ventricular function and disease severity. Amino acids (AAs) play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA) class II to IV) were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI), protein-, fat-, carbohydrate-intake, resting energy expenditure (REE), total daily energy expenditure (REE × 1.3), and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF) severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001) and cardiac index (r = 0.4243; p = 0.0028). The value of arterial aspartic acid (µmol/L) multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076). All NYHA groups had adequate protein intake (≥1.1 g/kg/day) and inadequate calorie intake (KcalI < REE × 1.3) was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction. PMID:29140312

Pharmacokinetics of aniracetam and its metabolites in rat brain.

PubMed

Ogiso, T; Uchiyama, K; Suzuki, H; Yoshimoro, M; Tanino, T; Iwakai, M; Uno, S

2000-04-01

The pharmacokinetics of aniracetam (AP) and its main metabolites, 4-p-anisamidobutyric acid (ABA), 2-pyrrolidinone (PD) and p-anisic acid (AA), in 3 brain regions (cerebral cortex, hippocampus and thalamus) was investigated after single intravenous (i.v.) and oral administrations of AP to rats. AP, AA and PD were rapidly distributed into the 3 brain regions after i.v. administration of AP, but the amounts of AP were low. The concentrations of AP and AA in brain regions rapidly declined, whereas PD levels were higher and more sustained than those of AP and AA. ABA levels in the regions were below the detection limit. There were no significant differences in the distribution of these compounds in the 3 brain regions. The AUCbrain/AUCplasma ratio of PD was 53--55%, in contrast to the low ratio of AP (2.4--3.2%) and AA (3.9--4.2%). On oral administration of AP, the AUCbrain/AUCplasma ratio of PD was also higher than that of AA. When the transport of PD was tested using the in situ brain perfusion technique, it was clarified that PD was not transported across the blood-brain barrier (BBB) by a neutral amino acid carrier system. The high brain levels of PD and the low levels of AP suggest that the clinical efficacy of dosed AP may partly result from PD penetrating into the brain.

A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology.

PubMed

Fan, Yang-Yi; Callaway, Evelyn; M Monk, Jennifer; S Goldsby, Jennifer; Yang, Peiying; Vincent, Logan; S Chapkin, Robert

2016-09-01

A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P < 0.05) in AA, PGE2, 6-keto PGF1α, TXB2, and EdU-positive proliferative cells in the colon. In subsequent experiments, null mice supplemented with 0.6% AA diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (P < 0.05) reduced levels/multiplicity of aberrant crypt foci (ACF) as compared with wild-type sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1-null mouse model for long-term cancer prevention studies and (ii) that AA content in the colonic epithelium modulates colon cancer risk. Cancer Prev Res; 9(9); 750-7. ©2016 AACR. ©2016 American Association for Cancer Research.

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.

PubMed

Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

2018-03-30

The metabolism of polyunsaturated fatty acids (PUFAs) remains poorly characterized in ovarian tissues of patients with polycystic ovary syndrome (PCOS). This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed between control, high-fat diet-fed and PCOS rats. The levels of prostaglandins, AA metabolites via the cyclooxygenase (COX) pathway, in ovarian tissues of the PCOS group were significantly increased compared to those in the controls. Further studies on the mechanism underlying this phenomenon showed a correlation between decreased expression of phosphorylated cytosolic phospholipase A2 (p-cPLA2) and increased mRNA and protein expression of COX2, potentially leading to a deeper understanding of altered AA and prostaglandin levels in ovarian tissues of PCOS rats. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

PubMed

Fu, Yuanqing; Liu, Xin; Zhou, Bing; Jiang, Alice C; Chai, Lingying

2016-10-01

We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, P<0·05). Data from the Asian region showed the highest DHA concentration but much lower AA concentration in breast milk compared with all other regions, independent of accessibility to marine foods. Comparison was made among Canada, Poland and Japan - three typical countries (each with sample size of more than 100 women) from different regions but all with high income and similar accessibility to fish/marine foods. The current review provides an update on worldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

Effects of seasonings on the stability of ascorbic acid in a cooking model system.

PubMed

Kishida, Etsu; Maeda, Tomoko; Nishihama, Akiko; Kojo, Shosuke; Masuzawa, Yasuo

2004-12-01

The thermolability of ascorbic acid (AA) in aqueous solution at 100 degrees C was assessed in the presence of various seasonings commonly used in Japanese-style cooking. A model system approximated Japanese cooking with regard to the concentrations of AA and seasonings and the heating time. The decrease of AA in the reaction system of this experiment was a first-order reaction with respect to the concentration of AA loss. Although kinetic constants for AA loss decreased with increasing concentrations of AA (25-400 microg/mL), the absolute amounts degraded were almost the same for all AA concentrations, suggesting that dissolved oxygen is one of main factors affecting the stability of AA solutions during heating at 100 degrees C. When each seasoning was added to AA solution, salt stabilized AA and Japanese alcohol-containing admixtures, such as sake and sweet sake (mirin), did not have a significant effect on the stability. Conversely, soy sauce, miso (fermented soybean paste) and broth powder from skipjack accelerated the decrease of AA in a concentration-dependent manner. The kinetic study suggested that oxygen was rapidly consumed and AA loss accelerated by addition of soy sauce or miso to AA solution. Consequently it is likely that a reaction mechanism shifts from aerobic to anaerobic and the forward reactions proceed. Of the constituents of Japanese seasonings, not only iron but also amino acids are involved in the acceleration of AA degradation. The presence of amino acids should be taken into account when considering the levels of AA in soups.

Altered Arachidonate Distribution in Macrophages from Caveolin-1 Null Mice Leading to Reduced Eicosanoid Synthesis*

PubMed Central

Astudillo, Alma M.; Pérez-Chacón, Gema; Meana, Clara; Balgoma, David; Pol, Albert; del Pozo, Miguel A.; Balboa, María A.; Balsinde, Jesús

2011-01-01

In this work we have studied the effect of caveolin-1 deficiency on the mechanisms that regulate free arachidonic acid (AA) availability. The results presented here demonstrate that macrophages from caveolin-1-deficient mice exhibit elevated fatty acid incorporation and remodeling and a constitutively increased CoA-independent transacylase activity. Mass spectrometry-based lipidomic analyses reveal stable alterations in the profile of AA distribution among phospholipids, manifested by reduced levels of AA in choline glycerophospholipids but elevated levels in ethanolamine glycerophospholipids and phosphatidylinositol. Furthermore, macrophages from caveolin-1 null mice show decreased AA mobilization and prostaglandin E2 and LTB4 production upon cell stimulation. Collectively, these results provide insight into the role of caveolin-1 in AA homeostasis and suggest an important role for this protein in the eicosanoid biosynthetic response. PMID:21852231

ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

EPA Science Inventory

ABSTRACT
Evidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study.

PubMed

Madsen, Trine; Christensen, Jeppe H; Svensson, My; Witt, Petra M; Toft, Egon; Schmidt, Erik B

2011-03-01

Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. A comparative study was carried out. This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

PubMed

Ghebremeskel, K; Min, Y; Crawford, M A; Nam, J H; Kim, A; Koo, J N; Suzuki, H

2000-05-01

Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P < 0.05) and palmitic and oleic acids higher (P < 0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P < 0.05) and higher palmitic and oleic acids (P < 0.01). The reduction in DHA and total n-3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n-6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n-6 series and DPA/DTA ratio did not increase with the decrease of the n-3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n-3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

Differential effects of military training on fat-free mass and plasma amino acid adaptations in men and women.

PubMed

Margolis, Lee M; Pasiakos, Stefan M; Karl, J Philip; Rood, Jennifer C; Cable, Sonya J; Williams, Kelly W; Young, Andrew J; McClung, James P

2012-12-18

Fat-free mass (FFM) adaptations to physical training may differ between sexes based on disparities in fitness level, dietary intake, and levels of plasma amino acids (AA). This investigation aimed to determine FFM and plasma AA responses to military training, examine whether adaptations differ between male and female recruits, and explore potential associations between FFM and AA responses to training. Body composition and plasma AA levels were assessed in US Army recruits (n = 209, 118 males, 91 females) before (baseline) and every three weeks during basic combat training (BCT), a 10-week military training course. Body weight decreased in men but remained stable in women during BCT (sex-by-time interaction, P < 0.05). Fifty-eight percent of recruits gained FFM during BCT, with more (P < 0.05) females (88%) gaining FFM than males (36%). Total plasma AA increased (P < 0.05) during BCT, with greater (P < 0.05) increases observed in females (17%) then in males (4%). Essential amino acids (EAA) and branched-chain amino acids (BCAA) were increased (P < 0.05) in females but did not change in males (sex-by-time interaction, P < 0.05). Independent of sex, changes in EAA (r = 0.34) and BCAA (r = 0.27) from baseline were associated with changes in FFM (P < 0.05); greater (P < 0.05) increases in AA concentrations were observed for those who gained FFM. Increases in FFM and plasma AA suggest that BCT elicits a more pronounced anabolic response in women compared to men, which may reflect sex-specific differences in the relative intensity of the combined training and physiological stimulus associated with BCT.

Differential Effects of Military Training on Fat-Free Mass and Plasma Amino Acid Adaptations in Men and Women

PubMed Central

Margolis, Lee M.; Pasiakos, Stefan M.; Karl, J. Philip; Rood, Jennifer C.; Cable, Sonya J.; Williams, Kelly W.; Young, Andrew J.; McClung, James P.

2012-01-01

Fat-free mass (FFM) adaptations to physical training may differ between sexes based on disparities in fitness level, dietary intake, and levels of plasma amino acids (AA). This investigation aimed to determine FFM and plasma AA responses to military training, examine whether adaptations differ between male and female recruits, and explore potential associations between FFM and AA responses to training. Body composition and plasma AA levels were assessed in US Army recruits (n = 209, 118 males, 91 females) before (baseline) and every three weeks during basic combat training (BCT), a 10-week military training course. Body weight decreased in men but remained stable in women during BCT (sex-by-time interaction, P < 0.05). Fifty-eight percent of recruits gained FFM during BCT, with more (P < 0.05) females (88%) gaining FFM than males (36%). Total plasma AA increased (P < 0.05) during BCT, with greater (P < 0.05) increases observed in females (17%) then in males (4%). Essential amino acids (EAA) and branched-chain amino acids (BCAA) were increased (P < 0.05) in females but did not change in males (sex-by-time interaction, P < 0.05). Independent of sex, changes in EAA (r = 0.34) and BCAA (r = 0.27) from baseline were associated with changes in FFM (P < 0.05); greater (P < 0.05) increases in AA concentrations were observed for those who gained FFM. Increases in FFM and plasma AA suggest that BCT elicits a more pronounced anabolic response in women compared to men, which may reflect sex-specific differences in the relative intensity of the combined training and physiological stimulus associated with BCT. PMID:23250145

A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity.

PubMed

Yu, Keshun; Soares, Juliana Moreira; Mandal, Mihir Kumar; Wang, Caixia; Chanda, Bidisha; Gifford, Andrew N; Fowler, Joanna S; Navarre, Duroy; Kachroo, Aardra; Kachroo, Pradeep

2013-04-25

Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P). Pathogen inoculation induced the release of free unsaturated fatty acids (FAs) and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Risk assessment of plant food supplements and other herbal products containing aristolochic acids using the margin of exposure (MOE) approach.

PubMed

Abdullah, Rozaini; Diaz, Leolean Nyle; Wesseling, Sebastiaan; Rietjens, Ivonne M C M

2017-02-01

After the incidences of induction of aristolochic acid nephropathy after consumption of herbal weight loss preparations that accidentally contained aristolochic acids (AAs), several countries defined national restrictions on the presence of AAs in food, including plant food supplements (PFS) and herbal products. This study investigates whether the risks associated with exposure to AAs via PFS and herbal products are at present indeed negligible. Data reported in literature on AA levels in PFS and other herbal products and also obtained from a new series of PFS in the present study were used to calculate the estimated daily intakes (EDIs) and corresponding margins of exposure (MOEs). Available literature data revealed that 206 out of 573 samples were found to contain aristolochic acid I (AAI) and/or aristolochic acid II (AAII). The results obtained from recently collected PFS revealed that both AAI and AAII were detected in three out of 18 analysed PFS at levels up to 594.8 and 235.3 µg g -1 , respectively, being in line with the levels reported in literature. The EDIs resulting from intake of these PFS resulted in MOEs that were generally below 10,000, corroborating the priority for risk management. Although these results refer to PFS collected by targeted sampling strategies, the data reveal that AA-containing PFS are still freely available. When considering that the use of these samples may be limited to shorter periods of time, the EDIs might be lower, but MOE values would still be lower than 10,000 for more than 50% of the AA-containing PFS and herbal products. In conclusion, the presence of AAs in PFS and herbal products even several years after instalment of the legal restrictions still raises concern, especially for people who frequently use the respective PFS and herbal products.

Enhancement of myofibrillar proteolysis following infusion of amino acid mixture correlates positively with elevation of core body temperature in rats.

PubMed

Yamaoka, Ippei; Mikura, Mayumi; Nishimura, Masuhiro; Doi, Masako; Kawano, Yuichi; Nakayama, Mitsuo

2008-12-01

Administration of an amino acid (AA) mixture stimulates muscle protein synthesis and elevates core body temperature (T(b)), as characteristically found under anesthetic conditions. We tested the hypothesis that not only AA given, but also AA produced by degradation of endogenous muscular protein are provided for muscle protein synthesis, which is further reflected in T(b) modifications. Rats were intravenously administered an AA mixture or saline in combination with the anesthetic propofol or lipid emulsion. We measured plasma 3-methylhistidine (MeHis) concentrations as an index of myofibrillar protein degradation, rectal temperature and mRNA expression of atrogin-1, MuRF-1 and ubiquitin in gastrocnemius and soleus muscles of rats following 3 h infusion of test solutions. T(b) did not differ significantly between conscious groups, but was higher in the AA group than in the saline group among anesthetized rats. Plasma MeHis concentrations were higher in the AA group than in the saline group under both conditions. Plasma MeHis levels correlated positively with T(b) of rats under both conditions. AA administration decreased mRNA levels of atrogin-1 and ubiquitin in gastrocnemius muscle and all mRNA levels in soleus muscle. These results suggest that AA administration enhances myofibrillar protein degradation and that the change is a determinant of T(b) modification by AA administration. However, the mechanisms underlying AA administration-associated enhancement of myofibrillar proteolysis remains yet to be determined.

The Ratio of Eicosapentaenoic Acid (EPA) to Arachidonic Acid may be a Residual Risk Marker in Stable Coronary Artery Disease Patients Receiving Treatment with Statin Following EPA Therapy.

PubMed

Tani, Shigemasa; Nagao, Ken; Kawauchi, Kenji; Yagi, Tsukasa; Atsumi, Wataru; Matsuo, Rei; Hirayama, Atsushi

2017-10-01

We investigated the relationship between the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio and non-high-density lipoprotein cholesterol (non-HDL-C) level, a major residual risk of coronary artery disease (CAD), in statin-treated CAD patients following EPA therapy. We conducted a 6-month, prospective, randomized clinical trial to investigate the effect of the additional administration of EPA on the EPA/AA ratio and the serum non-HDL-C level in stable CAD patients receiving statin treatment. We assigned CAD patients already receiving statin therapy to an EPA group (1800 mg/day; n = 50) or a control group (n = 50). A significant reduction in the serum non-HDL-C level was observed in the EPA group, compared with the control group (-9.7 vs. -1.2%, p = 0.01). A multiple-regression analysis with adjustments for coronary risk factors revealed that achieved EPA/AA ratio was more reliable as an independent and significant predictor of a reduction in the non-HDL-C level at a 6-month follow-up examination (β = -0.324, p = 0.033) than the absolute change in the EPA/AA ratio. Interestingly, significant negative correlations were found between the baseline levels and the absolute change values of both non-HDL-C and triglyceride-rich lipoproteins, both markers of residual risk of CAD, indicating that patients with a higher baseline residual risk achieved a greater reduction. The present results suggest that the achieved EPA/AA ratio, but not the absolute change in EPA/AA ratio, following EPA therapy might be a useful marker for the risk stratification of CAD among statin-treated patients with a high non-HDL-C level. UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000010452.

Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner

PubMed Central

Shibuya, Shuichi; Sakaguchi, Ikuyo; Ito, Shintaro; Kato, Eiko; Watanabe, Kenji; Izuo, Naotaka; Shimizu, Takahiko

2017-01-01

Ascorbic acid (AA) possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound’s high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action. In contrast, torisodium ascorbyl 6-palmitate 2-phosphate (APPS) treatment significantly enhanced the cellular AA level in skin cells despite the presence of inhibitors. In ex vivo experiments, APPS treatment also increased the AA content in a human epidermis model. Interestingly, APPS was readily metabolized and converted to AA in keratinocyte lysates via an intrinsic mechanism. Furthermore, APPS markedly repressed the intracellular superoxide generation and promoted viability associated with an enhanced AA level in Sod1-deficient skin cells. These findings indicate that APPS effectively restores the AA level and normalizes the redox balance in skin cells in an AA transporter-independent manner. Topical treatment of APPS is a beneficial strategy for supplying AA and improving the physiology of damaged skin. PMID:28640219

The effect of particle immersing in acetic acid solution on dimensional stability and strength properties of particleboard

NASA Astrophysics Data System (ADS)

Heri Iswanto, Apri; Hermanto, Samuel; Sucipto, Tito

2018-03-01

The objective of the research was to evaluate the effect of particle immersing treatments in acetic acid (AA) solution on dimensional stability and strength properties of particleboard. Particle was immersed in various level AA solution namely 0 (untreated), 1, 2, 3, 4% for 24 hours. Afterward, the particle was oven dried up to 5% moisture content. The amount of 12% UF resin level used for binding in manufacturing particleboard. Board size, thickness and density target in this experiment was 25 by 25 cm2, 1 cm, and 0.75 g/cm3 respectively. After mat forming, board pressed using 130°C temperature, 30 kg/cm2, and pressure for 10 minutes. The results showed that particles immersing in AA solution provide enhancement of thickness swelling (TS) parameters. Overall, 1% AA solution is the best treatment to improve dimensional stability. The similar results also showed by internal bond value. In general, the excess of 1% acetic acid level resulted in decreasing of IB value. A similar trend also occurs in modulus of rupture (MoR) and modulus of elasticity (MoE) parameters.

Amino Acids Inhibitory Effects and Mechanism on 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b]Pyridine (PhIP) Formation in the Maillard Reaction Model Systems.

PubMed

Linghu, Ziyi; Karim, Faris; Smith, J Scott

2017-12-01

This study was to investigate the inhibitory effects of amino acids (AAs) on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and to evaluate the inhibition mechanism of PhIP in Maillard model systems. Different AAs were individually added into model systems heat-treated at 180 °C/1 h. The PhIP, phenylacetaldehyde (PheAce), and pyrazines derivatives were determined using HPLC and GC-MS. AAs significantly reduced (P < 0.05) PhIP levels in a dose-dependent response, ranking as: Trp = Lys > Pro > Leu > Met > Val > Ile > Thr > Phe > Asp, at the highest molar ratio. The PheAce content was gradually reduced with increasing AAs levels, suggesting that AAs may inhibit PhIP formation through scavenging the available PheAce. A correlation between PhIP inhibition and PheAce-scavenging activity of AAs was observed when PheAce and AAs were heated. The variety and quantity of pyrazines formed are highly depending on the type of AAs. © 2017 Institute of Food Technologists®.

Omega-3 Fatty Acids Supplementation: Therapeutic Potential in a Mouse Model of Stargardt Disease.

PubMed

Prokopiou, Ekatherine; Kolovos, Panagiotis; Kalogerou, Maria; Neokleous, Anastasia; Nicolaou, Orthodoxia; Sokratous, Kleitos; Kyriacou, Kyriacos; Georgiou, Tassos

2018-06-01

To evaluate the therapeutic effects of omega-3 (ω3) fatty acids on retinal degeneration in the ABCA4-/- model of Stargardt disease when the blood level of arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is between 1 and 1.5. Eight-month-old mice were allocated to three groups: wild type (129S1), ABCA4-/- untreated, and ABCA4-/- ω3 treated. ω3 treatment lasted 3 months and comprised daily gavage administration of EPA and docosahexaenoic acid (DHA). Blood and retinal fatty acid analysis was performed using gas chromatography to adjust the blood AA/EPA ∼1 to 1.5. Eyecups were histologically examined using transmission electron microscopy and confocal microscopy to evaluate lipofuscin granules and the photoreceptor layer. Retinal N-retinylidene-N-retinylethanolamine (A2E), a major component of retinal pigment epithelium lipofuscin, was quantified using liquid chromatography and tandem mass spectrometry, in addition to retinal proteomic analysis to determine changes in inflammatory proteins. EPA levels increased and AA levels decreased in the blood and retinas of the treatment group. Significantly less A2E and lipofuscin granules were observed in the treatment group. The thickness of the outer nuclear layer was significantly greater in the treatment group (75.66 ± 4.80 μm) than in the wild-type (61.40 ± 1.84 μm) or untreated ABCA4-/- (56.50 ± 3.24 μm) groups. Proteomic analysis indicated lower levels of complement component 3 (C3) in the treatment group, indicative of lower complement-induced inflammatory response. Three months of ω3 supplementation (AA/EPA ∼1-1.5) reduces A2E levels, lipofuscin granules, and C3 levels in the ABCA4-/- mouse model of Stargardt disease, consistent with slowing of the disease.

Low Serum Levels of EPA are Associated with the Size and Growth Rate of Abdominal Aortic Aneurysm.

PubMed

Aikawa, Tatsuro; Miyazaki, Tetsuro; Shimada, Kazunori; Sugita, Yurina; Shimizu, Megumi; Ouchi, Shohei; Kadoguchi, Tomoyasu; Yokoyama, Yasutaka; Shiozawa, Tomoyuki; Hiki, Masaru; Takahashi, Shuhei; Al Shahi, Hamad; Dohi, Shizuyuki; Amano, Atsushi; Daida, Hiroyuki

2017-09-01

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to reduce the risk of cardiovascular disease. However, whether omega-3 PUFAs are involved in the pathogenesis of abdominal aortic aneurysms (AAA) remains unclear. We analyzed 67 consecutive patients admitted for the elective surgical repair of AAA. We investigated the association of serum EPA and DHA levels as well as the EPA/AA ratio with the size of AAA assessed using three-dimensional reconstructed computed tomography images. Mean patient age was 70±9 years and 60 patients were male. Serum EPA and DHA levels were 75.2±35.7 μg/mL and 146.1±48.5 μg/mL, respectively. EPA/AA ratio was 0.44±0.22, which was lower than those in healthy Japanese subject and equivalent to those in Japanese patients with coronary artery disease as previously reported. Mean of the maximum AAA diameter was 56.4±8.9 mm, and serum EPA levels and EPA/AA ratio negatively correlated with it (r=-0.32 and r=-0.32, respectively). Multiple liner regression analysis showed that EPA levels were significant independent factor contributing to the maximum AAA diameter. Furthermore, low serum EPA levels and low EPA/AA ratio were significantly associated with the growth rate of AAA diameter (r=-0.43 and r=-0.33, respectively). EPA levels in patients with AAA were relatively low. Low serum EPA levels and EPA/AA ratio were associated with the size and growth rate of AAA.

Variation in plasma amino acid concentrations during a cycling competition.

PubMed

Medelli, J; Lounana, J; Hill, D

2003-06-01

The variations in plasma concentrations of 24 amino acids (AAs) were measured, taking into account modifications in plasma volume, in 7 male subjects, professional cyclists, during the first 2 stages (EI and EII) of the competition "4 Days of Dunkirk 1999". Blood samples were taken before the start and at the end of each stage. At the end of EI a significant reduction (p<0.02) in alpha-aminobutyric acid was observed (-38%) and a significant increase (Wilcoxon 0.01

Low plasma eicosapentaenoic acid concentration as a possible risk factor for intracerebral hemorrhage.

PubMed

Ikeya, Yoshimori; Fukuyama, Naoto; Mori, Hidezo

2015-03-01

N-3 fatty acids, including eicosapentaenoic acid (EPA), prevent ischemic stroke. The preventive effect has been attributed to an antithrombic effect induced by elevated EPA and reduced arachidonic acid (AA) levels. However, the relationship between intracranial hemorrhage and N-3 fatty acids has not yet been elucidated. In this cross-sectional study, we compared common clinical and lifestyle parameters between 70 patients with intracranial hemorrhages and 66 control subjects. The parameters included blood chemistry data, smoking, alcohol intake, fish consumption, and the incidences of underlying diseases. The comparisons were performed using the Mann-Whitney U test followed by multiple logistic regression analysis. Nonparametric tests revealed that the 70 patients with intracerebral hemorrhages exhibited significantly higher diastolic blood pressures and alcohol intakes and lower body mass indices, high-density lipoprotein (HDL) cholesterol levels, EPA concentrations, EPA/AA ratios, and vegetable consumption compared with the 66 control subjects. A multiple logistic regression analysis revealed that higher diastolic blood pressure and alcohol intake and lower body mass index, HDL cholesterol, EPA/AA ratio, and vegetable consumption were relative risk factors for intracerebral hemorrhage. High HDL cholesterol was a common risk factor in both of the sex-segregated subgroups and the <65-year-old subgroup. However, neither EPA nor the EPA/AA ratio was a risk factor in these subgroups. Eicosapentaenoic acid was relative risk factor only in the ≥65-year-old subgroup. Rather than higher EPA levels, lower EPA concentrations and EPA/AA ratios were found to be risk factors for intracerebral hemorrhage in addition to previously known risk factors such as blood pressure, alcohol consumption, and lifestyle. Copyright © 2015 Elsevier Inc. All rights reserved.

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

PubMed Central

2011-01-01

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis. PMID:21375761

Synergistic protective role of mirazid (Commiphora molmol) and ascorbic acid against tilmicosin-induced cardiotoxicity in mice.

PubMed

Abdel-Daim, Mohamed M; Ghazy, Emad W; Fayez, Mostafa

2015-01-01

Tilmicosin (TIL) is a long-acting macrolide antibiotic approved for the treatment of cattle with Bovine Respiratory Disease. However, overdose of TIL has been reported to induce cardiotoxicity. The purpose of our experiment was to evaluate the protective effects of Commiphora molmol (mirazid (MRZ); myrrh) and (or) ascorbic acid (AA) against TIL-induced cardiotoxicity in mice. MRZ and AA were orally administered using stomach gavage, either alone or in combination for 5 consecutive days, followed with a single TIL overdose. TIL overdose induced a significant increase in serum levels of cardiac damage biomarkers (AST, LDH, CK, CK-MB, and cTnT), as well as cardiac lipid peroxidation, but cardiac levels of antioxidant biomarkers (GSH, SOD, CAT, and TAC) were decreased. Both MRZ and AA tended to normalize the elevated serum levels of cardiac injury biomarkers. Furthermore, MRZ and AA reduced TIL-induced lipid peroxidation and oxidative stress parameters. MRZ and AA combined produced a synergistic cardioprotective effect. We conclude that myrrh and (or) vitamin C administration minimizes the toxic effects of TIL through their free-radical-scavenging and potent antioxidant activities.

Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation.

PubMed

Liu, Yuguan; Weisberg, Lawrence S; Langman, Craig B; Logan, Amanda; Hunter, Krystal; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Berns, Jeffrey S; Handelman, Garry J; Sirover, William D

2016-10-01

Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100μM may be supratherapeutic, levels of at least 30μM may be needed to improve wound healing and levels may need to reach 70μM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30μM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels <30μM. This study focuses on the plasma Ox levels in HD patients. A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1μM to 6.4±3.2μM, P<0.001). In regression analysis, pre-HD plasma AA levels ≤100μM were not associated with a pre-HD plasma Ox level≥30μM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30μM were not associated with lower cumulative 4-year survival. Pre-HD plasma AA levels up to 100μM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Study of the protective effect of ascorbic acid against the toxicity of stannous chloride on oxidative damage, antioxidant enzymes and biochemical parameters in rabbits.

PubMed

Yousef, M I; Awad, T I; Elhag, F A; Khaled, F A

2007-06-25

Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the present study has been carried out to investigate the antioxidant action of l-ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation, antioxidant enzyme, and biochemical parameters in male New Zealand white rabbits. Animals were assigned to one of four treatment groups: 0mg AA and 0mg SnCl2/kg BW (control); 40 mg AA/kg BW; 20mg SnCl2/kg BW; 20mg SnCl2 plus 40 mg AA/kg BW. Rabbits were orally administered the respective doses every other day for 12 weeks. Results obtained showed that SnCl2 significantly (P<0.05) induced thiobarbituric acid-reactive substances (TBARS; the marker of lipid peroxidation) in plasma, while the activities of glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), and the level of sulfhydryl groups (SH-group) were decreased (P<0.05) in blood plasma. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP) and lactate dehydrogenase (LDH) activities were decreased (P<0.05). Stannous chloride significantly (P<0.05) increased the levels of plasma total lipid (TL), cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), glucose, urea and total bilirubin. On the other hand, the level of plasma high-density lipoprotein (HDL), total protein (TP), albumin (A) and globulin (G) were significantly (P<0.05) decreased. Ascorbic acid alone significantly decreased the levels of TBARS, lipids and urea, and increased the activities of GST, SOD and CAT, and the levels of SH-group and proteins. While the rest of the tested parameters were not affected. Also, the presence of AA with SnCl2 alleviated its harmful effects on most of the tested parameters. Therefore, the present results revealed that treatment with AA could minimize the toxic effects of stannous chloride.

Variation in the activities of late stage filaggrin processing enzymes, calpain-1 and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels, corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed facial stratum corneum of different ethnicities.

PubMed

Raj, N; Voegeli, R; Rawlings, A V; Summers, B; Munday, M R; Lane, M E

2016-12-01

Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and corneocyte maturation. Enzyme activities, PCA levels and corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature corneocytes. Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest that they can be used as markers for epidermal photodamage. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Variation of amino acid sequences of serum amyloid a (SAA) and immunohistochemical analysis of amyloid a (AA) in Japanese domestic cats.

PubMed

Tei, Meina; Uchida, Kazuyuki; Chambers, James K; Watanabe, Ken-Ichi; Tamamoto, Takashi; Ohno, Koichi; Nakayama, Hiroyuki

2018-02-02

Amyloid A (AA) amyloidosis, a fatal systemic amyloid disease, occurs secondary to chronic inflammatory conditions in humans. Although persistently elevated serum amyloid A (SAA) levels are required for its pathogenesis, not all individuals with chronic inflammation necessarily develop AA amyloidosis. Furthermore, many diseases in cats are associated with the elevated production of SAA, whereas only a small number actually develop AA amyloidosis. We hypothesized that a genetic mutation in the SAA gene may strongly contribute to the pathogenesis of feline AA amyloidosis. In the present study, genomic DNA from four Japanese domestic cats (JDCs) with AA amyloidosis and from five without amyloidosis was analyzed using polymerase chain reaction (PCR) amplification and direct sequencing. We identified the novel variation combination of 45R-51A in the deduced amino acid sequences of four JDCs with amyloidosis and five without. However, there was no relationship between amino acid variations and the distribution of AA amyloid deposits, indicating that differences in SAA sequences do not contribute to the pathogenesis of AA amyloidosis. Immunohistochemical analysis using antisera against the three different parts of the feline SAA protein-i.e., the N-terminal, central, and C-terminal regions-revealed that feline AA contained the C-terminus, unlike human AA. These results indicate that the cleavage and degradation of the C-terminus are not essential for amyloid fibril formation in JDCs.

Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats.

PubMed

Yogeeta, Surinder Kumar; Raghavendran, Hanumantha Rao Balaji; Gnanapragasam, Arunachalam; Subhashini, Rajakannu; Devaki, Thiruvengadam

2006-10-27

Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.

Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Olsson, Nils U.; Salem, Norman

2008-01-01

Background/Aims We reported that reduced dietary intake of polyunsaturated fatty acids (PUFA) such as arachidonic (AA,20:4n6, omega-6) and docosahexaenoic (DHA,22:6n3, omega-3) acids led to alcohol-induced fatty liver and fibrosis. This study was aimed at studying the mechanisms by which a DHA/AA-supplemented diet prevents alcohol-induced fatty liver. Methods Male Long-Evans rats were fed an ethanol or control liquid-diet with or without DHA/AA for 9 weeks. Plasma transaminase levels, liver histology, oxidative/nitrosative stress markers, and activities of oxidatively-modified mitochondrial proteins were evaluated. Results Chronic alcohol administration increased the degree of fatty liver but fatty liver decreased significantly in rats fed the alcohol-DHA/AA-supplemented diet. Alcohol exposure increased oxidative/nitrosative stress with elevated levels of ethanol-inducible CYP2E1, nitric oxide synthase, nitrite and mitochondrial hydrogen peroxide. However, these increments were normalized in rats fed the alcohol-DHA/AA-supplemented diet. The number of oxidatively-modified mitochondrial proteins was markedly increased following alcohol exposure but significantly reduced in rats fed the alcohol-DHA/AA-supplemented diet. The suppressed activities of mitochondrial aldehyde dehydrogenase, ATP synthase, and 3-ketoacyl-CoA thiolase in ethanol-exposed rats were also recovered in animals fed the ethanol-DHA/AA-supplemented diet. Conclusions Addition of DHA/AA prevents alcohol-induced fatty liver and mitochondrial dysfunction in an animal model by protecting various mitochondrial enzymes most likely through reducing oxidative/nitrosative stress. PMID:18571270

[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].

PubMed

Ding, Xiao-shuang; Liang, Ai-hua; Wang, Jin-hua; Xiao, Yong-qing; Wu, Zi-lun; Li, Chun-ying; Li, Li; He, Rong; Hui, Lian-qiang; Liu, Bao-yan

2005-07-01

The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

Characterization of the radical-scavenging reaction of 2-O-substituted ascorbic acid derivatives, AA-2G, AA-2P, and AA-2S: a kinetic and stoichiometric study.

PubMed

Takebayashi, Jun; Tai, Akihiro; Gohda, Eiichi; Yamamoto, Itaru

2006-04-01

The aim of this study was to characterize the antioxidant activity of three ascorbic acid (AA) derivatives O-substituted at the C-2 position of AA: ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S). The radical-scavenging activities of these AA derivatives and some common low molecular-weight antioxidants such as uric acid or glutathione against 1,1-diphenyl-picrylhydrazyl (DPPH) radical, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+), or galvinoxyl radical were kinetically and stoichiometrically evaluated under pH-controlled conditions. Those AA derivatives slowly and continuously reacted with DPPH radical and ABTS+, but not with galvinoxyl radical. They effectively reacted with DPPH radical under acidic conditions and with ABTS+ under neutral conditions. In contrast, AA immediately quenched all species of radicals tested at all pH values investigated. The reactivity of Trolox, a water-soluble vitamin E analogue, was comparable to that of AA in terms of kinetics and stoichiometrics. Uric acid and glutathione exhibited long-lasting radical-scavenging activity against these radicals under certain pH conditions. The radical-scavenging profiles of AA derivatives were closer to those of uric acid and glutathione rather than to that of AA. The number of radicals scavenged by one molecule of AA derivatives, uric acid, or glutathione was equal to or greater than that by AA or Trolox under the appropriate conditions. These data suggest the potential usage of AA derivatives as radical scavengers.

An Amino Acids Mixture Attenuates Glycemic Impairment but not Affects Adiposity Development in Rats Fed with AGEs-containing Diet

PubMed Central

Liao, Yi-Hung; Chen, Chung-Yu; Chen, Chiao-Nan; Wu, Chia-Ying; Tsai, Shiow-Chwen

2018-01-01

Background: Unhealthy western dietary patterns lead to over-consumption of fat and advanced glycation end-products (AGEs), and these account for the developments of obesity, diabetes, and related metabolic disorders. Certain amino acids (AAs) have been recently demonstrated to improve glycemia and reduce adiposity. Therefore, our primary aims were to examine whether feeding an isoleucine-enriched AA mixture (4.5% AAs; Ile: 3.0%, Leu: 1.0%, Val: 0.2%, Arg: 0.3% in the drinking water) would affect adiposity development and prevent the impairments of glycemic control in rats fed with the fat/AGE-containing diet (FAD). Methods: Twenty-four male Sprague-Dawley rats were assigned into 1) control diet (CD, N = 8), 2) FAD diet (FAD, N = 8), and 3) FAD diet plus AA (FAD/AA, N = 8). After 9-weeks intervention, the glycemic control capacity (glucose level, ITT, and HbA1c levels), body composition, and spontaneous locomotor activity (SLA) were evaluated, and the fasting blood samples were collected for analyzing metabolic related hormones (insulin, leptin, adiponectin, and corticosterone). The adipose tissues were also surgically collected and weighed. Results: FAD rats showed significant increases in weight gain, body fat %, blood glucose, HbA1c, leptin, and area under the curve of glucose during insulin tolerance test (ITT-glucose-AUC) in compared with the CD rats. However, the fasting levels of blood glucose, HbA1c, leptin, and ITT-glucose-AUC did not differ between CD and FAD/AA rats. FAD/AA rats also showed a greater increase in serum testosterone. Conclusion: The amino acid mixture consisting of Ile, Leu, Val, and Arg showed clear protective benefits on preventing the FAD-induced obesity and impaired glycemic control. PMID:29333102

An Amino Acids Mixture Attenuates Glycemic Impairment but not Affects Adiposity Development in Rats Fed with AGEs-containing Diet.

PubMed

Liao, Yi-Hung; Chen, Chung-Yu; Chen, Chiao-Nan; Wu, Chia-Ying; Tsai, Shiow-Chwen

2018-01-01

Background: Unhealthy western dietary patterns lead to over-consumption of fat and advanced glycation end-products (AGEs), and these account for the developments of obesity, diabetes, and related metabolic disorders. Certain amino acids (AAs) have been recently demonstrated to improve glycemia and reduce adiposity. Therefore, our primary aims were to examine whether feeding an isoleucine-enriched AA mixture (4.5% AAs; Ile: 3.0%, Leu: 1.0%, Val: 0.2%, Arg: 0.3% in the drinking water) would affect adiposity development and prevent the impairments of glycemic control in rats fed with the fat/AGE-containing diet (FAD). Methods: Twenty-four male Sprague-Dawley rats were assigned into 1) control diet (CD, N = 8), 2) FAD diet (FAD, N = 8), and 3) FAD diet plus AA (FAD/AA, N = 8). After 9-weeks intervention, the glycemic control capacity (glucose level, ITT, and HbA1c levels), body composition, and spontaneous locomotor activity (SLA) were evaluated, and the fasting blood samples were collected for analyzing metabolic related hormones (insulin, leptin, adiponectin, and corticosterone). The adipose tissues were also surgically collected and weighed. Results: FAD rats showed significant increases in weight gain, body fat %, blood glucose, HbA1c, leptin, and area under the curve of glucose during insulin tolerance test (ITT-glucose-AUC) in compared with the CD rats. However, the fasting levels of blood glucose, HbA1c, leptin, and ITT-glucose-AUC did not differ between CD and FAD/AA rats. FAD/AA rats also showed a greater increase in serum testosterone. Conclusion: The amino acid mixture consisting of Ile, Leu, Val, and Arg showed clear protective benefits on preventing the FAD-induced obesity and impaired glycemic control.

Bisphenol A alters n-6 fatty acid composition and decreases antioxidant enzyme levels in rat testes: a LC-QTOF-based metabolomics study.

PubMed

Chen, Minjian; Xu, Bin; Ji, Wenliang; Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2012-01-01

Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity.

Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives.

PubMed

Takebayashi, Jun; Kaji, Hiroaki; Ichiyama, Kenji; Makino, Kazutaka; Gohda, Eiichi; Yamamoto, Itaru; Tai, Akihiro

2007-10-15

Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo.

Molecular and functional characterization of single-box high-mobility group B (HMGB) chromosomal protein from Aedes aegypti.

PubMed

de Abreu da Silva, Isabel Caetano; Vicentino, Amanda Roberta Revoredo; Dos Santos, Renata Coutinho; da Fonseca, Rodrigo Nunes; de Mendonça Amarante, Anderson; Carneiro, Vitor Coutinho; de Amorim Pinto, Marcia; Aguilera, Estefania Anahi; Mohana-Borges, Ronaldo; Bisch, Paulo Mascarello; da Silva-Neto, Mario Alberto Cardoso; Fantappié, Marcelo Rosado

2018-05-30

High-mobility group B (HMGB) proteins have highly conserved, unique DNA-binding domains, HMG boxes, that can bind non-B-type DNA structures, such as bent, kinked and unwound structures, with high affinity. HMGB proteins also promote DNA bending, looping and unwinding. In this study, we determined the role of the Aedes aegypti single HMG-box domain protein AaHMGB; characterized its structure, spatiotemporal expression levels, subcellular localization, and nucleic acid binding activities; and compared these properties with those of its double-HMG-box counterpart protein, AaHMGB1. Via qRT-PCR, we showed that AaHMGB is expressed at much higher levels than AaHMGB1 throughout mosquito development. In situ hybridization results suggested a role for AaHMGB and AaHMGB1 during embryogenesis. Immunolocalization in the midgut revealed that AaHMGB is exclusively nuclear. Circular dichroism and fluorescence spectroscopy analyses showed that AaHMGB exhibits common features of α-helical structures and is more stably folded than AaHMGB1, likely due to the presence of one or two HMG boxes. Using several DNA substrates or single-stranded RNAs as probes, we observed significant differences between AaHMGB and AaHMGB1 in terms of their binding patterns, activity and/or specificity. Importantly, we showed that the phosphorylation of AaHMGB plays a critical role in its DNA-binding activity. Our study provides additional insight into the roles of single- versus double-HMG-box-containing proteins in nucleic acid interactions for better understanding of mosquito development, physiology and homeostasis. Copyright © 2017. Published by Elsevier B.V.

Osteo-maturation of adipose-derived stem cells required the combined action of vitamin D3, beta-glycerophosphate, and ascorbic acid.

PubMed

Gupta, Anurag; Leong, David Tai; Bai, Hui Fen; Singh, Shiv Brat; Lim, Thiam-Chye; Hutmacher, Dietmar Werner

2007-10-12

This study investigated the effects of various components [vitamin D3 (VD3), beta-glycerophosphate (BGP), and ascorbic acid (AA)] on the potential of human adipose-derived progenitor cells (ADPCs) to transdifferentiate into osteoblast-like cells. ADPCs were induced under four different supplement groups: (1) VD3+BGP+AA, (2) VD3 alone, (3) BGP+AA, and (4) no VD3, BGP or AA. Mineralization studies and presence of bone matrix-related proteins by immunostaining showed that the Group 1 ADPCs showed their ability to undergo osteoblastic differentiation. Further evaluation was made by estimation of levels of RUNX-2 and TAZ genes. Group 1 ADPCs showed the consistent expression of RUNX-2 and TAZ levels over the study period of 28days. The study showed good correlation among various parameters evaluated to conclude that ADPCs could be an alternative source for generating osteoblast-like cells.

Distinct functional domains within the acidic cluster of tegument protein pp28 required for trafficking and cytoplasmic envelopment of human cytomegalovirus.

PubMed

Seo, Jun-Young; Jeon, Hyejin; Hong, Sookyung; Britt, William J

2016-10-01

Human cytomegalovirus UL99-encoded tegument protein pp28 contains a 16 aa acidic cluster that is required for pp28 trafficking to the assembly compartment (AC) and the virus assembly. However, functional signals within the acidic cluster of pp28 remain undefined. Here, we demonstrated that an acidic cluster rather than specific sorting signals was required for trafficking to the AC. Recombinant viruses with chimeric pp28 proteins expressing non-native acidic clusters exhibited delayed viral growth kinetics and decreased production of infectious virus, indicating that the native acidic cluster of pp28 was essential for wild-type virus assembly. These results suggested that the acidic cluster of pp28 has distinct functional domains required for trafficking and for efficient virus assembly. The first half (aa 44-50) of the acidic cluster was sufficient for pp28 trafficking, whereas the native acidic cluster consisting of aa 51-59 was required for the assembly of wild-type levels of infectious virus.

Amino acid-assisted synthesis of zinc oxide nanostructures

NASA Astrophysics Data System (ADS)

Singh, Baljinder; Moudgil, Lovika; Singh, Gurinder; Kaura, Aman

2018-05-01

In this manuscript we have used experimental approach that can provide a fundamental knowledge about the role played by biomolecules in designing the shape of nanostructure (NS) at a microscopic level. The three different amino acids (AAs) - Arginine (Arg), Aspartic acid (Asp) and Histidine (His) coated Zinc oxide (ZnO) NSs to explain the growth mechanism of nanoparticles of different shapes. Based on the experimental methodology we propose that AA-ZnO (Asp and Arg) nanomaterials could form of rod like configuration and His-ZnO NPs could form tablet like configuration. The synthesized samples are characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). Results reveal that AAs are responsible for formation of different NSs

Structural and functional correlations in stable renal allografts.

PubMed

Fulladosa, Xavier; Moreso, Francesc; Torras, Joan; Hueso, Miquel; Grinyó, Josep M; Serón, Daniel

2003-05-01

Renal functional reserve (RFR) has been proposed as a surrogate marker of renal mass, but its significance in well-functioning renal transplants is controversial. Thus, we used early protocol biopsies to analyze structural and functional correlations in stable grafts. We studied 32 cyclosporine (CsA)-treated stable cadaveric transplants at 5 months. Biopsies were evaluated according to Banff criteria and histomorphometry. Inulin and p-aminohippurate clearances were used to calculate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). RFR after an amino acid infusion (RFR-AA) and after a combined amino acid and dopamine infusion (RFR-AA-DOPA) was evaluated. Baseline GFR was 54 +/- 16 mL/min/1.73 m2, and ERPF was 219 +/- 55 mL/min/1.73 m2. RFR-AA was 9% +/- 13%, and RFR-AA-DOPA was 22% +/- 20%. RFR-AA correlated with CsA dose (R = 0.39; P = 0.02), whereas RFR-AA-DOPA correlated with CsA dose (R = 0.36; P = 0.04) and CsA levels (R = 0.40; P = 0.02). The only histological parameter associated with RFR was the presence of arteriolar hyalinosis (AH). Patients showing an AH score of 1 or greater (n = 7) had lower RFR-AA (0% +/- 9% versus 11% +/- 13%; P = 0.02) and lower RFR-AA-DOPA (9% +/- 17% versus 26% +/- 19%; P = 0.03). Multivariate analysis showed that an AH score of 1 or greater, but not CsA dose or levels, was associated with RFR-AA (R = 0.42; P = 0.01). RFR-AA-DOPA was associated with hyaline arteriolar damage (R = 0.43; P = 0.01), as well as CsA levels (R = 0.54; P = 0.006). The presence of AH is the only histological parameter associated with impaired RFR in well-functioning grafts.

Acanthoic acid protectsagainst ethanol-induced liver injury: Possible role of AMPK activation and IRAK4 inhibition.

PubMed

Yao, You-Li; Han, Xin; Song, Jian; Zhang, Jing; Li, Ya-Mei; Lian, Li-Hua; Wu, Yan-Ling; Nan, Ji-Xing

2017-11-05

The aim of this study was to investigate the effects of acanthoic acid (AA) on the regulation of inflammatory response, lipid accumulation, and fibrosis via AMPK- IRAK4 signaling against chronic alcohol consumption in mice. Ethanol-induced liver injury was induced in male mice by Lieber-DeCarli diet for 28d. And mice in AA groups were gavaged with AA (20 or 40mg/kg) for 28d. AA treatment significantly decreased serum AST and TG, hepatic TG levels, serum ethanol and LPS levels compared with chronic ethanol administration. AA ameliorated histological changes, lipid droplets, hepatic fibrosis, and inflammation induced by ethanol. AA significantly increased the expressions of p-LKB1, p-AMPK, and SIRT1 caused by chronic ethanol administration, and attenuated the increasing protein expressions of IRAK1 and IRAK4.siRNA against AMPKα1 blocked AMPKα1 and increased IRAK4 protein expressions, compared with control-siRNA-transfected group, while AA treatment significantly decreased IRAK4 expressions compared with AMPKα1-siRNA-transfected group. AMPK-siRNA also blocked the decreased effect of AA on inflammatory factors. AA decreased over-expression of IRAK4 and inflammation under ethanol plus LPS challenge. AA recruited LKB1-AMPK phosphorylation and activated SIRT1 to regulate alcoholic liver injury, especially, inhibited IRAK1/4 signaling pathway to regulate lipid metabolism, hepatic fibrosis and inflammation caused by alcohol consumption. Copyright © 2017 Elsevier B.V. All rights reserved.

Elevated Prostaglandin E Metabolites and Abnormal Plasma Fatty Acids at Baseline in Pediatric Cystic Fibrosis Patients: A Pilot Study

PubMed Central

O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam

2016-01-01

Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. PMID:27720040

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

PubMed

O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

2016-10-01

Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations.

PubMed

Dai, Weiwei; Panserat, Stéphane; Kaushik, Sadasivam; Terrier, Frédéric; Plagnes-Juan, Elisabeth; Seiliez, Iban; Skiba-Cassy, Sandrine

2016-01-01

The link between dietary carbohydrate/protein and de novo lipogenesis (DNL) remains debatable in carnivorous fish. We aimed to evaluate and compare the response of hepatic lipogenic gene expression to dietary carbohydrate intake/glucose and dietary protein intake/amino acids (AAs) during acute stimulations using both in vivo and in vitro approaches. For the in vivo trial, three different diets and a controlled-feeding method were employed to supply fixed amount of dietary protein or carbohydrate in a single meal; for the in vitro trial, primary hepatocytes were stimulated with a low or high level of glucose (3 mM or 20 mM) and a low or high level of AAs (one-fold or four-fold concentrated AAs). In vitro data showed that a high level of AAs upregulated the expression of enzymes involved in DNL [fatty acid synthase (FAS) and ATP citrate lyase (ACLY)], lipid bioconversion [elongation of very long chain fatty acids like-5 (Elovl5), Elovl2, Δ6 fatty acyl desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD1)], NADPH production [glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME)], and transcriptional factor sterol regulatory element binding protein 1-like, while a high level of glucose only elevated the expression of ME. Data in trout liver also showed that high dietary protein intake induced higher lipogenic gene expression (FAS, ACLY, and Elovl2) regardless of dietary carbohydrate intake, while high carbohydrate intake markedly suppressed the expression of acetyl-CoA carboxylase (ACC) and Elovl5. Overall, we conclude that, unlike rodents or humans, hepatic fatty acid biosynthetic gene expression in rainbow trout is more responsive to dietary protein intake/AAs than dietary carbohydrate intake/glucose during acute stimulations. This discrepancy probably represents one important physiological and metabolic difference between carnivores and omnivores. Copyright © 2016 the American Physiological Society.

Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability.

PubMed

de la Ballina, Laura R; Cano-Crespo, Sara; González-Muñoz, Elena; Bial, Susanna; Estrach, Soline; Cailleteau, Laurence; Tissot, Floriane; Daniel, Hannelore; Zorzano, Antonio; Ginsberg, Mark H; Palacín, Manuel; Féral, Chloé C

2016-04-29

CD98hc functions as an amino acid (AA) transporter (together with another subunit) and integrin signaling enhancer. It is overexpressed in highly proliferative cells in both physiological and pathological conditions. CD98hc deletion induces strong impairment of cell proliferation in vivo and in vitro Here, we investigate CD98hc-associated AA transport in cell survival and proliferation. By using chimeric versions of CD98hc, the two functions of the protein can be uncoupled. Although recovering the CD98hc AA transport capacity restores the in vivo and in vitro proliferation of CD98hc-null cells, reconstitution of the integrin signaling function of CD98hc is unable to restore in vitro proliferation of those cells. CD98hc-associated transporters (i.e. xCT, LAT1, and y(+)LAT2 in wild-type cells) are crucial to control reactive oxygen species and intracellular AA levels, thus sustaining cell survival and proliferation. Moreover, in CD98hc-null cells the deficiency of CD98hc/xCT cannot be compensated, leading to cell death by ferroptosis. Supplementation of culture media with β-mercaptoethanol rescues CD98hc-deficient cell survival. Under such conditions null cells show oxidative stress and intracellular AA imbalance and, consequently, limited proliferation. CD98hc-null cells also present reduced intracellular levels of branched-chain and aromatic amino acids (BCAAs and ARO AAs, respectively) and induced expression of peptide transporter 1 (PEPT1). Interestingly, external supply of dipeptides containing BCAAs and ARO AAs rescues cell proliferation and compensates for impaired uptake of CD98hc/LAT1 and CD98hc/y(+)LAT2. Our data establish CD98hc as a master protective gene at the cross-road of redox control and AA availability, making it a relevant therapeutic target in cancer. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Protective effect of asiatic acid in an experimental cerulein-induced model of acute pancreatitis in mice

PubMed Central

Xiao, Wenqin; Jiang, Weiliang; Li, Kai; Hu, Yangyang; Li, Sisi; Zhou, Li; Wan, Rong

2017-01-01

Asiatic acid (AA), a triterpenoid derived from the medicinal plant Centella asiatica, is considered to have anti-inflammatory, anti-fibrotic and anti-tumor effects, but its effects in acute pancreatitis (AP) are unknown. Our purpose of this study was to investigate the effects of AA in a mouse model of cerulein-induced pancreatitis. We evaluated AA in an experimental model of AP induced in mice by six hourly intraperitoneal injections of cerulein 50 µg/kg. Mice were pretreated with vehicle or AA 50 mg/kg 2 h before the first cerulein injection. The severity of AP was evaluated histologically and by biochemistry, myeloperoxidase activity, proinflammatory cytokine production, and nuclear factor (NF)-κB activity. Administration of AA significantly reduced the severity of AP, and was associated with reduction of serum amylase and lipase levels, decreased pancreatic histological damage, and decreased myeloperoxidase activity. The serum levels and mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and NF-κB activity were reduced. AA also significantly improved the in vitro viability of pancreatic acinar cells induced by cholecystokinin (CCK) and suppressed NF-κB activity. AA protected against experimental AP, possibly by reducing production of proinflammatory cytokines via suppression NF-κB activation. PMID:28861174

[Comparison of long-chain polyunsaturated fatty acids in plasma and erythrocyte phospholipids for biological monitoring].

PubMed

Kawabata, Terue; Nakai, Kunihiko; Hagiwara, Chie; Kurokawa, Naoyuki; Murata, Katsuyuki; Yaginuma, Kozue; Satoh, Hiroshi

2011-01-01

Previous data have indicated that the erythrocyte membrane may be the preferred sample type for assessing long-chain polyunsaturated fatty acid (LCPUFA) contents in cardiac and cerebral membranes. In this epidemiological study, we examined whether plasma phospholipids can be used for accurate biological monitoring of the LCPUFA state or whether analysis of erythrocyte membrane phospholipids is indispensable. (1) The analysis of LCPUFA contents in erythrocyte membrane phospholipids was conducted at baseline and after 1 and 3 days at 4°C, and 21 days at -40°C, after blood drawing, and the changes in LCPUFA content were examined. (2) The LCPUFA compositions of plasma and erythrocyte phospholipids in 133 young women (18-30 years old) were examined and the relationships between the sample type and the levels of LCPUFAs were determined. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and DHA/arachidonic acid (AA) and (EPA+DHA)/AA ratios in erythrocyte membrane phospholipids after 21 days of blood drawing significantly decreased compared with the corresponding baseline data. Regarding AA, EPA and DHA, a significant positive correlation was shown between levels of erythrocyte membrane phospholipids and plasma phospholipids (AA, r=0.364; EPA, r=0.709; DHA, r=0.653). The predictive value of plasma phospholipids for determining the highest concentration quartile in erythrocyte phospholipids was better in EPA (70%) than in DHA (55%) and AA (42%). The measurement of LCPUFA content in erythrocyte membrane phospholipids is necessary for accurate biological monitoring. We also found that LCPUFA in erythrocyte membrane phospholipids is stable in cold storage (4°C) for 3 days after blood drawing.

AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells.

PubMed

Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

2016-01-01

Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.

AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

PubMed Central

Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

2016-01-01

Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy. PMID:27073325

The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Neural Damage in Rat Offspring's Hippocampus.

PubMed

Sadeghi, Akram; Ebrahimzadeh Bideskan, Alireza; Alipour, Fatemeh; Fazel, Alireza; Haghir, Hossein

2013-02-01

The aim of this study was to investigate ascorbic acid and garlic protective effects on lead-induced neurotoxicity during rat hippocampus development. 90 pregnant wistar rats were divided randomly into nine groups: 1- Animals received leaded water (L). 2- Rats received leaded water and ascorbic acid (L+AA). 3- Animals received leaded water and garlic juice (L+G). 4-Animals received leaded water, ascorbic acid and garlic juice (L+G+AA). 5- Rats treated with ascorbic acid (AA). 6- Rats treated with garlic juice (G). 7- Rats treated with ascorbic acid and garlic juice (AA+G). 8- Rats treated with tap water plus 0.4 ml/l normal hydrogen chloride (HCl) and 0.5 mg/l Glucose (Sham). 9- Normal group (N). Leaded water (1500 ppm), garlic juice (1 ml/100g/day, gavage) and ascorbic acid (500 mg/kg/day, IP) were used. Finally, blood lead levels (BLL) were measured in both rats and their offspring. The rat offspring brain sections were stained using Toluidine Blue and photographed. Dark neurons (DNs) were counted to compare all groups. BLL significantly increased in L group compared to control and sham groups and decreased in L+G and L+AA groups in comparison to the L group (P<0.05). the number of DNs in the CA1, CA3, and DG of rat offspring hippocampus significantly increased in L group in comparison to control and sham groups (P<0.05) and decreased in L+G and L+AA groups compared to L group (P<0.05). Garlic juice and ascorbic acid administration during pregnancy and lactation may protect lead-induced neural damage in rat offspring hippocampus.

Combining reduced glutathione and ascorbic acid has supplementary beneficial effects on boar sperm cryotolerance.

PubMed

Giaretta, Elisa; Estrada, Efrén; Bucci, Diego; Spinaci, Marcella; Rodríguez-Gil, Joan E; Yeste, Marc

2015-02-01

The main aim of this work was to evaluate how supplementing freezing and thawing media with reduced glutathione (GSH) and l-ascorbic acid (AA) affected the quality parameters of frozen-thawed boar spermatozoa. With this purpose, semen samples of 12 ejaculates coming from 12 boars were used. Each ejaculate was split into seven aliquots to which 5 mM of GSH and 100 μM of AA were added separately or together at two different steps of freeze-thawing. Various sperm parameters (levels of free cysteine residues in sperm nucleoproteins, sperm viability, acrosome membrane integrity, intracellular peroxide and superoxide levels [ROS], and total and progressive motility) were evaluated before freezing and at 30 and 240 minutes after thawing. Both GSH and AA significantly improved boar sperm cryotolerance when they were separately added to freezing and thawing media. However, the highest improvement was recorded when both freezing and thawing media were supplemented with 5 mM of GSH plus 100 μM of AA. This improvement was observed in sperm viability and acrosome integrity, sperm motility, and nucleoprotein structure. Although ROS levels were not much increased by freeze-thawing procedures, the addition of GSH and AA to both freezing and thawing extenders significantly decreased intracellular peroxide levels and had no impact on superoxide levels. According to our results, we can conclude that supplementation of freezing and thawing media with both GSH and AA has a combined, beneficial effect on frozen-thawed boar sperm, which is greater than that obtained with the separate addition of either GSH or AA. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of ascorbic acid enrichment by immersion of rainbow trout (Oncorhynchus mykiss, Walbaum 1792) eggs and embryos

USGS Publications Warehouse

Falahatkar, B.; Dabrowski, K.; Arslan, M.; Rinchard, J.

2006-01-01

This study was conducted to examine the effects of different forms and concentrations of ascorbic acid (vitamin C), and different enrichment times (24 and 48 h post ovulation) on egg, embryo and alevin ascorbate concentrations and survival of rainbow trout (enrichment was at the ova stage). In experiments 1 and 2, fertilized eggs were immersed in water containing ascorbate at 0 (control), 100, 1000 mg L-1 l-ascorbic acid (AA) and 2000 mg L -1 l-ascorbyl monophosphate (AP). In experiment 3, 0 (control), 500 and 1000 mg L-1 AA neutralized (N) with NaOH, 1000 mg L-1 AA non-neutralized (NN), 1000 and 2000 mg L-1 AP immersions were used. The mean total ascorbic acid (TAA) and dehydroascorbic acid (DHA) concentrations were measured before fertilization, at 3 and 24 h after fertilization, at the eyed stage, and in hatched alevins. We observed significant differences in TAA concentration at different immersion levels at 3 and 24 h after fertilization. Survival decreased significantly depending on the level of vitamin C, pH of the solutions and immersion time. We suggest that when broodstock rainbow trout do not have enough vitamin C in their ovaries, immersion of eggs in 1000 mg L-1 of neutralized AA may be useful. ?? 2006 Blackwell Publishing Ltd.

High-throughput quantification of the levels and labeling abundance of free amino acids by liquid chromatography tandem mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cocuron, Jean-Christophe; Tsogtbaatar, Enkhtuul; Alonso, Ana P.

Accurate assessment of mass isotopomer distributions (MIDs) of intracellular metabolites, such as free amino acids (AAs), is crucial for quantifying in vivo fluxes. To date, the majority of studies that measured AA MIDs have relied on the analysis of proteinogenic rather than free AAs by: i) GC–MS, which involved cumbersome process of derivatization, or ii) NMR, which requires large quantities of biological sample. In this work, the development and validation of a high-throughput LC–MS/MS method allowing the quantification of the levels and labeling of free AAs is described. Sensitivity in the order of the femtomol was achieved using multiple reactionmore » monitoring mode (MRM). The MIDs of all free AAs were assessed without the need of derivatization, and were validated (except for Trp) on a mixture of unlabeled AA standards. Finally, this method was applied to the determination of the 13C-labeling abundance in free AAs extracted from maize embryos cultured with 13C-glutamine or 13C-glucose. Although Cys was below the limit of detection in these biological samples, the MIDs of a total of 18 free AAs were successfully determined. Due to the increased application of tandem mass spectrometry for 13C-Metabolic Flux Analysis, this novel method will enable the assessment of more complete and accurate labeling information of intracellular AAs, and therefore a better definition of the fluxes.« less

High-throughput quantification of the levels and labeling abundance of free amino acids by liquid chromatography tandem mass spectrometry

DOE PAGES

Cocuron, Jean-Christophe; Tsogtbaatar, Enkhtuul; Alonso, Ana P.

2017-02-16

Accurate assessment of mass isotopomer distributions (MIDs) of intracellular metabolites, such as free amino acids (AAs), is crucial for quantifying in vivo fluxes. To date, the majority of studies that measured AA MIDs have relied on the analysis of proteinogenic rather than free AAs by: i) GC–MS, which involved cumbersome process of derivatization, or ii) NMR, which requires large quantities of biological sample. In this work, the development and validation of a high-throughput LC–MS/MS method allowing the quantification of the levels and labeling of free AAs is described. Sensitivity in the order of the femtomol was achieved using multiple reactionmore » monitoring mode (MRM). The MIDs of all free AAs were assessed without the need of derivatization, and were validated (except for Trp) on a mixture of unlabeled AA standards. Finally, this method was applied to the determination of the 13C-labeling abundance in free AAs extracted from maize embryos cultured with 13C-glutamine or 13C-glucose. Although Cys was below the limit of detection in these biological samples, the MIDs of a total of 18 free AAs were successfully determined. Due to the increased application of tandem mass spectrometry for 13C-Metabolic Flux Analysis, this novel method will enable the assessment of more complete and accurate labeling information of intracellular AAs, and therefore a better definition of the fluxes.« less

Effect of Dietary L-ascorbic Acid (L-AA) on Production Performance, Egg Quality Traits and Fertility in Japanese Quail (Coturnix japonica) at Low Ambient Temperature.

PubMed

Shit, N; Singh, R P; Sastry, K V H; Agarwal, R; Singh, R; Pandey, N K; Mohan, J

2012-07-01

Environmental stress boosts the levels of stress hormones and accelerates energy expenditure which subsequently imbalance the body's homeostasis. L-ascorbic acid (L-AA) has been recognized to mitigate the negative impact of environmental stress on production performances in birds. The present investigation was carried out to elucidate the effect of different dietary levels of L-AA on production performance, egg quality traits and fertility in Japanese quail at low ambient temperature. Sixty matured females (15 wks) were equally divided into three groups (20/group) based on the different dietary levels of L-AA (0, 250 and 500 ppm) and coupled with an equal number of males (1:1) obtained from the same hatch. They were managed in uniform husbandry conditions without restriction of feed and water at 14 h photo-schedule. Except for feed efficiency, body weight change, feed consumption and hen-day egg production were recorded highest in 500 ppm L-AA supplemented groups. Among the all egg quality traits studied, only specific gravity, shell weight and thickness differed significantly (p<0.05) in the present study. Fertility was improved significantly (p<0.01) to a dose dependent manner of L-AA. The findings of the present study concluded that dietary L-AA can be a caring management practice at least in part to alleviate the adverse effect of cold induced stress on production performance in Japanese quail.

Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

PubMed Central

Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2012-01-01

Background Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Methodology/Principal Findings Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. Conclusions/Significance BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity. PMID:23024759

Effects of dimethylaminoethanol and compound amino acid on D-galactose induced skin aging model of rat.

PubMed

Liu, Su; Chen, Zhenyu; Cai, Xia; Sun, Ying; Zhao, Cailing; Liu, Fangjun; Liu, Dalie

2014-01-01

A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat.

Effects of Dimethylaminoethanol and Compound Amino Acid on D-Galactose Induced Skin Aging Model of Rat

PubMed Central

Liu, Su; Chen, Zhenyu; Cai, Xia; Sun, Ying; Zhao, Cailing

2014-01-01

A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat. PMID:25133239

Vitamin C: an experimental and theoretical study on the gas-phase structure and ion energetics of protonated ascorbic acid.

PubMed

Ricci, Andreina; Pepi, Federico; Cimino, Paola; Troiani, Anna; Garzoli, Stefania; Salvitti, Chiara; Di Rienzo, Brunella; Barone, Vincenzo

2016-12-01

In order to investigate the gas-phase mechanisms of the acid catalyzed degradation of ascorbic acid (AA) to furan, we undertook a mass spectrometric (ESI/TQ/MS) and theoretical investigation at the B3LYP/6-31 + G(d,p) level of theory. The gaseous reactant species, the protonated AA, [C 6 H 8 O 6 ]H + , were generated by electrospray ionization of a 10 -3  M H 2 O/CH 3 OH (1 : 1) AA solution. In order to structurally characterize the gaseous [C 6 H 8 O 6 ]H + ionic reactants, we estimated the proton affinity and the gas-phase basicity of AA by the extended Cooks's kinetic method and by computational methods at the B3LYP/6-31 + G(d,p) level of theory. As expected, computational results identify the carbonyl oxygen atom (O2) of AA as the preferred protonation site. From the experimental proton affinity of 875.0 ± 12 kJ mol -1 and protonation entropy ΔS p 108.9 ± 2 J mol -1  K -1 , a gas-phase basicity value of AA of 842.5 ± 12 kJ mol -1 at 298 K was obtained, which is in agreement with the value issuing from quantum mechanical computations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Phenolic profiles and their contribution to the antioxidant activity of selected chickpea genotypes from Mexico and ICRISAT collections.

PubMed

Quintero-Soto, Maria F; Saracho-Peña, Ana G; Chavez-Ontiveros, Jeanett; Garzon-Tiznado, Jose A; Pineda-Hidalgo, Karen V; Delgado-Vargas, Francisco; Lopez-Valenzuela, Jose A

2018-06-01

Chickpea (Cicer arietinum L.) genotypes, nine kabuli from Mexico and 9 desi from other countries, were investigated for their phenolic profiles and antioxidant activity (AA). Phenolics in methanol extracts (ME) were analyzed by ultra-performance liquid chromatography coupled to diode array detection and mass spectrometry (UPLC-DAD-MS), whereas the AA was measured as Trolox equivalents (TE) by ABTS, DPPH and FRAP methods. Twenty phenolic compounds were identified in the ME and their levels showed a great variability among the chickpea genotypes. Phenolic acids and flavonoids were the most abundant compounds in kabuli and desi genotypes, respectively. The AA values (μmol TE/ 100 g dw) by ABTS (278-2417), DPPH (52-1650), and FRAP (41-1181) were mainly associated with the content of sinapic acid hexoside, gallic acid, myricetin, quercetin, catechin, and isorhamnetin, suggesting they are the main compounds responsible for the AA. The sum of the AA obtained for standards of these compounds evaluated at the concentration found in the extracts accounted for 34.3, 69.8, and 47.0% of the AA in the extract by ABTS, DPPH, and FRAP, respectively. In the AA by DPPH, most of the mixtures of these compounds resulted in synergistic interactions. Three desi genotypes with black seeds (ICC 4418, ICC 6306, and ICC 3761) showed the highest AA and flavonoids content, whereas the most promising kabuli genotypes were Surutato 77, Bco. Sin. 92, and Blanoro that showed the highest values of phenolic acids. These genotypes represent good sources of antioxidants for the improvement of nutraceutical properties in chickpea.

Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

PubMed

Tanaka, Toshiko; Shen, Jian; Abecasis, Gonçalo R; Kisialiou, Aliaksei; Ordovas, Jose M; Guralnik, Jack M; Singleton, Andrew; Bandinelli, Stefania; Cherubini, Antonio; Arnett, Donna; Tsai, Michael Y; Ferrucci, Luigi

2009-01-01

Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46)). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9)) and eicosapentanoic acid (EPA; p = 1.07 x 10(-14)). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6)). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.

Growth and Clinical Variables in Nitrogen-Restricted Piglets Fed an Adjusted Essential Amino Acid Mix: Effects of Partially Intact Protein-Based Diets.

PubMed

Worsøe, Päivi S; Sangild, Per T; van Goudoever, Johannes B; Koletzko, Berthold; van der Beek, Eline M; Abrahamse-Berkeveld, Marieke; Burrin, Douglas G; van de Heijning, Bert J M; Thymann, Thomas

2018-06-13

Current recommendations for protein levels in infant formula are intended to ensure that growth matches or exceeds growth of breastfed infants, but may provide a surplus of amino acids (AAs). Recent infant studies with AA-based formulas support specific adjustment of the essential amino acid (EAA) composition allowing for potential lowering of total protein levels. With the use of a combination of intact protein and free EAAs, we designed a formula that meets these adjusted EAA requirements for infants. Our objective was to test whether this adjusted formula is safe and supports growth in a protein-restricted piglet model, and whether it shows better growth than an isonitrogenous formula based on free AAs. Term piglets (Landrace × Yorkshire × Duroc, n = 72) were fed 1 of 4 isoenergetic formulas containing 70% intact protein and 30% of an EAA mixture or a complete AA-based control for 20 d: standard formula (ST-100), ST-100 with 25% reduction in proteinaceous nitrogen (ST-75), ST-75 with an adjusted EAA composition (O-75), or a diet as O-75, given as a complete AA-based diet (O-75AA). After an initial adaptation period, ST-75 and O-75 pigs showed similar growth rates, both lower than ST-100 pigs (∼25 compared with 31 g · kg-1 · d-1, respectively). The O-75AA pigs showed further reduced growth rate (15 g · kg-1 · d-1) and fat proportion (both P < 0.05, relative to O-75). Formula based partly on intact protein is superior to AA-based formula in this experimental setting. The 25% lower, but EAA-adjusted, partially intact protein-based formula resulted in similar weight gain with a concomitant increased AA catabolism, compared with the standard 25% lower standard formula in artificially reared, protein-restricted piglets. Further studies should investigate if and how the specific EAA adjustments that allow for lowering of total protein levels will affect growth and body composition development in formula-fed infants.

Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission Tomography Imaging of Tumors

NASA Astrophysics Data System (ADS)

Sun, Aixia; Liu, Xiang; Tang, Ganghua

2017-12-01

Tumor cells have an increased nutritional demand for amino acids(AAs) to satisfy their rapid proliferation. Positron-emitting nuclide labeled AAs are interesting probes and are of great importance for imaging tumors using positron emission tomography (PET). Carbon-11 and fluorine-18 labeled AAs include the [1-11C] amino acids, labeling alpha-C- amino acids, the branched-chain of amino acids and N-substituted carbon-11 labeled amino acids. These tracers target protein synthesis or amino acid(AA) transport, and their uptake mechanism mainly involves AA transport. AA PET tracers have been widely used in clinical settings to image brain tumors, neuroendocrine tumors, prostate cancer, breast cancer, non–small cell lung cancer (NSCLC) and hepatocellular carcinoma. This review focuses on the fundamental concepts and the uptake mechanism of AAs, AA PET tracers and their clinical applications.

The effects of the formula of amino acids enriched BCAA on nutritional support in traumatic patients.

PubMed

Wang, Xin-Ying; Li, Ning; Gu, Jun; Li, Wei-Qin; Li, Jie-Shou

2003-03-01

To investigate the formula of amino acid enriched BCAA on nutritional support in traumatic patients after operation. 40 adult patients after moderate or large abdominal operations were enrolled in a prospective, randomly and single-blind-controlled study, and received total parenteral nutrition (TPN) with either formula of amino acid (AA group, 20 cases) or formula of amino acid enriched BCAA (BCAA group, 20 cases). From the second day after operation, total parenteral nutrition was infused to the patients in both groups with equal calorie and equal nitrogen by central or peripheral vein during more than 12 hours per day for 6 days. Meanwhile, nitrogen balance was assayed by collecting 24 hours urine for 6 days. The markers of protein metabolism were investigated such as amino acid patterns, levels of total protein, albumin, prealbumin, transferrin and fibronectin in serum. The positive nitrogen balance in BCAA group occurred two days earlier than that in AA group. The serum levels of total protein and albumin in BCAA group were increased more obviously than that in AA group. The concentration of valine was notably increased and the concentration of arginine was markedly decreased in BCAA group after the formula of amino acids enriched BCAA transfusion. The formula of amino acid enriched BCAA may normalize the levels of serum amino acids, reduce the proteolysis, increase the synthesis of protein, improve the nutritional status of traumatic patients after operation.

Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver.

PubMed

Airanthi, M K Widjaja-Adhi; Sasaki, Naoya; Iwasaki, Sayaka; Baba, Nobuko; Abe, Masayuki; Hosokawa, Masashi; Miyashita, Kazuo

2011-04-27

Brown seaweed lipids from Undaria pinnatifida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUFA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomoku lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUFA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.

Amino acid utilization and body composition of growing pigs fed processed soybean meal or rapeseed meal with or without amino acid supplementation.

PubMed

Hulshof, T G; van der Poel, A F B; Hendriks, W H; Bikker, P

2017-07-01

Feed ingredients used in swine diets are often processed to improve nutritional value. However, (over-)processing may result in chemical reactions with amino acids (AAs) that decrease their ileal digestibility. This study aimed to determine effects of (over-)processing of soybean meal (SBM) and rapeseed meal (RSM) on post-absorptive utilization of ileal digestible AAs for retention and on body AA composition of growing pigs. Soybean meal and RSM were processed by secondary toasting in the presence of lignosulfonate to obtain processed soybean meal (pSBM) and processed rapeseed meal (pRSM). Four diets contained SBM, pSBM, RSM or pRSM as sole protein source. Two additional diets contained pSBM or pRSM and were supplemented with crystalline AA to similar standardized ileal digestible (SID) AA level as the SBM or RSM diet. These diets were used to verify that processing affected AA retention by affecting ileal AA digestibility rather than post-absorptive AA utilization. The SID AA levels of the protein sources were determined in a previous study. In total, 59 pigs were used (initial BW of 15.6±0.7 kg) of which five were used to determine initial body composition at the start of the experiment. In total, 54 pigs were fed one of six experimental diets and were slaughtered at a BW of 40 kg. The organ fraction (i.e. empty organs plus blood) and carcass were analyzed separately for N and AA content. Post-absorptive AA utilization was calculated from AA retention and SID AA intake. An interaction between diet type, comprising effects of processing and supplementing crystalline AA, and protein source was observed for CP content in the organ fraction, carcass and empty body and for nutrient retention. Processing reduced CP content and nutrient retention more for SBM than for RSM. Moreover, processing reduced (P<0.001) the lysine content in the organ fraction for both protein sources. Supplementing crystalline AA ameliorated the effect of processing on these variables. Thus, the data indicated that processing affected retention by reducing digestibility. Correcting AA retention for SID AA intake was, therefore, expected to result in similar post-absorptive AA utilization which was observed for the RSM diets. However, post-absorptive AA utilization was lower for the pSBM diet than for the SBM diet which might be related to an imbalanced post-absorptive AA supply. In conclusion, processing negatively affected nutrient retention for both protein sources and post-absorptive utilization of SID AA for retention for SBM. Effects of processing were compensated by supplementing crystalline AA.

Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo.

PubMed

Aliwarga, Theresa; Raccor, Brianne S; Lemaitre, Rozenn N; Sotoodehnia, Nona; Gharib, Sina A; Xu, Libin; Totah, Rheem A

2017-11-01

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) oxidation that have important cardioprotective and signaling properties. AA is an ω-6 polyunsaturated fatty acid (PUFA) that is prone to autoxidation. Although hydroperoxides and isoprostanes are major autoxidation products of AA, EETs are also formed from the largely overlooked peroxyl radical addition mechanism. While autoxidation yields both cis- and trans-EETs, cytochrome P450 (CYP) epoxygenases have been shown to exclusively catalyze the formation of all regioisomer cis-EETs, on each of the double bonds. In plasma and red blood cell (RBC) membranes, cis- and trans-EETs have been observed, and both have multiple physiological functions. We developed a sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay that separates cis- and trans- isomers of EETs and applied it to determine the relative distribution of cis- vs. trans-EETs in reaction mixtures of AA subjected to free radical oxidation in benzene and liposomes in vitro. We also determined the in vivo distribution of EETs in several tissues, including human and mouse heart, and RBC membranes. We then measured EET levels in heart and RBC of young mice compared to old. Formation of EETs in free radical reactions of AA in benzene and in liposomes exhibited time- and AA concentration-dependent increase and trans-EET levels were higher than cis-EETs under both conditions. In contrast, cis-EET levels were overall higher in biological samples. In general, trans-EETs increased with mouse age more than cis-EETs. We propose a mechanism for the non-enzymatic formation of cis- and trans-EETs involving addition of the peroxyl radical to one of AA's double bonds followed by bond rotation and intramolecular homolytic substitution (S H i). Enzymatic formation of cis-EETs by cytochrome P450 most likely occurs via a one-step concerted mechanism that does not allow bond rotation. The ability to accurately measure circulating EETs resulting from autoxidation or enzymatic reactions in plasma and RBC membranes will allow for future studies investigating how these important signaling lipids correlate with heart disease outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary ascorbic acid modulates the expression profile of stress protein genes in hepatopancreas of adult Pacific abalone Haliotis discus hannai Ino.

PubMed

Wu, Chenglong; Wang, Jia; Xu, Wei; Zhang, Wenbing; Mai, Kangsen

2014-12-01

This study was conducted to investigate the effects of dietary ascorbic acid (AA) on transcriptional expression patterns of antioxidant proteins, heat shock proteins (HSP) and nuclear factor kappa B (NF-κB) in the hepatopancreas of Pacific abalone Haliotis discus hannai Ino (initial average length: 84.36 ± 0.24 mm) using real-time quantitative PCR assays. L-ascorbyl-2-molyphosphate (LAMP) was added to the basal diet to formulate four experimental diets containing 0.0, 70.3, 829.8 and 4967.5 mg AA equivalent kg(-1) diets, respectively. Each diet was fed to triplicate groups of adult abalone in acrylic tanks (200 L) in a flow-through seawater system. Each tank was stocked with 15 abalone. Animals were fed once daily (17:00) to apparent satiation for 24 weeks. The results showed that the dietary AA (70.3 mg kg(-1)) could significantly up-regulate the expression levels of Cu/Zn superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), feritin (FT) and heat shock protein 26 (HSP26) in the hepatopancreas of abalone in this treatment compared to the controls. However, the expression levels of Mn-SOD, glutathione peroxidase (GPX), thioredoxin peroxidase (TPx), selenium-binding protein (SEBP), HSP70 and HSP90 were significantly down-regulated. Compared with those in the group with 70.3 mg kg(-1) dietary AA, the expression levels of CAT, GST and HSP26 were decreased in abalone fed with very high dietary AA (4967.5 mg kg(-1)). In addition, significant up-regulations of expression levels of Mn-SOD, GPX, TPx, SEBP, FT, HSP70, HSP90 and NF-κB were observed in abalone fed with apparently excessive dietary AA (829.8 and 4967.5 mg kg(-1)) as compared to those fed 70.3 mg kg(-1) dietary AA. These findings showed that dietary AA influenced the expression levels of antioxidant proteins, heat shock proteins and NF-κB in the hepatopancreas of abalone at transcriptional level. Levels of dietary AA that appeared adequate (70.3 mg kg(-1)) reduced the oxidative stress by influencing gene expression of antioxidant proteins, but excessive dietary AA (829.8 and 4967.5 mg kg(-1)) induced oxidative stress in Pacific abalone H. discus hannai. Copyright © 2014 Elsevier Ltd. All rights reserved.

Profiling of Amino Acids and Their Derivatives Biogenic Amines Before and After Antipsychotic Treatment in First-Episode Psychosis.

PubMed

Leppik, Liisa; Kriisa, Kärt; Koido, Kati; Koch, Kadri; Kajalaid, Kärolin; Haring, Liina; Vasar, Eero; Zilmer, Mihkel

2018-01-01

Schizophrenia (SCH) is a heterogeneous disorder, deriving from a potential multitude of etiopathogenetic factors. During the past few years there has been an increasing interest in the role of circulating amino acids (AAs) and biogenic amines (BAs) in the pathophysiology of SCH. In the present study, we aimed to provide an insight into the potential role of alterations in levels of AAs and BAs as well as examine their more specific metabolic shifts in relation to early stage of SCH. We measured 21 AAs and 17 BAs in serum samples of patients with first-episode psychosis (FEP) before and after 7-month antipsychotic treatment in comparison to control subjects (CSs). According to multivariate analysis, antipsychotic-naïve FEP patients had significantly higher levels of taurine and spermine, whereas values of proline (Pro), alpha-aminoadipic acid (alpha-AAA), kynurenine (Kyn), valine (Val), tyrosine (Tyr), citrulline (Citr), tryptophan (Trp), and histidine (His) were diminished compared to CSs. Increased levels of taurine and spermine, as well as reduced levels of alpha-AAA and Kyn probably reflect the compromised function of N -methyl-D-aspartate (NMDA) receptors in patients. The decreased levels of Pro (AA modulating the function of glutamate decarboxylase) likely reflect the imbalanced function of gamma-aminobutyric acid (GABA) system in the brain of FEP patients. The alterations in ratio between Tyr and phenylalanine (Phe) can be taken as a sign of compromised function of dopaminergic system. These metabolic shifts were reinstated by 7-month antipsychotic treatment. Serum metabolic profiles can be regarded as important indicators to investigate clinical course of SCH and treatment response.

Comparison of long chain polyunsaturated fatty acid content in human milk in preterm and term deliveries and its correlation with mothers' diet.

PubMed

Iranpour, Ramin; Kelishadi, Roya; Babaie, Sharareh; Khosravi-Darani, Kianoush; Farajian, Sanam

2013-01-01

Human milk (HM) is the main food for infants, and phospholipids, especially long chain polyunsaturated fatty acids (LCPUFAs), play an essential role in the growth and brain development. This study was designed to evaluate the fatty acid composition in HM of mothers with preterm and full-term newborns and to determine the relationships of dietary intake of docosahexaenoic acid (DHA) and arachidonic acid (AA) of mothers and the content of these fatty acids in their milks. The AA and DHA of HM were determined by gas chromatography at the 3(rd) day after birth from mothers of 59 term and 58 preterm infants. Mothers were selected from those who delivered in Shahid Beheshti Hospital, a referral teaching hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Dietary fat composition of mothers was examined by a food-frequency questionnaire. Total fat content, and DHA and AA levels of HM were compared in both groups. The correlation of dietary DHA and AA with DHA and AA of HM was determined in both groups. We found that maternal age, body mass index (BMI), and self-reported food-frequency questionnaire did not differ in the two groups. The mean AA (0.19 ± 0.10 mg/ml and 0.16 ± 0.09 mg/ml, respectively), DHA (0.10 ± 0.06 mg/ml and 0.08 ± 0.05 mg/ml, respectively), and total fat content (2.58 ± 2.16 g/dl and 2.06 ± 1.22 g/dl, respectively) of HM of mothers with preterm neonates were non-significantly higher than in mothers with term neonates. The percentage of DHA in the HM fat of preterm and term groups (0.45 ± 0.16% and 0.45 ± 0.18%, respectively) and the percentage of AA (0.85 ± 0.26% and 0.84 ± 0.20%, respectively) were comparable with worldwide standards. No correlations were documented between DHA and AA intake and DHA and AA content of HM in both groups. Although DHA and AA content of HM in preterm group was higher than in term group, this difference were not significant. In Isfahan, the percentage of DHA and AA was acceptable in the milk fat of mothers with term and preterm neonates.

Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance.

PubMed

Perez-Martinez, Pablo; Delgado-Lista, Javier; Garcia-Rios, Antonio; Tierney, Audrey C; Gulseth, Hanne L; Williams, Christine M; Karlström, Brita; Kieć-Wilk, Beata; Blaak, Ellen E; Helal, Olfa; Saris, Wim H M; Defoort, Catherine; Drevon, Christian A; Lovegrove, Julie A; Dembinska-Kieć, Aldona; Riserus, Ulf; Roche, Helen M; Lopez-Miranda, Jose

2012-02-01

Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects. Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038), higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of ω-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects. The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Change in blood levels of eicosapentaenoic acid and posttraumatic stress symptom: A secondary analysis of data from a placebo-controlled trial of omega3 supplements.

PubMed

Matsuoka, Yutaka J; Hamazaki, Kei; Nishi, Daisuke; Hamazaki, Tomohito

2016-11-15

Eicosapentaenoic acid (EPA) is suggested to be protective against posttraumatic stress disorder (PTSD) from two observational studies. We previously conducted a randomized controlled trial and found no effect of docosahexaenoic acid (DHA) for prevention of PTSD. This secondary analysis aimed to determine whether change in blood levels of EPA is associated with PTSD symptoms. The percentages of EPA, DHA, and arachidonic acid (AA) were measured in erythrocyte membranes at baseline and posttreatment in 110 participants with severe physical injury who were randomly assigned to receive either a daily dose of 1,470mg DHA and 147mg EPA or of placebo for 12 weeks. Associations between change in erythrocyte fatty acid levels during the trial controlling for each baseline level and PTSD severity at 12 weeks were analyzed by treatment arm. In the omega3 supplements arm, changes in EPA+DHA (p=.023) and EPA (p=.001) as well as the EPA:AA ratio (p=.000) and EPA: DHA ratio (p=.013) were inversely correlated with PTSD severity. Change in AA was positively correlated with PTSD severity (p=.001). This trial was conducted at a single-center in Japan and PTSD symptoms in most participants were not serious. Increased erythrocyte level of EPA during the trial was associated with low severity of PTSD symptoms in patients receiving omega3 supplements. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of aromatic amino acids, phenylacetate and phenylpropionate on fermentation of xylan by the rumen anaerobic fungi, Neocallimastix frontalis and Piromyces communis.

PubMed

Guliye, A Y; Wallace, R J

2007-10-01

Anaerobic fungi are important members of the fibrolytic community of the rumen. The aim of this study was to study their requirement for aromatic amino acids (AA) and related phenyl acids (phenylpropionic and phenylacetic acids) for optimal xylan fermentation. Neocallimastix frontalis RE1 and Piromyces communis P were grown in a defined medium containing oat spelts xylan as the sole energy source, plus one of the following N sources: ammonia; ammonia plus a complete mixture of 20 AA commonly found in protein; ammonia plus complete AA mixture minus aromatic AA; ammonia plus phenyl acids; ammonia plus complete AA mixture without aromatic AA plus phenyl acids. Both species grew in all the media, indicating no absolute requirement for AA. The complete AA mixture increased (P<0.05) acetate concentration by 18% and 15%, sugar utilization by 33% and 22% and microbial yield by about 22% and 15% in N. frontalis and P. communis, respectively, in comparison with the treatments that had ammonia as the only N source. Neither the supply of aromatic AA or phenol acids, nor their deletion from the complete AA mixture, affected the fermentation rate, products or yield of either species. AA were not essential for N. frontalis and P. communis, but their growth on xylan was stimulated. The effects could not be explained in terms of aromatic AA alone. Ruminant diets should contain sufficient protein to sustain optimal fibre digestion by ruminal fungi. Aromatic AA or phenyl acids alone cannot replace the complete AA mixture.

Five primary sources of organic aerosols in the urban atmosphere of Belgrade (Serbia).

PubMed

Zangrando, Roberta; Barbaro, Elena; Kirchgeorg, Torben; Vecchiato, Marco; Scalabrin, Elisa; Radaelli, Marta; Đorđević, Dragana; Barbante, Carlo; Gambaro, Andrea

2016-11-15

Biomass burning and primary biological aerosol particles (PBAPs) represent important primary sources of organic compounds in the atmosphere. These particles and compounds are able to affect climate and human health. In the present work, using HPLC-orbitrapMS, we determined the atmospheric concentrations of molecular markers such as anhydrosugars and phenolic compounds that are specific for biomass burning, as well as the concentrations of sugars, alcohol sugars and d- and l-amino acids (D-AAs and L-AAs) for studying PBAPs in Belgrade (Serbia) aerosols collected in September-December 2008. In these samples, high levels of all these biomarkers were observed in October. Relative percentages of vanillic (V), syringic compounds (S) and p-coumaric acid (PA), as well as levoglucosan/mannosan (L/M) ratios, helped us discriminate between open fire events and wood combustion for domestic heating during the winter. L-AAs and D-AAs (1% of the total) were observed in Belgrade aerosols mainly in September-October. During open fire events, mean D-AA/L-AA (D/L) ratio values of aspartic acid, threonine, phenylalanine, alanine were significantly higher than mean D/L values of samples unaffected by open fire. High levels of AAs were observed for open biomass burning events. Thanks to four different statistical approaches, we demonstrated that Belgrade aerosols are affected by five sources: a natural source, a source related to fungi spores and degraded material and three other sources linked to biomass burning: biomass combustion in open fields, the combustion of grass and agricultural waste and the combustion of biomass in stoves and industrial plants. The approach employed in this work, involving the determination of specific organic tracers and statistical analysis, proved useful to discriminate among different types of biomass burning events. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of the contents of various antioxidants of sea buckthorn berries using CE.

PubMed

Gorbatsova, Jelena; Lõugas, Tiina; Vokk, Raivo; Kaljurand, Mihkel

2007-11-01

The increased interest in sea buckthorn (Hippophae rhamnoides L.) made it possible to investigate the antioxidant content in it. To address this issue, the presence of following antioxidant compounds were analyzed: trans-resveratrol, catechin, myricetin, quercetin, p-coumaric acid, caffeic acid, L-ascorbic acid (AA), and gallic acid (linear range of 50-150 micromol/L) in six different varieties of sea buckthorn berries extracts (sea buckthorn varieties: "Trofimovskaja (TR)," "Podarok Sadu (PS)," and "Avgustinka (AV),") received from two local Estonian companies. Trans-Resveratrol, catechin, AA, myricetin, and quercetin were found in extracts of sea buckthorn. Moreover, AA, myricetin, and quercetin contents were quantified. The biggest average AA content was found in TR (740 mg/100 g of dried berries, respectively). Furthermore, the same varieties gave the biggest quercetin content 116 mg/100 g of dried berries, respectively. For analysis, CZE was used and the results were partly validated by HPLC. Statistically no big differences in levels of antioxidants were consistently found in different varieties of sea buckthorn extracts investigated in this work.

Influences of AMY1 gene copy number and protein expression on salivary alpha-amylase activity before and after citric acid stimulation in splenic asthenia children.

PubMed

Yang, Zemin; Lin, Jing; Chen, Longhui; Zhang, Min; Yang, Xiaorong; Chen, Weiwen

2015-06-01

To compare the correlations between salivary alpha-amylase (sAA) activity and amylase, alpha 1 (salivary) gene (AMYl) copy number or its gene expression between splenic asthenia and healthy children, and investigate the reasons of attenuated sAA activity ratio before and after citric acid stimulation in splenic asthenia children. Saliva samples from 20 splenic asthenia children and 29 healthy children were collected before and after citric acid stimulation. AMYl copy number, sAA activity, and total sAA and glycosylated sAA contents were determined, and their correlations were analyzed. Although splenic asthenia and healthy children had no differences in AMY1 copy number, splenic asthenia children had positive correlations between AMY1 copy number and sAA activity before or after citric acid stimulation. Splenic asthenia children had a higher sAA glycosylated proportion ratio and glycosylated sAA content ratio, while their total sAA content ratio and sAA activity ratio were lower compared with healthy children. The glycosylated sAA content ratio was higher than the total sAA content ratio in both groups. Splenic asthenia and healthy children had positive correlations between total sAA or glycosylated sAA content and sAA activity. However, the role played by glycosylated sAA content in sAA activity in healthy children increased after citric acid stimulation, while it decreased in splenic asthenia children. Genetic factors like AMY1 copy number variations, and more importantly, sAA glycosylation abnormalities leading to attenuated sAA activity after citric acid stimulation, which were the main reasons of the attenuated sAA activity ratio in splenic asthenia children compared with healthy children.

Pretreatment of Gymnema sylvestre revealed the protection against acetic acid-induced ulcerative colitis in rats

PubMed Central

2014-01-01

Background Overproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases. Gymnema sylvestre (GS) leaves extract is distinguished for its anti-diabetic, antioxidant and anti-inflammatory properties. Present study is designed to evaluate the preventative activities of GS against acetic acid (AA)-induced ulcerative colitis in Wistar rats. Methods Experimentally ulcerative colitis (UC) was induced by AA in animals pretreated with three different doses of GS leaves extract (50, 100, 200 mg/kg/day) and a single dose of mesalazine (MES, 300 mg/kg/day) for seven days. Twenty four hours later, animals were sacrificed and the colonic tissues were collected. Colonic mucus content was determined using Alcian blue dye binding technique. Levels of thiobarbituric acid reactive substances (TBARS), total glutathione sulfhydryl group (T-GSH) and non-protein sulfhydryl group (NPSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were estimated in colon tissues. Colonic nucleic acids (DNA and RNA) and total protein (TP) concentrations were also determined. Levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) as well as prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated in colonic tissues. The histopathological changes of the colonic tissues were also observed. Results In AA administered group TBARS levels were increased, while colonic mucus content, T-GSH and NP-SH, SOD and CAT were reduced in colon. Pretreatment with GS inhibited TBARS elevation as well as mucus content, T-GSH and NP-SH reduction. Enzymatic activities of SOD and CAT were brought back to their normal levels in GS pretreated group. A significant reduction in DNA, RNA and TP levels was seen following AA administration and this inhibition was significantly eliminated by GS treatment. GS pretreatment also inhibited AA-induced elevation of pro-inflammatory cytokines, PGE2 and NO levels in colon. The apparent UC protection was further confirmed by the histopathological screening. Conclusion The GS leaves extract showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property. PMID:24507431

Pretreatment of Gymnema sylvestre revealed the protection against acetic acid-induced ulcerative colitis in rats.

PubMed

Aleisa, Abdulaziz M; Al-Rejaie, Salim S; Abuohashish, Hatem M; Ola, Mohammed S; Parmar, Mihir Y; Ahmed, Mohammed M

2014-02-10

Overproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases. Gymnema sylvestre (GS) leaves extract is distinguished for its anti-diabetic, antioxidant and anti-inflammatory properties. Present study is designed to evaluate the preventative activities of GS against acetic acid (AA)-induced ulcerative colitis in Wistar rats. Experimentally ulcerative colitis (UC) was induced by AA in animals pretreated with three different doses of GS leaves extract (50, 100, 200 mg/kg/day) and a single dose of mesalazine (MES, 300 mg/kg/day) for seven days. Twenty four hours later, animals were sacrificed and the colonic tissues were collected. Colonic mucus content was determined using Alcian blue dye binding technique. Levels of thiobarbituric acid reactive substances (TBARS), total glutathione sulfhydryl group (T-GSH) and non-protein sulfhydryl group (NPSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were estimated in colon tissues. Colonic nucleic acids (DNA and RNA) and total protein (TP) concentrations were also determined. Levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) as well as prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated in colonic tissues. The histopathological changes of the colonic tissues were also observed. In AA administered group TBARS levels were increased, while colonic mucus content, T-GSH and NP-SH, SOD and CAT were reduced in colon. Pretreatment with GS inhibited TBARS elevation as well as mucus content, T-GSH and NP-SH reduction. Enzymatic activities of SOD and CAT were brought back to their normal levels in GS pretreated group. A significant reduction in DNA, RNA and TP levels was seen following AA administration and this inhibition was significantly eliminated by GS treatment. GS pretreatment also inhibited AA-induced elevation of pro-inflammatory cytokines, PGE2 and NO levels in colon. The apparent UC protection was further confirmed by the histopathological screening. The GS leaves extract showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property.

The effects of centrally injected arachidonic acid on respiratory system: Involvement of cyclooxygenase to thromboxane signaling pathway.

PubMed

Erkan, Leman Gizem; Guvenc, Gokcen; Altinbas, Burcin; Niaz, Nasir; Yalcin, Murat

2016-05-01

Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Spraque Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA2 signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Mildly abnormal general movement quality in infants is associated with higher Mead acid and lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio.

PubMed

van Goor, S A; Schaafsma, A; Erwich, J J H M; Dijck-Brouwer, D A J; Muskiet, F A J

2010-01-01

We showed that docosahexaenoic acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic acid (AA), DHA/AA and Mead acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable. Copyright 2009 Elsevier Ltd. All rights reserved.

Purified fish oil eliminating linoleic and alpha linolenic acid meets essential fatty acid requirements in rats.

PubMed

Ling, Pei-Ra; Puder, Mark; Bistrian, Bruce R

2012-10-01

This study examined whether purified fish oil (PFO) supplemented to an essential fatty acid deficient (EFAD) diet meets EFA needs in rats. The EFAD diet contained 10% hydrogenated coconut oil (HCO). A similar diet contained 7% HCO and 3% PFO which also provided 2.84% arachidonic acid (AA), 52.50% eicosapentaenoic acid (EPA) and 35.73% docosahexaenoic acid (DHA) but no linoleic acid (LA) or alpha linolenic acid (ALA). A 10% soybean oil control diet provided ample LA and ALA. After 4 weeks of feeding, blood glucose, plasma triglyceride and phospholipid fatty acid profiles, C-reactive protein (CRP), TNF and IL-6 were determined after saline or LPS injection. EFAD developed with the HCO diet with triene:tetraene ratios in plasma phospholipids >.20, which remained <.02 with the control and HCO+PFO diets. Mead acid levels significantly increased by a factor of 10 with the HCO diet compared to the AIN and HCO+PFO diets and were significantly lowest with the HCO+PFO diet. 18:1 n9 levels were significantly higher in plasma phospholipids and triglycerides with the HCO diet. CRP levels were significantly highest with the control diet and significantly lowest with the HCO diet. LPS significantly increased 18:1 n9 and cytokines, and decreased AA and plasma glucose in all diets and significantly increased plasma triglycerides and decreased plasma glucose in controls. Providing AA, EPA and DHA in EFAD prevents EFAD over the short-term as reflected in Mead acid production, triene:tetraene ratio, and de novo lipogenesis and may reduce the inflammatory response to LPS. Copyright © 2012 Elsevier Inc. All rights reserved.

Amino acid and energy interrelationships in growing beef steers: I. The effect of level of feed intake on ruminal characteristics and intestinal amino acid flows.

PubMed

Ludden, P A; Kerley, M S

1997-09-01

Five cannulated Holstein steers (538 +/- 35 kg) were used in a 4 x 4 Latin square design experiment with extra observations to examine the influence of level of feed intake on postruminal flow and intestinal disappearance of N and amino acids (AA). Treatments consisted of a single diet fed at four levels of energy intake (1.5, 2.0, 2.5, and 3.0 times NEm requirement). The diet was formulated on a DM basis to contain 13.25% CP using cracked corn (56.1%), soybean hulls (18%), cottonseed hulls (15%), soybean oil (4.25%), and corn gluten meal (5.6%). Increasing feed intake linearly increased (P < .0001) the quantity of OM truly digested in the stomach but tended to decrease (P = .11) OM digestion as a percentage of intake. Level of feed intake had no effect (P > .10) on ruminal pH, NH3 N, or peptide concentration or on particulate and fluid passage rates. However, total VFA concentration increased linearly (P < .0001) and the acetate: propionate ratio decreased linearly (P < .0001) as feed intake increased. Flows of microbial and nonmicrobial N at the duodenum linearly increased (P < .002) with increasing intake but did not differ (P > .10) as a percentage of intake. Level of feed intake did not affect (P > .10) microbial efficiency, N disappearance from the small intestine, or total tract N digestibility. With the exception of tryptophan, flows of all individual AA increased linearly (P < .01) with increasing intake. As a percentage of duodenal flow, AA digestion in the small intestine did not differ (P > .10), leading to a linear increase (P < .10) in the net quantity of individual (with the exception of tryptophan) and total AA disappearing from the small intestine as feed intake increased. Likewise, the profile of AA (except tryptophan) disappearing from the small intestine was unaffected (P > .10) by level of feed intake. When compared with predicted requirements for a 227-kg growing beef steer, Arg, Met, His, and Lys were suggested to be the most limiting AA for growth when this diet is fed. We conclude that altering energy intake by restricting intake of a single diet has only minor effects on the profile of digestible AA or other nutrients presented to the animal.

SVCT-2 determines the sensitivity to ascorbate-induced cell death in cholangiocarcinoma cell lines and patient derived xenografts.

PubMed

Wang, Changzheng; Lv, Hongwei; Yang, Wen; Li, Ting; Fang, Tian; Lv, Guishuai; Han, Qin; Dong, Liwei; Jiang, Tianyi; Jiang, Beige; Yang, Guangshun; Wang, Hongyang

2017-07-10

Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (l-ascorbic acid, ascorbate) in several types of cancer. However, the effect of l-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo. Intriguingly, sodium-dependent vitamin C transporter 2 (SVCT-2) expression was inversely correlated with IC50 values of AA. Knockdown of SVCT-2 dramatically alleviated DNA damage, ATP depletion, and inhibition of mTOR pathway induced by AA. Furthermore, SVCT-2 knockdown endowed CC cells with the resistance to AA treatment. Finally, the inhibitory effects of AA were further confirmed in patient-derived CC xenograft models. Thus, our results unravel therapeutic potential of AA alone or in combination with cisplatin for CC. SVCT2 expression level may serve as a positive outcome predictor for AA treatment in CC. Copyright © 2017 Elsevier B.V. All rights reserved.

Amino and fatty acid dynamics of octopus (Octopus vulgaris) early life stages under ocean warming.

PubMed

Lopes, Vanessa M; Faleiro, Filipa; Baptista, Miguel; Pimentel, Marta S; Paula, José R; Couto, Ana; Bandarra, Narcisa; Anacleto, Patrícia; Marques, António; Rosa, Rui

2016-01-01

The oceans are becoming warmer, and the higher temperatures are expected to have a major impact on marine life at different levels of biological organization, especially at the most vulnerable early life stages. Thus, we hypothesize that the future warmer scenarios (here +3 °C) will affect the biochemical composition (amino acid - AA, and fatty acid-FA) of octopod (Octopus vulgaris) embryos and recently-hatched pelagic paralarvae. The main essential amino acids found in octopus embryos were arginine, leucine and lysine; while aspartic and glutamic acids, and taurine were the main non-essential amino acids. Palmitic, eicosapentaenoic and docosahexaenoic acids were the main FAs found in octopus tissues. Relevant ontogenetic changes were observed, namely a steep decrease in the content of many AAs, and a selective retention of FAs, thus evidencing the protein-based metabolism of these cephalopods. Temperature per si did not elicit significant changes in the overall FA composition, but was responsible for a significant decrease in the content of several AAs, indicating increased embryonic consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis.

PubMed

Umemoto, Norio; Ishii, Hideki; Kamoi, Daisuke; Aoyama, Toru; Sakakibara, Takashi; Takahashi, Hiroshi; Tanaka, Akihito; Yasuda, Yoshinari; Suzuki, Susumu; Matsubara, Tatsuaki; Murohara, Toyoaki

2016-06-01

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events. Carotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound. Carotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12-0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25-0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone. These data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of ascorbic acid or increasing metabolizable energy level with or without supplementation of some essential amino acids on productive and physiological traits of slow-growing chicks exposed to chronic heat stress.

PubMed

Attia, Y A; Hassan, R A; Tag El-Din, A E; Abou-Shehema, B M

2011-12-01

Four hundred and twenty, 21-day-old slow-growing chicks were divided randomly into seven treatments, each containing five replicates. Each replicate was kept in a 1 × 1-m floor pen. One treatment was kept under thermo-neutral conditions in a semi-open house and fed a corn-soybean meal diet (positive control). The other six groups were kept under chronic heat stress (CHS) at 38 °C and 60% RH for 4 h from 12:00 to 16:00 pm for three successive days per week. Chicks in CHS treatments were fed a corn-soybean meal diet without (negative control) or with increasing metabolizable energy (ME) level by oil supplementation alone, or also with increasing some essential amino acids (EAA) such as methionine (Met), methionine and lysine (Met+Lys) or methionine, lysine and arginine (Met+Lys+Arg) or supplemented with 250 mg of ascorbic acid (AA)/kg. CHS impaired (p < 0.05) growth performance, increased plasma triglycerides and total serum Ca while decreasing (p < 0.05) plasma glucose and total serum protein. Meanwhile 250 mg AA/kg diet or an increasing ME without or with some EAA partially alleviated (p < 0.0001) the negative effect of CHS on growth while increasing (p < 0.05) feed intake and improving (p < 0.05) feed:gain ratio (F:G) and crude protein (CP) digestibility (p < 0.05). AA or increasing ME with or without EAA increased (p < 0.05) percentage dressing, liver and giblets to those of the positive control. AA or increasing ME with or without EAA partially alleviated the negative effect of CHS on blood pH, packed cell volume (PCV), haemoglobin (Hgb), total serum protein and total Ca, plasma glucose and triglyceride, rectal temperature and respiration rate. Increasing ME level improved chickens' tolerance to CHS without a significant difference from those supplemented with AA. However, increasing Met, Lys and Arg concentration did not improve performance over that recorded with increasing ME level alone. Under CHS, 250 mg AA/kg diet or increasing ME level by addition of 3% vegetable oil could be an useful approach to improve productive and physiological traits of slow-growing chicks, which may be applicable also to fast-growing one. © 2010 Blackwell Verlag GmbH.

University of Hawai‘i Cancer Center Connection

PubMed Central

Halm, Brunhild M; Lai, Jennifer F; Li, Xingnan; Custer, Laurie J; Pagano, Ian; Cooney, Robert V; Turner, Helen C; Brenner, David J

2015-01-01

Computed tomography (CT) is an imaging modality that exposes patients to ionizing radiation (IR). We review and report findings from our pilot study evaluating whether blood markers are altered in 17 children undergoing medically indicated CT scans. Blood was drawn before (‘pre-CT’) and 1 hour after (‘post-CT’ CT scans. Plasma carotenoids, tocopherols, Q10, ascorbic acid (AA) and uric acid (UA) were analyzed by RP-HPLC with diode-array and electrochemical detection. Dehydroascorbic acid (DHAA) was calculated by subtraction from total AA. Total antioxidant capacity (TAC) was measured using the ORAC assay. Cytokines were quantified using a multiplex immunoassay. γ-H2AX foci were visualized using immunofluorescence. Mean pre- and post-CT changes were compared using t-tests; P-levels < .05 indicated significance. All major plasma lipid soluble antioxidant levels were lower post- vs pre-CT (P < .05) possibly from the scavenging of free radicals formed by CT-induced IR. Average AA levels increased (134%) while DHAA levels were decreased (29%) post-CT, probably due to intracellular recycling of AA from DHAA. TAC levels in lipophilic and hydrophilic extracts were unchanged, suggesting that other antioxidants may have assisted in free radical quenching, which would corroborate their lower concentrations post-CT. Cytokine levels were unchanged and dose-dependent increases in γ-H2AX foci, a measure of double strand DNA breaks, were observed (P = .046, n = 3 children). Our results suggest that CT-derived IR can influence the antioxidant system and may elicit detrimental responses on the cellular level of young children. When possible and if appropriate non-IR based techniques such as ultrasound or magnetic resonance imaging should be used. PMID:25821654

Pilot study for the establishment of biomarkers for radiation damage after computed tomography in children.

PubMed

Halm, Brunhild M; Franke, Adrian A; Lai, Jennifer F; Li, Xingnan; Custer, Laurie J; Pagano, Ian; Cooney, Robert V; Turner, Helen C; Brenner, David J

2015-03-01

Computed tomography (CT) is an imaging modality that exposes patients to ionizing radiation (IR). We review and report findings from our pilot study evaluating whether blood markers are altered in 17 children undergoing medically indicated CT scans. Blood was drawn before ('pre-CT') and 1 hour after ('post-CT' CT scans. Plasma carotenoids, tocopherols, Q10, ascorbic acid (AA) and uric acid (UA) were analyzed by RP-HPLC with diode-array and electrochemical detection. Dehydroascorbic acid (DHAA) was calculated by subtraction from total AA. Total antioxidant capacity (TAC) was measured using the ORAC assay. Cytokines were quantified using a multiplex immunoassay. γ-H2AX foci were visualized using immunofluorescence. Mean pre- and post-CT changes were compared using t-tests; P-levels < .05 indicated significance. All major plasma lipid soluble antioxidant levels were lower post- vs pre-CT (P < .05) possibly from the scavenging of free radicals formed by CT-induced IR. Average AA levels increased (134%) while DHAA levels were decreased (29%) post-CT, probably due to intracellular recycling of AA from DHAA. TAC levels in lipophilic and hydrophilic extracts were unchanged, suggesting that other antioxidants may have assisted in free radical quenching, which would corroborate their lower concentrations post-CT. Cytokine levels were unchanged and dose-dependent increases in γ-H2AX foci, a measure of double strand DNA breaks, were observed (P = .046, n = 3 children). Our results suggest that CT-derived IR can influence the antioxidant system and may elicit detrimental responses on the cellular level of young children. When possible and if appropriate non-IR based techniques such as ultrasound or magnetic resonance imaging should be used.

In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation

PubMed Central

Wang, Shu; Wu, Dayong; Lamon-Fava, Stefania; Matthan, Nirupa R.; Honda, Kaori L.; Lichtenstein, Alice H.

2010-01-01

Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MΦ). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFα, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MΦ scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA- and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA- and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MΦ which are not related to the n position of the first double bond, chain length or degree of saturation. PMID:19660150

Evaluation of Toxicity and Biodegradability of Cholinium Amino Acids Ionic Liquids

PubMed Central

Hou, Xue-Dan; Liu, Qiu-Ping; Smith, Thomas J.; Li, Ning; Zong, Min-Hua

2013-01-01

Cholinium amino acid ionic liquids ([Ch][AA] ILs), which are wholly composed of renewable biomaterials, have recently been demonstrated to have very promising properties for applications in organic synthesis and biomass pretreatment. In this work, the toxicity of these ILs toward enzymes and bacteria was assessed, and the effect of the anion on these properties is discussed. The inhibitory potentials of this type of ILs to acetylcholinesterase were weaker approximately an order of magnitude than the traditional IL 1-butyl-3-methylimidazolium tetrafluoroborate. Additionally, the [Ch][AA] ILs displayed low toxicity toward the bacteria tested. Furthermore, the biodegradability of the [Ch][AA] ILs was evaluated via the closed bottle and CO2 headspace tests using wastewater microorganisms. All the ILs were classified as ‘readily biodegradable’ based on their high levels of mineralization (62-87%). The presence of extra carboxyl or amide groups on the amino acid side chain rendered the ILs significantly more susceptible to microbial breakdown. In addition, for most of the [Ch][AA] ILs, low toxicity correlated with good biodegradability. The low toxicity and high biodegradability of these novel [Ch][AA] make them promising candidates for use as environmentally friendly solvents in large-scale applications. PMID:23554985

Changes in the amino acid profiles and free radical scavenging activities of Tenebrio molitor larvae following enzymatic hydrolysis.

PubMed

Tang, Yujiao; Debnath, Trishna; Choi, Eun-Ju; Kim, Young Wook; Ryu, Jung Pyo; Jang, Sejin; Chung, Sang Uk; Choi, Young-Jin; Kim, Eun-Kyung

2018-01-01

Tenebrio molitor (T. molitor) larvae provide food at low environmental cost and contribute positively to livelihoods. In this research, we compared the amino acids compositions and antioxidant activities of various extracts of T. molitor to enhance their quality as food. For the comparison, distilled water extracts, enzymatic hydrolysates, and condensed enzymatic hydrolysates of T. molitor larvae were prepared. Their amino acids (AAs) profiles and antioxidant activities, including ferric-reducing antioxidant power, oxygen radical absorption capacity, and DPPH, hydroxyl radical, and hydrogen peroxide radical scavenging properties assay were analyzed. DW extracts had the lowest AAs contents and antioxidant activity compared with enzymatic extracts. Condensed hydrolysates with a combination of alcalase and flavourzyme (C-A+F) exhibited the highest levels of total free AAs (11.1759 g/100 g). C-A+F produced higher total hydrolyzed AAs (32.5292 g/100 g) compared with the other groups. The C-A+F possessed the strongest antioxidant activity. Notably, the antioxidant activities of the hydrolysates and the total hydrolyzed AAs amount were correlated. Taken together, our findings showed that C-A+F was a promising technique for obtaining extracts of T. molitor larvae with antioxidant activity as potential nutritious functional food.

Amino acid metabolism in dairy cows and their regulation in milk synthesis.

PubMed

Wang, Feiran; Shi, Haitao; Wang, Shuxiang; Wang, Yajing; Cao, Zhijun; Li, Shengli

2018-06-10

Reducing dietary crude protein (CP) and supplementing with certain amino acids (AAs) has been known as a potential solution to improve nitrogen (N) efficiency in dairy production. Thus understanding how AAs are utilized in various sites along the gut is critical. AA flow from the intestine to portal-drained viscera (PDV) and liver then to the mammary gland was elaborated in this article. Recoveries in individual AA in PDV and liver seem to share similar AA pattern with input: output ratio in mammary gland, which subdivides essential AA (EAA) into two groups, lysine (Lys) and branched-chain AA (BCAA) in group 1, input: output ratio > 1; methionine (Met), histidine (His), phenylalanine (Phe) etc. in group 2, input: output ratio close to 1. AAs in the mammary gland are either utilized for milk protein synthesis or retained as body tissue, or catabolized. The fractional removal of AAs and the number and activity of AA transporters together contribute to the ability of AAs going through mammary cells. Mammalian target of rapamycin (mTOR) pathway is closely related to milk protein synthesis and provides alternatives for AA regulation of milk protein synthesis, which connects AA with lactose synthesis via α-lactalbumin (gene: LALBA) and links with milk fat synthesis via sterol regulatory element-binding transcription protein 1 (SREBP1) and peroxisome proliferator-activated receptor (PPAR). Overall, AA flow across various tissues reveal AA metabolism and utilization in dairy cows on one hand. While the function of AA in the biosynthesis of milk protein, fat and lactose at both transcriptional and posttranscriptional level from another angle provides the possibility for us to regulate them for higher efficiency. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

True ileal amino acid digestibility and endogenous ileal amino acid losses in growing pigs fed wheat shorts- or casein-based diets.

PubMed

Libao-Mercado, A J; Yin, Y; van Eys, J; de Lange, C F M

2006-06-01

Use of dietary AA in growing pigs reflects digestion and use of digested AA for various body functions. Before evaluating dietary effects on use of digestible AA intake for body protein deposition, a digestibility study was conducted to investigate true ileal AA digestibility and endogenous ileal AA losses in growing pigs fed graded levels of wheat shorts (WS) or casein (CS; control). A casein-based basal diet (basal) was formulated to contain 0.27 g of standardized ileal digestible (SID) Lys per MJ of DE, to which extra Lys was added from WS (WS2, +0.10 g of SID Lys per MJ of DE; WS3, +0.20 g of SID Lys per MJ of DE) or casein (CS3, +0.20 g of SID Lys per MJ of DE). A fifth diet was formulated to be similar in CP level and source as CS3 but in which 6% pectin, a source of soluble non-starch polysaccharides (NSP), was included at the expense of cornstarch (CS3 + pectin). Five Yorkshire barrows (17.5 +/- 1.5 kg of BW) were fitted with a T-cannula at the distal ileum and randomly assigned to 1 of the 5 experimental diets in a 5 x 5 Latin Square design. Apparent ileal digestibility (AID), true ileal digestibility (TID), and endogenous ileal protein losses (EPL) were determined using the homoarginine method. Diet CS level did not influence (P > or = 0.10) TID of most essential AA or EPL (10.4 g/kg of DM intake). Including pectin in the diet did not influence TID of AA (P > or = 0.10) but increased EPL (15.6 g/kg of DM intake; P > or = 0.01). Inclusion of WS in the diet reduced TID of most essential AA (P < 0.01). The TID values for most essential AA, however, were the same (P > or = 0.10) for both dietary WS levels, except for Lys and Met, which were further reduced at the greatest dietary WS level. Increased EPL (P < 0.01) was only observed for WS3 (16 g/kg of DMI). We concluded that (1) the effects of dietary protein source on AID of AA can be attributed both to reduced TID of AA and increased EPL, (2) the impact of dietary WS level on TID of AA and EPL does not seem to be linear, (3) soluble NSP from pectin or WS exerts a greater effect on EPL than insoluble NSP, and (4) because of the metabolic cost associated with EPL and the impacts of feed composition on microbial fermentation in the gut lumen, the effects of feed ingredients on the use of ileal digestible AA for protein deposition should be investigated further.

Arjunolic acid, a peroxisome proliferator-activated receptor α agonist, regresses cardiac fibrosis by inhibiting non-canonical TGF-β signaling.

PubMed

Bansal, Trisha; Chatterjee, Emeli; Singh, Jasdeep; Ray, Arjun; Kundu, Bishwajit; Thankamani, V; Sengupta, Shantanu; Sarkar, Sagartirtha

2017-10-06

Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna, which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA), in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target. Our data revealed that AA significantly represses collagen expression and improves cardiac function during hypertrophy. We found that AA binds to and stabilizes the ligand-binding domain of peroxisome proliferator-activated receptor α (PPARα) and increases its expression during cardiac hypertrophy. PPARα knockdown during AA treatment in hypertrophy samples, including angiotensin II-treated adult cardiac fibroblasts and renal artery-ligated rat heart, suggests that AA-driven cardioprotection primarily arises from PPARα agonism. Moreover, AA-induced PPARα up-regulation leads to repression of TGF-β signaling, specifically by inhibiting TGF-β-activated kinase1 (TAK1) phosphorylation. We observed that PPARα directly interacts with TAK1, predominantly via PPARα N-terminal transactivation domain (AF-1) thereby masking the TAK1 kinase domain. The AA-induced PPARα-bound TAK1 level thereby shows inverse correlation with the phosphorylation level of TAK1 and subsequent reduction in p38 MAPK and NF-κBp65 activation, ultimately culminating in amelioration of excess collagen synthesis in cardiac hypertrophy. In conclusion, our findings unravel the mechanism of AA action in regressing hypertrophy-associated cardiac fibrosis by assigning a role of AA as a PPARα agonist that inactivates non-canonical TGF-β signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

PubMed Central

Elsherbiny, Marwa E.; Goruk, Susan; Monckton, Elizabeth A.; Richard, Caroline; Brun, Miranda; Emara, Marwan; Field, Catherine J.; Godbout, Roseline

2015-01-01

Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains. PMID:26506385

Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

PubMed

Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

2017-10-01

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria

PubMed Central

MacLeod, Erin L.; Clayton, Murray K.; van Calcar, Sandra C.; Ney, Denise M.

2010-01-01

Phenylketonuria (PKU) requires a lifelong low-phenylalanine (phe) diet where protein needs are met by consumption of a phe-free amino acid (AA) formula; complaints of persistent hunger are common. Foods made with glycomacropeptide (GMP), an intact protein that contains minimal phe and may promote satiety, provide an alternative to AA formula. The objective was to assess the ability of a GMP breakfast to promote satiety and affect plasma concentrations of AAs, insulin, and the appetite stimulating hormone ghrelin in those with PKU, when compared to an AA-based breakfast. Eleven PKU subjects (8 adults and 3 boys ages 11–14) served as their own controls in an inpatient metabolic study with two 4-day treatments: an AA-based diet followed by a diet replacing all AA formula with GMP foods. Plasma concentrations of AAs, insulin and ghrelin were obtained before and/or 180 minutes after breakfast. Satiety was assessed using a visual analog scale before, immediately after and 180 minutes after breakfast. Postprandial ghrelin concentration was significantly lower (p=0.03) with GMP compared to an AA-based breakfast, with no difference in fasting ghrelin. Lower postprandial ghrelin concentrations were associated with greater feelings of fullness 180 minutes after breakfast suggesting greater satiety with GMP compared to AAs. Postprandial concentrations of insulin and total plasma AAs were higher after a GMP breakfast compared to an AA-based breakfast consistent with slower absorption of AAs from GMP. These results show sustained ghrelin suppression, and suggest greater satiety with ingestion of a meal containing GMP compared with AAs. PMID:20466571

Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.

PubMed

Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

2017-03-01

The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the pancreas and plasma TNF-α levels in T1- and T2DM; Nrf2, Glut2, COX2, and iNOS proteins in pancreatic tissue of T1DM and LPCLN2, NF-κb, IKB I in adipose tissue of T2DM reverted to normal in LXA4-treated animals. Both AA and LXA4 prevented STZ-induced cytotoxicity to RIN5 F cells in vitro and T1- and T2DM in vivo, suggesting that these two bioactive lipids may function as antidiabetic molecules. AA is beneficial against STZ-induced cytotoxicity and T1- and T2DM by enhancing the production of LXA4. Copyright © 2016 Elsevier Inc. All rights reserved.

[Levels of autoantibodies against AT1-receptor in hypertensive patients with acute coronary syndromes and its role in coronary artery vasoconstriction].

PubMed

Wang, Jingping; Zhang, Yuean; Wang, Huixian; Zeng, Xiaoxia; Yang, Jinjing; Dong, Jin; Wang, Jianling; Yang, Yan; Wang, Rijun; Zhang, Xiaojuan; Chai, Xiaohong; Zhang, Haozhou; Li, Bao

2015-02-17

To explore the levels of autoantibodies against AT1-receptor (AT1-AA) in hypertensive patients with acute coronary syndrome (ACS) and observe the in vitro effects of AT1-AA on resting tension of isolated anterior descending artery of vascular ring in male Wistar rats. All patients were recruited from June 2007 to August 2008. There were hypertensive patients with ACS (n = 120), those with simple hypertension (n = 253) and those with simple ACS (n = 115). And the outpatients for health examination during the same period were selected as healthy control group (n = 188). The second extracellular loop amino acid sequences of peptides of ATI receptor was synthesized and used as antigen (AT1-Ag) and sialic acid-enzyme-linked immunosorbent assay (SA-ELISA) for detect the serum levels of AT1-AA. Microvascular ring tension technology was used to test the vascular loop resting tension of anterior descending coronary artery from rats induced by a high-fat diet. The positive rates of AT1-AA in patients with simple hypertension (35.2%) and those with simple ACS (30.4%) were significantly higher than those in healthy control group (7.2%, P < 0.01). And the positive rate of AT1-AA in hypertensive patients with ACS (43.3%) was significantly higher than that in those with simple hypertension (35.2%, P < 0.05) and that in healthy control group (7.2%, P < 0.05).Furthermore, AT1-AA increased the vascular loop resting tension of anterior descending coronary artery rings in rats induced by a high-fat diet in a dose-dependant manner. And the vasoconstrictive action of AT1-AA was equal to 46.4% of AngII's action. And such an action was blocked by losartan and antigens. The level of AT1-AA increases markedly in hypertensive patients with ACS. And AT1-AA induces vasoconstrictive effects on anterior descending artery rings in rats induced by a high-fat diet.

The simultaneous electrochemical detection of ascorbic acid, dopamine, and uric acid using graphene/size-selected Pt nanocomposites.

PubMed

Sun, Chia-Liang; Lee, Hsin-Hsien; Yang, Jen-Ming; Wu, Ching-Chou

2011-04-15

In this study, a graphene/Pt-modified glassy carbon (GC) electrode was created to simultaneously characterize ascorbic acid (AA), dopamine (DA), and uric acid (UA) levels via cyclic voltammetry (CV) and differential pulse voltammetry (DPV). During the preparation of the nanocomposite, size-selected Pt nanoparticles with a mean diameter of 1.7 nm were self-assembled onto the graphene surface. In the simultaneous detection of the three aforementioned analytes using CV, the electrochemical potential differences among the three detected peaks were 185 mV (AA to DA), 144 mV (DA to UA), and 329 mV (AA and UA), respectively. In comparison to the CV results of bare GC and graphene-modified GC electrodes, the large electrochemical potential difference that is achieved via the use of the graphene/Pt nanocomposites is essential to the distinguishing of these three analytes. An optimized adsorption of size-selected Pt colloidal nanoparticles onto the graphene surface results in a graphene/Pt nanocomposite that can provide a good platform for the routine analysis of AA, DA, and UA. Copyright © 2011 Elsevier B.V. All rights reserved.

Use of Shark Dental Protein to Estimate Trophic Position via Amino Acid Compound-Specific Isotope Analysis

NASA Astrophysics Data System (ADS)

Hayes, M.; Herbert, G.; Ellis, G.

2017-12-01

The diets of apex predators such as sharks are expected to change in response to overfishing of their mesopredator prey, but pre-anthropogenic baselines necessary to test for such changes are lacking. Stable isotope analysis (SIA) of soft tissues is commonly used to study diets in animals based on the bioaccumulation of heavier isotopes of carbon and nitrogen with increasing trophic level. In specimens representing pre-anthropogenic baselines, however, a modified SIA approach is needed to deal with taphonomic challenges, such as loss of soft tissues or selective loss of less stable amino acids (AAs) in other sources of organic compounds (e.g., teeth or bone) which can alter bulk isotope values. These challenges can be overcome with a compound-specific isotope analysis of individual AAs (AA-CSIA), but this first requires a thorough understanding of trophic enrichment factors for individual AAs within biomineralized tissues. In this study, we compare dental and muscle proteins of individual sharks via AA-CSIA to determine how trophic position is recorded within teeth and whether that information differs from that obtained from soft tissues. If skeletal organics reliably record information about shark ecology, then archaeological and perhaps paleontological specimens can be used to investigate pre-anthropogenic ecosystems. Preliminary experiments show that the commonly used glutamic acid/phenylalanine AA pairing may not be useful for establishing trophic position from dental proteins, but that estimated trophic position determined from alternate AA pairs are comparable to those from muscle tissue within the same species.

Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation

PubMed Central

Christian, Lisa M.; Blair, Lisa M.; Porter, Kyle; Lower, Mary; Cole, Rachel M.; Belury, Martha A.

2016-01-01

Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20–27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio. PMID:26859301

Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration

PubMed Central

Prokopiou, Ekatherine; Kolovos, Panagiotis; Kalogerou, Maria; Neokleous, Anastasia; Papagregoriou, Gregory; Deltas, Constantinos; Malas, Stavros; Georgiou, Tassos

2017-01-01

Purpose To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2−/− model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1–1.5). Methods Nine-month-old animals were allocated to different groups: (A) C57BL/6 untreated , (B) CCL2−/− untreated, (C) CCL2−/− treated with ω-3+ω-6, and (D) CCL2−/− treated with ω-3. Treatment was daily administered by gavage for 3 months. Fatty acids analysis was performed and retinas were histologically examined. Three-month-old wild type mice were used for comparison purposes. Real-time PCR and Western blot were performed for retinal inflammatory mediators. Results Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment groups. The outer nuclear layer thickness was increased in groups C (45.0±3.9 µm) and D (62.8±4.9 µm), compared with groups B (65.6±3.0 µm) and A (71.1±4.2 µm), and in younger mice, it was 98.0±3.9 µm. A decrease in NF-κB expression was noted in the treatment groups. Interleukin (IL) 18 protein levels demonstrated a significant reduction in the ω-3-treated group only. Conclusion Supplementation with ω-3+ω-6 or ω-3 alone (AA/EPA=1–1.5) suggests a protective mechanism in the CCL2−/− animal model of dry AMD, with a more beneficial effect when ω-3 are used alone. Our findings indicated that inflammation is not the only determining factor; perhaps a regenerative process might be involved following administration of ω-3 fatty acids. PMID:29354704

Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration.

PubMed

Prokopiou, Ekatherine; Kolovos, Panagiotis; Kalogerou, Maria; Neokleous, Anastasia; Papagregoriou, Gregory; Deltas, Constantinos; Malas, Stavros; Georgiou, Tassos

2017-01-01

To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2 -/- model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1-1.5). Nine-month-old animals were allocated to different groups: (A) C57BL/6 untreated , (B) CCL2 -/- untreated, (C) CCL2 -/- treated with ω-3+ω-6, and (D) CCL2 -/- treated with ω-3. Treatment was daily administered by gavage for 3 months. Fatty acids analysis was performed and retinas were histologically examined. Three-month-old wild type mice were used for comparison purposes. Real-time PCR and Western blot were performed for retinal inflammatory mediators. Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment groups. The outer nuclear layer thickness was increased in groups C (45.0±3.9 µm) and D (62.8±4.9 µm), compared with groups B (65.6±3.0 µm) and A (71.1±4.2 µm), and in younger mice, it was 98.0±3.9 µm. A decrease in NF-κB expression was noted in the treatment groups. Interleukin (IL) 18 protein levels demonstrated a significant reduction in the ω-3-treated group only. Supplementation with ω-3+ω-6 or ω-3 alone (AA/EPA=1-1.5) suggests a protective mechanism in the CCL2 -/- animal model of dry AMD, with a more beneficial effect when ω-3 are used alone. Our findings indicated that inflammation is not the only determining factor; perhaps a regenerative process might be involved following administration of ω-3 fatty acids.

Arachidonic acid-containing phosphatidylcholine characterized by consolidated plasma and liver lipidomics as an early onset marker for tamoxifen-induced hepatic phospholipidosis.

PubMed

Saito, Kosuke; Goda, Keisuke; Kobayashi, Akio; Yamada, Naohito; Maekawa, Kyoko; Saito, Yoshiro; Sugai, Shoichiro

2017-08-01

Lipid profiling has emerged as an effective approach to not only screen disease and drug toxicity biomarkers but also understand their underlying mechanisms of action. Tamoxifen, a widely used antiestrogenic agent for adjuvant therapy against estrogen-positive breast cancer, possesses side effects such as hepatic steatosis and phospholipidosis (PLD). In the present study, we administered tamoxifen to Sprague-Dawley rats and used lipidomics to reveal tamoxifen-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. Treatment with tamoxifen for 28 days caused hepatic PLD in rats. We compared the plasma and liver lipid profiles in treated vs. untreated rats using a multivariate analysis to determine differences between the two groups. In total, 25 plasma and 45 liver lipids were identified and altered in the tamoxifen-treated group. Of these lipids, arachidonic acid (AA)-containing phosphatidylcholines (PCs), such as PC (17:0/20:4) and PC (18:1/20:4), were commonly reduced in both plasma and liver. Conversely, tamoxifen increased other phosphoglycerolipids in the liver, such as phosphatidylethanolamine (18:1/18:1) and phosphatidylinositol (18:0/18:2). We also examined alteration of AA-containing PCs and some phosphoglycerolipids in the pre-PLD stage and found that these lipid alterations were initiated before pathological alteration in the liver. In addition, changes in plasma and liver levels of AA-containing PCs were linearly associated. Moreover, levels of free AA and mRNA levels of AA-synthesizing enzymes, such as fatty acid desaturase 1 and 2, were decreased by tamoxifen treatment. Therefore, our study demonstrated that AA-containing PCs might have potential utility as novel and predictive biomarkers for tamoxifen-induced PLD. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liver.

PubMed

Howard, Timothy D; Mathias, Rasika A; Seeds, Michael C; Herrington, David M; Hixson, James E; Shimmin, Lawrence C; Hawkins, Greg A; Sellers, Matthew; Ainsworth, Hannah C; Sergeant, Susan; Miller, Leslie R; Chilton, Floyd H

2014-01-01

Levels of omega-6 (n-6) and omega-3 (n-3), long chain polyunsaturated fatty acids (LcPUFAs) such as arachidonic acid (AA; 20:4, n-6), eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3) impact a wide range of biological activities, including immune signaling, inflammation, and brain development and function. Two desaturase steps (Δ6, encoded by FADS2 and Δ5, encoded by FADS1) are rate limiting in the conversion of dietary essential 18 carbon PUFAs (18C-PUFAs) such as LA (18:2, n-6) to AA and α-linolenic acid (ALA, 18:3, n-3) to EPA and DHA. GWAS and candidate gene studies have consistently identified genetic variants within FADS1 and FADS2 as determinants of desaturase efficiencies and levels of LcPUFAs in circulating, cellular and breast milk lipids. Importantly, these same variants are documented determinants of important cardiovascular disease risk factors (total, LDL, and HDL cholesterol, triglycerides, CRP and proinflammatory eicosanoids). FADS1 and FADS2 lie head-to-head (5' to 5') in a cluster configuration on chromosome 11 (11q12.2). There is considerable linkage disequilibrium (LD) in this region, where multiple SNPs display association with LcPUFA levels. For instance, rs174537, located ∼ 15 kb downstream of FADS1, is associated with both FADS1 desaturase activity and with circulating AA levels (p-value for AA levels = 5.95 × 10(-46)) in humans. To determine if DNA methylation variation impacts FADS activities, we performed genome-wide allele-specific methylation (ASM) with rs174537 in 144 human liver samples. This approach identified highly significant ASM with CpG sites between FADS1 and FADS2 in a putative enhancer signature region, leading to the hypothesis that the phenotypic associations of rs174537 are likely due to methylation differences. In support of this hypothesis, methylation levels of the most significant probe were strongly associated with FADS1 and, to a lesser degree, FADS2 activities.

Renal function in children suffering from sickle cell disease: challenge of early detection in highly resource-scarce settings.

PubMed

Aloni, Michel Ntetani; Ngiyulu, René Makwala; Gini-Ehungu, Jean-Lambert; Nsibu, Célestin Ndosimao; Ekila, Mathilde Bothale; Lepira, François Bompeka; Nseka, Nazaire Mangani

2014-01-01

The prevalence of Sickle cell disease is extremely high in Democratic Republic of Congo. Despite this high prevalence of the disease, data on renal abnormalities in children are rare. The study proposed to assess blood pressure, glomerular function, urea and uric acid levels in 65 steady state Congolese children with homozygous sickle cell disease and 67 normal controls. In Hb-SS group, blood pressure level tended to be lower than Hb-AA groups but there was no statistically significant difference (p>0.05) between the two groups. The absolute values for GFR corrected for BSA were significantly higher in Hb-SS group compared to Hb-AA group (130.5±34.1 ml/min/1.73 m2 vs 113.7±24.5 ml/min/1.73 m2; p = 0.004). Children with Hb-SS were more likely to hyperfiltrate (30.8% of subjects) than children with Hb-AA (6.1% of subjects). Proteinuria was found in 4 (6.2%) children with Hb-SS. Uric acid level was significantly increased in children with Hb-SS compared to corresponding values in control group (4.4±1.3 mg/dl vs 3.5±1.1 mg/dl; p<0.001). Urea level was significantly decreased compared to corresponding values in Hb-AA group (15.3±8.3 mg/dl vs 22.9±10.1 mg/dl; p<0.001). Hyperfiltration, low creatinine, lower urea and high uric acid are more common in children with sickle cell disease than in normal controls.

Applying complex models to poultry production in the future--economics and biology.

PubMed

Talpaz, H; Cohen, M; Fancher, B; Halley, J

2013-09-01

The ability to determine the optimal broiler feed nutrient density that maximizes margin over feeding cost (MOFC) has obvious economic value. To determine optimal feed nutrient density, one must consider ingredient prices, meat values, the product mix being marketed, and the projected biological performance. A series of 8 feeding trials was conducted to estimate biological responses to changes in ME and amino acid (AA) density. Eight different genotypes of sex-separate reared broilers were fed diets varying in ME (2,723-3,386 kcal of ME/kg) and AA (0.89-1.65% digestible lysine with all essential AA acids being indexed to lysine) levels. Broilers were processed to determine carcass component yield at many different BW (1.09-4.70 kg). Trial data generated were used in model constructed to discover the dietary levels of ME and AA that maximize MOFC on a per broiler or per broiler annualized basis (bird × number of cycles/year). The model was designed to estimate the effects of dietary nutrient concentration on broiler live weight, feed conversion, mortality, and carcass component yield. Estimated coefficients from the step-wise regression process are subsequently used to predict the optimal ME and AA concentrations that maximize MOFC. The effects of changing feed or meat prices across a wide spectrum on optimal ME and AA levels can be evaluated via parametric analysis. The model can rapidly compare both biological and economic implications of changing from current practice to the simulated optimal solution. The model can be exploited to enhance decision making under volatile market conditions.

Inhibition of calcium-independent phospholipase A2 prevents arachidonic acid incorporation and phospholipid remodeling in P388D1 macrophages.

PubMed Central

Balsinde, J; Bianco, I D; Ackermann, E J; Conde-Frieboes, K; Dennis, E A

1995-01-01

Cellular levels of free arachidonic acid (AA) are controlled by a deacylation/reacylation cycle whereby the fatty acid is liberated by phospholipases and reincorporated by acyltransferases. We have found that the esterification of AA into membrane phospholipids is a Ca(2+)-independent process and that it is blocked up to 60-70% by a bromoenollactone (BEL) that is a selective inhibitor of a newly discovered Ca(2+)-independent phospholipase A2 (PLA2) in macrophages. The observed inhibition correlates with a decreased steady-state level of lysophospholipids as well as with the inhibition of the Ca(2+)-independent PLA2 activity in these cells. This inhibition is specific for the Ca(2+)-independent PLA2 in that neither group IV PLA2, group II PLA2, arachidonoyl-CoA synthetase, lysophospholipid:arachidonoyl-CoA acyltransferase, nor CoA-independent transacylase is affected by treatment with BEL. Moreover, two BEL analogs that are not inhibitors of the Ca(2+)-independent PLA2--namely a bromomethyl ketone and methyl-BEL--do not inhibit AA incorporation into phospholipids. Esterification of palmitic acid is only slightly affected by BEL, indicating that de novo synthetic pathways are not inhibited by BEL. Collectively, the data suggest that the Ca(2+)-independent PLA2 in P388D1 macrophages plays a major role in regulating the incorporation of AA into membrane phospholipids by providing the lysophospholipid acceptor employed in the acylation reaction. PMID:7667324

Chiral capillary electrophoresis with UV-excited fluorescence detection for the enantioselective analysis of 9-fluorenylmethoxycarbonyl-derivatized amino acids.

PubMed

Prior, Amir; Coliva, Giulia; de Jong, Gerhardus J; Somsen, Govert W

2018-05-29

The potential of capillary electrophoresis (CE) with ultraviolet (UV)-excited fluorescence detection for sensitive chiral analysis of amino acids (AAs) was investigated. DL-AAs were derivatized with 9-fluorenylmethoxycarbonyl chloride (FMOC)-Cl to allow their fluorescence detection and enhance enantioseparation. Fluorescence detection was achieved employing optical fibers, leading UV excitation light (< 300 nm) from a Xe-Hg lamp to the capillary window, and fluorescence emission to a spectrograph equipped with a charge-coupled device (CCD). Signal averaging over time and emission wavelength intervals was carried out to improve the signal-to-noise ratio of the FMOC-AAs. A background electrolyte (BGE) of 40 mM sodium tetraborate (pH 9.5), containing 15% isopropanol (v/v), 30 mM sodium dodecyl sulfate (SDS), and 30 mM β-cyclodextrin (β-CD), was found optimal for AA chemo- and enantioseparation. Enantioresolutions of 1.0 or higher were achieved for 16 proteinogenic DL-AAs. Limits of detection (LODs) were in the 10-100-nM range (injected concentration) for the D-AA enantiomers, except for FMOC-D-tryptophan (536 nM) which showed intramolecular fluorescence quenching. Linearity (R 2  > 0.997) and repeatability for peak height (relative standard deviations (RSDs) < 7.0%; n = 5) and electrophoretic mobility (RSDs < 0.6%; n = 5) of individual AA enantiomers were established for chiral analysis of DL-AA mixtures. The applicability of the method was investigated by the analysis of cerebrospinal fluid (CSF). Next to L-AAs, endogenous levels of D-glutamine and D-aspartic acid could be measured in CSF revealing enantiomeric ratios of 0.35 and 19.6%, respectively. This indicates the method's potential for the analysis of low concentrations of D-AAs in presence of abundant L-AAs.

Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells.

PubMed

Wu, Ximei; Iguchi, Takuma; Itoh, Norio; Okamoto, Kousuke; Takagi, Tatsuya; Tanaka, Keiichi; Nakanishi, Tsuyoshi

2008-01-01

Reduced vitamin C [ascorbic acid (AA)], which is taken up into cells by sodium-dependent vitamin C transporter (SVCT) 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. To determine the steroidogenic effect of AA and the role of SVCT2 in AA-induced steroidogenesis, we tested the effects of AA treatment and SVCT2 knockdown on steroidogenesis in human choriocarcinoma cell lines. AA treatment of JEG-3, BeWo, and JAR cells for 48-h dose dependently increased progesterone and estradiol levels. In JEG-3 cells, AA increased the mRNA expression of P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase, key enzymes for steroidogenesis. Stable knockdown of SVCT2 in JEG-3 cells by retrovirally mediated RNA interference decreased the maximal velocity of AA uptake by approximately 50%, but apparent affinity values were not affected. SVCT2 knockdown in JEG-3 cells significantly suppressed the AA-induced mRNA expression of placental P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase. This suppression of the AA-induced mRNA expression of steroidogenic enzymes subsequently decreased progesterone and estradiol production. In addition, inhibition of MAPK kinase-ERK signaling, which is a major pathway for AA-regulated gene expression, failed to affect AA-induced steroidogenesis. Our observations indicate that SVCT2-mediated AA uptake into cells is necessary for AA-induced steroidogenesis in human choriocarcinoma cell, but MAPK kinase-ERK signaling is not involved in AA-induced steroidogenesis.

Improved plasma amino acids pattern following 12 months of supplemented low-protein diet in peritoneal dialysis patients.

PubMed

Jiang, Na; Qian, Jiaqi; Lin, Aiwu; Fang, Wei; Cao, Liou; Wang, Qin; Ni, Zhaohui; Lindholm, Bengt; Axelsson, Jonas; Yao, Qiang

2010-07-01

Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low-protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients. This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography. Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p < 0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly. A low-protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients.

Antioxidant action of ganghwayakssuk (Artemisia princeps Pamp.) in combination with ascorbic acid to increase the shelf life in raw and deep fried chicken nuggets.

PubMed

Hwang, Ko-Eun; Choi, Yun-Sang; Choi, Sun-Mi; Kim, Hyun-Wook; Choi, Ji-Hun; Lee, Mi-Ai; Kim, Cheon-Jei

2013-11-01

Raw and deep fried chicken nuggets containing various levels of ganghwayakssuk ethanolic extract (GE) in combination with ascorbic acid (Aa) were evaluated for shelf-life during refrigerated storage (4°C). The pH and color (lightness, redness, and yellowness) values of raw and deep fried samples were significantly affected by the addition of GE (P<0.05). All antioxidant combinations except for Aa+GE 0.01 were effective at delaying lipid oxidation (CD, POV, and TBARS) when compared to the control or Aa. Raw samples with GE 0.2 and Aa+GE 0.1 exhibited lower bacterial populations during storage. The sensory characteristics (color, juiciness, flavor, tenderness, and overall acceptability) did not differ significantly in all deep fried chicken nugget samples, except color, whereas storage time had a significant effect (P<0.05). The results suggest the possibility of utilizing raw and deep fried chicken nuggets with a mixture of ganghwayakssuk and ascorbic acid for the increase of shelf-life and quality. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amino Acid Isotopic Trophic Enrichment in Mesozooplankton: Is Alanine a Better Predictor of Protistan Grazer Steps?

NASA Astrophysics Data System (ADS)

Decima, M.; Landry, M. R.; Bradley, C. J.; Fogel, M. L.

2016-02-01

Food-web studies within marine environments are increasingly reliant upon results from compound-specific isotope analysis of amino acids (CSIA-AA). The approach is advantageous because it allows consumer trophic positions to be estimated without sampling the dynamic primary producers. The baseline signal in the source AA phenylalanine is preserved, and a constant enrichment in glutamic acid at each trophic step is assumed, regardless of consumer type or diet. However, a number of recent studies challenge the assumption of universal and invariant isotopic fractionation of glutamic acid for all trophic levels, as well as its specific applicability to the main grazers in the ocean: the protistan microzooplankton. We present results from both laboratory and field studies that further explore this issue. Experiments include six 2-stage chemostats, using two different microzooplankton-phytoplankton pairs and one copepod-phytoplankton pair, and one 3-stage experiment using a copepod-microzooplankton-phytoplankton chain. We confirm previous observations of negligible fractionation of glutamic acid in protistan consumers when nutrients are limiting. In contrast, a consistent trophic enrichment effect was observed for alanine, with increasing δ15N values by trophic level for both metazoan and protistan consumers. A re-analysis of published CSIA-AA data of zooplankton species show that an index using alanine and phenylalanine gives trophic level estimates closer to expected given current understanding of the linkages within microbial food webs. Our results examine the details of isotopic fractionation of alanine within defined food chains and generally support its potential use as a trophic level indicator that includes the protistan contribution to mesozooplankton diet.

Determination of furan precursors and some thermal damage markers in baby foods: ascorbic acid, dehydroascorbic acid, hydroxymethylfurfural and furfural.

PubMed

Mesías-García, Marta; Guerra-Hernández, Eduardo; García-Villanova, Belén

2010-05-26

The presence of ascorbic acid (AA), vitamin C (AA + dehydroascorbic acid (DHAA)) and furfural as potential precursors of furan in commercial fruit and vegetable jarred baby food was studied. Hydroxymethylfurfural (HMF) was also determined and used, together with furfural levels, as markers of thermal damage. AA, calculated DHAA and vitamin C values ranged between 22.4 and 103, 2.9 and 13.8, and 32.1 and 113.2 mg/100 g, respectively, in fruit-based baby food. However, no trace of AA was found in the vegetable-based baby food samples tested, probably because these samples are not enriched in vitamin C and the content of this vitamin in fresh vegetables is destroyed during processing. Furfural values ranged from not detected to 236 microg/100 g, being higher in vegetable samples than in fruit samples possibly because of greater AA degradation favored by a higher pH in the vegetable samples. HMF values (range: not detected-959 microg/100 g), however, were higher in the fruit samples, probably due to greater carbohydrate content degradation and as a consequence of the Maillard reaction, favored by a lower pH in these samples. According to these results, HMF would be the optimum indicator of thermal treatment for fruits, and furfural for vegetables. The higher furfural content of vegetable baby food could be considered an index of greater AA degradation and, therefore, the furan content might be higher in this kind of sample than in fruit-based baby food.

Effect of ascorbic acid and alpha tocopherol supplementation on acute restraint stress induced changes in testosterone, corticosterone and nor epinephrine levels in male Sprague Dawley rats.

PubMed

Lodhi, Ghulam Mustafa; Latif, Rabia; Hussain, Muhammad Mazhar; Naveed, Abdul Khaliq; Aslam, Muhammad

2014-01-01

Stress of various origins suppresses male reproductive functions through releasing stress hormones. Antioxidant like ascorbic acid (AA) and alpha tocopherol (AT) have been thought to protect the body against stress induced damage. Whether, these antioxidants confer protection against the stress induced increased levels of corticosterone and nor-epinephrine, and decreased testosterone secretion have been investigated in this study. This quasi experimental study was carried out at the Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March to September 2009. Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group-I served as the control without stress while group-II was exposed to restraint stress for 6 hours, group-III was administered AA, group-IVAT and group-V was supplemented with both the antioxidants along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for 6 hours. Immediately after the stress episode, blood sample was obtained for the assay of serum testosterone, serum corticosterone by EIA and plasma nor-epinephrine levels by ELISA. Data were analyzed on SPSS-13 and p-value less than 0.05 was considered significant. Acute restraint stress resulted in a statistically significant rise in corticosterone and nor-epinephrine levels and fall in serum testosterone levels. AA supplementation for one month revealed insignificant changes in stress induced hormonal parameters. AT alone and in combination with ascorbic acid prevented the fall in testosterone level as well as rise in corticosterone, however nor-epinephrine levels remained unchanged. Supplementation with AT alone or in combination with AA prevent reduction in testosterone and rise in corticosterone levels while keeping the nor-epinephrine levels unchanged after acute restraint stress in Sprague Dawley rats.

Respiratory Symptoms in Hospital Cleaning Staff Exposed to a Product Containing Hydrogen Peroxide, Peracetic Acid, and Acetic Acid

PubMed Central

Hawley, Brie; Casey, Megan; Virji, Mohammed Abbas; Cummings, Kristin J.; Johnson, Alyson; Cox-Ganser, Jean

2017-01-01

Cleaning and disinfecting products consisting of a mixture of hydrogen peroxide (HP), peracetic acid (PAA), and acetic acid (AA) are widely used as sporicidal agents in health care, childcare, agricultural, food service, and food production industries. HP and PAA are strong oxidants and their mixture is a recognized asthmagen. However, few exposure assessment studies to date have measured HP, PAA, and AA in a health care setting. In 2015, we performed a health and exposure assessment at a hospital where a new sporicidal product, consisting of HP, PAA, and AA was introduced 16 months prior. We collected 49 full-shift time-weighted average (TWA) air samples and analyzed samples for HP, AA, and PAA content. Study participants were observed while they performed cleaning duties, and duration and frequency of cleaning product use was recorded. Acute upper airway, eye, and lower airway symptoms were recorded in a post-shift survey (n = 50). A subset of 35 cleaning staff also completed an extended questionnaire that assessed symptoms reported by workers as regularly occurring or as having occurred in the previous 12 months. Air samples for HP (range: 5.5 to 511.4 ppb) and AA (range: 6.7 to 530.3 ppb) were all below established US occupational exposure limits (OEL). To date, no full-shift TWA OEL for PAA has been established in the United States, however an OEL of 0.2 ppm has been suggested by several research groups. Air samples for PAA ranged from 1.1 to 48.0 ppb and were well below the suggested OEL of 0.2 ppm. Hospital cleaning staff using a sporicidal product containing HP, PAA, and AA reported work-shift eye (44%), upper airway (58%), and lower airway (34%) symptoms. Acute nasal and eye irritation were significantly positively associated with increased exposure to the mixture of the two oxidants: HP and PAA, as well as the total mixture (TM) of HP, PAA, and AA. Shortness of breath when hurrying on level ground or walking up a slight hill was significantly associated with increased exposure to the oxidant mixture (P = 0.017), as well as the TM (P = 0.026). Our results suggest that exposure to a product containing HP, PAA, and AA contributed to eye and respiratory symptoms reported by hospital cleaning staff at low levels of measured exposure. PMID:29077798

Relationship between polyunsaturated fatty acid levels in maternal diets and human milk in the first month post-partum.

PubMed

Liu, G; Ding, Z; Li, X; Chen, X; Wu, Y; Xie, L

2016-08-01

The present study evaluated the relationship between dietary fatty acid (FA) intakes and human milk FA levels. Healthy lactating women (n = 514) from Northern China participated in the study. Dietary intake was assessed with a 24-h dietary recall questionnaire and evaluated using golden key maternal nutrition software (Wincome, Shanghai, China) and China Food Composition 2009. Human milk FA composition was determined by gas chromatography. The maternal daily median intakes of linoleic acid (LA), α-linolenic acid (ALA) and arachidonic acid (AA) were 19.93 g, 3.08 g and 16.33 mg, respectively. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were below the recommended levels. FA levels in 100 g of human milk were 0.363 g LA, 0.038 g γ-linolenic acid (GLA), 0.052 g dihomo γ-linolenic acid (DGLA), 0.144 g ALA, 0.079 g AA, 0.007 g EPA, 0.018 g docosatetraenoic acid (DTA) and 0.048 g DHA. Multiple linear regression analysis revealed that human milk DGLA levels were negatively correlated with dietary LA intake (β = -0.223, P = 0.030), and human milk GLA and DTA levels were negatively correlated with dietary ALA intake (β = -2.189, P = 0.031; β = -2.252, P = 0.027) after adjusting for possible confounding factors. The results of the present study suggest the presence of competitive interactions between n-3 fatty acids (ALA) and n-6 fatty acids (GLA and DTA). © 2015 The British Dietetic Association Ltd.

In search of druggable targets for GBM amino acid metabolism.

PubMed

Panosyan, Eduard H; Lin, Henry J; Koster, Jan; Lasky, Joseph L

2017-02-28

Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database ( http://r2.amc.nl ) analyses were carried out to screen for such targets among 95 AA related enzymes. First, we identified the genes that were differentially expressed in GBMs (3 datasets) compared to non-GBM brain tissues (5 datasets), or were associated with survival differences. Further, protein expression for these enzymes was also analyzed in high grade gliomas (HGGs) (proteinatlas.org). Finally, AA enzyme and gene expression were compared among the 4 TCGA (The Cancer Genome Atlas) subtypes of GBMs. We detected differences in enzymes involved in glutamate and urea cycle metabolism in GBM. For example, expression levels of BCAT1 (branched chain amino acid transferase 1) and ASL (argininosuccinate lyase) were high, but ASS1 (argininosuccinate synthase 1) was low in GBM. Proneural and neural TCGA subtypes had low expression of all three. High expression of all three correlated with worse outcome. ASL and ASS1 protein levels were mostly undetected in high grade gliomas, whereas BCAT1 was high. GSS (glutathione synthetase) was not differentially expressed, but higher levels were linked to poor progression free survival. ASPA (aspartoacylase) and GOT1 (glutamic-oxaloacetic transaminase 1) had lower expression in GBM (associated with poor outcomes). All three GABA related genes -- glutamate decarboxylase 1 (GAD1) and 2 (GAD2) and 4-aminobutyrate aminotransferase (ABAT) -- were lower in mesenchymal tumors, which in contrast showed higher IDO1 (indoleamine 2, 3-dioxygenase 1) and TDO2 (tryptophan 2, 3-diaxygenase). Expression of PRODH (proline dehydrogenase), a putative tumor suppressor, was lower in GBM. Higher levels predicted poor survival. Several AA-metabolizing enzymes that are higher in GBM, are also linked to poor outcome (such as BCAT1), which makes them potential targets for therapeutic inhibition. Moreover, existing drugs that deplete asparagine and arginine may be effective against brain tumors, and should be studied in conjunction with chemotherapy. Last, AA metabolism is heterogeneous in TCGA subtypes of GBM (as well as medulloblastomas and other pediatric tumors), which may translate to variable responses to AA targeted therapies.

Propylisopropylacetic acid (PIA), a constitutional isomer of valproic acid, uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA synthetase 4: a potential drug for bipolar disorder

PubMed Central

Modi, Hiren R.; Basselin, Mireille; Taha, Ameer Y.; Li, Lei O.; Coleman, Rosalind A.; Bialer, Meir; Rapoport, Stanley I.

2013-01-01

Background Mood stabilizers used for treating bipolar disorder (BD) selectively downregulate arachidonic acid (AA) turnover (deacylation-reacylation) in brain phospholipids, when given chronically to rats. In vitro studies suggest that one of these, valproic acid (VPA), which is teratogenic, reduces AA turnover by inhibiting the brain acyl-CoA synthetase (Acsl)-4 mediated acylation of AA to AA-CoA. We tested whether non-teratogenic VPA analogues might also inhibit Acsl-4 catalyzed acylation, and thus have potential anti-BD action. Methods Rat Acsl4-flag protein was expressed in E. coli, and the ability of three VPA analogues, propylisopropylacetic acid (PIA), propylisopropylacetamide (PID) and N-methyl-2,2,3,3-tetramethylcyclopropanecarboxamide (MTMCD), and of sodium butyrate, to inhibit conversion of AA to AA-CoA by Acsl4 was quantified using Michaelis-Menten kinetics. Results Acsl4-mediated conversion of AA to AA-CoA in vitro was inhibited uncompetitively by PIA, with a Ki of 11.4 mM compared to a published Ki of 25 mM for VPA, while PID, MTMCD and sodium butyrate had no inhibitory effect. Conclusions PIA's ability to inhibit conversion of AA to AA-CoA by Acsl4 in vitro suggests that, like VPA, PIA may reduce AA turnover in brain phospholipids in unanesthetized rats, and if so, may be effective as a non-teratogenic mood stabilizer in BD patients. PMID:23354024

Toward Radiocarbon Measurement of Individual Amino Acids in Marine Dissolved Organic Matter (DOM): Δ14C Blank Quantification for an HPLC Purification Method.

NASA Astrophysics Data System (ADS)

Bour, A. L.; Broek, T.; Walker, B. D.; Mccarthy, M. D.

2014-12-01

The presence of much of the marine dissolved organic nitrogen (DON) pool as uncharacterized, biologically recalcitrant molecules is a central mystery in the marine nitrogen cycle. Radiocarbon (Δ14C) isotopic measurements have been perhaps the most important data constraining the cycling of dissolved organic matter (DOM), but little Δ14C data specific to DON is available. Amino acids (AAs) are the major component of DON that can be isolated on a molecular level. Δ14C measurements for the operational "protein-like" fraction of DOM in the deep ocean indicate that this compound class has radiocarbon ages greater than several ocean mixing cycles, suggesting remarkable preservation of labile AAs exported from the surface. However, it is possible that the previously defined operational "protein-like" fraction may also contain non-AA material. Radiocarbon measurement of purified individual AAs would provide a more direct and reliable proxy for DON Δ14C age and cycling rate. We present here Δ14C blank characterization of an AA purification method based on HPLC, with on-line fraction collection. This method allows the recovery of unmodified AAs, but accurate measurement of small AA samples that can be extracted from DOM requires a system with extremely low Δ 14C blanks. Here we assess the impact of HPLC purification on the Δ14C age of known amino acids standards. Individual AA standards with contrasting (modern vs. dead) and well- characterized Δ14C ages were processed in a range of sample sizes. The eluted peaks were collected and dried, and measurement of their post-chromatography Δ14C content allowed for determination of the Δ14C blank by method of additions. The same protocol was applied to a mixture of six AA standards, to evaluate tailing effects in consecutive AA peaks of contrasting Δ14C age. AA standards were selected to include both Δ14C modern and dead AAs that elute both early and late in the chromatographic solvent program. We discuss implications for future Δ14C analysis of AAs purified from DOM by this method.

A cobalt oxyhydroxide-modified upconversion nanosystem for sensitive fluorescence sensing of ascorbic acid in human plasma

NASA Astrophysics Data System (ADS)

Cen, Yao; Tang, Jun; Kong, Xiang-Juan; Wu, Shuang; Yuan, Jing; Yu, Ru-Qin; Chu, Xia

2015-08-01

Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is a crucial micronutrient involved in many biochemical processes. Here, we have developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for fluorescence sensing of AA activity in human plasma. The nanosystem consists of upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as efficient energy acceptors. The fluorescence resonance energy transfer (FRET) process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co2+, leading to the inhibition of FRET, and resulting in the recovery of upconversion emission spectra. On the basis of these features, the nanosystem can be used for sensing AA activity with sensitivity and selectivity. Moreover, due to the minimizing background interference provided by UCNPs, the nanosystem has been applied to monitoring AA levels in human plasma sample with satisfactory results. The proposed approach may potentially provide an analytical platform for research and clinical diagnosis of AA related diseases.Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is a crucial micronutrient involved in many biochemical processes. Here, we have developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for fluorescence sensing of AA activity in human plasma. The nanosystem consists of upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as efficient energy acceptors. The fluorescence resonance energy transfer (FRET) process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co2+, leading to the inhibition of FRET, and resulting in the recovery of upconversion emission spectra. On the basis of these features, the nanosystem can be used for sensing AA activity with sensitivity and selectivity. Moreover, due to the minimizing background interference provided by UCNPs, the nanosystem has been applied to monitoring AA levels in human plasma sample with satisfactory results. The proposed approach may potentially provide an analytical platform for research and clinical diagnosis of AA related diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03588k

Ileal endogenous losses in pigs feeding a protein-free diet or diets with different contents of casein or crystalline amino acids.

PubMed

Brestenský, Matej; Nitrayová, Soňa; Patráš, Peter

2017-06-01

The common usage of protein-free diets to estimate unspecific AA losses has been criticised as unphysiological and incorrect. Therefore, in this study different diets were tested for the determination of endogenous losses (EL) of amino acids (AA) and nitrogen (N) assuming a complete absorption in the small intestine. Seven cannulated gilts received a protein-free diet (Diet PF) or diets with 3%, 6% or 10% crude protein (CP) from crystalline AA (Diets CA) or casein (Diets CAS) according to a 7 × 7 Latin square design. After 6 d adaptation to the diet, ileal digesta was collected for 24 h and thereafter analysed for AA, N and the digestibility markers Cr 2 O 3 and acid insoluble ash (AIA). Generally, among all AA, the highest amounts of EL were found for Pro, Glu and Gly, and the smallest for Met. Different levels of CP in Diets CA and CAS had no effect on EL. Significant differences between treatments were observed only for the EL of Glu, Ile, Ser (higher in Diets CA and PF), Pro and Tyr (higher in Diet PF) (p < 0.05). There were no differences in determined EL using Cr 2 O 3 or AIA as digestibility markers.

Dietary Acrylamide and the Risks of Developing Cancer: Facts to Ponder.

PubMed

Kumar, Jaya; Das, Srijit; Teoh, Seong Lin

2018-01-01

Acrylamide (AA) is a water soluble white crystalline solid commonly used in industries. It was listed as an industrial chemical with potential carcinogenic properties. However to date, AA was used to produce polyacrylamide polymer, which was widely used as a coagulant in water treatment; additives during papermaking; grouting material for dams, tunnels, and other underground building constructions. AA in food could be formed during high-temperature cooking via several mechanisms, i.e., formation via acrylic acid which may be derived from the degradation of lipid, carbohydrates, or free amino acids; formation via the dehydration/decarboxylation of organic acids (malic acid, lactic acid, and citric acid); and direct formation from amino acids. The big debate is whether this compound is toxic to human beings or not. In the present review, we discuss the formation of AA in food products, its consumption, and possible link to the development of any cancers. We discuss the body enzymatic influence on AA and mechanism of action of AA on hormone, calcium signaling pathways, and cytoskeletal filaments. We also highlight the deleterious effects of AA on nervous system, reproductive system, immune system, and the liver. The present and future mitigation strategies are also discussed. The present review on AA may be beneficial for researchers, food industry, and also medical personnel.

Dietary Acrylamide and the Risks of Developing Cancer: Facts to Ponder

PubMed Central

Kumar, Jaya; Das, Srijit; Teoh, Seong Lin

2018-01-01

Acrylamide (AA) is a water soluble white crystalline solid commonly used in industries. It was listed as an industrial chemical with potential carcinogenic properties. However to date, AA was used to produce polyacrylamide polymer, which was widely used as a coagulant in water treatment; additives during papermaking; grouting material for dams, tunnels, and other underground building constructions. AA in food could be formed during high-temperature cooking via several mechanisms, i.e., formation via acrylic acid which may be derived from the degradation of lipid, carbohydrates, or free amino acids; formation via the dehydration/decarboxylation of organic acids (malic acid, lactic acid, and citric acid); and direct formation from amino acids. The big debate is whether this compound is toxic to human beings or not. In the present review, we discuss the formation of AA in food products, its consumption, and possible link to the development of any cancers. We discuss the body enzymatic influence on AA and mechanism of action of AA on hormone, calcium signaling pathways, and cytoskeletal filaments. We also highlight the deleterious effects of AA on nervous system, reproductive system, immune system, and the liver. The present and future mitigation strategies are also discussed. The present review on AA may be beneficial for researchers, food industry, and also medical personnel. PMID:29541638

Cannabis, tobacco, and caffeine use modify the blood pressure reactivity protection of ascorbic acid.

PubMed

Brody, Stuart; Preut, Ragnar

2002-07-01

Cannabis, caffeine, and tobacco use are associated with increased mesolimbic dopamine activity. Ascorbic acid (AA) modulates some dopaminergic agent effects, and was recently found to decrease systolic blood pressure (SBP) stress reactivity. To examine how AA SBP stress reactivity protection varies by use of these substances, data from an AA trial (Cetebe, 3000 mg/day for 14 days; N=108) were compared by substance use level regarding SBP reactivity to the anticipation and actual experience phases of a standardized psychological stressor (10 min of public speaking and arithmetic). Self-reported never users of cannabis, persons not currently smoking tobacco, and persons consuming three or more caffeine beverages daily all exhibited AA SBP stress reactivity protection to the actual stressor, but not during the anticipation phase. Conversely, self-reported ever cannabis users, current tobacco smokers, and persons consuming less than three caffeine beverages daily exhibited the AA SBP protection during the anticipation phase, but only the lower caffeine consumption group exhibited AA protection during both phases. Covariates (neuroticism, extraversion, and depression scores, age, sex, body mass index) were all nonsignificant. Results are discussed in terms of dopaminergic effects of these substances, modulation of catecholaminergic and endothelial activity, and AA support of coping styles.

Is diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose?

PubMed

Cooper-Dehoff, Rhonda M; Hou, Wei; Weng, Liming; Baillie, Rebecca A; Beitelshees, Amber L; Gong, Yan; Shahin, Mohamed H A; Turner, Stephen T; Chapman, Arlene; Gums, John G; Boyle, Stephen H; Zhu, Hongjie; Wikoff, William R; Boerwinkle, Eric; Fiehn, Oliver; Frye, Reginald F; Kaddurah-Daouk, Rima; Johnson, Julie A

2014-04-01

The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment. Among 234 European American participants enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, we prospectively followed a nested cohort that had both metabolomics profiling and genotype data available for the development of IFG. We assessed the association between baseline circulating levels of isoleucine, leucine, valine, tyrosine, and phenylalanine, as well as single-nucleotide polymorphisms in branched-chain amino-acid transaminase 1 (BCAT1) and phenylalanine hydroxylase (PAH) with development of IFG. All baseline AA levels were strongly associated with IFG development. Each increment in standard deviation of the 5 AAs was associated with the following odds ratio and 95% confidence interval for IFG based on a fully adjusted model: isoleucine 2.29 (1.31-4.01), leucine 1.80 (1.10-2.96), valine 1.77 (1.07-2.92), tyrosine 2.13 (1.20-3.78), and phenylalanine 2.04 (1.16-3.59). The composite P value was 2×10(-5). Those with PAH (rs2245360) AA genotype had the highest incidence of IFG (P for trend=0.0003). Our data provide important insight into the metabolic and genetic mechanisms underlying atenolol-associated adverse metabolic effects. Clinical Trial Registration- http://www.clinicaltrials.gov; Unique Identifier: NCT00246519.

Efficacy of silkworm (Bombyx mori L.) chrysalis oil as a lipid source in adult Wistar rats.

PubMed

Mentang, Feny; Maita, Masashi; Ushio, Hideki; Ohshima, Toshiaki

2011-08-01

The effects of silkworm chrysalis oil, rich in n-3 α-linolenic acid (ALA), on lipid metabolism in Wistar rats were investigated. The rats were fed diets containing 7% soybean oil (control), silkworm chrysalis oil (SWO), or fish oil (FO) for 8weeks. Plasma triglyceride and glucose levels were significantly lower in the SWO group after 8weeks compared to the control and FO groups. The total cholesterol and blood urea nitrogen levels were higher in the control group than in the SWO and FO groups at 8weeks post-consumption. However, aspartate amino transferase and alanine amino transferase levels were not significantly different among all groups. A higher arachidonic acid (AA) content was detected in the control group, while lower AA levels were observed with the increase in EPA and DHA in the SWO and FO groups. These results suggest that n-3 α-linolenic acid-rich silkworm chrysalis oil can improve hyperlipidaemia and hyperglycaemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin.

PubMed

Carlson, S E; Ford, A J; Werkman, S H; Peeples, J M; Koo, W W

1996-05-01

Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.

Arachidonic acid metabolites follow the preferential course of cyclooxygenase pathway for the basal tone in the internal anal sphincter.

PubMed

de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

2009-04-01

Present studies determined the roles of the cyclooxygenase (COX) versus the lipoxygenase (LO) pathways in the metabolic pathway of arachidonic acid (AA) in the internal anal sphincter (IAS) tone. Studies were performed in the rat IAS versus the nontonic rectal smooth muscle (RSM). Indomethacin, the dual COX inhibitor, but not nordihydroguaiaretic acid (NDGA), the LO inhibitor, produced a precipitous decrease in the IAS tone. However, when added in the background of indomethacin, NDGA caused significant reversal of the IAS tone. These inhibitors had no significant effect on the RSM. To follow the significance of COX versus LO pathways, we examined the effects of AA and its metabolites. In the IAS, AA caused an increase in the IAS tone (Emax=38.8+/-3.0% and pEC50=3.4+/-0.1). In the RSM, AA was significantly less efficacious and potent (Emax=11.3+/-3.5% and pEC50=2.2+/-0.3). The AA metabolites (via COXs) PGF2alpha and U-46619 (a stable analog of thromboxane A2) produced increases in the IAS tone and force in the RSM. Conversely, AA metabolites (via 5-LO) lipoxin A4, 5-HETE, and leukotriene C4 decreased the IAS tone. Finally, the contractile effects of AA in the IAS were selectively attenuated by the COX-1 but not the COX-2 inhibitor. Collectively, the specific effects of AA and the COX inhibitor, the Western blot and RT-PCR analyses showing specifically higher levels of COX-1, suggest a preferential role of the COX (specifically COX-1) pathway versus the LO in the regulation of the IAS tone.

Preparation and Properties of Ethylene Vinyl Acetate Copolymer/Silica Nanocomposites in Presence of EVA-g-Acrylic Acid.

PubMed

Tham, Do Quang; Tuan, Vu Manh; Thanh, Dinh Thi Mai; Chinh, Nguyen Thuy; Giang, Nguyen Vu; Trang, Nguyen Thi Thu; Hang, To Thi Xuan; Huong, Ho Thu; Dung, Nguyen Thi Kim; Hoang, Thai

2015-04-01

Here we report a facile approach to enhance the dispersibility of ethylene vinyl acetate copolymer (EVA)/silica nanocomposites (for the EVA/silica nanocomposites and interaction between silica nanoparticles (nanosilica) and EVA by adding EVA-g-acrylic acid (EVAgAA) as a compatibilizer, which was formed by grafting acrylic acid onto EVA chains with the aid of dicumyl peroxide). The above nanocomposites with and without EVAgAA were prepared by melt mixing in a Haake intermixer with different contents of silica and EVAgAA. Their structure and morphology were characterized by Fourier transform infra-red (FT-IR) spectroscopy, field emission scanning electron microscopy (FE-SEM), and the mechanical, rheological, dielectrical, and flammability properties of the nanocomposites were also investigated. The FT-IR spectra of the nanocomposites confirmed the formation of hydrogen bonds between the surface silanol groups of nanosilica and C=O groups of EVA and/or EVAgAA. The presence of EVAgAA remarkably increased the intensity of hydrogen bonding between nanosilica and EVA which not only enhanced the dispersion of nanosilica in EVA matrix but also increased the mechanical, viscosity and storage modulus of EVA/silica nanocomposites. In addition, the flammability of EVA/silica nanocomposites is also significantly reduced after the functionalization with EVAgAA. However, the mechanical properties of EVA/silica nanocomposites tended to level off when its content was above 1.5 wt.%. It has also been found that the dielectric constant value of the EVA/EVAgAA/silica nanocomposites is much lower than that of the EVA/silica nanocomposites, which is another evidence of the hydrogen bonding formation between EVAgAA and nanosilica.

Amino acid and hexosamine in the equatorial western Pacific: vertical fluxes and individual preservation through water column to surface sediments

NASA Astrophysics Data System (ADS)

Kawahata, H.; Gupta, L. P.; Ishizuka, T.

2002-12-01

Amino acids (AA) and hexosamines (HA) are major constituents for all living organisms, constituting important fractions of labile organic carbon and nitrogen. They usually decompose rapidly than bulk OM and must be expected to be closely linked to biogeochemical processes. In spite of such importance, our understanding of degradation processes of labile components is still limited. Therefore vertical fluxes and preservation of AA and HA from water column to surface sediments are investigated at the western equatorial Pacific. The settling particles were composed of fairly fresh AA, which could be derived from siliceous diatom with less amount of calcareous plankton. In contrast, AA were degraded in sediments and porewaters. Each AA showed highly variable preservation ratio from settling to sedimentary particles. Compared with glycine, the calculated preservation ratio was the lowest (0%) for cysteine, followed by phenylalanine (6%), tyrosine (17%), methionine (47%), leucine (60%), isoleucine (65%), proline (67%), valine (91%), serine (99%), arginine (107%), threonine (112%), alanine (115%), glutamic acid (114%), aspartic acid (150%), lysine (166%) and histidine (186%). Beta-alanine and gamma-aminobutyric acid were the least labile AA. Probably they are so difficult to degrade for bacteria to get biochemical energy that the degradation proceeds fairly slowly. In contrast, after burial, even most labile, aromatic and sulfur-containing AA, degrade at a rate similar to the other protein AA. In spite of complicated reactions, most of the AA showed first-order reaction kinetics during the degradation in the sediments. The decomposition rate constant k (kyr-1) in this study was 2-3 orders lower than those in coastal marine environments. Better preservation of HA over AA in the sediments was probably due to the general incorporation of HA into structural biopolymer matrices, such as bacterial cell-walls and chitinous material. Abundant glycine in the AA in the sediments is due to contribution from diatom cell-walls, bacterial peptidoglycan, and the degradation by bacterial activity. Dissolved combined AA (DCAA) showed enrichment in glutamic acid, glycine and threonine, and depletion in aspartic acid and alanine. Bacterial biomass and/or activity influences DCAA in porewaters more than AA in the sediments. Phenylalanine was abundant in the dissolved free AA (DFAA). Both aromatic and acidic AA are generally concentrated in diatom cell protoplasm, which is more rapidly degraded than cell-walls. Good correlation between aspartic acid and carbonate contents in the sediments and poor correlation in the settling particles indicates that aspartic acid is significantly controlled by the reaction or adsorption with carbonates during early diagenesis. Abundant occurrence of clay minerals in sediments would be responsible for the enhanced accumulation of basic AA and arginine. During diagenesis, bulk Corganic/N ratios are mainly controlled by more contribution of ammonium, which is incorporated into the lattice of clay minerals, not by the compositional change in AA. Microbial degradation continued to reduce AA and OM in the sediments, which has implications for appreciable under-estimates of paleoproductivity.

Branched chains support postoperative protein synthesis.

PubMed

Cerra, F B; Upson, D; Angelico, R; Wiles, C; Lyons, J; Faulkenbach, L; Paysinger, J

1982-08-01

A blinded, prospective trial of the effects of branched-chain amino acid (BcAA)-enriched total parenteral nutrition (TPN) versus standard TPN was undertaken in nonseptic noncirrhotic abdominal surgery patients and patients with multiple traumatic injuries. The study reflected data from the immediate 7-day postoperative period. With isocaloric and isonitrogenous input, the BcAA-TPN patients achieved positive nitrogen balance on day 3. Although the urinary nitrogen output was decreased by day 3 in BcAA-TPN, the plasma BcAA levels did not increase until day 6. With no change in 3-methylhistidine urinary excretion, the early nitrogen retention with BcAA-TPN probably reflects a stimulation of protein synthesis. The ability to favorably modulate the metabolic stress response with alternate fuels has become a clinical reality.

Aristolochic Acid in the Etiology of Renal Cell Carcinoma

PubMed Central

Hoang, Margaret L.; Chen, Chung-Hsin; Chen, Pau-Chung; Roberts, Nicholas J.; Dickman, Kathleen G.; Yun, Byeong Hwa; Turesky, Robert J.; Pu, Yeong-Shiau; Vogelstein, Bert; Papadopoulos, Nickolas; Grollman, Arthur P.; Kinzler, Kenneth W.; Rosenquist, Thomas A.

2017-01-01

Background Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)–DNA adducts. Here we investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC). Methods We conducted a population-based case–control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole-exome sequences of ccRCC tumors from 10 Taiwanese ccRCC patients with prior exposure to AA were determined. Results Cumulative ingestion of more than 250 mg of AA increased risk of ccRCC (OR, 1.25), and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Furthermore, the distinctive AA mutational signature was evident in six of 10 sequenced ccRCC exomes from Taiwanese patients. Conclusions This study strongly suggests that AA contributes to the etiology of certain RCCs. Impact The current study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiologic, molecular, and genetic data in the investigation of cancer etiology. PMID:27555084

IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids

USDA-ARS?s Scientific Manuscript database

D-amino acids (D-aas) are reported to bind to IgE antibodies from people with allergy and asthma. The objectives of this study were to determine if D-aas bind or inhibit IgE binding to peanut allergens, and if they are more effective than L-amino acids (L-aas) in this respect. Several D-aa cocktails...

Genetic Code Expansion as a Tool to Study Regulatory Processes of Transcription

NASA Astrophysics Data System (ADS)

Schmidt, Moritz; Summerer, Daniel

2014-02-01

The expansion of the genetic code with noncanonical amino acids (ncAA) enables the chemical and biophysical properties of proteins to be tailored, inside cells, with a previously unattainable level of precision. A wide range of ncAA with functions not found in canonical amino acids have been genetically encoded in recent years and have delivered insights into biological processes that would be difficult to access with traditional approaches of molecular biology. A major field for the development and application of novel ncAA-functions has been transcription and its regulation. This is particularly attractive, since advanced DNA sequencing- and proteomics-techniques continue to deliver vast information on these processes on a global level, but complementing methodologies to study them on a detailed, molecular level and in living cells have been comparably scarce. In a growing number of studies, genetic code expansion has now been applied to precisely control the chemical properties of transcription factors, RNA polymerases and histones, and this has enabled new insights into their interactions, conformational changes, cellular localizations and the functional roles of posttranslational modifications.

Point-of-service, quantitative analysis of ascorbic acid in aqueous humor for evaluating anterior globe integrity

NASA Astrophysics Data System (ADS)

Gartia, Manas R.; Misra, Santosh K.; Ye, Mao; Schwartz-Duval, Aaron; Plucinski, Lisa; Zhou, Xiangfei; Kellner, David; Labriola, Leanne T.; Pan, Dipanjan

2015-11-01

Limited training, high cost, and low equipment mobility leads to inaccuracies in decision making and is concerning with serious ocular injuries such as suspected ruptured globe or post-operative infections. Here, we present a novel point-of-service (POS) quantitative ascorbic acid (AA) assay with use of the OcuCheck Biosensor. The present work describes the development and clinical testing of the paper-based biosensor that measures the changes in electrical resistance of the enzyme-plated interdigitated electrodes to quantify the level of AA present in ocular fluid. We have demonstrated the proof-of-concept of the biosensor testing 16 clinical samples collected from aqueous humor of patients undergoing therapeutic anterior chamber paracentesis. Comparing with gold standard colorimetric assay for AA concentration, OcuCheck showed accuracy of >80%, sensitivity of >88% and specificity of >71%. At present, there are no FDA-approved POS tests that can directly measures AA concentration levels in ocular fluid. We envisage that the device can be realized as a handheld, battery powered instrument that will have high impact on glaucoma care and point-of-care diagnostics of penetrating ocular globe injuries.

Point-of-service, quantitative analysis of ascorbic acid in aqueous humor for evaluating anterior globe integrity.

PubMed

Gartia, Manas R; Misra, Santosh K; Ye, Mao; Schwartz-Duval, Aaron; Plucinski, Lisa; Zhou, Xiangfei; Kellner, David; Labriola, Leanne T; Pan, Dipanjan

2015-11-03

Limited training, high cost, and low equipment mobility leads to inaccuracies in decision making and is concerning with serious ocular injuries such as suspected ruptured globe or post-operative infections. Here, we present a novel point-of-service (POS) quantitative ascorbic acid (AA) assay with use of the OcuCheck Biosensor. The present work describes the development and clinical testing of the paper-based biosensor that measures the changes in electrical resistance of the enzyme-plated interdigitated electrodes to quantify the level of AA present in ocular fluid. We have demonstrated the proof-of-concept of the biosensor testing 16 clinical samples collected from aqueous humor of patients undergoing therapeutic anterior chamber paracentesis. Comparing with gold standard colorimetric assay for AA concentration, OcuCheck showed accuracy of >80%, sensitivity of >88% and specificity of >71%. At present, there are no FDA-approved POS tests that can directly measures AA concentration levels in ocular fluid. We envisage that the device can be realized as a handheld, battery powered instrument that will have high impact on glaucoma care and point-of-care diagnostics of penetrating ocular globe injuries.

Point-of-service, quantitative analysis of ascorbic acid in aqueous humor for evaluating anterior globe integrity

PubMed Central

Gartia, Manas R.; Misra, Santosh K.; Ye, Mao; Schwartz-Duval, Aaron; Plucinski, Lisa; Zhou, Xiangfei; Kellner, David; Labriola, Leanne T.; Pan, Dipanjan

2015-01-01

Limited training, high cost, and low equipment mobility leads to inaccuracies in decision making and is concerning with serious ocular injuries such as suspected ruptured globe or post-operative infections. Here, we present a novel point-of-service (POS) quantitative ascorbic acid (AA) assay with use of the OcuCheck Biosensor. The present work describes the development and clinical testing of the paper-based biosensor that measures the changes in electrical resistance of the enzyme-plated interdigitated electrodes to quantify the level of AA present in ocular fluid. We have demonstrated the proof-of-concept of the biosensor testing 16 clinical samples collected from aqueous humor of patients undergoing therapeutic anterior chamber paracentesis. Comparing with gold standard colorimetric assay for AA concentration, OcuCheck showed accuracy of >80%, sensitivity of >88% and specificity of >71%. At present, there are no FDA-approved POS tests that can directly measures AA concentration levels in ocular fluid. We envisage that the device can be realized as a handheld, battery powered instrument that will have high impact on glaucoma care and point-of-care diagnostics of penetrating ocular globe injuries. PMID:26525715

ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

PubMed Central

Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

2012-01-01

Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

PubMed

Fadel, Fatina I; Elshamaa, Manal F; Essam, Rascha G; Elghoroury, Eman A; El-Saeed, Gamila S M; El-Toukhy, Safinaz E; Ibrahim, Mona Hamed

2014-03-01

The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0.0001). On multiple linear regression, urea was the only variable independently associated with an elevated plasma glutamine level (Beta=0.77, P=0.02). This study indicates that the advanced stages of CKD are associated with increased plasma concentrations of glutamine and homocysteine. Glutamine retained in the plasma of children with CRF, possibly producing higher levels of the waste products (urea and NH3). Dialysis alone is insufficient to redress completely the abnormalities in AA metabolism in ESRD children. Careful consideration of dialysis and dietary measures are necessary.

Diet quality influences isotopic discrimination among amino acids in an aquatic vertebrate

PubMed Central

Chikaraishi, Yoshito; Steffan, Shawn A; Takano, Yoshinori; Ohkouchi, Naohiko

2015-01-01

Stable nitrogen isotopic composition of amino acids (δ15NAA) has recently been employed as a powerful tool in ecological food web studies, particularly for estimating the trophic position (TP) of animal species in food webs. However, the validity of these estimates depends on the consistency of the trophic discrimination factor (TDF; - Δδ15NAA at each shift of trophic level) among a suite of amino acids within the tissues of consumer species. In this study, we determined the TDF values of amino acids in tadpoles (the Japanese toad, Bufo japonicus) reared exclusively on one of three diets that differed in nutritional quality. The diets were commercial fish-food pellets (plant and animal biomass), bloodworms (animal biomass), and boiled white rice (plant carbohydrate), representing a balanced, protein-rich, and protein-poor diet, respectively. The TDF values of two “source amino acids” (Src-AAs), methionine and phenylalanine, were close to zero (0.3–0.5‰) among the three diets, typifying the values reported in the literature (∼0.5‰ and ∼0.4‰, respectively). However, TDF values of “trophic amino acids” (Tr-AAs) including alanine, valine, leucine, isoleucine, and glutamic acid varied by diet: for example, the glutamic acid TDF was similar to the standard value (∼8.0‰) when tadpoles were fed either the commercial pellets (8.0‰) or bloodworms (7.9‰), but when they were fed boiled rice, the TDF was significantly reduced (0.6‰). These results suggest that a profound lack of dietary protein may alter the TDF values of glutamic acid (and other Tr-AAs and glycine) within consumer species, but not the two Src-AAs (i.e., methionine and phenylalanine). Knowledge of how a nutritionally poor diet can influence the TDF of Tr- and Src-AAs will allow amino acid isotopic analyses to better estimate TP among free-roaming animals. PMID:26045955

Performance of AA5052 alloy anode in alkaline ethylene glycol electrolyte with dicarboxylic acids additives for aluminium-air batteries

NASA Astrophysics Data System (ADS)

Wang, DaPeng; Zhang, DaQuan; Lee, KangYong; Gao, LiXin

2015-11-01

Dicarboxylic acid compounds, i.e. succinic acid (SUA), adipic acid (ADA) and sebacic acid (SEA), are used as electrolyte additives in the alkaline ethylene glycol solution for AA5052 aluminium-air batteries. It shows that the addition of dicarboxylic acids lowers the hydrogen gas evolution rate of commercial AA5052 aluminium alloy anode. AA5052 aluminium alloy has wide potential window for electrochemical activity and better discharge performance in alkaline ethylene glycol solution containing dicarboxylic acid additives. ADA has the best inhibition effect for the self-corrosion of AA5052 anode among the three dicarboxylic acid additives. Fourier transform infrared spectroscopy (FT-IR) reveals that dicarboxylic acids and aluminium ions can form coordination complexes. Quantum chemical calculations shows that ADA has a smaller energy gap (ΔE, the energy difference between the lowest unoccupied orbital and the highest occupied orbital), indicating that ADA has the strongest interaction with aluminium ions.

In vitro gastrointestinal digestion promotes the protective effect of blackberry extract against acrylamide-induced oxidative stress

NASA Astrophysics Data System (ADS)

Chen, Wei; Su, Hongming; Xu, Yang; Jin, Chao

2017-01-01

Acrylamide (AA)-induced toxicity has been associated with accumulation of excessive reactive oxygen species. The present study was therefore undertaken to investigate the protective effect of blackberry digests produced after (BBD) in vitro gastrointestinal (GI) digestion against AA-induced oxidative damage. The results indicated that the BBD (0.5 mg/mL) pretreatment significantly suppressed AA-induced intracellular ROS generation (56.6 ± 2.9% of AA treatment), mitochondrial membrane potential (MMP) decrease (297 ± 18% of AA treatment) and glutathione (GSH) depletion (307 ± 23% of AA treatment), thereby ameliorating cytotoxicity. Furthermore, LC/MS/MS analysis identified eight phenolic compounds with high contents in BBD, including ellagic acid, ellagic acid pentoside, ellagic acid glucuronoside, methyl-ellagic acid pentoside, methyl-ellagic acid glucuronoside, cyanidin glucoside, gallic acid and galloyl esters, as primary active compounds responsible for antioxidant action. Collectively, our study uncovered that the protective effect of blackberry was reserved after gastrointestinal digestion in combating exogenous pollutant-induced oxidative stress.

Arachidonic Acid Stress Impacts Pneumococcal Fatty Acid Homeostasis

PubMed Central

Eijkelkamp, Bart A.; Begg, Stephanie L.; Pederick, Victoria G.; Trapetti, Claudia; Gregory, Melissa K.; Whittall, Jonathan J.; Paton, James C.; McDevitt, Christopher A.

2018-01-01

Free fatty acids hold dual roles during infection, serving to modulate the host immune response while also functioning directly as antimicrobials. Of particular importance are the long chain polyunsaturated fatty acids, which are not commonly found in bacterial organisms, that have been proposed to have antibacterial roles. Arachidonic acid (AA) is a highly abundant long chain polyunsaturated fatty acid and we examined its effect upon Streptococcus pneumoniae. Here, we observed that in a murine model of S. pneumoniae infection the concentration of AA significantly increases in the blood. The impact of AA stress upon the pathogen was then assessed by a combination of biochemical, biophysical and microbiological assays. In vitro bacterial growth and intra-macrophage survival assays revealed that AA has detrimental effects on pneumococcal fitness. Subsequent analyses demonstrated that AA exerts antimicrobial activity via insertion into the pneumococcal membrane, although this did not increase the susceptibility of the bacterium to antibiotic, oxidative or metal ion stress. Transcriptomic profiling showed that AA treatment also resulted in a dramatic down-regulation of the genes involved in fatty acid biosynthesis, in addition to impacts on other metabolic processes, such as carbon-source utilization. Hence, these data reveal that AA has two distinct mechanisms of perturbing the pneumococcal membrane composition. Collectively, this work provides a molecular basis for the antimicrobial contribution of AA to combat pneumococcal infections. PMID:29867785

RNAi down-regulation of cinnamate-4-hydroxylase increases artemisinin biosynthesis in Artemisia annua.

PubMed

Kumar, Ritesh; Vashisth, Divya; Misra, Amita; Akhtar, Md Qussen; Jalil, Syed Uzma; Shanker, Karuna; Gupta, Madan Mohan; Rout, Prashant Kumar; Gupta, Anil Kumar; Shasany, Ajit Kumar

2016-05-25

Cinnamate-4-hydroxylase (C4H) converts trans-cinnamic acid (CA) to p-coumaric acid (COA) in the phenylpropanoid/lignin biosynthesis pathway. Earlier we reported increased expression of AaCYP71AV1 (an important gene of artemisinin biosynthesis pathway) caused by CA treatment in Artemisia annua. Hence, AaC4H gene was identified, cloned, characterized and silenced in A. annua with the assumption that the elevated internal CA due to knock down may increase the artemisinin yield. Accumulation of trans-cinnamic acid in the plant due to AaC4H knockdown was accompanied with the reduction of p-coumaric acid, total phenolics, anthocyanin, cinnamate-4-hydroxylase (C4H) and phenylalanine ammonia lyase (PAL) activities but increase in salicylic acid (SA) and artemisinin. Interestingly, feeding trans-cinnamic acid to the RNAi line increased the level of artemisinin along with benzoic (BA) and SA with no effect on the downstream metabolites p-coumaric acid, coniferylaldehyde and sinapaldehyde, whereas p-coumaric acid feeding increased the content of downstream coniferylaldehyde and sinapaldehyde with no effect on BA, SA, trans-cinnamic acid or artemisinin. SA is reported earlier to be inducing the artemisinin yield. This report demonstrates the link between the phenylpropanoid/lignin pathway with artemisinin pathway through SA, triggered by accumulation of trans-cinnamic acid because of the blockage at C4H.

RNAi down-regulation of cinnamate-4-hydroxylase increases artemisinin biosynthesis in Artemisia annua

PubMed Central

Kumar, Ritesh; Vashisth, Divya; Misra, Amita; Akhtar, Md Qussen; Jalil, Syed Uzma; Shanker, Karuna; Gupta, Madan Mohan; Rout, Prashant Kumar; Gupta, Anil Kumar; Shasany, Ajit Kumar

2016-01-01

Cinnamate-4-hydroxylase (C4H) converts trans-cinnamic acid (CA) to p-coumaric acid (COA) in the phenylpropanoid/lignin biosynthesis pathway. Earlier we reported increased expression of AaCYP71AV1 (an important gene of artemisinin biosynthesis pathway) caused by CA treatment in Artemisia annua. Hence, AaC4H gene was identified, cloned, characterized and silenced in A. annua with the assumption that the elevated internal CA due to knock down may increase the artemisinin yield. Accumulation of trans-cinnamic acid in the plant due to AaC4H knockdown was accompanied with the reduction of p-coumaric acid, total phenolics, anthocyanin, cinnamate-4-hydroxylase (C4H) and phenylalanine ammonia lyase (PAL) activities but increase in salicylic acid (SA) and artemisinin. Interestingly, feeding trans-cinnamic acid to the RNAi line increased the level of artemisinin along with benzoic (BA) and SA with no effect on the downstream metabolites p-coumaric acid, coniferylaldehyde and sinapaldehyde, whereas p-coumaric acid feeding increased the content of downstream coniferylaldehyde and sinapaldehyde with no effect on BA, SA, trans-cinnamic acid or artemisinin. SA is reported earlier to be inducing the artemisinin yield. This report demonstrates the link between the phenylpropanoid/lignin pathway with artemisinin pathway through SA, triggered by accumulation of trans-cinnamic acid because of the blockage at C4H. PMID:27220407

Quantum chemical density functional theory studies on the molecular structure and vibrational spectra of Gallic acid imprinted polymers

NASA Astrophysics Data System (ADS)

Pardeshi, Sushma; Dhodapkar, Rita; Kumar, Anupama

2013-12-01

Gallic acid (GA) is known by its antioxidant, anticarcinogenic properties and scavenger activity against several types of harmful free radicals. Molecularly imprinted polymers (MIPs) are used in separation of a pure compound from complex matrices. A stable template-monomer complex generates the MIPs with the highest affinity and selectivity for the template. The quantum chemical computations based on density functional theory (DFT) was used on the template Gallic acid (GA), monomer acrylic acid (AA) and GA-AA complex to study the nature of interactions involved in the GA-AA complex. B3LYP/6-31+G(2d,2p) model chemistry was used to optimize their structures and frequency calculations. The effect of porogen acetonitrile (ACN) on complex formation was included by using polarizable continuum model (PCM). The results demonstrated the formation of a stable GA-AA complex through the intermolecular hydrogen bonding between carboxylic acid groups of GA and AA. The Mulliken atomic charge analysis and simulated vibrational spectra also supported the stable hydrogen bonding interaction between the carboxylic acid groups of GA and AA with minimal interference of porogen ACN. Further, simulations on GA-AA mole ratio revealed that 1:4 GA-AA was optimum for synthesis of MIP for GA.

A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

PubMed

Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

2015-08-13

Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.

Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels- The PREOBE follow-up

PubMed Central

de la Garza Puentes, Andrea; Montes Goyanes, Rosa; Chisaguano Tonato, Aida Maribel; Torres-Espínola, Francisco José; Arias García, Miriam; de Almeida, Leonor; Bonilla Aguirre, María; Guerendiain, Marcela; Castellote Bargalló, Ana Isabel; Segura Moreno, Maite; García-Valdés, Luz; Campoy, Cristina; Lopez-Sabater, M. Carmen

2017-01-01

Single nucleotide polymorphisms (SNPs) in the genes encoding the fatty acid desaturase (FADS) and elongase (ELOVL) enzymes affect long-chain polyunsaturated fatty acid (LC-PUFA) production. We aimed to determine if these SNPs are associated with body mass index (BMI) or affect fatty acids (FAs) in pregnant women. Participants (n = 180) from the PREOBE cohort were grouped according to pre-pregnancy BMI: normal-weight (BMI = 18.5–24.9, n = 88) and overweight/obese (BMI≥25, n = 92). Plasma samples were analyzed at 24 weeks of gestation to measure FA levels in the phospholipid fraction. Selected SNPs were genotyped (7 in FADS1, 5 in FADS2, 3 in ELOVL2 and 2 in ELOVL5). Minor allele carriers of rs174545, rs174546, rs174548 and rs174553 (FADS1), and rs1535 and rs174583 (FADS2) were nominally associated with an increased risk of having a BMI≥25. Only for the normal-weight group, minor allele carriers of rs174537, rs174545, rs174546, and rs174553 (FADS1) were negatively associated with AA:DGLA index. Normal-weight women who were minor allele carriers of FADS SNPs had lower levels of AA, AA:DGLA and AA:LA indexes, and higher levels of DGLA, compared to major homozygotes. Among minor allele carriers of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher DHA:EPA index than the normal-weight group; however, they did not present higher DHA concentrations than the normal-weight women. In conclusion, minor allele carriers of FADS SNPs have an increased risk of obesity. Maternal weight changes the effect of genotype on FA levels. Only in the normal-weight group, minor allele carriers of FADS SNPs displayed reduced enzymatic activity and FA levels. This suggests that women with a BMI≥25 are less affected by FADS genetic variants in this regard. In the presence of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes than women with normal weight, but this was not enough to obtain a higher n-3 LC-PUFA concentration. PMID:28598979

Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy.

PubMed

Duchén, K; Casas, R; Fagerås-Böttcher, M; Yu, G; Björkstén, B

2000-02-01

The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and beta-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6:total n-3 and the arachidonic acid, C20:4 n-6 (AA):EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA: EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low alpha-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine.

PubMed

Xu, Cheng; Li, Ying-Chun; Yang, Hua; Long, Yan; Chen, Min-Jian; Qin, Yu-Feng; Xia, Yan-Kai; Song, Ling; Gu, Ai-Hua; Wang, Xin-Ru

2014-01-01

Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star TM (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

Kinetic modelling of ascorbic and dehydroascorbic acids concentrations in a model solution at different temperatures and oxygen contents.

PubMed

Gómez Ruiz, Braulio; Roux, Stéphanie; Courtois, Francis; Bonazzi, Catherine

2018-04-01

The degradation kinetics of vitamin C (ascorbic and dehydroascorbic acids, AA and DHA) were determined under controlled conditions of temperature (50-90 °C) and oxygen concentrations in the gas phase (10-30% mol/mol) using a specific reactor. The degradation of vitamin C in malate buffer (20 mM, pH 3.8), mimetic of an apple puree, was assessed by sampling at regular intervals and spectrophotometric quantification of AA and DHA levels at 243 nm. The results showed that AA degradation increased with temperature and oxygen concentration, while DHA exhibited the behaviour of an intermediate species, appearing then disappearing. A kinetic model was successfully developed to simulate the experimental data by two first order consecutive reactions. The first one represented AA degradation as a function of temperature and concentration in dissolved oxygen, and the second reflected DHA degradation as a function of temperature only, both adequately following Arrhenius' law. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interactions of collagen molecules in the presence of N-hydroxysuccinimide activated adipic acid (NHS-AA) as a crosslinking agent.

PubMed

Zhang, Min; Wu, Kun; Li, Guoying

2011-11-01

The effect of crosslinking agent on pepsin-soluble bovine collagen solution was examined using N-hydroxysuccinimide activated adipic acid (NHS-AA) as a crosslinker. Electrophoretic patterns indicated that crosslinks formed when NHS-AA was added. A higher polarity level deduced from the changes in the fluorescence emission spectrum of pyrene in the crosslinked collagen solution indicated that the formation of well-ordered aggregates was suppressed. The random aggregation of collagens was also observed by atomic force microscopy (AFM). Furthermore, the association of collagens into fibrils was influenced by crosslinking. Self-assembly was suppressed at 37°C; however, as temperature was increased to 39°C, a small amount of NHS-AA leaded to an improvement in the ability of self-aggregation. Although more random structure was brought about by crosslinking, self-aggregation might still be promoted as temperature was increased, accompanying by the thermal stability improvement of fibrils. Copyright © 2011 Elsevier B.V. All rights reserved.

Targeting fatty acid amide hydrolase and transient receptor potential vanilloid-1 simultaneously to modulate colonic motility and visceral sensation in the mouse: A pharmacological intervention with N-arachidonoyl-serotonin (AA-5-HT).

PubMed

Bashashati, M; Fichna, J; Piscitelli, F; Capasso, R; Izzo, A A; Sibaev, A; Timmermans, J-P; Cenac, N; Vergnolle, N; Di Marzo, V; Storr, M

2017-12-01

Endocannabinoid anandamide (AEA) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and abdominal pain. Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically induced contractility, excitatory junction potential (EJP) and fast (f) and slow (s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion and visceromotor response (VMR) to rectal distension were studied. The colonic levels of endocannabinoids and fatty acid amides were measured. CB1-positive neurons exhibited TRPV1; only some TRPV1 positive neurons did not express CB1. CB1 and FAAH did not colocalize. AA-5-HT (100 nM-10 μM) decreased colonic contractility by ~60%; this effect was abolished by TRPV1 antagonist 5'-IRTX, but not by CB1 antagonist, SR141716. AA-5-HT (1 μM-10 μM) inhibited EJP by ~30% and IJPs by ~50%. The effects of AA-5-HT on junction potentials were reversed by SR141716 and 5`-IRTX. AA-5-HT (20 mg/kg; i.p.) inhibited colonic propulsion by ~30%; SR141716 but not 5`-IRTX reversed this effect. AA-5-HT decreased VMR by ~50%-60%; these effects were not blocked by SR141716 or 5`-IRTX. AA-5-HT increased AEA in the colon. The effects of AA-5-HT on visceral sensation and colonic motility are differentially mediated by CB1, TRPV1 and non-CB1/TRPV1 mechanisms, possibly reflecting the distinct neuromodulatory roles of endocannabinoid and endovanilloid FAAH substrates in the mouse intestine. © 2017 John Wiley & Sons Ltd.

On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid[S

PubMed Central

Robichaud, Philippe Pierre; Poirier, Samuel J.; Boudreau, Luc H.; Doiron, Jérémie A.; Barnett, David A.; Boilard, Eric; Surette, Marc E.

2016-01-01

Alkyne and azide analogs of natural compounds that can be coupled to sensitive tags by click chemistry are powerful tools to study biological processes. Arachidonic acid (AA) is a FA precursor to biologically active compounds. 19-Alkyne-AA (AA-alk) is a sensitive clickable AA analog; however, its use as a surrogate to study AA metabolism requires further evaluation. In this study, AA-alk metabolism was compared with that of AA in human cells. Jurkat cell uptake of AA was 2-fold greater than that of AA-alk, but significantly more AA-Alk was elongated to 22:4. AA and AA-alk incorporation into and remodeling between phospholipid (PL) classes was identical indicating equivalent CoA-independent AA-PL remodeling. Platelets stimulated in the pre­sence of AA-alk synthesized significantly less 12-lipoxygenase (12-LOX) and cyclooxygenase products than in the presence of AA. Ionophore-stimulated neutrophils produced significantly more 5-LOX products in the presence of AA-alk than AA. Neutrophils stimulated with only exogenous AA-alk produced significantly less 5-LOX products compared with AA, and leukotriene B4 (LTB4)-alk was 12-fold less potent at stimulating neutrophil migration than LTB4, collectively indicative of weaker leukotriene B4 receptor 1 agonist activity of LTB4-alk. Overall, these results suggest that the use of AA-alk as a surrogate for the study of AA metabolism should be carried out with caution. PMID:27538823

Amino acid nitrogen isotopic fractionation patterns as indicators of heterotrophy in plankton, particulate, and dissolved organic matter

NASA Astrophysics Data System (ADS)

McCarthy, Matthew D.; Benner, Ronald; Lee, Cindy; Fogel, Marilyn L.

2007-10-01

Bulk nitrogen (N) isotope signatures have long been used to investigate organic N source and food web structure in aquatic ecosystems. This paper explores the use of compound-specific δ 15N patterns of amino acids (δ 15N-AA) as a new tool to examine source and processing history in non-living marine organic matter. We measured δ 15N-AA distributions in plankton tows, sinking particulate organic matter (POM), and ultrafiltered dissolved organic matter (UDOM) in the central Pacific Ocean. δ 15N-AA patterns in eukaryotic algae and mixed plankton tows closely resemble those previously reported in culture. δ 15N differences between individual amino acids (AA) strongly suggest that the sharply divergent δ 15N enrichment for different AA with trophic transfer, as first reported by [McClelland, J.W. and Montoya, J.P. (2002) Trophic relationships and the nitrogen isotopic composition of amino acids. Ecology83, 2173-2180], is a general phenomenon. In addition, differences in δ 15N of individual AA indicative of trophic transfers are clearly preserved in sinking POM, along with additional changes that may indicate subsequent microbial reworking after incorporation into particles. We propose two internally normalized δ 15N proxies that track heterotrophic processes in detrital organic matter. Both are based on isotopic signatures in multiple AA, chosen to minimize potential problems associated with any single compound in degraded materials. A trophic level indicator (ΔTr) is derived from the δ 15N difference between selected groups of AA based on their relative enrichment with trophic transfer. We propose that a corresponding measure of the variance within a sub-group of AA (designated Σ V) may indicate total AA resynthesis, and be strongly tied to heterotrophic microbial reworking in detrital materials. Together, we hypothesize that ΔTr and Σ V define a two dimensional trophic "space", which may simultaneously express relative extent of eukaryotic and bacterial heterotrophic processing. In the equatorial Pacific, ΔTr indicates an average of 1.5-2 trophic transfers between phytoplankton and sinking POM at all depths and locations. The Σ V parameter suggests that substantial variation may exist in bacterial heterotrophic processing between differing regions and time periods. In dissolved material δ 15N-AA patterns appear unrelated to those in POM. In contrast to POM, δ 15N-AA signatures in UDOM show no clear changes with depth, and suggest that dissolved AA preserved throughout the oceanic water column have undergone few, if any, trophic transfers. Together these data suggest a sharp divide between processing histories, and possibly sources, of particulate vs. dissolved AA.

Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats

PubMed Central

Al-Rejaie, Salim S; Abuohashish, Hatem M; Al-Enazi, Maher M; Al-Assaf, Abdullah H; Parmar, Mihir Y; Ahmed, Mohammed M

2013-01-01

AIM: To evaluate the ameliorative effect of naringenin (NG) during ulcerative colitis (UC) in rats. METHODS: Rats were treated with three different doses (25, 50 and 100 mg/kg per day) of NG and a single dose of mesalazine (MES, 300 mg/kg per day) for seven days prior to ulcerative colitis induction by 4% acetic acid (AA). Twenty four hours after AA rectal administration, animals were scarified and the colonic tissues were dissected. Colonic mucus content was estimated using Alcian blue dye binding technique. In colon tissues, levels of total glutathione sulphadryls (T-GSH), non-protein sulphadryls (NP-SH) and thiobarbituric acid reactive substances (TBARS) were evaluated. The activities of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were measured. Concentrations of nucleic acids (DNA and RNA) and total protein were also estimated in colon tissues. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated. In cross section of colitis tissue the histopathological changes were observed. RESULTS: Colonic mucus content was decreased in AA compared to controls (587.09 ± 65.59 mg/kg vs 941.78 ± 68.41 mg/kg, P < 0.001). AA administration markedly reduced T-GSH (5.25 ± 0.37 nmol/L vs 3.04 ± 0.24 nmol/L, P < 0.01), NP-SH (3.16 ± 0.04 nmol/L vs 2.16 ± 0.30 nmol/L, P < 0.01), CAT (6.77 ± 0.40 U/mg vs 3.04 ± 0.2 U/mg, P < 0.01) and SOD (3.10 ± 0.11 U/mg vs 1.77 ± 0.18 U/mg, P < 0.01) while TBARS, TNF-α, IL-1β, IL-6, PGE2 and NO levels (15.09 ± 3.84 nmol/L vs 59.90 ± 16.34 nmol/L, P < 0.01; 113.56 ± 1.91 pg/mg vs 134.24 ± 4.77 pg/mg, P < 0.01; 209.20 ± 36.38 pg/mg vs 422.19 ± 31.47 pg/mg, P < 0.01; 250.83 ± 25.09 pg/mg vs 638.58 ± 115.9 pg/mg, P < 0.01; 248.19 ± 36.98 pg/mg vs 541.74 ± 58.34 pg/mg, P < 0.01 and 81.26 ± 2.98 mmol/g vs 101.90 ± 10.73 mmol/g, P < 0.001) were increased in colon of rats with UC compared controls respectively.Naringenin supplementation, significantly and dose dependently increased the colonic mucus content. The elevated TBARS levels were significantly decreased (39.35 ± 5.86 nmol/L, P < 0.05; 26.74 ± 3.17 nmol/L, P < 0.01 nmol/L and 17.74 ± 2.69 nmol/L, P < 0.01) compared to AA (59.90 ± 16.34 nmol/L) group while the decreased levels of T-GSH and NP-SH and activities of CAT and SOD found increased by NG treatments in dose dependent manner. The decreased values of nucleic acids and total protein in AA group were also significantly (P < 0.01) increased in all three NG supplemented groups respectively. NG pretreatment inhibited the TNF-α levels (123.76 ± 3.76 pg/mg, 122.62 ± 3.41 pg/mg and 121.51 ± 2.61 pg/mg vs 134.24 ± 4.78 pg/mg, P < 0.05) compared to AA group, respectively. Interleukins, IL-1β and IL-6 levels were also decreased in NG50 + AA (314.37 ± 16.31 pg/mg and 292.58 ± 23.68 pg/mg, P < 0.05) and NG100 + AA (416.72 ± 49.62 pg/mg and 407.96 ± 43.87 pg/mg, P < 0.05) when compared to AA (352.46 ± 8.58 pg/mg and 638.58 ± 115.98 pg/mg) group. Similar decrease (P < 0.05) was seen in PGE2 and NO values when compared to AA group. The group pretreated with MES, as a reference drug, showed significant (P < 0.01) protection against the changes induced in colon tissue by AA administration respectively. CONCLUSION: In present study, NG produced antioxidant and anti-inflammatory effects demonstrating protective effect in inflammatory bowel disease. PMID:24039355

Effect of nitrogen fertilisation on the amino acid digestibility of different triticale genotypes in caecectomised laying hens.

PubMed

Siegert, Wolfgang; Boguhn, Jeannette; Maurer, Hans Peter; Weiss, Jochen; Zuber, Tobias; Möhring, Jens; Rodehutscord, Markus

2017-01-01

The influence of nitrogen fertilisation and genotype on the amino acid (AA) digestibility of triticale grain was investigated in caecectomised laying hens. Three genotypes, Grenado, EAW6002 and Lasko, were cultivated with and without nitrogen fertilisation at the end of the heading stage. The six triticale variants as well as a basal diet were each used to feed seven laying hens in a 7 × 7 Latin square design. Nitrogen fertilisation influenced the digestibility of Cys, Glu, Phe and Ser in some triticale genotypes and reduced Ala, Ile, Lys, Met and Val digestibility in all genotypes (P < 0.05). Nitrogen fertilisation increased the concentration of all AAs in the grain. Consequently, the concentration of digestible AAs in the grains was increased for most AAs upon nitrogen fertilisation. Overall, Lys had the lowest digestibility, whereas that of Glu and Pro was the highest. For the triticale genotypes, the level of AA digestibility was highest for EAW6002 followed by Lasko and Grenado, with significant differences (P < 0.05) between genotypes for some but not all AAs. The results indicated that the accuracy of the digestible AA supply for hen feeding might benefit from considering fertilisation and genotype-specific digestibility data in feed formulation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Determination of amino acid profile of mare milk produced in the highlands of the Kyrgyz Republic during the milking season.

PubMed

Mazhitova, A T; Kulmyrzaev, A A

2016-04-01

This study was carried out to determine the influence of milking season on amino acid (AA) profile and chemical composition of milk samples from Kyrgyz native breed mares under traditional pasture conditions. Milk samples were collected monthly from May to August 2014 from mares grazing at 2,200 m above sea level. The AA composition was determined by precolumn derivatization with diethyl ethoxymethylenemalonate in HPLC and 18 AA were determined in mare milk. The analytical parameters of linearity (0.01-4 μg/mL), precision of the method (0.26-4.88% relative standard deviation), derivatization procedure (0.82-2.80% relative standard deviation), and instrument precision (0.08-1.00% relative standard deviation) were determined. The most abundant AA were glutamic acid (0.393-480 g/100g of milk), leucine (0.192-0.230 g/100g of milk), and lysine (0.192-0.230 g/100g of milk). The amount of ornithine was small (0.002-0.015 g/100g of milk). The percentages of essential AA in the protein of mare milk were 46, 46, 51, and 48% for May, June, July, and August, respectively, which demonstrate the high biological value of milk during the whole milking season. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Antioxidant potential of mulberry and non-mulberry silk sericin and its implications in biomedicine.

PubMed

Kumar, Jadi Praveen; Mandal, Biman B

2017-07-01

Sericin, a principal constituent of silk, is widely used in various biomedical applications. In addition, conferring protection against free radicals and oxidative damage add more value to its therapeutic potential. However, the antioxidant (AO) properties of silk sericin (SS) remains contingent on extraction procedures. In the present study, we have evaluated the effect of different extraction methods (conventional, autoclaving, urea, alkali and acid-degradation) on AO properties of SS from three Indian silk varieties [Antheraea assamensis (AA), Philosamia ricini (PR) and Bombyx mori (BM)]. The physico-chemical characterization studies revealed that the molecular weight of SS isolates of each method ranged from 10 to 220kDa along with varied protein structural biochemistry. SS extracts using urea-degradation (BM, PR and AA), conventional method and alkali-degradation (BM) displayed high percentage of β-sheets, random coils and turns. Acid-degraded SS (PR, followed by AA and BM) showed the highest total flavonoid content while conventional method (PR), autoclaving (AA) and alkali-degradation (BM) displayed lowest flavonoid levels. Interestingly, SS extracted by autoclaving (BM and AA), acid-degradation (PR), conventional and alkali-degradation (BM, AA and PR) methods exhibited 50% reduction of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical. Moreover, the efficacy of antioxidant potential of SS extracted by different methods was found to be in the order of "alkali>autoclaving>conventional" as demonstrated in L929 cells. Correspondingly, the anti-lipid peroxidation activity of SS extracted by alkali method (AA, BM and PR) further confirmed better AO properties amid others. Thus, the present study demonstrates that the extraction methods may significantly affect AO activity of SS which might be of importance for potential cosmetic applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Anacardic Acids from Cashew Nuts Prevent Behavioral Changes and Oxidative Stress Induced by Rotenone in a Rat Model of Parkinson's Disease.

PubMed

Medeiros-Linard, Cybelle Façanha Barreto; Andrade-da-Costa, Belmira Lara da Silveira; Augusto, Ricielle Lopes; Sereniki, Adriana; Trevisan, Maria Teresa Sales; Perreira, Renata de Cássia Ribas; de Souza, Francisco Thiago Correia; Braz, Glauber Ruda Feitoza; Lagranha, Claudia Jacques; de Souza, Ivone Antônia; Wanderley, Almir Gonçalves; Smailli, Soraya S; Lafayette, Simone Sette Lopes

2018-03-08

Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100 mg/kg/day) 1 h before rotenone (3 mg/kg; s.c.) for five consecutive days. The behavioral testing strategies, including tests for general locomotor activity (open field), motor coordination (rotarod), and spatial memory performance (elevated T-maze), were carried out. Lipoperoxidation levels and total superoxide dismutase (t-SOD) activity, as well as cytoplasmic and mitochondrial SOD gene expression, were assessed in the substantia nigra (SN), striatum, and cerebral cortex. The results showed that AAs dose-dependently prevented the rotenone-induced learning and motor impairment from 10 mg/kg/day. AAs also precluded rotenone-induced lipoperoxidation in all doses, acting directly on the mitochondria, and improved the t-SOD activity in the doses 25-100 mg/kg/day. AAs per se (100 mg/kg/day) increased SOD gene expression and t-SOD activity. Our findings indicate that the oral administration of AAs prevents rotenone-induced behavioral changes and oxidative stress, in part due to a modulatory action on the mitochondria and SOD gene expression. These data suggest that AAs have promising neuroprotective action against degenerative changes in Parkinson's disease.

Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.

PubMed

Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

2014-04-06

Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults.

PubMed

Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M

2017-01-31

High arachidonic acid (AA; 20:4 n - 6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n - 6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2 n - 6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25-80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44-74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3 n - 6), alpha-linolenic acid (ALA; 18:3 n - 3), eicosapentaenoic acid (EPA; 20:5 n - 3), and docosahexaenoic acid (DHA; 22:6 n - 3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population.

Pharmacokinetics of aniracetam and its metabolites in rats.

PubMed

Ogiso, T; Iwaki, M; Tanino, T; Ikeda, K; Paku, T; Horibe, Y; Suzuki, H

1998-05-01

The pharmacokinetics of aniracetam (AP), a new cognitive performance enhancer, and its main metabolites was investigated after intravenous (iv) and oral administrations to rat. The plasma levels of AP, 4-p-anisamidobutyric acid (ABA), and p-anisic acid (AA) were determined simultaneously by the HPLC method. The plasma concentrations of the parent drug and ABA quickly declined in a biexponential manner, with rapid terminal decay and a small mean residence time. However, AA yielded nonlinearly high levels at the initial times and the plasma concentrations of 2-pyrrolidinone (PD) were sustained over a relatively long time. When AA was administered intravenously, nonlinearity of the plasma concentrations was also found at higher doses. To describe the time course of the plasma levels of AP and its metabolites after iv administration, a pharmacokinetic model with seven compartments was applied, which included 10 first-order rate constants and one Michaelis-Menten constant. An approximate fit was obtained between the observed and calculated curves based on the model, except for the plasma concentrations of ABA. The plasma concentration-time profiles of AP and its metabolites following oral administration of AP (50 and 100 mg/kg) were similar to those after iv dosing, with the exception of PD, which showed much lower plasma levels than those after iv administration. Elimination of AP and ABA was rapid after oral dosing, and the bioavailability of AP was extremely small (11.4 and 8.6%). As a result, AP was largely metabolized to ABA, AA, and PD in rat.

Respiratory Symptoms in Hospital Cleaning Staff Exposed to a Product Containing Hydrogen Peroxide, Peracetic Acid, and Acetic Acid.

PubMed

Hawley, Brie; Casey, Megan; Virji, Mohammed Abbas; Cummings, Kristin J; Johnson, Alyson; Cox-Ganser, Jean

2017-12-15

Cleaning and disinfecting products consisting of a mixture of hydrogen peroxide (HP), peracetic acid (PAA), and acetic acid (AA) are widely used as sporicidal agents in health care, childcare, agricultural, food service, and food production industries. HP and PAA are strong oxidants and their mixture is a recognized asthmagen. However, few exposure assessment studies to date have measured HP, PAA, and AA in a health care setting. In 2015, we performed a health and exposure assessment at a hospital where a new sporicidal product, consisting of HP, PAA, and AA was introduced 16 months prior. We collected 49 full-shift time-weighted average (TWA) air samples and analyzed samples for HP, AA, and PAA content. Study participants were observed while they performed cleaning duties, and duration and frequency of cleaning product use was recorded. Acute upper airway, eye, and lower airway symptoms were recorded in a post-shift survey (n = 50). A subset of 35 cleaning staff also completed an extended questionnaire that assessed symptoms reported by workers as regularly occurring or as having occurred in the previous 12 months. Air samples for HP (range: 5.5 to 511.4 ppb) and AA (range: 6.7 to 530.3 ppb) were all below established US occupational exposure limits (OEL). To date, no full-shift TWA OEL for PAA has been established in the United States, however an OEL of 0.2 ppm has been suggested by several research groups. Air samples for PAA ranged from 1.1 to 48.0 ppb and were well below the suggested OEL of 0.2 ppm. Hospital cleaning staff using a sporicidal product containing HP, PAA, and AA reported work-shift eye (44%), upper airway (58%), and lower airway (34%) symptoms. Acute nasal and eye irritation were significantly positively associated with increased exposure to the mixture of the two oxidants: HP and PAA, as well as the total mixture (TM)of HP, PAA, and AA. Shortness of breath when hurrying on level ground or walking up a slight hill was significantly associated with increased exposure to the oxidant mixture (P = 0.017), as well as the TM (P = 0.026). Our results suggest that exposure to a product containing HP, PAA, and AA contributed to eye and respiratory symptoms reported by hospital cleaning staff at low levels of measured exposure. Published by Oxford University Press on behalf of the British Occupational Hygiene Society 2017.

Determination of D- and L-amino acids produced by cyanobacteria using gas chromatography on Chirasil-Val after derivatization with pentafluoropropyl chloroformate.

PubMed

Zahradnícková, Helena; Husek, Petr; Simek, Petr; Hartvich, Petr; Marsálek, Blahoslav; Holoubek, Ivan

2007-08-01

A rapid and simple method was developed for the determination of free amino acids (AAs) released from cyanobacteria. The procedure involves trapping of AAs from the centrifuged cyanobacterial culture fluid on a cation-exchange resin, their release together with the resin by direct treatment with the reaction medium, followed by immediate derivatization with a corresponding chloroformate. The extractive alkylation transfers the analytes into an organic phase, an aliquot of which is subjected to GC analysis. Identification and quantification of AAs was performed by GC/MS and GC/FID, respectively, using propyl chloroformate (PCF) as the derivatization reagent. For chiral analysis, the cyanobacteria extracts were treated with 2,2,3,3,3-pentafluoropropyl chloroformate (PFPCF) to create more volatile analytes. Separation of the AA enantiomers was accomplished on a Chirasil-Val capillary column and the D/L enantiomeric ratios were determined. AAs of cyanobacteria are considered to be important for the assessment of energy flow in an aquatic food web, nutrition value of cyanobacteria in a food web and for cell-cell communication within cyanobacteria. The highest levels of AAs were found in the summer period at the beginning of the season (July). In the September and October samples, the amount of AAs was lower, the number of D-AAs decreased and the D/L ratio was higher than in the July sample. Based on the obtained results it can be assumed that young populations excrete AAs in higher concentrations and a different composition compared to actively growing populations.

Biochemical Reversal of Aging

NASA Astrophysics Data System (ADS)

Ely, John T. A.

2006-03-01

We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

Renal Liver-Type Fatty Acid Binding Protein (L-FABP) Attenuates Acute Kidney Injury in Aristolochic Acid Nephrotoxicity

PubMed Central

Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

2011-01-01

Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of Nε-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of Nε-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID. PMID:21356355

Associations With Eicosapentaenoic Acid to Arachidonic Acid Ratio and Mortality in Hospitalized Heart Failure Patients.

PubMed

Watanabe, Shunsuke; Yoshihisa, Akiomi; Kanno, Yuki; Takiguchi, Mai; Yokokawa, Tetsuro; Sato, Akihiko; Miura, Shunsuke; Shimizu, Takeshi; Abe, Satoshi; Sato, Takamasa; Suzuki, Satoshi; Oikawa, Masayoshi; Sakamoto, Nobuo; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Takeishi, Yasuchika

2016-12-01

Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) lowers the risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, the ratio of eicosapentaenoic acid (EPA; n-3 PUFA) to arachidonic acid (AA; n-6 PUFA) has recently been recognized as a risk marker of cardiovascular disease. In contrast, the prognostic impact of the EPA/AA ratio on patients with heart failure (HF) remains unclear. A total of 577 consecutive patients admitted for HF were divided into 2 groups based on median of the EPA/AA ratio: low EPA/AA (EPA/AA <0.32 mg/dl, n = 291) and high EPA/AA (EPA/AA ≥0.32, n = 286) groups. We compared laboratory data and echocardiographic findings and followed cardiac mortality. Although body mass index, blood pressure, B-type natriuretic peptide, hemoglobin, estimated glomerular filtration rate, total protein, albumin, sodium, C-reactive protein, and left ventricular ejection fraction did not differ between the 2 groups, cardiac mortality was significantly higher in the low EPA/AA group than in the high EPA/AA group (12.7 vs 5.9%, log-rank P = .004). Multivariate Cox proportional hazard analysis revealed that the EPA/AA ratio was an independent predictor of cardiac mortality (hazard ratio 0.677, 95% confidence interval 0.453-0.983, P = .041) in patients with HF. The EPA/AA ratio was an independent predictor of cardiac mortality in patients with HF; therefore, the prognosis of patients with HF may be improved by taking appropriate management to control the EPA/AA balance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Oxidative stress in the hippocampus during experimental seizures can be ameliorated with the antioxidant ascorbic acid

PubMed Central

Santos, Ítala Mônica Sales; da Rocha Tomé, Adriana; Saldanha, Gláucio Barros; Ferreira, Paulo Michel Pinheiro; Militão, Gardenia Carmem Gadelha

2009-01-01

Ascorbic acid has many nonenzymatic actions and is a powerful water-soluble antioxidant. It protects low density lipoproteins from oxidation and reduces harmful oxidants in the central nervous system. Pilocarpine-induced seizures have been suggested to be mediated by increases in oxidative stress. Current studies have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures. The objective of the present study was to evaluate the neuroprotective effects of ascorbic acid (AA) in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), ascorbic acid (500 mg/kg, i.p., AA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of ascorbic acid (500 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of ascorbic acid (AA plus pilocarpine group). After the treatments all groups were observed for 6 h. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of ascorbic acid were also evaluated on the same parameters. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite level. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content as well as increased the superoxide dismutase and catalase activities in hippocampus of adult rats after seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, proving that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and also imply that a strong protective effect could be achieved using ascorbic acid. PMID:20716907

Uncovering the Design Principle of Amino Acid-Derived Photoluminescent Biodots with Tailor-Made Structure-Properties and Applications for Cellular Bioimaging.

PubMed

Xu, Hesheng Victor; Zheng, Xin Ting; Zhao, Yanli; Tan, Yen Nee

2018-06-13

Natural amino acids possess side chains with different functional groups (R groups), which make them excellent precursors for programmable synthesis of biomolecule-derived nanodots (biodots) with desired properties. Herein, we report the first systematic study to uncover the material design rules of biodot synthesis from 20 natural α-amino acids via a green hydrothermal approach. The as-synthesized amino acid biodots (AA dots) are comprehensively characterized to establish a structure-property relationship between the amino acid precursors and the corresponding photoluminescent properties of AA dots. It was found that the amino acids with reactive R groups, including amine, hydroxyl, and carboxyl functional groups form unique C-O-C/C-OH and N-H bonds in the AA dots which stabilize the surface defects, giving rise to brightly luminescent AA dots. Furthermore, the AA dots were found to be amorphous and the length of the R group was observed to affect the final morphology (e.g., disclike nanostructure, nanowire, or nanomesh) of the AA dots, which in turn influence their photoluminescent properties. It is noteworthy to highlight that the hydroxyl-containing amino acids, that is, Ser and Thr, form the brightest AA dots with a quantum yield of 30.44% and 23.07%, respectively, and possess high photostability with negligible photobleaching upon continuous UV exposure for 3 h. Intriguingly, by selective mixing of Ser or Thr with another amino acid precursor, the resulting mixed AA dots could inherit unique properties such as improved photostability and significant red shift in their emission wavelength, producing enhanced green and red fluorescent intensity. Moreover, our cellular studies demonstrate that the as-synthesized AA dots display outstanding biocompatibility and excellent intracellular uptake, which are highly desirable for imaging applications. We envision that the material design rules discovered in this study will be broadly applicable for the rational selection of amino acid precursors in the tailored synthesis of biodots.

Ascorbic Acid Attenuates Multifidus Muscles Injury and Atrophy after Posterior Lumbar Spine Surgery by Suppressing Inflammation and Oxidative Stress in a Rat Model.

PubMed

Tang, Pan; Gu, Yu; Gu, Jia-Ming; Xie, Zi-Ang; Xu, Jia-Qi; Zhao, Xiang-De; Huang, Kang-Mao; Wang, Ji-Ying; Jiang, Xue-Sheng; Fan, Shun-Wu; Hu, Zhi-Jun

2018-04-11

A rat model of multifidus muscles injury and atrophy after posterior lumbar spine surgery. We determined the effect of ascorbic acid (AA) on the postoperative multifidus muscles in rat model. Previous studies show oxidative stress and inflammation are two main molecular mechanisms in multifidus muscle injury and atrophy after posterior lumbar surgery. AA may have a protective effect in postoperative multifidus muscles. Rats were divided into sham surgery, control surgery, and surgery plus AA groups. Multifidus muscles of the control and AA groups were excised from the osseous structures. The muscles were retracted continuously for 2 h. In the sham and AA groups, AA was administered via oral gavage daily in the first week. In each group, the oxidative stress was evaluated by measuring malondialdehyde (MDA) and Total superoxide dismutase (T-SOD). The inflammation, fat degeneration or fibrosis of multifidus muscle were evaluated by Q-PCR, histology or immunohistochemical analysis. T-SOD activity was significantly lower in the control group than that in the AA group in the first week. MDA levels were significantly higher in the AA group. Interleukin-6 and tumor necrosis factor-α in multifidus muscles also showed significant differences when treated with AA. The inflammation score on histology was significantly lower in the AA group postoperatively in the first week. In the long run, marker genes for fibrosis and fat degeneration, and fibrosis and fat degeneration scores, were significantly lower in the AA than the control group on days 14 and 28 postoperatively. In conclusion, AA attenuated the oxidative stress and inflammation response in the postoperative multifidus muscles, and remarkable differences were observed from the histological assessment and related marker genes expression. Our results provided important insight into the anti-inflammatory and anti-oxidative effects of AA in the postoperative multifidus muscles. N/A.

Molecular simulation insights on the in vacuo adsorption of amino acids on graphene oxide surfaces with varying surface oxygen densities

NASA Astrophysics Data System (ADS)

Rahmani, Farzin; Nouranian, Sasan; Mahdavi, Mina; Al-Ostaz, Ahmed

2016-11-01

In this fundamental study, a series of molecular dynamics simulations were performed in vacuo to investigate the energetics and select geometries of 20 standard amino acids (AAs) on pristine graphene (PG) and graphene oxide (GO) surfaces as a function of graphene surface oxygen density. These interactions are of key interest to graphene/biomolecular systems. Our results indicate that aromatic AAs exhibit the strongest total interactions with the PG surfaces due to π-π stacking. Tryptophan (Trp) has the highest aromaticity due to its indole side chain and, hence, has the strongest interaction among all AAs (-16.66 kcal/mol). Aliphatic, polar, and charged AAs show various levels of affinity to the PG sheets depending on the strength of their side chain hydrophobic interactions. For example, arginine (Arg) with its guanidinium side chain exhibits the strongest interaction with the PG sheets (-13.81 kcal/mol) following aromatic AAs. Also, glycine (Gly; a polar AA) has the weakest interaction with the PG sheets (-7.29 kcal/mol). When oxygen-containing functional groups are added to the graphene sheets, the π-π stacking in aromatic AAs becomes disrupted and perfect parallelism of the aromatic rings is lost. Moreover, hydrogen bonding and/or electrostatic interactions become more pronounced. Charged AAs exhibit the strongest interactions with the GO surfaces. In general, the AA-GO interactions increase with increasing surface oxygen density, and the effect is more pronounced at higher O/C ratios. This study provides a quantitative measure of AA-graphene interactions for the design and tuning of biomolecular systems suitable for biosensing, drug delivery, and gene delivery applications.

Hydrogen isotopes in individual amino acids reflect differentiated pools of hydrogen from food and water in Escherichia coli.

PubMed

Fogel, Marilyn L; Griffin, Patrick L; Newsome, Seth D

2016-08-09

Hydrogen isotope (δ(2)H) analysis is widely used in animal ecology to study continental-scale movement because δ(2)H can trace precipitation and climate. To understand the biochemical underpinnings of how hydrogen is incorporated into biomolecules, we measured the δ(2)H of individual amino acids (AAs) in Escherichia coli cultured in glucose-based or complex tryptone-based media in waters with δ(2)H values ranging from -55‰ to +1,070‰. The δ(2)H values of AAs in tryptone spanned a range of ∼250‰. In E. coli grown on glucose, the range of δ(2)H among AAs was nearly 200‰. The relative distributions of δ(2)H of AAs were upheld in cultures grown in enriched waters. In E. coli grown on tryptone, the δ(2)H of nonessential AAs varied linearly with the δ(2)H of media water, whereas δ(2)H of essential AAs was nearly identical to δ(2)H in diet. Model calculations determined that as much as 46% of hydrogen in some nonessential AAs originated from water, whereas no more than 12% of hydrogen in essential AAs originated from water. These findings demonstrate that δ(2)H can route directly at the molecular level. We conclude that the patterns and distributions in δ(2)H of AAs are determined through biosynthetic reactions, suggesting that δ(2)H could become a new biosignature for studying novel microbial pathways. Our results also show that δ(2)H of AAs in an organism's tissues provides a dual tracer for food and environmental (e.g., drinking) water.

Hydrogen isotopes in individual amino acids reflect differentiated pools of hydrogen from food and water in Escherichia coli

PubMed Central

Fogel, Marilyn L.; Griffin, Patrick L.; Newsome, Seth D.

2016-01-01

Hydrogen isotope (δ2H) analysis is widely used in animal ecology to study continental-scale movement because δ2H can trace precipitation and climate. To understand the biochemical underpinnings of how hydrogen is incorporated into biomolecules, we measured the δ2H of individual amino acids (AAs) in Escherichia coli cultured in glucose-based or complex tryptone-based media in waters with δ2H values ranging from −55‰ to +1,070‰. The δ2H values of AAs in tryptone spanned a range of ∼250‰. In E. coli grown on glucose, the range of δ2H among AAs was nearly 200‰. The relative distributions of δ2H of AAs were upheld in cultures grown in enriched waters. In E. coli grown on tryptone, the δ2H of nonessential AAs varied linearly with the δ2H of media water, whereas δ2H of essential AAs was nearly identical to δ2H in diet. Model calculations determined that as much as 46% of hydrogen in some nonessential AAs originated from water, whereas no more than 12% of hydrogen in essential AAs originated from water. These findings demonstrate that δ2H can route directly at the molecular level. We conclude that the patterns and distributions in δ2H of AAs are determined through biosynthetic reactions, suggesting that δ2H could become a new biosignature for studying novel microbial pathways. Our results also show that δ2H of AAs in an organism’s tissues provides a dual tracer for food and environmental (e.g., drinking) water. PMID:27444017

Comparative estimation of inevitable endogenous ileal flow of amino acids in Pekin ducks under varying dietary or physiological conditions and their significance to nutritional requirements for amino acids.

PubMed

Akinde, D O

2017-10-01

In 2 experiments in Pekin ducks the inevitable endogenous ileal flow (IEIF) of AA was estimated at changing intake and source of crude fiber (CF) or soybean oil (SO) level. Also the roles of dry matter intake (DMI) and BW or age as well as the proportion of IEIF in the dietary requirement for AA were studied. In experiment 1 three basal CP (20, 60, or 100 g/kg) diets were formulated containing a low CF (LCF, 30 g/kg) or high (HCF, 80 g/kg) level; achieved with cellulose supplementation. All diets were similar in every other respect including having SO content of 40 g/kg. Four floor pens of eight 85-day-old ducks were randomly allocated to each diet. Similar diets were mixed in experiment 2 but corn cob meal replaced cellulose as the fiber source. A high SO (HSO) series was also formed by increasing the SO level from 40 g/kg in the basal series to 100 g/kg. Thus the LCF series was concurrently classified as low SO (LSO) series to control SO effect. Each of the eventual 9 diets were fed to 5 floor pens of ten 65-day-old ducks. Ileal AA flow was measured after a 5 day feeding period in both experiments. Linear regression was calculated between ileal flow and dietary intake of individual AA. The IEIF interpreted as the y-intercept of each linear function responded neither to elevated ingestion of each CF type nor to SO level. Age and DMI had no effect on IEIF computed in relation to BW, but wide discrepancies resulted when related to DMI. Overall IEIF of AA varied between 14.3 to 129.8 mg/kg BW d-1. These flows were established in model computations to account for 10 to 64% of the recommended intake of limiting AA. In conclusion the ileal inevitable flow is constant within the dietary/age conditions investigated. However it is modulated by feed intake and accounts for a significant portion of total amino acid requirement. © 2017 Poultry Science Association Inc.

Synthesis and characterization of agricultural controllable humic acid superabsorbent.

PubMed

Gao, Lijuan; Wang, Shiqiang; Zhao, Xuefei

2013-12-01

Humic acid superabsorbent polymer (P(AA/AM-HA)) and superabsorbent polymer (P(AA/AM)) were synthesized by aqueous solution polymerization method using acrylic acid (AA), acrylamide (AM) and humic acid (HA) as raw material. The effects of N,N'-methylenebisacrylamide (MBA) crosslinking agent, potassium peroxydisulfate (KPS) initiator, reaction temperature, HA content, ratio of AA to AM, concentration of monomer and neutralization of AA on water absorption were investigated. Absorption and desorption ratios of nitrogen fertilizer and phosphate fertilizer were also investigated by determination of absorption and desorption ratio of NH4(+), PO4(3-) on P(AA/AM-HA) and P(AA/AM). The P(AA/AM-HA) and P(AA/AM) were characterized by Fourier translation infrared spectroscopy, biological photomicroscope and scanning electron microscopy (SEM). The optimal conditions obtained were as follows: the weight ratio of MBA to AA and AM was 0.003; the weight ratio of KPS to AA and AM was 0.008; the weight ratio of HA to AA was 0.1; the mole ratio of AM to AA is 0.1; the mole ratio of NaOH to AA is 0.9; the reaction temperature was 60°C. P(AA/AM-HA) synthesized under optimal conditions, has a good saline tolerance, its water absorbency in distilled water and 0.9 wt.% saline solution is 1180 g/g and 110 g/g, respectively. P(AA/AM-HA) achieves half saturation in 6.5 min. P(AA/AM-HA) is superior to P(AA/AM) on absorption of NH4(+), PO4(3-). The SEM micrograph of P(AA/AM-HA) shows a fine alveolate structure. The biological optical microscope micrograph of P(AA/AM-HA) shows a network structure. Graft polymerization between P(AA/AM) and HA was demonstrated by infrared spectrum. The P(AA/AM-HA) superabsorbent has better absorbing ability of water and fertilizer, electrolytic tolerance and fewer cost than P(AA/AM) superabsorbent. Copyright © 2013 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins.

PubMed

Gan, Rui; Perez, Jessica G; Carlson, Erik D; Ntai, Ioanna; Isaacs, Farren J; Kelleher, Neil L; Jewett, Michael C

2017-05-01

The ability to site-specifically incorporate non-canonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the bio synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e.g., translation elements that specifically use a ncAA and do not interact with the cell's natural translation apparatus). Here, we show that evolving and tuning expression levels of multiple components of an engineered translation system together as a whole enhances ncAA incorporation efficiency. Specifically, we increase protein yield when incorporating multiple p-azido-phenylalanine(pAzF) residues into proteins by (i) evolving the Methanocaldococcus jannaschii p-azido-phenylalanyl-tRNA synthetase anti-codon binding domain, (ii) evolving the elongation factor Tu amino acid-binding pocket, and (iii) tuning the expression of evolved translation machinery components in a single vector. Use of the evolved translation machinery in a genomically recoded organism lacking release factor one enabled enhanced multi-site ncAA incorporation into proteins. We anticipate that our approach to orthogonal translation system development will accelerate and expand our ability to site-specifically incorporate multiple ncAAs into proteins and biopolymers, advancing new horizons for synthetic and chemical biotechnology. Biotechnol. Bioeng. 2017;114: 1074-1086. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

NASA Technical Reports Server (NTRS)

Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Creson, Daniel L.; Sanford, Arthur P.; Wolf, Steven E.; Wolfe, Robert R.; Ferrando, Arny A.

2003-01-01

Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 microg. kg(-1). h(-1)) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 microg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol. kg(-1). min(-1)) of l-[ring-(2)H(5)]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 +/- 2.1 (C + AA) vs. 9.0 +/- 1.0 microg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

Serum Markers of Neurodegeneration in Maple Syrup Urine Disease.

PubMed

Scaini, Giselli; Tonon, Tássia; de Souza, Carolina F Moura; Schuk, Patricia F; Ferreira, Gustavo C; Neto, Joao Seda; Amorin, Tatiana; Schwartz, Ida Vanessa D; Streck, Emilio L

2017-09-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD.

Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients

PubMed Central

Rao, Jagadeesh Sridhara; Kim, Hyung-Wook; Harry, Gaylia Jean; Rapoport, Stanley Isaac; Reese, Edmund Arthur

2013-01-01

Schizophrenia (SZ) is a progressive, neuropsychiatric disorder associated with cognitive impairment. A number of brain alterations have been linked to cognitive impairment, including neuroinflammation, excitotoxicity, increased arachidonic acid (AA) signaling and reduced synaptic protein. On this basis, we tested the hypothesis that SZ pathology is associated with these pathological brain changes. To do this, we examined postmortem frontal cortex from 10 SZ patients and 10 controls and measured protein and mRNA levels of cytokines, and astroglial, microglial, neuroinflammatory excitotoxic, AA cascade, apoptotic and synaptic markers. Mean protein and mRNA levels of interleukin-1β, tumor necrosis factor-α, glial acidic fibrillary protein (GFAP), a microglial marker CD11b, and nuclear factor kappa B subunits were significantly increased in SZ compared with control brain. Protein and mRNA levels of cytosolic and secretory phospholipase A2 and cyclooxygenase were significantly elevated in postmortem brains from SZ patients. N-methyl-D-aspartate receptor subunits 1 and 2B, inducible nitric oxide synthase and c-FOS were not significantly different. In addition, reduced protein and mRNA levels of brain-derived neurotrophic factor, synaptophysin and drebrin were found in SZ compared with control frontal cortex. Increased neuroinflammation and AA cascade enzyme markers with synaptic protein loss could promote disease progression and cognitive defects in SZ patients. Drugs that downregulate these changes might be considered for new therapies in SZ. PMID:23566496

Data on the effect of oral feeding of Arachidonic acid or Docosahexanoic acid on haematopoiesis in mice.

PubMed

Limbkar, Kedar; Dhenge, Ankita; Jadhav, Dipesh D; Thulasiram, Hirekodathakallu V; Kale, Vaijayanti; Limaye, Lalita

2017-10-01

Stem cells have peculiar property to self-renew and differentiate. It is important to control their fate in safe and effective ways for their therapeutic use. The mediators of essential polyunsaturated fatty acids (PUFAs) namely Arachidonic acid (AA) and Docosahexanoic acid (DHA) are known to play a role in haematopoiesis via various metabolic pathways [1]. However the direct effect of purified AA or DHA on haematopoiesis has not been well investigated yet. We have reported that oral administration of PUFAs enhanced haematopoiesis in mice [2]. Signaling Leukocyte Antigen Molecule (SLAM) (CD48 - CD150 + ) phenotype consists of pure population of haematopoietic stem cells (HSCs). Herein we observed higher percentage of SLAM (CD48 - CD150 + ) phenotype in the bone marrow (BM) cells of mice fed with AA or DHA compared to PBS fed control mice. Data from engraftment study depicts that BM from AA/DHA-fed mice showed higher absolute number of donor cells in recipient mice compared to control. The enhanced hematopoiesis observed in AA/DHA-fed mice was returned to normal when the mice were kept on normal diet for six weeks (after ten days of oral feeding). We confirmed GCMS (Gas Chromatography-Mass Spectroscopy) retention times of AA and DHA by co-injecting fatty acid extract from AA or DHA fed mice with purified AA or DHA standards respectively. Representative flow cytometry profile of Lin - Sca-1 + c-kit + (LSK) cells showed higher expression of CXCR4 protein and ligands of Wnt, Notch1 signaling in BM of AA/DHA-fed mice.

TOR Pathway-Mediated Juvenile Hormone Synthesis Regulates Nutrient-Dependent Female Reproduction in Nilaparvata lugens (Stål)

PubMed Central

Lu, Kai; Chen, Xia; Liu, Wen-Ting; Zhou, Qiang

2016-01-01

The “target of rapamycin” (TOR) nutritional signaling pathway and juvenile hormone (JH) regulation of vitellogenesis has been known for a long time. However, the interplay between these two pathways regulating vitellogenin (Vg) expression remains obscure. Here, we first demonstrated the key role of amino acids (AAs) in activation of Vg synthesis and egg development in Nilaparvata lugens using chemically defined artificial diets. AAs induced the expression of TOR and S6K (S6 kinase), whereas RNAi-mediated silencing of these two TOR pathway genes and rapamycin application strongly inhibited the AAs-induced Vg synthesis. Furthermore, knockdown of Rheb (Ras homologue enriched in brain), TOR, S6K and application of rapamycin resulted in a dramatic reduction in the mRNA levels of jmtN (juvenile hormone acid methyltransferase, JHAMT). Application of JH III on the RNAi (Rheb and TOR) and rapamycin-treated females partially rescued the Vg expression. Conversely, knockdown of either jmtN or met (methoprene-tolerant, JH receptor) and application of JH III had no effects on mRNA levels of Rheb, TOR and S6K and phosphorylation of S6K. In summary, our results demonstrate that the TOR pathway induces JH biosynthesis that in turn regulates AAs-mediated Vg synthesis in N. lugens. PMID:27043527

TOR Pathway-Mediated Juvenile Hormone Synthesis Regulates Nutrient-Dependent Female Reproduction in Nilaparvata lugens (Stål).

PubMed

Lu, Kai; Chen, Xia; Liu, Wen-Ting; Zhou, Qiang

2016-03-28

The "target of rapamycin" (TOR) nutritional signaling pathway and juvenile hormone (JH) regulation of vitellogenesis has been known for a long time. However, the interplay between these two pathways regulating vitellogenin (Vg) expression remains obscure. Here, we first demonstrated the key role of amino acids (AAs) in activation of Vg synthesis and egg development in Nilaparvata lugens using chemically defined artificial diets. AAs induced the expression of TOR and S6K (S6 kinase), whereas RNAi-mediated silencing of these two TOR pathway genes and rapamycin application strongly inhibited the AAs-induced Vg synthesis. Furthermore, knockdown of Rheb (Ras homologue enriched in brain), TOR, S6K and application of rapamycin resulted in a dramatic reduction in the mRNA levels of jmtN (juvenile hormone acid methyltransferase, JHAMT). Application of JH III on the RNAi (Rheb and TOR) and rapamycin-treated females partially rescued the Vg expression. Conversely, knockdown of either jmtN or met (methoprene-tolerant, JH receptor) and application of JH III had no effects on mRNA levels of Rheb, TOR and S6K and phosphorylation of S6K. In summary, our results demonstrate that the TOR pathway induces JH biosynthesis that in turn regulates AAs-mediated Vg synthesis in N. lugens.

Reductive dechlorination of carbon tetrachloride using buffered alkaline ascorbic acid.

PubMed

Lin, Ya-Ting; Liang, Chenju

2015-10-01

Alkaline ascorbic acid (AA) was recently discovered as a novel in-situ chemical reduction (ISCR) reagent for remediating chlorinated solvents in the subsurface. For this ISCR process, the maintenance of an alkaline pH is essential. This study investigated the possibility of the reduction of carbon tetrachloride (CT) using alkaline AA solution buffered by phosphate and by NaOH. The results indicated that CT was reduced by AA, and chloroform (CF) was a major byproduct at a phosphate buffered pH of 12. However, CT was completely reduced by AA in 2M NaOH without CF formation. In the presence of iron/soil minerals, iron could be reduced by AA and Fe(2+) tends to precipitate on the mineral surface to accelerate CT degradation. A simultaneous transfer of hydrogenolysis and dichloroelimination would occur under phosphate buffered pH 12. This implies that a high alkaline environment is a crucial factor for maintaining the dominant pathway of two electron transfer from dianionic AA to dehydroascorbic acid, and to undergo dichloroelimination of CT. Moreover, threonic acid and oxalic acid were identified to be the major AA decomposition products in alkaline solutions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of ion channels and subcellular Ca2+ signaling in arachidonic acid-induced dilation of pressurized retinal arterioles.

PubMed

Kur, Joanna; McGahon, Mary K; Fernández, Jose A; Scholfield, C Norman; McGeown, J Graham; Curtis, Tim M

2014-05-02

To investigate the mechanisms responsible for the dilatation of rat retinal arterioles in response to arachidonic acid (AA). Changes in the diameter of isolated, pressurized rat retinal arterioles were measured in the presence of AA alone and following pre-incubation with pharmacologic agents inhibiting Ca(2+) sparks and oscillations and K(+) channels. Subcellular Ca(2+) signals were recorded in arteriolar myocytes using Fluo-4-based confocal imaging. The effects of AA on membrane currents of retinal arteriolar myocytes were studied using whole-cell perforated patch clamp recording. Arachidonic acid dilated pressurized retinal arterioles under conditions of myogenic tone. Eicosatetraynoic acid (ETYA) exerted a similar effect, but unlike AA, its effects were rapidly reversible. Arachidonic acid-induced dilation was associated with an inhibition of subcellular Ca(2+) signals. Interventions known to block Ca(2+) sparks and oscillations in retinal arterioles caused dilatation and inhibited AA-induced vasodilator responses. Arachidonic acid accelerated the rate of inactivation of the A-type Kv current and the voltage dependence of inactivation was shifted to more negative membrane potentials. It also enhanced voltage-activated and spontaneous large-conductance calcium-activated K(+) (BK) currents, but only at positive membrane potentials. Pharmacologic inhibition of A-type Kv and BK currents failed to block AA-induced vasodilator responses. Arachidonic acid suppressed L-type Ca(2+) currents. These results suggest that AA induces retinal arteriolar vasodilation by inhibiting subcellular Ca(2+)-signaling activity in retinal arteriolar myocytes, most likely through a mechanism involving the inhibition of L-type Ca(2+)-channel activity. Arachidonic acid actions on K(+) currents are inconsistent with a model in which K(+) channels contribute to the vasodilator effects of AA.

Activation by Insulin and Amino Acids of Signaling Components Leading to Translation Initiation in Skeletal Muscle of Neonatal Pigs Is Developmentally Regulated

PubMed Central

Suryawan, Agus; Orellana, Renan A.; Nguyen, Hanh V.; Jeyapalan, Asumthia S.; Fleming, Jillian R.; Davis, Teresa A.

2009-01-01

Insulin (INS) and amino acids (AA) act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight fasted 6-day-old (n=4/group) and 26-day-old (n=6/group) pigs were studied during: 1) euinsulinemic-euglycemic-euaminoacidemic conditions (controls), 2) euinsulinemic-euglycemic-hyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and these responses were higher in 6-day-old compared to 26-day-old pigs. Both INS and AA decreased the binding of 4E-BP1 to eIF4E and increased eIF4E binding to eIF4G; these effects were greater in 6-day-old than in 26-day-old pigs. Neither INS nor AA altered the composition of mTORC1 (raptor, mTOR, and GβL) or mTORC2 (rictor, mTOR, and GβL) complexes. Furthermore, neither INS, AA, nor age had any effect on the abundance of Rheb and the phosphorylation of AMP-activated kinase (AMPK) and eukaryotic elongation factor 2 (eEF2). Our results suggest that the activation by insulin and amino acids of signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs. PMID:17878222

Affinity resins as new tools for identifying target proteins of ascorbic acid.

PubMed

Iwaoka, Yuji; Nishino, Kohei; Ishikawa, Takahiro; Ito, Hideyuki; Sawa, Yoshihiro; Tai, Akihiro

2018-02-12

l-Ascorbic acid (AA) has diverse physiological functions, but little is known about the functional mechanisms of AA. In this study, we synthesized two types of affinity resin on which AA is immobilized in a stable form to identify new AA-targeted proteins, which can provide important clues for elucidating unknown functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a ligand is immobilized has not been prepared, because AA is very unstable and rapidly degraded in an aqueous solution. By using the affinity resins, cytochrome c (cyt c) was identified as an AA-targeted protein, and we showed that oxidized cyt c exhibits specific affinity for AA. These results suggest that two kinds of AA-affinity resin can be powerful tools to identify new target proteins of AA.

Portable electrochemical sensor based on 4-aminobenzoic acid-functionalized herringbone carbon nanotubes for the determination of ascorbic acid and uric acid in human fluids.

PubMed

Abellán-Llobregat, A; González-Gaitán, C; Vidal, L; Canals, A; Morallón, E

2018-06-30

A new portable electrochemical sensor based on 4-aminobenzoic acid-modified herringbone carbon nanotubes (hCNTs-4ABA/Au-IDA) has been developed for the simultaneous determination of ascorbic acid (AA) and uric acid (UA) in physiological fluids. AA and UA were quantified by chronoamperometry at 0.1 and 0.32 V, respectively, in phosphate buffer solution (PBS 0.25 M, pH 7.0). Significant results were obtained for the separate quantification of AA and UA, with a limit of detection (LOD) of 0.65 μM for both analytes, and sensitivities of (9.0 ± 0.4) A g -1 mM -1 and (8.8 ± 0.3) A g -1 mM -1 for AA and UA, respectively. Repeatability was studied at 50 μM for AA and UA, providing relative standard deviations (RSD) lower than 9%. Additions of glucose, dopamine and epinephrine did not interfere with the AA and UA determination. Furthermore, UA did not interfere with AA determination at 0.1 V, although AA additions increased the current recorded at 0.32 V. The method has been successfully applied to human urine, perspiration and serum samples, without significant matrix effects, which allows for the use of an external calibration and the analysis of all the matrices investigated. Copyright © 2018 Elsevier B.V. All rights reserved.

Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

PubMed

Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

2017-04-01

Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

Single tag for total carbohydrate analysis.

PubMed

Anumula, Kalyan Rao

2014-07-15

Anthranilic acid (2-aminobenzoic acid, 2-AA) has the remarkable property of reacting rapidly with every type of reducing carbohydrate. Reactivity of 2-AA with carbohydrates in aqueous solutions surpasses all other tags reported to date. This unique capability is attributed to the strategically located -COOH which accelerates Schiff base formation. Monosaccharides, oligosaccharides (N-, O-, and lipid linked and glycans in secretory fluids), glycosaminoglycans, and polysaccharides can be easily labeled with 2-AA. With 2-AA, labeling is simple in aqueous solutions containing proteins, peptides, buffer salts, and other ingredients (e.g., PNGase F, glycosidase, and transferase reaction mixtures). In contrast, other tags require relatively pure glycans for labeling in anhydrous dimethyl sulfoxide-acetic acid medium. Acidic conditions are known to cause desialylation, thus requiring a great deal of attention to sample preparation. Simpler labeling is achieved with 2-AA within 30-60 min in mild acetate-borate buffered solution. 2-AA provides the highest sensitivity and resolution in chromatographic methods for carbohydrate analysis in a simple manner. Additionally, 2-AA is uniquely qualified for quantitative analysis by mass spectrometry in the negative mode. Analyses of 2-AA-labeled carbohydrates by electrophoresis and other techniques have been reported. Examples cited here demonstrate that 2-AA is the universal tag for total carbohydrate analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

Arachidonic acid is involved in the regulation of hCG induced steroidogenesis in rat Leydig cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Didolkar, A.K.; Sundaram, K.

1987-07-27

Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to insositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA) could significantly stimulate testosterone (T) secretion from Leydig cells. Arachidonic acid (AA) stimulated T secretion by about 2 fold. The steroidogenic effect of PLC and AA was biphasic. At low concentrations both PLC and AA augmented hCG induced T secretion, while at higher concentrations they inhibited steroid production. AA also had a biphasic effect on hCG induced cyclic AMP secretion. 5,8,11,14 Eicosatetrayenoic acid, a general inhibitor of AA metabolism, and Nordihydroguaiaretic acid, an inhibitor ofmore » the lipoxygenase pathway of AA metabolism, inhibited hCG induced T secretion while indomethacin, an inhibitor of cyclo-oxygenase pathway, had no effect on hCG induced T secretion. The authors conclude from these data that AA plays a role in the regulation of hCG induced steroidogenic responses in rat Leydig cells and that the metabolite(s) of AA that are involved are not cyclo-oxygenase products. 28 references, 4 figures, 2 tables.« less

Protein Carbamylation in Peritoneal Dialysis and the Effect of Low Glucose Plus Amino Acid Solutions.

PubMed

Trottier, Caitlin; Perl, Jeffrey; Freeman, Megan; Thadhani, Ravi; Berg, Anders; Kalim, Sahir

2018-01-01

Protein carbamylation is a post-translational urea-driven protein modification associated with mortality. Free amino acids (AAs) competitively inhibit protein carbamylation and parenteral AA therapy reduces carbamylation in hemodialysis (HD) patients. Peritoneal dialysis (PD) yields differences in urea clearance and AA balance compared with HD, but the influence of PD and intraperitoneal AA solutions on carbamylation is unclear. Thus, we first measured carbamylated albumin (C-Alb; a marker of carbamylation load) in 100 diabetic HD patients frequency-matched by age, sex, and race to 98 diabetic PD subjects from the IMPENDIA trial, which originally compared the metabolic effects of low-glucose PD solutions (incorporating icodextrin and AAs) to a control group (dextrose-only solutions). We then determined the effects of the AA-enriched PD solutions by measuring the 6-month change in C-Alb within the IMPENDIA cohort by treatment allocation (48 treated vs 50 controls). Peritoneal dialysis patients, when compared with HD patients, had higher baseline urea and higher C-Alb. Among IMPENDIA participants, there was no difference in C-Alb change in either arm, but treated subjects showed a trend towards increased carbamylation. Treated subjects also demonstrated an increase in urea, possibly explaining the carbamylation trend. In summary, carbamylation levels in PD patients appeared higher than in matched HD patients. A regimen of AA and low-glucose PD solutions did not reduce C-Alb in IMPENDIA subjects. Copyright © 2018 International Society for Peritoneal Dialysis.

Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults

PubMed Central

Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M.

2017-01-01

High arachidonic acid (AA; 20:4n-6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n-6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2n-6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3n-6), alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), and docosahexaenoic acid (DHA; 22:6n-3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population. PMID:28146136

Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion.

PubMed

Limberg, Jacqueline K; Kellawan, J Mikhail; Harrell, John W; Johansson, Rebecca E; Eldridge, Marlowe W; Proctor, Lester T; Sebranek, Joshua J; Schrage, William G

2014-09-15

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. Copyright © 2014 the American Physiological Society.

Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion

PubMed Central

Limberg, Jacqueline K.; Kellawan, J. Mikhail; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

2014-01-01

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise − rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = −0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. PMID:25038148

Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior.

PubMed

Zuo, Dai-Ying; Zhang, Ya-Hong; Cao, Yue; Wu, Chun-Fu; Tanaka, Masatoshi; Wu, Ying-Liang

2006-04-04

The present study was designed to investigate the effects of acute and chronic administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal cortex (PFC) of freely moving mice using in vivo microdialysis with open-field behavior. In line with earlier studies, acute administration of MK-801 induced an increase of Glu in the PFC. We also observed single MK-801 treatment increased AA release in the PFC. In addition, our results indicated that the basal AA levels in the PFC after MK-801 administration for 7 consecutive days were significantly decreased, and basal Glu levels also had a decreased tendency. After chronic administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly decreased dialysate levels of AA and Glu. Our study also found that both acute and chronic administration of MK-801 induced hyperactivity in mice, but the intensity of acute administration was more than that of chronic administration. Furthermore, in all acute treatment mice, individual changes in Glu dialysate concentrations and the numbers of locomotion were positively correlated. In conclusion, this study may provide new evidence that a single MK-801 administration induces increases of dialysate AA and Glu concentrations in the PFC of freely moving mice, which are opposite to those induced by repeated MK-801 administration, with an unknown mechanism. Our results suggested that redox-response might play an important role in the model of schizophrenic symptoms induced by MK-801.

Polyoxometalate-Graphene Nanocomposite Modified Electrode for Electrocatalytic Detection of Ascorbic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Weiying; Du, Dan; Gunaratne, Don

Phosphomolybdate functionalized graphene nanocomposite (PMo 12-GS) has been successfully formed on a glassy carbon electrode (GCE) for the detection of ascorbic acid (AA). The obtained PMo 12-GS modified GCE, was characterized by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) spectroscopy and compared with GCE, GS modified GCE, and PMo 12 modified GCE. It shows an increased current and a decrease in over-potential of ~210 mV. The amperometric signals are linearly proportional to the AA concentration in a wide concentration range from 1×10 -6 M to 8×10 -3 M, with a detection limit ofmore » 0.5×10 -6 M. Finally, the PMo 12-GS modified electrode was employed for the determination of the AA level in vitamin C tablets, with recoveries between 96.3 and 100.8 %.« less

The emerging role of mTORC1 signaling in placental nutrient-sensing.

PubMed

Jansson, T; Aye, I L M H; Goberdhan, D C I

2012-11-01

Nutrient-sensing signaling pathways regulate cell metabolism and growth in response to altered nutrient levels and growth factor signaling. Because trophoblast cell metabolism and associated signaling influence fetal nutrient availability, trophoblast nutrient sensors may have a unique role in regulating fetal growth. We review data in support of a role for mammalian target of rapamycin complex 1 (mTORC1) in placental nutrient-sensing. Placental insulin/IGF-I signaling and fetal levels of oxygen, glucose and amino acids (AAs) are altered in pregnancy complications such as intrauterine growth restriction, and all these factors are well-established upstream regulators of mTORC1. Furthermore, mTORC1 is a positive regulator of placental AA transporters, suggesting that trophoblast mTORC1 modulates AA transfer across the placenta. In addition, placental mTORC1 signaling is also known to be modulated in pregnancy complications associated with altered fetal growth and in animal models in which maternal nutrient availability has been altered experimentally. Recently, significant progress has been made in identifying the molecular mechanisms by which mTORC1 senses AAs, a process requiring shuttling of mTOR to late endosomal and lysosomal compartments (LELs). We recently identified members of the proton-assisted amino acid transporter (PAT/SLC36) family as critical components of the AA-sensing system or 'nutrisome' that regulates mTORC1 on LEL membranes, placing AA transporters and their subcellular regulation both upstream and downstream of mTORC1-driven processes. We propose a model in which placental mTORC1 signaling constitutes a critical link between maternal nutrient availability and fetal growth, thereby influencing the long-term health of the fetus. Copyright © 2012 Elsevier Ltd. All rights reserved.

Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids.

PubMed

Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Placko, R

1989-03-01

The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.

Arachidonic acid stimulates DNA synthesis in brown preadipocytes through the activation of protein kinase C and MAPK.

PubMed

Garcia, Bibian; Martinez-de-Mena, Raquel; Obregon, Maria-Jesus

2012-10-01

Arachidonic acid (AA) is a polyunsaturated fatty acid that stimulates the proliferation of many cellular types. We studied the mitogenic potential of AA in rat brown preadipocytes in culture and the signaling pathways involved. AA is a potent mitogen which induces 4-fold DNA synthesis in brown preadipocytes. The AA mitogenic effect increases by NE addition. AA also increases the mitogenic action of different growth factor combinations. Other unsaturated and saturated fatty acids do not stimulate DNA synthesis to the same extent as AA. We analyzed the role of PKC and MEK/MAPK signaling pathways. PKC inhibition by bisindolilmaleimide I (BIS) abolishes AA and phorbol ester stimulation of DNA synthesis and reduces the mitogenic activity of different growth factors in brown preadipocytes. Brown preadipocytes in culture express PKC α, δ, ε and ζ isoforms. Pretreatment with high doses of the phorbol ester PDBu, induces downregulation of PKCs ε and δ and reproduces the effect of BIS indicating that AA-dependent induction of DNA synthesis requires PKC activity. AA also activates MEK/MAPK pathway and the inhibition of MEK activity inhibits AA stimulation of DNA synthesis and brown adipocyte proliferation. Inhibition of PKC δ by rottlerin abolishes AA-dependent stimulation of DNA synthesis and MAPK activation, whereas PKC ε inhibition does not produce any effect. In conclusion, our results identify AA as a potent mitogen for brown adipocytes and demonstrate the involvement of the PDBu-sensitive PKC δ isoform and MEK/MAPK pathway in AA-induced proliferation of brown adipocytes. Increased proliferative activity might increase the thermogenic capacity of brown fat. Copyright © 2012 Elsevier B.V. All rights reserved.

Functional characterisation of a SNP in the ABCC11 allele - effects on axillary skin metabolism, odour generation and associated behaviours.

PubMed

Harker, Mark; Carvell, Ann-Marie; Marti, Vernon P J; Riazanskaia, Svetlana; Kelso, Hailey; Taylor, David; Grimshaw, Sally; Arnold, David S; Zillmer, Ruediger; Shaw, Jane; Kirk, Jayne M; Alcasid, Zee M; Gonzales-Tanon, Sheila; Chan, Gertrude P; Rosing, Egge A E; Smith, Adrian M

2014-01-01

A single nucleotide polymorphism (SNP), 538G→A, leading to a G180R substitution in the ABCC11 gene results in reduced concentrations of apocrine derived axillary odour precursors. Determine the axillary odour levels in the SNP ABCC11 genotype variants and to investigate if other parameters associated with odour production are affected. Axillary odour was assessed by subjective quantification and gas chromatography headspace analysis. Metabolite profiles, microbiome diversity and personal hygiene habits were also assessed. Axillary odour in the A/A homozygotes was significantly lower compared to the G/A and G/G genotypes. However, the perception-based measures still detected appreciable levels of axillary odour in the A/A subjects. Metabolomic analysis highlighted significant differences in axillary skin metabolites between A/A subjects compared to those carrying the G allele. These differences resulted in A/A subjects lacking specific volatile odourants in the axillary headspace, but all genotypes produced odoriferous short chain fatty acids. Microbiomic analysis revealed differences in the relative abundance of key bacterial genera associated with odour generation between the different genotypes. Deodorant usage indicated a high level of self awareness of axillary odour levels with A/A individuals less likely to adopt personal hygiene habits designed to eradicate/mask its presence. The SNP in the ABCC11 gene results in lower levels of axillary odour in the A/A homozygotes compared to those carrying the G allele, but A/A subjects still produce noticeable amounts of axillary odour. Differences in axillary skin metabolites, bacterial genera and personal hygiene behaviours also appear to be influenced by this SNP. Copyright © 2013. Published by Elsevier Ireland Ltd.

In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.

PubMed

Maes, Michael; Mihaylova, Ivana; Leunis, Jean-Claude

2005-12-01

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.

Strain of Escherichia coli with a temperature-sensitive mutation affecting ribosomal ribonucleic acid accumulation.

PubMed Central

Frey, T; Newlin, L L; Atherly, A G

1975-01-01

A mutant of Escherichia coli has been isolated that has a temperature-sensitive mutation that results in specific loss of ribosomal ribonucleic acid (RNA) synthesis and some reduction in messenger RNA synthesis. When the strain was grown in glucose medium at a restrictive temperature, RNA accumulation ceased, but both messenger RNA and protein synthesis continued for an extended time. Because carbon metabolism was slowed drastically when strain AA-157 was placed at the restrictive temperature, this phenotype can be compared with carbon depletion conditions present during diauxic lag. However, the phenotype of mutant AA-157 differs from shift-down conditions in that guanosine-3',5'-tetraphosphate levels are unaffected; therefore, a different site is affected. This mutant strain (AA-157) thus shows many characteristics similar to an aldolase mutant previously reported (Böck and Neidhardt, 1966). However, the mutation occurred in a different position on the E. coli genetic map, and furthermore, aldolase was not temperature sensitive in strain AA-157. In this paper we present a study of macromolecular biosynthesis in this mutant. PMID:1090609

Deletion of Monoglyceride Lipase in Astrocytes Attenuates Lipopolysaccharide-induced Neuroinflammation*

PubMed Central

Grabner, Gernot F.; Eichmann, Thomas O.; Wagner, Bernhard; Gao, Yuanqing; Farzi, Aitak; Taschler, Ulrike; Radner, Franz P. W.; Schweiger, Martina; Lass, Achim; Holzer, Peter; Zinser, Erwin; Tschöp, Matthias H.; Yi, Chun-Xia; Zimmermann, Robert

2016-01-01

Monoglyceride lipase (MGL) is required for efficient hydrolysis of the endocannabinoid 2-arachidonoylglyerol (2-AG) in the brain generating arachidonic acid (AA) and glycerol. This metabolic function makes MGL an interesting target for the treatment of neuroinflammation, since 2-AG exhibits anti-inflammatory properties and AA is a precursor for pro-inflammatory prostaglandins. Astrocytes are an important source of AA and 2-AG, and highly express MGL. In the present study, we dissected the distinct contribution of MGL in astrocytes on brain 2-AG and AA metabolism by generating a mouse model with genetic deletion of MGL specifically in astrocytes (MKOGFAP). MKOGFAP mice exhibit moderately increased 2-AG and reduced AA levels in brain. Minor accumulation of 2-AG in the brain of MKOGFAP mice does not cause cannabinoid receptor desensitization as previously observed in mice globally lacking MGL. Importantly, MKOGFAP mice exhibit reduced brain prostaglandin E2 and pro-inflammatory cytokine levels upon peripheral lipopolysaccharide (LPS) administration. These observations indicate that MGL-mediated degradation of 2-AG in astrocytes provides AA for prostaglandin synthesis promoting LPS-induced neuroinflammation. The beneficial effect of astrocyte-specific MGL-deficiency is not fully abrogated by the inverse cannabinoid receptor 1 agonist SR141716 (Rimonabant) suggesting that the anti-inflammatory effects are rather caused by reduced prostaglandin synthesis than by activation of cannabinoid receptors. In conclusion, our data demonstrate that MGL in astrocytes is an important regulator of 2-AG levels, AA availability, and neuroinflammation. PMID:26565024

Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study.

PubMed

Stepien, Magdalena; Duarte-Salles, Talita; Fedirko, Veronika; Floegel, Anne; Barupal, Dinesh Kumar; Rinaldi, Sabina; Achaintre, David; Assi, Nada; Tjønneland, Anne; Overvad, Kim; Bastide, Nadia; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Saieva, Calogero; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Gavrila, Diana; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Sund, Malin; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Schmidt, Julie A; Gunter, Marc; Cross, Amanda; Vineis, Paolo; Romieu, Isabelle; Scalbert, Augustin; Jenab, Mazda

2016-01-15

Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development. © 2015 UICC.

Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Yuting; Zhou, Lubing; Gunnet, Joseph W.

2006-06-23

HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A{sub 2} (PLA{sub 2})/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeuticmore » effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca{sup 2+}-mobilization and enhanced bradykinin-promoted Ca{sup 2+}-mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPAR{gamma} agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs.« less

Myosin heavy chain 2A and α-Actin expression in human and murine skeletal muscles at feeding; particularly amino acids

PubMed Central

2012-01-01

Background Protein dynamics during non-steady state conditions as feeding are complex. Such studies usually demand combinations of methods to give conclusive information, particularly on myofibrillar proteins with slow turnover. Therefore, time course transcript analyses were evaluated as possible means to monitor changes in myofibrillar biosynthesis in skeletal muscles in conditions with clinical nutrition; i.e. long term exposure of nutrients. Methods Muscle tissue from overnight intravenously fed surgical patients were used as a model combined with muscle tissue from starved and refed mice as well as cultured L6 muscle cells. Transcripts of acta 1 (α-actin), mhc2A (myosin) and slc38 a2/Snat 2 (amino acid transporter) were quantified (qPCR) as markers of muscle protein dynamics. Results Myosin heavy chain 2A transcripts decreased significantly in skeletal muscle tissue from overnight parenterally fed patients but did not change significantly in orally refed mice. Alpha-actin transcripts did not change significantly in muscle cells from fed patients, mice or cultured L6 cells during provision of AA. The AA transporter Snat 2 decreased in L6 cells refed by all AA and by various combinations of AA but did not change during feeding in muscle tissue from patients or mice. Conclusion Our results confirm that muscle cells are sensitive to alterations in extracellular concentrations of AA for induction of protein synthesis and anabolism. However, transcripts of myofibrillar proteins and amino acid transporters showed complex alterations in response to feeding with provision of amino acids. Therefore, muscle tissue transcript levels of actin and myosin do not reflect protein accretion in skeletal muscles at feeding. PMID:23190566

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

PubMed

Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

2006-12-01

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

A Comprehensive Approach to Assess Feathermeal as an Alternative Protein Source in Aquafeed.

PubMed

Jasour, Mohammad Sedigh; Wagner, Liane; Sundekilde, Ulrik K; Larsen, Bodil K; Greco, Ines; Orlien, Vibeke; Olsen, Karsten; Rasmussen, Hanne T; Hjermitslev, Niels H; Hammershøj, Marianne; Dalsgaard, Anne J T; Dalsgaard, Trine K

2017-12-06

The effect of partially replacing fishmeal in aquafeed with feathermeal (FTH) at three levels (0%: FTH0, 8%: FTH8, 24%: FTH24) and two extrusion temperatures (100 and 130 °C) was evaluated in rainbow trout (Oncorhynchus mykiss) with respect to growth performance, metabolism response, and oxidative status of the feed proteins. Multivariate data analyses revealed that FTH24 correlated positively with high levels of oxidation products, amino acids (AA) racemization, glucogenic AAs level in liver, feed intake (FI), specific growth rate (SGR), and feed conversion ratio (FCR); and low AAs digestibility. Both FI and SGR were significantly increased when 8 and 24% feathermeal was included in the feed extruded at 100 °C, while there was a negative effect on FCR in fish fed FTH24. In conclusion, higher oxidation levels in FTH24 may give rise to metabolic alterations while lower levels of FTH may be considered as fishmeal substitute in aquafeed for rainbow trout.

Antioxidant activity, anti-proliferative activity, and amino acid profiles of ethanolic extracts of edible mushrooms.

PubMed

Panthong, S; Boonsathorn, N; Chuchawankul, S

2016-10-17

Biological activities of various mushrooms have recently been discovered, particularly, immunomodulatory and antitumor activities. Herein, three edible mushrooms, Auricularia auricula-judae (AA), Pleurotus abalonus (PA) and Pleurotus sajor-caju (PS) extracted using Soxhlet ethanol extraction were evaluated for their antioxidative, anti-proliferative effects on leukemia cells. Using the Folin-Ciocalteau method and Trolox equivalent antioxidant capacity assay, phenolics and antioxidant activity were found in all sample mushrooms. Additionally, anti-proliferative activity of mushroom extracts against U937 leukemia cells was determined using a viability assay based on mitochondrial activity. PA (0.5 mg/mL) and AA (0.25-0.5 mg/mL) significantly reduced cell viability. Interestingly, PS caused a hormetic-like biphasic dose-response. Low doses (0-0.25 mg/L) of PS promoted cell proliferation up to 140% relative to control, whereas higher doses (0.50 mg/mL) inhibited cell proliferation. Against U937 cells, AA IC 50 was 0.28 ± 0.04 mg/mL, which was lower than PS or PA IC 50 (0.45 ± 0.01 and 0.49 ± 0.001 mg/mL, respectively). Furthermore, lactate dehydrogenase (LDH) leakage conferred cytotoxicity. PS and PA were not toxic to U937 cells at any tested concentration; AA (0.50 mg/mL) showed high LDH levels and caused 50% cytotoxicity. Additionally, UPLC-HRMS data indicated several phytochemicals known to support functional activities as either antioxidant or anti-proliferative. Glutamic acid was uniquely found in ethanolic extracts of AA, and was considered an anti-cancer amino acid with potent anti-proliferative effects on U937 cells. Collectively, all mushroom extracts exhibited antioxidant effects, but their anti-proliferative effects were dose-dependent. Nevertheless, the AA extract, with highest potency, is a promising candidate for future applications.

Ascorbic acid supplementation does not alter oxidative stress markers in healthy volunteers engaged in a supervised exercise program.

PubMed

Bunpo, Piyawan; Anthony, Tracy G

2016-02-01

The purpose of this study was to investigate the impact of ascorbic acid (AA) consumption on the oxidative stress status of untrained volunteers participating in a supervised exercise program. The study included 46 young adults (average age, 23.5 ± 0.59 years; 37 females, 9 males) who remained sedentary (n = 16) or participated in 30 min of outdoor aerobic running (n = 30) at an intensity corresponding to 65%-75% of maximum heart rate for 3 times per week for 12 weeks. Exercised subjects were randomly assigned to an exercise group without AA supplementation (control; n = 10) or received either 250 mg (n = 10) or 500 mg (n = 10) of AA supplementation previous to each exercise session. Blood samples were taken on day 0 and day 84 to evaluate metabolic profiles and antioxidant status. Sedentary subjects underwent in a single bout of aerobic running to determine total antioxidant status (TAS) and malondiadehyde (MDA) at pre- and postexercise with or without AA supplementation. No significant change in TAS was observed. Plasma MDA significantly increased at postexercise (P < 0.05), and AA supplementation decreased MDA level significantly (P < 0.05). After 3 months of exercise, there was no significant change in blood glucose, lipid profile, MDA, TAS, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities amongst groups. Supplementation of AA was associated with minor and inconsistent reductions in SOD, GPx, and catalase activities (P < 0.05). These findings indicate that pre-exercise supplementation of ascorbic acid does not alter oxidative stress markers in the plasma and erythrocytes of young adults engaged in a supervised exercise program.

Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder.

PubMed

McNamara, Robert K; Welge, Jeffrey A

2016-05-01

Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biomarker monitoring of controlled dietary acrylamide exposure indicates consistent human endogenous background.

PubMed

Goempel, Katharina; Tedsen, Laura; Ruenz, Meike; Bakuradze, Tamara; Schipp, Dorothea; Galan, Jens; Eisenbrand, Gerhard; Richling, Elke

2017-11-01

The aim of the present study was to explore the relation of controlled dietary acrylamide (AA) intake with the excretion of AA-related urinary mercapturic acids (MA), N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Excretion kinetics of these short-term exposure biomarkers were monitored under strictly controlled conditions within a duplicate diet human intervention study. One study arm (group A, n = 6) ingested AA via coffee (0.15-0.17 µg/kg bw) on day 6 and in a meal containing an upper exposure level of AA (14.1-15.9 μg/kg bw) on day 10. The other arm (group B) was on AA minimized diet (washout, 0.05-0.06 µg/kg bw) throughout the whole 13-day study period. On day 6, these volunteers ingested 13 C 3 D 3 -AA (1 μg/kg bw). In both arms, urinary MA excretion was continuously monitored and blood samples were taken to determine hemoglobin adducts. Ingestion of four cups of coffee resulted in a slightly enhanced short-term biomarker response within the background range of group B. At the end of the 13-day washout period, group B excreted an AAMA baseline level of 0.14 ± 0.10 µmol/d although AA intake was only about 0.06 µmol/d. This sustained over-proportional AAMA background suggested an endogenous AA baseline exposure level of 0.3-0.4 µg/kg bw/d. The excretion of 13 C 3 D 3 -AA was practically complete within 72-96 h which rules out delayed release of AA (or any other MA precursor) from deep body compartments. The results provide compelling support for the hypothesis of a sustained endogenous AA formation in the human body.

Investigation into the plasma concentration of ω3 polyunsaturated fatty acids in Japanese attention-deficit hyperactivity disorder patients.

PubMed

Yonezawa, Ken; Nonaka, Shunsuke; Iwakura, Yuka; Kusano, Yuka; Funamoto, Yuko; Kanchi, Nobukazu; Yamaguchi, Naohiro; Kusumoto, Yuko; Imamura, Akira; Ozawa, Hiroki

2018-06-20

Several studies report that patients with attention-deficit hyperactivity disorder (ADHD) have a low plasma concentration of polyunsaturated fatty acids (PUFAs). Since fish intake varies among countries and is high in Japan, those results may not apply to Japanese patients with ADHD. However, there is currently not enough evidence to support this. We compared the plasma PUFAs levels of patients with ADHD with the standard reference levels for healthy subjects, and examined the relationship between those PUFAs levels and the subject's psychological evaluation. The subjects were 24 patients (age < 20 years) previously diagnosed with ADHD (according to the DSM-IV-TR criteria) at the psychiatric department of the Nagasaki University Hospital, between November 2010 and November 2015. The plasma concentrations of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) were measured using gas chromatography. Data pertaining to global assessment of functioning (GAF), clinical global impressions, ADHD Rating Scale-IV, and the drug used for treatment (atomoxetine or methylphenidate) were obtained from the medical records. The plasma concentrations of DHA, EPA, and EPA/AA were significantly lower than the normal reference range, indicating that ADHD patients present an imbalance in PUFAs levels. This trend is similar to ADHD patients in other countries and replacement therapy in Japanese ADHD patients may be useful.

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids.

PubMed

Nickling, Jessica H; Baumann, Tobias; Schmitt, Franz-Josef; Bartholomae, Maike; Kuipers, Oscar P; Friedrich, Thomas; Budisa, Nediljko

2018-05-04

Nature has a variety of possibilities to create new protein functions by modifying the sequence of the individual amino acid building blocks. However, all variations are based on the 20 canonical amino acids (cAAs). As a way to introduce additional physicochemical properties into polypeptides, the incorporation of non-canonical amino acids (ncAAs) is increasingly used in protein engineering. Due to their relatively short length, the modification of ribosomally synthesized and post-translationally modified peptides by ncAAs is particularly attractive. New functionalities and chemical handles can be generated by specific modifications of individual residues. The selective pressure incorporation (SPI) method utilizes auxotrophic host strains that are deprived of an essential amino acid in chemically defined growth media. Several structurally and chemically similar amino acid analogs can then be activated by the corresponding aminoacyl-tRNA synthetase and provide residue-specific cAA(s) → ncAA(s) substitutions in the target peptide or protein sequence. Although, in the context of the SPI method, ncAAs are also incorporated into the host proteome during the phase of recombinant gene expression, the majority of the cell's resources are assigned to the expression of the target gene. This enables efficient residue-specific incorporation of ncAAs often accompanied with high amounts of modified target. The presented work describes the in vivo incorporation of six proline analogs into the antimicrobial peptide nisin, a lantibiotic naturally produced by Lactococcus lactis. Antimicrobial properties of nisin can be changed and further expanded during its fermentation and expression in auxotrophic Escherichia coli strains in defined growth media. Thereby, the effects of residue-specific replacement of cAAs with ncAAs can deliver changes in antimicrobial activity and specificity. Antimicrobial activity assays and fluorescence microscopy are used to test the new nisin variants for growth inhibition of a Gram-positive Lactococcus lactis indicator strain. Mass spectroscopy is used to confirm ncAA incorporation in bioactive nisin variants.

Brassinosteroids Improve Quality of Summer Tea (Camellia sinensis L.) by Balancing Biosynthesis of Polyphenols and Amino Acids.

PubMed

Li, Xin; Ahammed, Golam J; Li, Zhi-Xin; Zhang, Lan; Wei, Ji-Peng; Shen, Chen; Yan, Peng; Zhang, Li-Ping; Han, Wen-Yan

2016-01-01

Summer grown green tea is less popular due to bitterness and high astringency, which are attributed to high levels of tea polyphenols (TP) and low levels of amino acids (AA) in tea leaves (Camellia sinensis L.). Brassinosteroids (BRs), a group of steroidal plant hormones can regulate primary and secondary metabolism in a range of plant species under both normal and stress conditions. However, specific effects of BRs on the photosynthesis of tea plants and the quality of summer green tea are largely unknown. Here we show that 24-epibrassinolide (EBR), a bioactive BR, promoted photosynthesis in tea plants in a concentration-dependent manner. Stimulation in photosynthesis by EBR resulted in an increased summer tea yield. Although all tested concentrations (0.01, 0.05, 0.1, 0.5, and 1.0 ppm) of EBR increased concentrations of TP and AA, a moderate concentration (0.5 ppm) caused the highest decrease in TP to AA ratio, an important feature of quality tea. Time-course analysis using 0.5 ppm EBR as foliar spray revealed that TP or AA concentration increased as early as 3 h after EBR application, reaching the highest peak at 24 h and that remained more or less stable. Importantly, such changes in TP and AA concentration by EBR resulted in a remarkably decreased but stable TP to AA ratio at 24 h and onward. Furthermore, concentrations of catechins and theanine increased, while that of caffeine remained unaltered following treatment with EBR. EBR improved activity of phenylalanine ammonia-lyase (PAL) and glutamine: 2-oxoglutarate aminotransferase (GOGAT) enzymes involved in catechins and theanine biosynthesis, respectively. Transcript analysis revealed that transcript levels of CsPAL and CsGS peaked as early as 6 h, while that of CsGOGAT peaked at 12 h following application of EBR, implying that EBR increased the concentration of TP and AA by inducing their biosynthesis. These results suggest a positive role of BR in enhancing green tea quality, which might have potential implication in improving quality of summer tea.

Brassinosteroids Improve Quality of Summer Tea (Camellia sinensis L.) by Balancing Biosynthesis of Polyphenols and Amino Acids

PubMed Central

Li, Xin; Ahammed, Golam J.; Li, Zhi-Xin; Zhang, Lan; Wei, Ji-Peng; Shen, Chen; Yan, Peng; Zhang, Li-Ping; Han, Wen-Yan

2016-01-01

Summer grown green tea is less popular due to bitterness and high astringency, which are attributed to high levels of tea polyphenols (TP) and low levels of amino acids (AA) in tea leaves (Camellia sinensis L.). Brassinosteroids (BRs), a group of steroidal plant hormones can regulate primary and secondary metabolism in a range of plant species under both normal and stress conditions. However, specific effects of BRs on the photosynthesis of tea plants and the quality of summer green tea are largely unknown. Here we show that 24-epibrassinolide (EBR), a bioactive BR, promoted photosynthesis in tea plants in a concentration-dependent manner. Stimulation in photosynthesis by EBR resulted in an increased summer tea yield. Although all tested concentrations (0.01, 0.05, 0.1, 0.5, and 1.0 ppm) of EBR increased concentrations of TP and AA, a moderate concentration (0.5 ppm) caused the highest decrease in TP to AA ratio, an important feature of quality tea. Time-course analysis using 0.5 ppm EBR as foliar spray revealed that TP or AA concentration increased as early as 3 h after EBR application, reaching the highest peak at 24 h and that remained more or less stable. Importantly, such changes in TP and AA concentration by EBR resulted in a remarkably decreased but stable TP to AA ratio at 24 h and onward. Furthermore, concentrations of catechins and theanine increased, while that of caffeine remained unaltered following treatment with EBR. EBR improved activity of phenylalanine ammonia-lyase (PAL) and glutamine: 2-oxoglutarate aminotransferase (GOGAT) enzymes involved in catechins and theanine biosynthesis, respectively. Transcript analysis revealed that transcript levels of CsPAL and CsGS peaked as early as 6 h, while that of CsGOGAT peaked at 12 h following application of EBR, implying that EBR increased the concentration of TP and AA by inducing their biosynthesis. These results suggest a positive role of BR in enhancing green tea quality, which might have potential implication in improving quality of summer tea. PMID:27625668

Arachidonic Acid Enhances Reproduction in Daphnia magna and Mitigates Changes in Sex Ratios Induced by Pyriproxyfen

PubMed Central

Ginjupalli, Gautam K.; Gerard, Patrick D.; Baldwin, William S.

2016-01-01

Arachidonic acid (AA) is one of only two unsaturated fatty acids retained in the ovaries of crustaceans, and an inhibitor of HR97g, a nuclear receptor expressed in adult ovaries. We hypothesized that as a key fatty acid, AA may be associated with reproduction and potentially environmental sex determination in Daphnia. Reproduction assays with AA indicate that it alters female/male sex ratios by increasing female production. This reproductive effect only occurred during a restricted P. subcapitata diet. Next, we tested whether enriching a poorer algal diet (C. vulgaris) with AA enhances overall reproduction and sex ratios. AA enrichment of a C. vulgaris diet also enhances fecundity at 1.0 and 4.0μM by 30–40% in the presence and absence of pyriproxyfen. This indicates that AA is crucial in reproduction regardless of environmental sex determination. Furthermore, our data indicates that P. subcapitata may provide a threshold concentration of AA needed for reproduction. Diet switch experiments from P. subcapitata to C. vulgaris mitigate some but not all of AA’s effects when compared to a C. vulgaris only diet, suggesting that some AA provided by P. subcapitata is retained. In summary, AA supplementation increases reproduction and represses pyriproxyfen-induced environmental sex determination in D. magna in restricted diets. A diet rich in AA may provide protection from some reproductive toxicants such as the juvenile hormone agonist, pyriproxyfen. PMID:25393616

Arachidonic and oleic acid exert distinct effects on the DNA methylome

PubMed Central

Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda; Vaquero, Alejandro; Esteller, Manel; Carmona, F. Javier; Moran, Sebastian; Nielsen, Finn C.; Wickström-Lindholm, Marie; Wrobel, Katarzyna; Wrobel, Kazimierz; Barbosa-Sabanero, Gloria; Zaina, Silvio; Lund, Gertrud

2016-01-01

ABSTRACT Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic (AA) or oleic acid (OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP-1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated in mouse embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hypermethylation and hypomethylation in the 1–200 μM range, respectively, with a maximal differential response at the 100 μM dose. The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA-induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity, and autism, but relatively dissimilar from OA-induced profiles. Furthermore, human atherosclerosis grade-associated DNA methylation profiles were significantly enriched in AA-induced profiles. Biochemical evidence pointed to β-oxidation, PPAR-α, and sirtuin 1 as important mediators of AA-induced DNA methylation changes. In conclusion, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases, supports and expands current diet-based therapeutic and preventive efforts. PMID:27088456

Kolaviron and L-Ascorbic Acid Attenuate Chlorambucil-Induced Testicular Oxidative Stress in Rats

PubMed Central

2014-01-01

Chlorambucil (4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid) is an alkylating agent, indicated in chronic lymphocytic leukaemia. Kolaviron (KV), a biflavonoid complex from Garcinia kola, and L-ascorbic acid (AA) are known to protect against oxidative damage in vivo. This study evaluates the protective capacity of KV and AA on chlorambucil-induced oxidative stress in the testes of rat. Twenty male Wistar rats (180–200 g) were randomized into four groups: I: control, II: chlorambucil (0.2 mg/kg b.w.), III: 0.2 mg/kg chlorambucil and 100 mg/kg KV, and IV: 0.2 mg/kg chlorambucil and 100 mg/kg AA. After 14 days of treatments, results indicated that chlorambucil caused significant reduction (P < 0.05) in testicular vitamin C and glutathione by 32% and 39%, respectively, relative to control. Similarly, activities of testicular GST, SOD, and CAT reduced significantly by 48%, 47%, and 49%, respectively, in chlorambucil-treated rats relative to control. Testicular MDA and activities of ALP, LDH, and ACP were increased significantly by 53%, 51%, 64%, and 70%, respectively, in the chlorambucil-treated rat. However, cotreatment with KV and AA offered protection and restored the levels of vitamin C, GSH, and MDA as well as SOD, CAT, GST, ACP, ALP, and LDH activities. Overall, kolaviron and L-ascorbic acid protected against chlorambucil-induced damage in the testes of the rat. PMID:25309592

Nutritional status survey of aplastic anemia patients--a single center experience in China.

PubMed

Li, Xinli; Feng, Yanyan; Wang, Hongyan; Song, Meijuan; Jin, Jingjing; Cui, Zhenzhu; Zheng, Yizhou

2016-05-01

To analyze the nutritional status of aplastic anemia (AA) patients. The nutrition-related anthropometric indicators and blood biochemical index of 622 newly-diagnosed AA patients were retrospectively analyzed. Of the cohort of AA patients, body mass index of non-severe AA (NSAA) patients were higher than those of severe AA (SAA) (p<0.05). The serum total protein and albumin protein levels of SAA patients differed from those of NSAA, and lower hemoglobin was correlated with lower serum albumin protein concentration (p<0.01). The concentration of B vitamins (folic acid and vitamin B12) of urban patients significantly differed from rural ones (P<0.01). Of the 97 cases of iron overload (15.6% of the entire patient group), the iron overload rate of SAA patients (19.1%) was much higher than that of NSAA (8.1%). AA patients exhibited malnutrition conditions; it would be helpful to conduct individualized dietary guidance and health education for patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

PubMed Central

Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.

2017-01-01

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877

Atomic Absorption Spectroscopy of Calcium in Foodstuffs in Non-Science-Major Courses

NASA Astrophysics Data System (ADS)

Kostecka, Keith S.

2000-10-01

Non-science-major students at Columbia College-Chicago are introduced to the concept of ppm, prepare AAS standard solutions, digest foodstuffs in nitric acid, conduct AAS analysis for Ca, determine mass percentage of calcium in the sample, and check calcium levels in various food items on the Internet with a critical eye. Students work cooperatively in a setting that allows them to see how wet chemistry and understandable use of instrumental methods can be linked together. Overall response to this activity has been favorable and continues to spawn new projects dealing with the AAS analysis of metals in hair, vitamins, and additional foods.

Uptake and conversion of D-amino acids in Arabidopsis thaliana.

PubMed

Gördes, Dirk; Kolukisaoglu, Üner; Thurow, Kerstin

2011-02-01

The D-enantiomers of proteinogenic amino acids fulfill essential functions in bacteria, fungi and animals. Just in the plant kingdom, the metabolism and role of D-amino acids (D-AAs) still remains unclear, although plants have to cope with significant amounts of these compounds from microbial decay in the rhizosphere. To fill this gap of knowledge, we tested the inhibitory effects of D-AAs on plant growth and established a method to quantitate 16 out of 19 proteinogenic amino acids and their D-enantiomers in plant tissue extracts. Therefore, the amino acids in the extracts were derivatized with Marfey's reagent and separated by HPLC-MS. We used two ecotypes (Col-0 and C24) and a mutant (lht1) of the model plant Arabidopsis thaliana to determine the influence and fate of exogenously applied D-AAs. All of them were found in high concentrations in the plant extracts after application, even in lht1, which points to additional transporters facilitating the import of D-AAs. The addition of particular amino acids (D-Trp, D-Phe, D-Met and D-His) led to the accumulation of the corresponding L-amino acid. In almost all cases, the application of a D-AA resulted in the accumulation of D-Ala and D-Glu. The presented results indicate that soil borne D-AAs can actively be taken up and metabolized via central metabolic routes.

Ethylene signaling triggered by low concentrations of ascorbic acid regulates biomass accumulation in Arabidopsis thaliana.

PubMed

Caviglia, M; Mazorra Morales, L M; Concellón, A; Gergoff Grozeff, G E; Wilson, M; Foyer, C H; Bartoli, C G

2018-02-02

Ascorbic acid (AA) is a major redox buffer in plant cells. The role of ethylene in the redox signaling pathways that influence photosynthesis and growth was explored in two independent AA deficient Arabidopsis thaliana mutants (vtc2-1 and vtc2-4). Both mutants, which are defective in the AA biosynthesis gene GDP-L-galactose phosphorylase, produce higher amounts of ethylene than wt plants. In contrast to the wt, the inhibition of ethylene signaling increased leaf conductance, photosynthesis and dry weight in both vtc2 mutant lines. The AA-deficient mutants showed altered expression of genes encoding proteins involved in the synthesis/responses to phytohormones that control growth, particularly auxin, cytokinins, abscisic acid, brassinosterioids, ethylene and salicylic acid. These results demonstrate that AA deficiency modifies hormone signaling in plants, redox-ethylene interactions providing a regulatory node controlling shoot biomass accumulation. Copyright © 2018 Elsevier Inc. All rights reserved.

Dietary protein reduction on microbial protein, amino acid digestibility, and body retention in beef cattle: 2. Amino acid intestinal absorption and their efficiency for whole-body deposition.

PubMed

Mariz, L D S; Amaral, P M; Valadares Filho, S C; Santos, S A; Detmann, E; Marcondes, M I; Pereira, J M V; Silva Júnior, J M; Prados, L F; Faciola, A P

2018-03-06

The objective of this study was to determine the apparent and true intestinal digestibility of total and individual AA, and to estimate the efficiency of whole-body AA retention from individual and total absorbed AA. Four Nellore animals (241.3 kg initial BW) and four crossbred Angus × Nellore (263.4 kg initial BW) cannulated in rumen and ileum were randomly allocated in two 4 × 4 Latin squares. The experiment lasted four 17 d periods, with 10 d for adaptation to diets and another 7 d for data collection. The diets consisted of increasing CP levels: 100, 120, or 140 g/kg of DM offered ad libitum, and restricted intake diet with 120 g CP/kg DM (experiment 1). In experiment 2, forty-four bulls (22 Nellore and 22 crossbred F1 Angus × Nellore) with 8 months and initial shrunk BW 215.0 ± 15.0 kg (Nellore = 208.0 ± 12.78 kg; Angus × Nellore = 221.9 ± 14.16 kg) were used. Eight of those animals were slaughtered at the beginning of the experiment. The remaining 36 bulls were allocated in a completely randomized design with six replicates, in a 2 (genetic groups) × 3 (CP contents) factorial scheme. The amount of essential AA (EAA) and nonessential AA (NEAA) reaching the small intestine increased linearly (P < 0.05) in response to CP content. The apparent digestibility of EAA was not affected (P > 0.05) by CP content, with exception for histidine (P = 0.07, linear effect), leucine (P = 0.01, linear effect), and methionine (P = 0.05, linear effect). Differences existed among AA when compared the apparent digestibility of NEAA. The apparent digestibility of alanine (P = 0.05), aspartic acid (P = 0.07), glutamic acid (P = 0.02), glycine (P = 0.05), proline (P = 0.02), and serine (P = 0.04) responded quadratically to CP content increase. However, the apparent digestibility of cystine and tyrosine was not affected (P > 0.05) by increasing dietary CP. The true intestinal digestibilities of total, essential, nonessential AA, lysine, and methionine were 75.0%, 77.0%, 74.0%, 77.0%, and 86%, respectively. The true intestinal digestibility of total microbial AA was 80%. The efficiency of utilization of total AA for whole-body protein deposition was 40%. The efficiency of utilization of lysine and methionine was 37% and 58%, respectively. It was concluded that the AA flow to the omasum increases in response to dietary CP content. In addition, there are differences among AA in the efficiency that they are used by beef cattle.

Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.; Chen, Y.; Tjandrawinata, R. R.

2001-01-01

It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells.

PubMed

Hughes-Fulford, M; Chen, Y; Tjandrawinata, R R

2001-05-01

It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Amino acid adsorption on anatase (101) surface at vacuum and aqueous solution: a density functional study.

PubMed

Liu, Liuxie; Li, Kai; Chen, Xiao; Liang, Xiaoqin; Zheng, Yan; Li, Laicai

2018-03-29

The adsorption of 20 amino acids (AAs) on the (101) surface of anatase titanium dioxide (TiO 2 ) has been investigated under the scheme of density functional theory. Through the analysis of adsorption geometries, amino group and side chains of AAs have been identified as the major side to adsorb on TiO 2 , while the carboxyl group prefers to stay outside to avoid the repulsion between negatively charged oxygen from TiO 2 and AAs. On the surface, two-coordinated oxygen is the major site to stabilize AAs through O-H interactions. The above conclusion does not change when it is in the aqueous solution based on the calculations with AAs surrounded by explicit water molecules. The above knowledge is helpful in predicting how AAs and even peptides adsorb on inorganic materials. Graphical abstract The adsorption of 20 amino acids (AAs) on the (101) surface of anatase titanium dioxide (TiO 2 ) has been investigated under the scheme of density functional theory.

Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall And Brent REvisited) Study.

PubMed

Tillin, Therese; Hughes, Alun D; Wang, Qin; Würtz, Peter; Ala-Korpela, Mika; Sattar, Naveed; Forouhi, Nita G; Godsland, Ian F; Eastwood, Sophie V; McKeigue, Paul M; Chaturvedi, Nish

2015-05-01

South Asian individuals have an increased risk of diabetes compared with Europeans that is unexplained by obesity and traditional or established metabolic measures. Circulating amino acids (AAs) may provide additional explanatory insights. In a unique cohort of European and South Asian men, we compared cross-sectional associations between AAs, metabolic and obesity traits, and longitudinal associations with incident diabetes. Nuclear magnetic spectroscopy was used to measure the baseline (1988-1991) levels of nine AAs in serum samples from a British population-based cohort of 1,279 European and 1,007 South Asian non-diabetic men aged 40-69 years. Follow-up was complete for 19 years in 801 European and 643 South Asian participants. The serum concentrations of isoleucine, phenylalanine, tyrosine and alanine were significantly higher in South Asian men, while cross-sectional correlations of AAs with glycaemia and insulin resistance were similar in the two ethnic groups. However, most AAs were less strongly correlated with measures of obesity in the South Asian participants. Diabetes developed in 227 (35%) South Asian and 113 (14%) European men. Stronger adverse associations were observed between branched chain and aromatic AAs and incident diabetes in South Asian men. Tyrosine was a particularly strong predictor of incident diabetes in South Asian individuals, even after adjustment for metabolic risk factors, including obesity and insulin resistance (adjusted OR for a 1 SD increment, 1.47, 95% CI 1.17,1.85, p = 0.001) compared with Europeans (OR 1.10, 0.87, 1.39, p = 0.4; p = 0.045 for ethnicity × tyrosine interaction). Branched chain and aromatic AAs, particularly tyrosine, may be a focus for identifying novel aetiological mechanisms and potential treatment targets for diabetes in South Asian populations and may contribute to their excess risk of diabetes.

Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated.

PubMed

Suryawan, Agus; Orellana, Renan A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Fleming, Jillian R; Davis, Teresa A

2007-12-01

Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight-fasted 6- (n = 4/group) and 26-day-old (n = 6/ group) pigs were studied during 1) euinsulinemic-euglycemiceuaminoacidemic conditions (controls), 2) euinsulinemic-euglycemichyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), and these responses were higher in 6-day-old compared with 26-day-old pigs. Both INS and AA decreased the binding of 4E-BP1 to eIF4E and increased eIF4E binding to eIF4G; these effects were greater in 6-day-old than in 26-day-old pigs. Neither INS nor AA altered the composition of mTORC1 (raptor, mTOR, and GbetaL) or mTORC2 (rictor, mTOR, and GbetaL) complexes. Furthermore, neither INS, AA, nor age had any effect on the abundance of Rheb and the phosphorylation of AMP-activated protein kinase and eukaryotic elongation factor 2. Our results suggest that the activation by insulin and amino acids of signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs.

Injectable biocompatible and biodegradable pH-responsive hollow particle gels containing poly(acrylic acid): the effect of copolymer composition on gel properties.

PubMed

Halacheva, Silvia S; Adlam, Daman J; Hendow, Eseelle K; Freemont, Tony J; Hoyland, Judith; Saunders, Brian R

2014-05-12

The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.

Effect of insulin sensitizer therapy on amino acids and their metabolites.

PubMed

Irving, Brian A; Carter, Rickey E; Soop, Mattias; Weymiller, Audrey; Syed, Husnain; Karakelides, Helen; Bhagra, Sumit; Short, Kevin R; Tatpati, Laura; Barazzoni, Rocco; Nair, K Sreekumaran

2015-06-01

Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg twice per day, N=12 participants) or placebo (N=13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of aristolochic acids by high-performance liquid chromatography with fluorescence detection.

PubMed

Wang, Yinan; Chan, Wan

2014-06-25

Nephrotoxic and carcinogenic aristolochic acids (AAs) are naturally occurring nitrophenanthrene carboxylic acids in the herbal genus Aristolochia. The misuse of AA-containing herbs in preparing slimming drugs has caused hundred of cases of kidney disease in Belgium women in a slimming regime in the early 1990s. Accumulating evidence also suggested that prolong dietary intake of AA-contaminated food is one of the major causes to the Balkan endemic nephropathy that was first observed in the late 1950s. Therefore, analytical methods of high sensitivity are extremely important for safeguarding human exposure to AA-containing herbal medicines, herbal remedies, and food composites. In this paper, we describe the development of a new high-performance liquid chromatography coupled fluorescence detector (HPLC-FLD) method for the sensitive determination of AAs. The method makes use of a novel cysteine-induced denitration reaction that "turns on" the fluorescence of AAs for fluorometric detections. Our results showed that the combination of cysteine-induced denitration and HPLC-FLD analysis allows for sensitive quantification of AA-I and AA-II at detection limits of 27.1 and 25.4 ng/g, respectively. The method was validated and has been successfully applied in quantifying AAs in Chinese herbal medicines.

Effects of unsaturated fatty acids on the kinetics of voltage‐gated proton channels heterologously expressed in cultured cells

PubMed Central

Kawanabe, Akira

2016-01-01

Key points Arachidonic acid (AA) greatly enhances the activity of the voltage‐gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear.In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells.The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage‐dependence of activation.Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms.Application of phospholipase A2, which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Abstract Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage‐gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside‐out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current–voltage relationship. In monomeric channels lacking the coiled‐coil region of the channel protein, the shift in the current–voltage relationship was diminished but activation and deactivation remained accelerated. Studies with several AA derivatives showed that double bonds and hydrophilic head groups are essential for the effect of AA, although charge was not important. The application of phospholipase A2 (PLA2), which generates AA from cell membrane phospholipids, stimulated mHv1 activity to a similar extent as direct application of ∼20 μm AA, suggesting that endogenous AA may regulate Hv channel activity. PMID:26563684

Amino acid supplementation of calf milk replacers containing plasma protein.

PubMed

Morrison, S Y; Campbell, J M; Drackley, J K

2017-06-01

We determined the effects of calf milk replacers containing 0, 5, or 10% bovine plasma protein (PP), either without or with the supplemental amino acids (AA) Ile and Thr, on growth and health of male Holstein calves (n = 104) for 56 d. Milk replacers were formulated to contain 22% crude protein (CP), 20% fat, and 2.0% Lys. Milk replacers (12.5% solids) were fed at a rate of 1.5% of body weight (BW) on a dry matter basis during wk 1 and 1.75% of BW beginning on d 8. Starter was introduced on d 36 so that effects of PP and AA balance in milk replacers could be isolated. Intake, respiratory scores, and fecal scores were measured daily. Body weight and stature were measured weekly and blood serum samples were obtained during wk 4. Treatments had no effects on intakes of dry matter, CP, or metabolizable energy. During wk 6 and 8, BW was less as PP inclusion increased without AA supplementation compared with the other treatments. In wk 7, calves fed the higher level of PP without AA had lower BW than calves fed either the lower level of PP without supplemented AA or the higher inclusion of PP with supplemented AA. Average daily gain and gain:feed were lowest for calves fed the higher inclusion of PP without supplemented AA; heart girth in wk 7 was smallest for those calves. During the first 21 d, occurrence of scours was greater in calves fed the control milk replacer than in calves fed milk replacers containing the higher inclusion of PP either without or with supplemental AA. Occurrence of scours was also greater for the lower inclusion of PP compared with the higher inclusion of PP when AA were supplemented. Throughout the 56-d experiment, the chance of antibiotic treatment was greater for calves fed the control milk replacer than for all other treatments except the higher inclusion of PP without supplemental AA. Additionally, chance of antibiotic treatment was greater for the higher inclusion of PP without supplemental AA than for other milk replacers with PP. Calves fed treatments with the higher inclusion of PP had fewer days of scours than the controls. All milk replacers with PP, except the milk replacer containing higher PP without supplemental AA, had fewer days of treatment with antibiotics compared to the all-milk control. Inclusion of PP provided similar performance and improved health as long as milk replacers were balanced for Ile and Thr. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Changes in mammary metabolism in response to the provision of an ideal amino acid profile at 2 levels of metabolizable protein supply in dairy cows: Consequences on efficiency.

PubMed

Haque, M N; Guinard-Flament, J; Lamberton, P; Mustière, C; Lemosquet, S

2015-06-01

The aim of this study was to compare the modifications in mammary gland metabolism by supplying an ideal versus an imbalanced essential AA (EAA) profile at low and high metabolizable protein (or PDIE, its equivalent in the INRA feeding system). Four lactating, multiparous Holstein cows received 4 treatments composed of 2 basal diets containing 2 levels of PDIE (LP or HP) and 2 different infusions of AA mixtures (AA- or AA+) in the duodenum. The AA+ mixture contained Lys, Met, Leu, His, Ile, Val, Phe, Arg, Trp, and Glu, whereas the AA- mixture contained Glu, Pro, and Ser. The infusion mixtures were iso-PDIE. The diet plus infusions provided 13.9 versus 15.8% of crude protein that corresponded to 102 versus 118g/kg of dry matter of PDIE in LP and HP treatments, respectively. The treatments were designed as a 2×2 crossover design of 2 levels of PDIE supply (LP vs. HP) with 28-d periods. Infusions of AA in the duodenum (AA- vs. AA+) were superimposed to diet within each 28-d period according to 2×2 crossover designs with 14-d subperiods. Increasing the PDIE supply tended to increase milk protein yield; however, the efficiency of PDIE utilization decreased and the plasma urea concentration increased, indicating a higher catabolism of AA. The AA+ treatments increased milk protein yield and content similarly at both levels of protein supply. This was explained by an increase in the mammary uptake of all EAA except His and Trp. The mammary uptake of non-EAA (NEAA) was altered to the increase in EAA uptake so that the total AA uptake was almost equal to milk protein output on a nitrogen basis. The ratio between NEAA to total AA uptake decreased from 46% in LPAA- to 40% in LPAA+, HPAA-, and HPAA+ treatments. The PDIE efficiency tended to increase in the AA+ versus the AA- treatments because the NEAA supply and the amount of NEAA not used by the mammary both decreased. Nevertheless, our AA+ treatments seemed not to be the ideal profile: the mammary uptake-to-output ratio for Thr was higher than 1 in LPAA-, but it decreased to 1 in all the other treatments, suggesting that Thr was deficient in these treatments. Conversely, an excess of His was indicated because its uptake was similar in AA+ and AA- treatments. In conclusion, balancing the EAA profile increased milk protein yield and metabolizable protein efficiency at both levels of protein supply by increasing the mammary uptake of EAA and altering the NEAA uptake, leading to less AA available for catabolism. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment.

PubMed

Schuchardt, J P; Köbe, T; Witte, V; Willers, J; Gingrich, A; Tesky, V; Pantel, J; Rujescu, D; Illig, T; Flöel, A; Hahn, A

2016-01-01

Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.

Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

PubMed

Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

2017-08-01

Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

Amino acid specific stable nitrogen isotope values in avian tissues: Insights from captive American kestrels and wild herring gulls

USGS Publications Warehouse

Hebert, Craig E.; Popp, B.N.; Fernie, K.J.; Ka'apu-Lyons, C.; Rattner, Barnett A.; Wallsgrove, N.

2016-01-01

Through laboratory and field studies, the utility of amino acid compound-specific nitrogen isotope analysis (AA-CSIA) in avian studies is investigated. Captive American kestrels (Falco sparverius) were fed an isotopically characterized diet and patterns in δ15N values of amino acids (AAs) were compared to those in their tissues (muscle and red blood cells) and food. Based upon nitrogen isotope discrimination between diet and kestrel tissues, AAs could mostly be categorized as source AAs (retaining baseline δ15N values) and trophic AAs (showing 15N enrichment). Trophic discrimination factors based upon the source (phenylalanine, Phe) and trophic (glutamic acid, Glu) AAs were 4.1 (muscle) and 5.4 (red blood cells), lower than those reported for metazoan invertebrates. In a field study involving omnivorous herring gulls (Larus argentatus smithsonianus), egg AA isotopic patterns largely retained those observed in the laying female’s tissues (muscle, red blood cells, and liver). Realistic estimates of gull trophic position were obtained using bird Glu and Phe δ15N values combined with β values (difference in Glu and Phe δ15N in primary producers) for aquatic and terrestrial food webs. Egg fatty acids were used to weight β values for proportions of aquatic and terrestrial food in gull diets. This novel approach can be applied to generalist species that feed across ecosystem boundaries.

Evaluation of the anxiolytic and antidepressant effects of asiatic acid, a compound from Gotu kola or Centella asiatica, in the male Sprague Dawley rat.

PubMed

Ceremuga, Tomás Eduardo; Valdivieso, Debra; Kenner, Catherine; Lucia, Amy; Lathrop, Keith; Stailey, Owen; Bailey, Heather; Criss, Jonathan; Linton, Jessica; Fried, Jordan; Taylor, Andrew; Padron, Gina; Johnson, Arthur Don

2015-04-01

Herbal medication use continues to rise and interactions with existing medications propose risks and may have significant effects and consequences on the administration of anesthesia. The purpose of this study was to investigate the anxiolytic and antidepressant effects of asiatic acid and its potential modulation of the γ-aminobutyric acid (GABAA) receptor. Fifty-five male Sprague Dawley rats were divided into 5 groups: vehicle (DMSO), asiatic acid (AA), midazolam, or a combination of flumazenil + AA or midazolam + AA, and injected intraperitoneally 30 minutes prior to testing. The rats were tested on the Elevated Plus Maze (EPM) and the Forced Swim Test (FST). Data were analyzed using a two-tailed multivariate analysis of variance (MANOVA). Significance was found regarding the ratio of open arm time, maximum speed, and time spent mobile in the AA group and the midazolam + AA group (P < .05). Flumazenil decreased the anxiolytic effects, suggesting that AA modulates the benzodiazepine site on the GABAA receptor. Further studies are recommended to determine the efficacy of prolonged treatment for anxiety and depression.

A novel and simple strategy for simultaneous determination of dopamine, uric acid and ascorbic acid based on the stacked graphene platelet nanofibers/ionic liquids/chitosan modified electrode.

PubMed

Niu, Xiuli; Yang, Wu; Guo, Hao; Ren, Jie; Yang, Fusheng; Gao, Jinzhang

2012-09-15

A promising electrochemical sensor for simultaneous determination of dopamine (DA), uric acid (UA) and ascorbic acid (AA) was fabricated based on the stacked graphene platelet nanofibers (SGNF)/ionic liquid (IL)/chitosan (CS) modified electrode. The SGNF/IL/CS modified electrode possessed excellent electrocatalytic activity towards the oxidation of DA, UA and AA with obvious reduction of over-potential and increased peak current, and the separations of oxidation peak potentials of DA-UA, DA-AA, and UA-AA were of 151, 213 and 364 mV, respectively. Under the optimum conditions, the linear range for the detection of DA, UA and AA were 0.05-240, 0.12-260, and 30-350 μM with the lowest detection limits of 0.05, 0.10 and 14.8 μM for DA, UA and AA, respectively. In addition, the electrochemical sensor showed high sensitivity, excellent selectivity, reproducibility and long-term stability. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of replacing calcium salts of palm oil with camelina seed at 2 dietary ether extract levels on digestion, ruminal fermentation, and nutrient flow in a dual-flow continuous culture system.

PubMed

Brandao, V L N; Dai, X; Paula, E M; Silva, L G; Marcondes, M I; Shenkoru, T; Poulson, S R; Faciola, A P

2018-06-01

Camelina is a drought- and salt-tolerant oil seed, which in total ether extract (EE) contains up to 74% polyunsaturated fatty acids. The objective of this study was to assess the effects of replacing calcium salts of palm oil (Megalac, Church & Dwight Co. Inc., Princeton, NJ) with camelina seed (CS) on ruminal fermentation, digestion, and flows of fatty acids (FA) and AA in a dual-flow continuous culture system when supplemented at 5 or 8% dietary EE. Diets were randomly assigned to 8 fermentors in a 2 × 2 factorial arrangement of treatments in a replicated 4 × 4 Latin square design, with four 10-d experimental periods consisting of 7 d for diet adaptation and 3 d for sample collection. Treatments were (1) calcium salts of palm oil supplementation at 5% EE (MEG5); (2) calcium salts of palm oil supplementation at 8% EE (MEG8); (3) 7.7% CS supplementation at 5% EE (CS5); and (4) 17.7% CS supplementation at 8% EE (CS8). Diets contained 55% orchardgrass hay, and fermentors were fed 72 g of dry matter/d. On d 8, 9, and 10 of each period, digesta effluent samples were taken for ruminal NH 3 , volatile fatty acids, nitrogen metabolism analysis, and long-chain FA and AA flows. Statistical analysis was performed using the MIXED procedure (SAS Institute Inc., Cary, NC). We detected an interaction between FA source and dietary EE level for acetate, where MEG8 had the greatest molar proportion of acetate. Molar proportions of propionate were greater and total volatile fatty acids were lower on CS diets. Supplementation of CS decreased overall ruminal nutrient true digestibility, but dietary EE level did not affect it. Diets containing CS had greater biohydrogenation of 18:2 and 18:3; however, biohydrogenation of 18:1 was greater in MEG diets. Additionally, CS diets had greater ruminal concentrations of trans-10/11 18:1 and cis-9,trans-11 conjugated linoleic acid. Dietary EE level at 8% negatively affected flows of NH 3 -N (g/d), nonammonia N, and bacterial N as well as the overall AA outflow. However, treatments had minor effects on individual ruminal AA digestibility. The shift from acetate to propionate observed on diets containing CS may be advantageous from an energetic standpoint. Moreover, CS diets had greater ruminal outflow of trans-10/11 18:1 and cis-9,trans-11 conjugated linoleic acid than MEG diets, suggesting a better FA profile available for postruminal absorption. However, dietary EE at 8% was deleterious to overall N metabolism and AA outflow, indicating that CS can be fed at 5% EE without compromising N metabolism. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

PubMed

Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Silva, Paula Regina Pereira; Borelli, Primavera; Fock, Ricardo Ambrósio; Trevisan, Maria Teresa Salles; Mauad, Thais

2011-06-01

Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Indications of human activity from amino acid and amino sugar analyses on Holocene sediments from lake Lonar, central India

NASA Astrophysics Data System (ADS)

Menzel, P.; Gaye, B.; Wiesner, M.; Prasad, S.; Basavaiah, N.; Stebich, M.; Anoop, A.; Riedel, N.; Brauer, A.

2012-04-01

The DFG funded HIMPAC (Himalaya: Modern and Past Climates) programme aims to reconstruct Holocene Indian Monsoon climate using a multi-proxy and multi-archive approach. First investigations made on sediments from a ca. 10 m long core covering the whole Holocene taken from the lake Lonar in central India's state Maharashtra, Buldhana District, serve to identify changes in sedimentation, lake chemistry, local vegetation and regional to supra-regional climate patterns. Lake Lonar occupies the floor of an impact crater that formed on the ~ 65 Ma old basalt flows of the Deccan Traps. It covers an area of ca. 1 km2 and is situated in India's core monsoon area. The modern lake has a maximum depth of about 5 m, is highly alkaline, and hyposaline, grouped in the Na-Cl-CO3 subtype of saline lakes. No out-flowing stream is present and only three small streams feed the lake, resulting in a lake level highly sensitive to precipitation and evaporation. The lake is eutrophic and stratified throughout most of the year with sub- to anoxic waters below 2 m depth. In this study the core sediments were analysed for their total amino acid (AA) and amino sugar (AS) content, the amino acid bound C and N percentage of organic C and total N in the sediment and the distribution of individual amino acids. The results roughly show three zones within the core separated by distinct changes in their AA content and distribution. (i) The bottom part of the core from ca. 12000 cal a BP to 11400 cal a BP with very low AA and AS percentage indicating high lithogenic contribution, most probably related to dry conditions. (ii) From 11400 cal a BP to 1200 cal a BP the sediments show moderate AA and AS percentages and low values for the ratios of proteinogenic AAs to their non-proteinogenic degradation products (e.g. ASP/β-ALA; GLU/γ-ABA). (iii) The top part of the core (< 1200 cal a BP) is characterised by an intense increase in total AA and AS, AA-C/Corg and AA-N/Ntotas well as in the ratio of proteinogenic to non-proteinogenic AAs. This indicates a strong increase in aquatic production which seems to be the result of eutrophication likely caused by human activity like forest clearance and agricultural land use. This hypothesis is corroborated by the dating of more than 10 temple ruins surrounding the lake, which were built in the 12thcentury, indicating early urbanisation.

Some distinguishable properties between acid-stable and neutral types of alpha-amylases from acid-producing koji.

PubMed

Suganuma, Toshihiko; Fujita, Kiyotaka; Kitahara, Kanefumi

2007-11-01

The highly humid climate of Japan facilitates the growth of various molds. Among these molds, Aspergillus oryzae is the most important and popular in Japan, and has been used as yellow-koji in producing many traditional fermented beverages and foods, such as Japanese sake, and soy sauce. Taka-amylase A (TAA), a major enzyme produced by the mold, is well known worldwide to be a leading enzyme for industrial utilization and academic study, since many extensive studies have been carried out with TAA. In southern Kyushu, the other koji's of citric acid-producing molds have often been used, such as in the production of a traditional distilled liquor of shochu. The koji molds black-koji and white-koji produce two types of alpha-amylase, namely, acid-stable (AA) and common neutral (NA). The latter enzyme is enzymatically and genetically similar to TAA. In this review, we investigate AA from three molds, Aspergillus niger, A. kawachii and A. awamori, and the yeast Cryptococcus sp. regarding the distinguishable properties between AA and NA. (i) The N-terminus amino acid sequences of AA determined by molecular cloning started with the sequence of L-S-A-, whereas those of NA started with A-T-P-. (ii) Most of the full sequences of AA were composed of, besides a core catalytic domain, an extra domain of a hinge region and a carbohydrate binding domain, which could be responsible for raw-starch-digestibility. The AA from A. niger has no exceptionally extra domain, similarly to NA. (iii) Simple methods for distinguishing AA from NA using CNP-alpha-G3 and G5 as substrates were developed by our group. (iv) The number of subsite in AA on the basis of its cleavage pattern of maltooligosaccharides was estimated to be five, which differs from that of TAA, 7-9. AA has many advantages in industrial applications, such as its acid-stability, thermostability, and raw-starch digesting properties.

Engineering posttranslational proofreading to discriminate nonstandard amino acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kunjapur, Aditya M.; Stork, Devon A.; Kuru, Erkin

Accurate incorporation of nonstandard amino acids (nsAAs) is central for genetic code expansion to increase the chemical diversity of proteins. However, aminoacyl-tRNA synthetases are polyspecific and facilitate incorporation of multiple nsAAs. We investigated and repurposed a natural protein degradation pathway, the N-end rule pathway, to devise an innovative system for rapid assessment of the accuracy of nsAA incorporation. Using this tool to monitor incorporation of the nsAA biphenylalanine allowed the identification of tyrosyl-tRNA synthetase (TyrRS) variants with improved amino acid specificity. The evolved TyrRS variants enhanced our ability to contain unwanted proliferation of genetically modified organisms. In conclusion, this posttranslationalmore » proofreading system will aid the evolution of orthogonal translation systems for specific incorporation of diverse nsAAs.« less

Engineering posttranslational proofreading to discriminate nonstandard amino acids

DOE PAGES

Kunjapur, Aditya M.; Stork, Devon A.; Kuru, Erkin; ...

2018-01-04

Accurate incorporation of nonstandard amino acids (nsAAs) is central for genetic code expansion to increase the chemical diversity of proteins. However, aminoacyl-tRNA synthetases are polyspecific and facilitate incorporation of multiple nsAAs. We investigated and repurposed a natural protein degradation pathway, the N-end rule pathway, to devise an innovative system for rapid assessment of the accuracy of nsAA incorporation. Using this tool to monitor incorporation of the nsAA biphenylalanine allowed the identification of tyrosyl-tRNA synthetase (TyrRS) variants with improved amino acid specificity. The evolved TyrRS variants enhanced our ability to contain unwanted proliferation of genetically modified organisms. In conclusion, this posttranslationalmore » proofreading system will aid the evolution of orthogonal translation systems for specific incorporation of diverse nsAAs.« less

Developmental nephrotoxicity of aristolochic acid in a zebrafish model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Yu-Ju; Chen, Yau-Hung, E-mail: yauhung@mail.tku.edu.tw

2012-05-15

Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ±more » 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.« less

The relationship between acute changes in the systemic inflammatory response and plasma ascorbic acid, alpha-tocopherol and lipid peroxidation after elective hip arthroplasty.

PubMed

Conway, F J S; Talwar, D; McMillan, D C

2015-08-01

Vitamin C (ascorbic acid, AA) is a water soluble vitamin with many functions including antioxidative properties, haemostasis, hormone synthesis, collagen synthesis, carnitine synthesis, bile salt production and enhancing iron absorption. There is some evidence that there is a negative inverse relationship between plasma vitamin C concentration and the systemic inflammatory response as measured by C-reactive protein (CRP). The aim of the present study was to examine, in the context of a longitudinal study, the change in plasma concentrations of ascorbic acid (AA) and Vitamin E (α-tocopherol, AT) and their relationship to free radical damage during the evolution of the systemic inflammatory response. Venous blood samples were obtained pre-operatively and at 1, 2, 3 and 90 days post-operatively from 11 patients undergoing elective hip arthroplasty at Glasgow Royal Infirmary. AA, AT, cholesterol, MDA (marker of free radical damage), CRP and albumin were measured in plasma. Plasma AA fell significantly by 74% (P < 0.01), AT fell by 36% (P < 0.01), cholesterol by 40% (P < 0.01), MDA by 38% (P < 0.01), albumin by 29% (P < 0.01) and CRP increased significantly by 160 fold (P < 0.01) during the systemic inflammatory response. The fall in plasma AA remained significant when adjusted for albumin (P < 0.01). Plasma AT adjusted for cholesterol did not change significantly during the study period. The fall in plasma MDA remained significant when adjusted for albumin (P 0.01). At 3 months post-operatively, all measurements (including AA) except albumin had returned to baseline values. Plasma AA levels are unlikely to be a reliable measurement of Vitamin C where there is evidence of a systemic inflammatory response. The decrease in plasma AA concentration is likely to be secondary to increased consumption, increased usage neutralising free radicals, increased utilisation in supporting AT regeneration and increased urinary excretion. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A reliable compound-specific nitrogen isotope analysis of amino acids by GC-C-IRMS following derivatisation into N-pivaloyl-iso-propyl (NPIP)esters for high-resolution food webs estimation.

PubMed

Zhang, Zhongyi; Tian, Jing; Xiao, Hongwei; Zheng, Nengjian; Gao, Xiaofei; Zhu, Renguo; Xiao, Huayun

2016-10-15

The signatures of natural stable nitrogen isotopic composition (δ(15)N) of individual amino acid (AA) have been confirmed to be a potentially effective tool for elucidating nitrogen cycling and trophic position of various organisms in food webs. In the present study, a two-stage derivatisation approach of esterification followed by acylation was evaluated. The biological samples underwent acid hydrolysis and the released individual AA was derivatived into corresponding N-pivaloyl-isopropyl (NPIP) esters for nitrogen isotopic analysis in gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Usually, 13 individual AA derivatives were separated with fine baseline resolution based on a nonpolar gas chromatography column (DB-5ms). The minimum sample amount required under the presented conditions is larger than 20ngN on column in order to accurately determine the δ(15)N values. The δ(15)N values determined by GC-C-IRMS with a precision of better than 1‰, were within 1‰ after empirical correction compared to the corresponding measured by element analysis (EA)-IRMS. Bland-Altman plot showed highly consistency of the δ(15)N values determined by the two measurement techniques. Cation-exchange chromatography was applied to remove interfering fraction from the extracts of plant and animal samples and without nitrogen isotope fractionation during the treatment procedure. Moreover, this approach was carried out to estimate the trophic level of various natural organisms in a natural lake environment. Results highly proved that the trophic level estimated via the presented AA method well reflected the actual food web structure in natural environments. Copyright © 2016 Elsevier B.V. All rights reserved.

Designing logical codon reassignment - Expanding the chemistry in biology.

PubMed

Dumas, Anaëlle; Lercher, Lukas; Spicer, Christopher D; Davis, Benjamin G

2015-01-01

Over the last decade, the ability to genetically encode unnatural amino acids (UAAs) has evolved rapidly. The programmed incorporation of UAAs into recombinant proteins relies on the reassignment or suppression of canonical codons with an amino-acyl tRNA synthetase/tRNA (aaRS/tRNA) pair, selective for the UAA of choice. In order to achieve selective incorporation, the aaRS should be selective for the designed tRNA and UAA over the endogenous amino acids and tRNAs. Enhanced selectivity has been achieved by transferring an aaRS/tRNA pair from another kingdom to the organism of interest, and subsequent aaRS evolution to acquire enhanced selectivity for the desired UAA. Today, over 150 non-canonical amino acids have been incorporated using such methods. This enables the introduction of a large variety of structures into proteins, in organisms ranging from prokaryote, yeast and mammalian cells lines to whole animals, enabling the study of protein function at a level that could not previously be achieved. While most research to date has focused on the suppression of 'non-sense' codons, recent developments are beginning to open up the possibility of quadruplet codon decoding and the more selective reassignment of sense codons, offering a potentially powerful tool for incorporating multiple amino acids. Here, we aim to provide a focused review of methods for UAA incorporation with an emphasis in particular on the different tRNA synthetase/tRNA pairs exploited or developed, focusing upon the different UAA structures that have been incorporated and the logic behind the design and future creation of such systems. Our hope is that this will help rationalize the design of systems for incorporation of unexplored unnatural amino acids, as well as novel applications for those already known.

Impact of EPA ingestion on COX- and LOX-mediated eicosanoid synthesis in skin with and without a pro-inflammatory UVR challenge – Report of a randomised controlled study in humans

PubMed Central

Pilkington, Suzanne M; Rhodes, Lesley E; Al-Aasswad, Naser M I; Massey, Karen A; Nicolaou, Anna

2014-01-01

Scope Eicosapentaenoic acid (EPA), abundant in oily fish, is reported to reduce skin inflammation and provide photoprotection, potential mechanisms include competition with arachidonic acid (AA) for metabolism by cyclooxygenases/lipoxygenases to less pro-inflammatory mediators. We thus examine impact of EPA intake on levels of AA, EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation (UVR) challenge. Methods and results In a double-blind randomised controlled study, 79 females took 5 g EPA-rich or control lipid for 12 wk. Pre- and post-supplementation, red blood cell and skin polyunsaturated fatty acids were assessed by GC, and eicosanoids from unexposed and UVR-exposed skin by LC-MS/MS. Active supplementation increased red blood cell and dermal EPA versus control (both p < 0.001), lowering relative AA:EPA content (4:1 versus 15:1 and 5:1 versus 11:1, respectively; both p < 0.001). Pre-supplementation, UVR increased PGE2, 12-hydroxyeicosatetraenoic acids, 12-HEPE (all p < 0.001) and PGE3 (p < 0.05). Post-EPA, PGE2 was reduced in unchallenged skin (p < 0.05) while EPA-derived PGE3 (non-sign) and 12-HEPE (p < 0.01) were elevated post-UVR. Thus, post-EPA, PGE2:PGE3 was lower in unchallenged (12:1 versus 28:1; p < 0.05) and UVR exposed (12:1 versus 54:1; p < 0.01) skin; 12-hydroxyeicosatetraenoic acids:12-HEPE was lower in UVR-exposed skin (3:1 versus 11:1; p < 0.001). Conclusion Dietary EPA augments skin EPA:AA content, shifting eicosanoid synthesis towards less pro-inflammatory species, and promoting a regulatory milieu under basal conditions and in response to inflammatory insult. PMID:24311515

Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner.

PubMed

Rharass, Tareck; Lantow, Margareta; Gbankoto, Adam; Weiss, Dieter G; Panáková, Daniela; Lucas, Stéphanie

2017-10-16

Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis from NPCs in cultures although the mechanisms of its action remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive WNT/β-catenin signaling pathway. We therefore aimed to investigate how AA interacts with this pathway and potentiates neurogenesis. Effects of 200 μM AA were compared with the pro-neurogenic reagent and WNT/β-catenin signaling agonist lithium chloride (LiCl), and molecules with antioxidant activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in differentiating neural progenitor ReNcell VM cells. Cells were supplemented with reagents for two periods of treatment: a full period encompassing the whole differentiation process versus an early short period that is restricted to the cell fate commitment stage. Intracellular redox balance and reactive oxygen species (ROS) metabolism were examined by flow cytometry using redox and ROS sensors. Confocal microscopy was performed to assess cell viability, neuronal yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/β-catenin signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was measured by fluorescence resonance energy transfer (FRET). In contrast to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at the early stage of the differentiation as no changes were held beyond the neuronal fate commitment stage. FRET studies showed that AA treatment accelerated the redox-dependent release of the initial pool of DVL2 from its sequestration by NXN, while RuR treatment hampered the dissociation of the two proteins. Accordingly, AA increased WNT/β-catenin signaling output i.e. MYC mRNA level, whereas RuR attenuated it. Moreover, AA improved neurogenesis as much as LiCl as both TUBB3-positive cell yield and TUBB3 mRNA level increased, while NAC or RuR attenuated neurogenesis. Markedly, the neurogenesis outputs between the short and the full treatment with either NAC or AA were found unchanged, supporting our model that neuronal yield is altered by events taking place at the early phase of differentiation. Our findings demonstrate that AA treatment elevates ROS metabolism in a non-lethal manner prior to the NPCs commitment to their neuronal fate. Such effect stimulates the redox-sensitive DVL2 activation and WNT/β-catenin signaling response that would enhance the ensuing neuronal cell differentiation.

Effects of polyunsaturated fatty acids and prostaglandins on oocyte maturation in a marine teleost, the European sea bass (Dicentrarchus labrax).

PubMed

Sorbera, L A; Asturiano, J F; Carrillo, M; Zanuy, S

2001-01-01

The effects of the polyunsaturated fatty acids (PUFAs), arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and prostaglandins (PGs) on oocyte maturation were investigated in a marine teleost, the sea bass (Dicentrarchus labrax). Follicle-enclosed postvitellogenic, preovulatory oocytes were cultured in vitro and maturation was verified by assessing volume increase, lipid droplet coalescence, yolk clarification, and germinal vesicle migration and breakdown. Human chorionic gonadotropin was administered as the maturation-inducing gonadotropin (GTH) and was capable of inducing maturation in a time- and dose-dependent manner. Free AA induced maturation in a dose- and time-dependent manner and enhanced GTH-induced maturation, while EPA, DHA, and oleic acid were ineffective. Maturation induced by GTH was significantly suppressed by a phospholipase A(2) blocker, suggesting that mobilization of AA was involved in GTH-induced maturation. Moreover, EPA and DHA exhibited a significant, dose-dependent attenuation of GTH-induced maturation. Maturation induced by GTH was inhibited in the presence of a cyclooxygenase inhibitor, indomethacin, and this inhibition was reversed by addition of AA, PGE(2), or PGF(2alpha). PGE(2) and PGF(2alpha) alone were both effective stimulators of maturation, while PGE(1) and PGE(3) were ineffective. The effect of PUFAs on oocyte maturation in vitro were corroborated with studies in vivo. Oocytes were obtained from females fed a commercial, PUFA-enriched diet (RD) and maturational behavior was compared with oocytes from females fed a natural diet (ND) with a higher EPA content and n-3:n-6 ratio. Although no significant difference was observed in the rate of spontaneous oocyte maturation, a higher percentage of GTH-induced maturation and lower percentage of atresia were observed in RD oocytes. Moreover, while basal PGE production from oocytes from both groups was the same, RD oocytes produced significantly higher levels of PGE in the presence of hCG. The results from this study provide evidence for the participation of AA metabolism in GTH-induced oocyte maturation, and suggest that other PUFAs and PGs may play important roles in the induction of maturation in a marine teleost.

Consumption of Diet Containing Free Amino Acids Exacerbates Colitis in Mice

PubMed Central

Souza, Adna Luciana; Fiorini Aguiar, Sarah Leão; Gonçalves Miranda, Mariana Camila; Lemos, Luisa; Freitas Guimaraes, Mauro Andrade; Reis, Daniela Silva; Vieira Barros, Patrícia Aparecida; Veloso, Emerson Soares; Carvalho, Toniana Gonçalves; Ribeiro, Fabiola Mara; Ferreira, Enio; Cara, Denise Carmona; Gomes-Santos, Ana Cristina; Faria, Ana Maria Caetano

2017-01-01

Dietary proteins can influence the maturation of the immune system, particularly the gut-associated lymphoid tissue, when consumed from weaning to adulthood. Moreover, replacement of dietary proteins by amino acids at weaning has been shown to impair the generation of regulatory T cells in the gut as well as immune activities such as protective response to infection, induction of oral and nasal tolerance as well as allergic responses. Polymeric and elemental diets are used in the clinical practice, but the specific role of intact proteins and free amino acids during the intestinal inflammation are not known. It is plausible that these two dietary nitrogen sources would yield distinct immunological outcomes since proteins are recognized by the immune system as antigens and amino acids do not bind to antigen-recognition receptors but instead to intracellular receptors such as mammalian target of rapamycin (mTOR). In this study, our aim was to evaluate the effects of consumption of an amino acid-containing diet (AA diet) versus a control protein-containing diet in adult mice at steady state and during colitis development. We showed that consumption of a AA diet by adult mature mice lead to various immunological changes including decrease in the production of serum IgG as well as increase in the levels of IL-6, IL-17A, TGF-β, and IL-10 in the small and large intestines. It also led to changes in the intestinal morphology, to increase in intestinal permeability, in the number of total and activated CD4+ T cells in the small intestine as well as in the frequency of proliferating cells in the colon. Moreover, consumption of AA diet during and prior to development of dextran sodium sulfate-induced colitis exacerbated gut inflammation. Administration of rapamycin during AA diet consumption prevented colitis exacerbation suggesting that mTOR activation was involved in the effects triggered by the AA diet. Therefore, our study suggests that different outcomes can result from the use of diets containing either intact proteins or free amino acids such as elemental, semielemental, and polymeric diets during intestinal inflammation. These results may contribute to the design of nutritional therapeutic intervention for inflammatory bowel diseases. PMID:29209321

Sulfamide-Lattice Restructuring To Form Dimensionally Controlled Molecular Arrays and Gel-Forming Systems.

PubMed

Raghava, Saripalli V; Gopinath, Pushparathinam; Srivastava, Bhartendu K; Ramkumar, Venkatachalam; Muraleedharan, Kannoth M

2017-03-13

A design approach that incorporates structural requirements for the formation of a 1D assembly, fibril stability, and fibril-fibril interactions for gelation was attempted by using amino acid-based sulfamides with the general structure Aa-NH-SO 2 -NH-Aa (Aa=amino acid). A preference for 1D assembly alone was not a sufficient condition for gelation, which became evident from studies involving sulfamide esters 1-5. Reducing the crystallization tendency without hindering unidirectional growth was executed through diacids of the sulfamide precursors with various amines that form an envelope around the sulfamide core through salt bridges. This strategy was fruitful, and gels of a wide variety of solvents could be formed by varying the acid and amine components. The use of dodecylamine or benzylamine, which could stabilize the molecular layers through alkyl-chain segregation or π-π interactions improved the gelation tendency, whereas the nature of the amino acid side chain, especially the rotational freedom and hydrophobicity, had a direct role in dictating the solvent preference. Crystallographic studies of these two-component systems gave molecular-level insight into the assembly and showed the importance of anisotropy in the distribution of secondary interactions in gelation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway[S

PubMed Central

Fischer, Robert; Konkel, Anne; Mehling, Heidrun; Blossey, Katrin; Gapelyuk, Andrej; Wessel, Niels; von Schacky, Clemens; Dechend, Ralf; Muller, Dominik N.; Rothe, Michael; Luft, Friedrich C.; Weylandt, Karsten; Schunck, Wolf-Hagen

2014-01-01

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept EPA and DHA to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase (LOX)-, and CYP-dependent pathways. Raising the Omega-3 Index from about four to eight primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived LOX-dependent monohydroxy-metabolites including the precursors of the resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold higher efficiency and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation. PMID:24634501

Analysis of abietic acid and dehydroabietic acid residues in raw ducks and cooked ducks.

PubMed

Zhu, Yongzhi; Zhang, Suzhen; Geng, Zhiming; Wang, Daoying; Liu, Fang; Zhang, Muhan; Bian, Huan; Xu, Weimin

2014-10-01

Rosin was once widely used for removal of duck feathers in China and is still being used secretly in some poultry processing enterprises. Abietic acid (AA) and dehydroabietic acid (DHAA) are the major compounds of rosin. In the present study, 90 duck samples were collected for investigation of AA and DHAA residues. Abietic acid and DHAA were simultaneously detected in 13 out 40 raw ducks, 8 out of 26 water-boiled salted ducks, and 7 out of 24 roasted ducks, respectively. In positive samples, averages of AA were significantly higher than those of DHAA in positive samples of the 3 types of ducks (P < 0.05). Averages of AA and DHAA in positive raw ducks were significantly higher than those in positive roasted ducks (P < 0.05). The results indicated that almost one-third of raw ducks were defeathered by means of rosin-containing defeathering agent, and cooking processes could reduce the AA and DHAA residues to some extent, but could not eliminate them completely. ©2014 Poultry Science Association Inc.

Levels of Red Blood Cell Fatty Acids in Patients With Psychosis, Their Unaffected Siblings, and Healthy Controls

PubMed Central

Medema, Suzanne; Mocking, Roel J. T.; Koeter, Maarten W. J.; Vaz, Frédéric M.; Meijer, Carin; de Haan, Lieuwe; van Beveren, Nico J. M.; Kahn, René; de Haan, Lieuwe; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; Meijer, Carin; Myin-Germeys, Inez

2016-01-01

Background: Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder. Methods: For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups. Results: Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings. Conclusions: We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients. PMID:26385764

Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.

PubMed

Wiest, Elani F; Walsh-Wilcox, Mary T; Rothe, Michael; Schunck, Wolf-Hagen; Walker, Mary K

2016-11-01

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against cardiovascular morbidity and mortality; however, many individuals avoid fish consumption due to concerns about pollutants. We tested the hypothesis that n-3 PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each diet. Aortic vasoconstriction mediated by arachidonic acid (AA) ± SKF525 (P450 inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagonist) was assessed. RBC fatty acids and expression of n-3 and n-6 PUFA metabolites were analyzed. Cytochrome P4501A1 (CYP1A1), CYP1B1, and aryl hydrocarbon receptor (AHR) expression was measured. TCDD significantly increased AA-mediated vasoconstriction on a chow diet by increasing the contribution of P450s and TP receptor to the constriction response. In contrast, the n-3 PUFA diet prevented the TCDD-induced increase in AA vasoconstriction and normalized the contribution of P450s and TP receptor. Although TCDD increased the levels of AA vasoconstrictors on the chow diet, this increase was prevent by the n-3 PUFA diet. Additionally, the n-3 PUFA diet significantly increased the levels of n-3 PUFA-derived vasodilators and TCDD increased these levels further. Interestingly, the n-3 PUFA diet significantly attenuated CYP1A1 induction by TCDD without a significant effect on AHR expression. These data suggest that n-3 PUFAs can prevent TCDD-induced vascular dysfunction by decreasing vasoconstrictors, increasing vasodilators, and attenuating CYP1A1 induction, which has been shown previously to contribute to TCDD-induced vascular dysfunction. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Screening of Catalyst and Important Variable for The Esterification of Acrylic Acid with 2 Ethylhexanol

NASA Astrophysics Data System (ADS)

Ahmad, M. A. A.; Chin, S. Y.

2017-06-01

The global demand of 2-ethylhexyl acrylate (2EHA) market has witnessed a significant growth in the past few years and this growth is anticipated to increase in the coming years. 2EHA is one of the basic organic building blocks that mainly used in the production of coatings, adhesives, superabsorbents, thickeners and plastic additives. Homogenous acid-catalysed esterification of acrylic acid (AA) with 2-ethylhexanol (2EH) is commonly used for the production of 2EHA. The homogeneous catalysts such as sulfuric and para-toluene sulfonic acid have resulted the costly and complicated downstream process that generates acidic, corrosive and non-environmental friendly waste. Therefore, it is importance to develop a cheaper process that employing heterogeneous catalysts and alternative raw material from wastewater containing acrylic acid. In this research, the study for the esterification of AA with 2EH catalysed by ion-exchange resin was conducted. The best sulfonic acid functional cation-exchange resin among SK104, SK1B, PK208, PK216, PK228, RCP145, and RCP160 was screened. PK208 outperformed the other resins and it was used subsequently in the parametric studies. The effect of important parameters (initial concentration of acrylic acid (AA), temperature, molar ratio of reactant (AA and 2EH), catalyst loading, and polymerisation inhibitor loading) was studied using 2 factorial design to determine the significant parameters to the esterification. It was found that the initial concentration of AA and temperature were most significantly affecting the esterification of AA with 2EH.

Endoplasmic reticulum stress-mediated neuronal apoptosis by acrylamide exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komoike, Yuta, E-mail: komoike@research.twmu.ac.jp

Acrylamide (AA) is a well-known neurotoxic compound in humans and experimental animals. However, intracellular stress signaling pathways responsible for the neurotoxicity of AA are still not clear. In this study, we explored the involvement of the endoplasmic reticulum (ER) stress response in AA-induced neuronal damage in vitro and in vivo. Exposure of SH-SY5Y human neuroblastoma cells to AA increased the levels of phosphorylated form of eukaryotic translation initiation factor 2α (eIF2α) and its downstream effector, activating transcription factor 4 (ATF4), indicating the induction of the unfolded protein response (UPR) by AA exposure. Furthermore, AA exposure increased the mRNA level ofmore » c/EBP homologous protein (CHOP), the ER stress-dependent apoptotic factor, and caused the accumulation of reactive oxygen species (ROS) in SH-SY5Y cells. Treatments of SH-SY5Y cells with the chemical chaperone, 4-phenylbutyric acid and the ROS scavenger, N-acetyl-cysteine reduced the AA-induced expression of ATF4 protein and CHOP mRNA, and resulted in the suppression of apoptosis. In addition, AA-induced eIF2α phosphorylation was also suppressed by NAC treatment. In consistent with in vitro study, exposure of zebrafish larvae at 6-day post fertilization to AA induced the expression of chop mRNA and apoptotic cell death in the brain, and also caused the disruption of brain structure. These findings suggest that AA exposure induces apoptotic neuronal cell death through the ER stress and subsequent eIF2α–ATF4–CHOP signaling cascade. The accumulation of ROS by AA exposure appears to be responsible for this ER stress-mediated apoptotic pathway. - Highlights: • Exposure of SH-SY5Y cells to AA activates the eIF2α–ATF4 pathway of the UPR. • Exposure of SH-SY5Y cells to AA induces the CHOP expression and apoptosis. • Exposure of zebrafish to AA induces the chop expression and apoptosis in the brain. • AA possibly induces apoptotic neuronal cell death through the ER stress response. • AA-induced ROS production is involved in this ER stress response.« less

Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains.

PubMed

Vanaveski, Taavi; Narvik, Jane; Innos, Jürgen; Philips, Mari-Anne; Ottas, Aigar; Plaas, Mario; Haring, Liina; Zilmer, Mihkel; Vasar, Eero

2018-01-01

The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days) of d-amphetamine (AMPH, 3 mg/kg i. p.), indirect agonist of dopamine (DA), in widely used 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6) mouse strains. Acute administration of AMPH (acute AMPH) induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH) caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA), whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA), alpha-aminoadipic acid (alpha-AAA), kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4), phosphatidylcholine (PC) diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4) and alkyl-acyls (PC ae C38:4, PC ae C40:4). However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1), PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6), PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3) and sphingolipids [SM(OH)C22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization. Simultaneously a significant decline of hexoses, citrulline, ADMA, and kynurenine occurred. The reduced levels of kynurenine, ADMA, and citrulline likely reflect altered function of N-methyl-D-aspartate (NMDA) and NO systems caused by repeated AMPH. Altogether, 129Sv strain displays stronger sensitization toward AMPH and larger variance in metabolite levels than Bl6.

Branched-chain amino acids and brain function.

PubMed

Fernstrom, John D

2005-06-01

Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood-brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose-response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.

PubMed

Weininger, J; King, J C

1982-06-01

Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains.

PubMed

Li, Weiwei; Chan, Chi-Kong; Wong, Yee-Lam; Chan, K K Jason; Chan, Ho Wai; Chan, Wan

2018-10-30

Emerging evidence suggests that aristolochic acids (AA) produced naturally by a common weed Aristolochia clematitis in the cultivation fields is contaminating the food products in Balkan Peninsula and acting as the etiological agent in the development of Balkan endemic nephropathy. In this study, we investigated the combined use of natural anti-oxidative "food additives" and different cooking methods to find a solution for the widespread contamination of AA in food products. The results indicated that the addition of healthy dietary supplements (such as cysteine, glutathione, ascorbic acid, citric acid and magnesium) during cooking, is a highly efficient method in lowering the concentration of AA in the final food products. Because previous observation indicated one of the toxicological mechanisms by which AA exert its toxicity is to induce oxidative stress in internal organs, it is anticipated that these added anti-oxidants will also help to attenuate the nephrotoxicity of AA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of ascorbic acid supplementation on male reproductive system during exposure to hypoxia

NASA Astrophysics Data System (ADS)

Havazhagan, G.; Riar, S. S.; Kain, A. K.; Bardhan, Jaya; Thomas, Pauline

1989-09-01

Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.

Characterization of chiral amino acids from different milk origins using ultra-performance liquid chromatography coupled to ion-mobility mass spectrometry

NASA Astrophysics Data System (ADS)

Tian, He; Zheng, Nan; Li, Songli; Zhang, Yangdong; Zhao, Shengguo; Wen, Fang; Wang, Jiaqi

2017-04-01

Milk contains free amino acids (AAs) that play essential roles in maintaining the growth and health of infants, and D-AA isomers are increasingly being recognized as important signalling molecules. However, there are no studies of the different characteristics of chiral AA (C-AA) from different milk origins. Here, UPLC coupled to ion-mobility high-resolution MS (IM-HRMS) was employed to characterize 18 pairs of C-AAs in human, cow, yak, buffalo, goat, and camel milk. The results proved that milk origins can be differentiated based on the D- to L- AA ratio-based projection scores by principal component analysis. The present study gives a deeper understanding of the D- to L- AA ratio underlying the biological functions of different animal milks, and provide a new strategy for the study of AA metabolic pathways.

Amino Acid Availability and Age Affect the Leucine Stimulation of Protein Synthesis and eIF4F Formation in Muscle

PubMed Central

Escobar, Jeffery; Frank, Jason W.; Suryawan, Agus; Nguyen, Hanh V.; Davis, Teresa A.

2009-01-01

We have previously shown that a physiological increase in plasma leucine for 60- and 120-min increases translation initiation factor activation in muscle of neonatal pigs. Although muscle protein synthesis is increased by leucine at 60 min, it is not maintained at 120 min, perhaps due to the decrease in plasma amino acids (AA). In the current study, 7- and 26-day-old pigs were fasted overnight and infused with leucine (0 or 400 µmol· kg−1· h−1) for 120 min to raise leucine within the postprandial range. The leucine was infused in the presence or absence of a replacement AA mixture (without leucine) to maintain baseline plasma AA levels. AA administration prevented the leucine-induced reduction in plasma AA in both age groups. At 7 days, leucine infusion alone increased eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) phosphorylation, decreased inactive 4E-BP1·eIF4E complex abundance, and increased active eIF4G·eIF4E complex formation in skeletal muscle; leucine infusion with replacement AA also stimulated these, as well as S6K1, rpS6, and eIF4G phosphorylation. At 26 days, leucine infusion alone increased 4E-BP1 phosphorylation and decreased the inactive 4E-BP1·eIF4E complex only; leucine with AA also stimulated these, as well as S6K1 and rpS6 phosphorylation. Muscle protein synthesis was increased in 7-day-old (+60%) and 26-day-old (+40%) pigs infused with leucine and replacement AA, but not with leucine alone. Thus, the ability of leucine to stimulate eIF4F formation and protein synthesis in skeletal muscle is dependent on AA availability and age. PMID:17878223

Analysis of the Cytotoxic Potential of Anisomelic Acid Isolated from Anisomeles malabarica

PubMed Central

Preethy, Christo Paul; Alshatwi, Ali Abdullah; Gunasekaran, Muthukumaran; Akbarsha, Mohammad Abdulkadher

2013-01-01

Anisomelic acid (AA), one of the major compounds in Anisomeles malabarica, was tested for its cytotoxicity and apoptosis-inducing potential in breast and cervical cancer cells. The MTT assay for cell viability indicated that AA is cytotoxic to all of the four cell lines tested in a dose- and duration-dependent manner. Acridine Orange & Ethidium Bromide (AO & EB) and Hoechst 33258 staining of AA-treated cells revealed typical apoptotic morphology such as condensed chromatin and formation of apoptotic bodies. The comet assay revealed DNA strand break(s), indicating that AA induces DNA damage which culminates in apoptosis. Thus, the study revealed the anti-proliferative and apoptosis-inducing properties of AA in both breast and cervical cancer cells. Therefore, anisomelic acid offers potential for application in breast and cervical cancer therapy. PMID:23833721

Current issues in dietary acrylamide: formation, mitigation and risk assessment.

PubMed

Pedreschi, Franco; Mariotti, María Salomé; Granby, Kit

2014-01-15

Acrylamide (AA) is known as a neurotoxin in humans and it is classified as a probable human carcinogen by the International Agency of Research on Cancer. AA is produced as by-product of the Maillard reaction in starchy foods processed at high temperatures (>120 °C). This review includes the investigation of AA precursors, mechanisms of AA formation and AA mitigation technologies in potato, cereal and coffee products. Additionally, most relevant issues of AA risk assessment are discussed. New technologies tested from laboratory to industrial scale face, as a major challenge, the reduction of AA content of browned food, while still maintaining its attractive organoleptic properties. Reducing sugars such as glucose and fructose are the major contributors to AA in potato-based products. On the other hand, the limiting substrate of AA formation in cereals and coffee is the free amino acid asparagine. For some products the addition of glycine or asparaginase reduces AA formation during baking. Since, for potatoes, the limiting substrate is reducing sugars, increases in sugar content in potatoes during storage then introduce some difficulties and potentially quite large variations in the AA content of the final product. Sugars in potatoes may be reduced by blanching. Levels of AA in different foods show large variations and no general upper limit is easily applicable, since some formation will always occur. Current policy is that practical measures should be taken voluntarily to reduce AA formation in vulnerable foods since AA is considered a health risk at the concentrations found in foods. © 2013 Society of Chemical Industry.

Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

PubMed

Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

2010-08-01

Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

Isolation and Characterization of Three New Monoterpene Synthases from Artemisia annua

PubMed Central

Ruan, Ju-Xin; Li, Jian-Xu; Fang, Xin; Wang, Ling-Jian; Hu, Wen-Li; Chen, Xiao-Ya; Yang, Chang-Qing

2016-01-01

Artemisia annua, an annual herb used in traditional Chinese medicine, produces a wealth of monoterpenes and sesquiterpenes, including the well-known sesquiterpene lactone artemisinin, an active ingredient in the treatment for malaria. Here we report three new monoterpene synthases of A. annua. From a glandular trichome cDNA library, monoterpene synthases of AaTPS2, AaTPS5, and AaTPS6, were isolated and characterized. The recombinant proteins of AaTPS5 and AaTPS6 produced multiple products with camphene and 1,8-cineole as major products, respectively, and AaTPS2 produced a single product, β-myrcene. Although both Mg2+ and Mn2+ were able to support their catalytic activities, altered product spectrum was observed in the presence of Mn2+ for AaTPS2 and AaTPS5. Analysis of extracts of aerial tissues and root of A. annua with gas chromatography–mass spectrometry detected more than 20 monoterpenes, of which the three enzymes constituted more than 1/3 of the total. Mechanical wounding induced the expression of all three monoterpene synthase genes, and transcript levels of AaTPS5 and AaTPS6 were also elevated after treatments with phytohormones of methyl jasmonate, salicylic acid, and gibberellin, suggesting a role of these monoterpene synthases in plant–environment interactions. The three new monoterpene synthases reported here further our understanding of molecular basis of monoterpene biosynthesis and regulation in plant. PMID:27242840

Keto analogues and amino acids supplementation induces a decrease of white blood cell counts and a reduction of muscle damage during intense exercise under thermoneutral conditions.

PubMed

Lima, R C P; Camerino, S R A S; França, T C L; Rodrigues, D S A; Gouveia, M G S; Ximenes-da-Silva, A; Bassini, A; Prado, E S; Cameron, L C

2017-04-19

This study evaluated the acute effect of keto analogue and amino acid (AA-KAAA) supplementation on both white blood cell counts and the established biomarkers of muscle damage during exercise under thermoneutral conditions. Sixteen male cyclists received a ketogenic diet for two days and were divided into two equal groups: a group taking AA-KAAA (KA) or a control group (PL). The athletes performed a two hour cycling session followed by a maximum incremental test until voluntary exhaustion (VExh). Blood samples were obtained at rest and during exercise for further hematological and biochemical analyses. Exercise-induced ammonemia increased in the PL group at VExh (75%) but remained unchanged in the KA group. Both groups exhibited a significant increase in leukocyte and neutrophil counts of ∼85% (∼13 × 10 9 L -1 ), but the shape of the lymphocytes and the eosinophil counts suggest that AA-KAAA supplementation helps prevent lymphocytosis. AA-KAAA supplementation induced a decrease in creatine kinase and aspartate aminotransferase levels at VExh while showing a significant decrease in lactate dehydrogenase at 120 min. We found that AA-KAAA supplementation decreases both the lymphocyte count response in blood and the established biomarkers of muscle damage after intense exercise under a low heat stress environment.

Influence of toll-like receptor 4 gene variants and plasma fatty acid profile on systemic inflammation: A population-based cross-sectional study.

PubMed

Norde, Marina Maintinguer; Oki, Erica; Carioca, Antonio A F; Castro, Inar A; Souza, José M P; Marchioni, Dirce M L; Fisberg, Regina M; Rogero, Marcelo M

2017-03-01

The aim of this study was to investigate the interaction of toll-like receptor 4 (TLR4) gene single nucleotide polymorphism (SNP) and plasma fatty acid (FA) profile in modulating risk for systemic inflammation. In all, 262 adult (19-59 y) participants of the Health Survey of São Paulo met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and four SNPs of the TLR4 gene (rs4986790, rs4986791, rs11536889, and rs5030728) were genotyped. Multivariate cluster analysis was performed to stratify individuals based on levels of 11 plasma inflammatory biomarkers into two groups: inflammatory (INF) and noninflammatory (NINF). No association was found between any of the SNPs studied and systemic inflammation. The INF cluster had higher palmitic acid levels (P = 0.039) and estimated stearoyl coenzyme A desaturase activity (P = 0.045) and lower polyunsaturated fatty acid (P = 0.011), ω-6 fatty acid (P = 0.018), arachidonic acid (P = 0.002) levels, and estimated δ-5 desaturase activity (P = 0.025) compared with the NINF cluster. Statistically significant interaction between rs11536889 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio (P = 0.034) was found to increase the odds of belonging to the INF cluster when individuals had the variant allele C and were at the higher percentile of AA/EPA plasma ratio. Plasma fatty acid profile modulated the odds of belonging to the INF cluster depending on genotypes of TRL4 gene polymorphisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Prebiotic synthesis and degradation of amino acids by UV-irradiation at room temperature and 77K.

NASA Astrophysics Data System (ADS)

Mita, H.; Shimoyama, A.

Amino acids (AAs) were synthesized prebioticaly by UV irradiation to aqueous solution of amines and nitriles, and mixtures of graphite-ammonia-water (GAW mix.) at room temperature (RT, model of the primitive ocean) and 77 K (model of comet ice), using a Xe excimer lamp (max is 172 nm) and a low-pressure mercury lamp (max is 185/254 nm). Degradation of glycine and, degradation and racemization of aspartic acid were carried out by UV irradiation at RT. AAs in the irradiated samples were determined quantitatively by a gas chromatograph combined with a mass spectrometer after derivatized with HCl/2-propanol and trifluoroacetic anhydride. Maximum 16 hydrolyzed AAs from C2 to C6 were detected quantitatively. Amino acids have chiral center were nearly racemic. Therefore, those amino acids were not contaminants. In the most case, glycine was the most abundant AA and its concentration was 4.1 μmol/l from 1mmol/l acetonitrile solu. at RT for 3 h, 1 nmol/l from 100 mmol/l acetonitrile solu. at 77K for 1 h, 3.8?μmol/l from 10 mmol/l methylamine solu. at RT for 15 h, 278 μmol/l from 1 mol/l methylamine solu. At 77K for 4h, and 38.6 pmol/g-Carbon from GAW mix. at RT for 24 h. Maximum producing time of glycine from acetonitrile was 3 h and the shortest, that from GAW mix. was the longest among our experiments. Amount of glycine was decreased in gradually, after maximum producing time. Yields of glycine from acetonitrile and methylamine at 77K were lower than those at RT. Amounts of large AAs were lower than those of small AAs as glycine and alanine. Half-life time of glycine UV irradiation at RT was nearly 30 min. and similar to that of aspartic acid. Half-life time of racemization of aspartic acid was 2.1 h. It was able to confirm that a lot of AAs were synthesized by UV irradiation in the model experiments of primitive environments, even in simulated comet ice, from different starting materials. AA formation from developed material, as acetonitrile was more rapid and higher yield than that from primitive material as GAW mix. Degradation rate of AAs was faster than formation rate of AAs. Therefore, some protective systems are required for accumulation of AAs.

Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated

USDA-ARS?s Scientific Manuscript database

Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to tr...

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis.

PubMed

Raj, Dominic S C; Adeniyi, Oladipo; Dominic, Elizabeth A; Boivin, Michel A; McClelland, Sandra; Tzamaloukas, Antonios H; Morgan, Nancy; Gonzales, Lawrence; Wolfe, Robert; Ferrando, Arny

2007-06-01

Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol.min(-1).100 ml (-1)) was more negative during HD-O compared with pre-HD (-33.7 +/- 1.5 vs. -6.0 +/- 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (-16.9 +/- 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively (P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

In silico cloning and B/T cell epitope prediction of triosephosphate isomerase from Echinococcus granulosus.

PubMed

Wang, Fen; Ye, Bin

2016-10-01

Cystic echinococcosis is a worldwide zoonosis caused by Echinococcus granulosus. Because the methods of diagnosis and treatment for cystic echinococcosis were limited, it is still necessary to screen target proteins for the development of new anti-hydatidosis vaccine. In this study, the triosephosphate isomerase gene of E. granulosus was in silico cloned. The B cell and T cell epitopes were predicted by bioinformatics methods. The cDNA sequence of EgTIM was composition of 1094 base pairs, with an open reading frame of 753 base pairs. The deduced amino acid sequences were composed of 250 amino acids. Five cross-reactive epitopes, locating on 21aa-35aa, 43aa-57aa, 94aa-107aa, 115-129aa, and 164aa-183aa, could be expected to serve as candidate epitopes in the development of vaccine against E. granulosus. These results could provide bases for gene cloning, recombinant expression, and the designation of anti-hydatidosis vaccine.

β-Cell lipotoxicity after an overnight intravenous lipid challenge and free fatty acid elevation in African American versus American white overweight/obese adolescents.

PubMed

Hughan, Kara S; Bonadonna, Riccardo C; Lee, SoJung; Michaliszyn, Sara F; Arslanian, Silva A

2013-05-01

Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents. Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively. Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs. Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts.

IDH1 deficiency attenuates gluconeogenesis in mouse liver by impairing amino acid utilization.

PubMed

Ye, Jing; Gu, Yu; Zhang, Feng; Zhao, Yuanlin; Yuan, Yuan; Hao, Zhenyue; Sheng, Yi; Li, Wanda Y; Wakeham, Andrew; Cairns, Rob A; Mak, Tak W

2017-01-10

Although the enzymatic activity of isocitrate dehydrogenase 1 (IDH1) was defined decades ago, its functions in vivo are not yet fully understood. Cytosolic IDH1 converts isocitrate to α-ketoglutarate (α-KG), a key metabolite regulating nitrogen homeostasis in catabolic pathways. It was thought that IDH1 might enhance lipid biosynthesis in liver or adipose tissue by generating NADPH, but we show here that lipid contents are relatively unchanged in both IDH1-null mouse liver and IDH1-deficient HepG2 cells generated using the CRISPR-Cas9 system. Instead, we found that IDH1 is critical for liver amino acid (AA) utilization. Body weights of IDH1-null mice fed a high-protein diet (HPD) were abnormally low. After prolonged fasting, IDH1-null mice exhibited decreased blood glucose but elevated blood alanine and glycine compared with wild-type (WT) controls. Similarly, in IDH1-deficient HepG2 cells, glucose consumption was increased, but alanine utilization and levels of intracellular α-KG and glutamate were reduced. In IDH1-deficient primary hepatocytes, gluconeogenesis as well as production of ammonia and urea were decreased. In IDH1-deficient whole livers, expression levels of genes involved in AA metabolism were reduced, whereas those involved in gluconeogenesis were up-regulated. Thus, IDH1 is critical for AA utilization in vivo and its deficiency attenuates gluconeogenesis primarily by impairing α-KG-dependent transamination of glucogenic AAs such as alanine.

Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs.

PubMed

Asha, G S; Indira, M

2004-02-01

Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.

Amino Acid Enantiomeric Ratios in Semi-Labile vs. Refractory Dissolved Organic Matter: Implications for a Microbial N Pump

NASA Astrophysics Data System (ADS)

Bour, A. L.; Broek, T.; Gier, E. J.; Mccarthy, M. D.

2016-02-01

Microbes are key moderators in the cycling of marine dissolved organic matter (DOM), most of which remains unidentifiable at the molecular level. A major current question, however, is to what degree heterotrophic bacteria directly mediate C and N sequestration in the deep sea. Amino acids (AA) represent almost all organic N that can be identified at the molecular level, while D-AA enantiomers represent unique source-specific biomarkers for prokaryotes, known to be highly enriched in ocean DOM. If increasing bacterial-sourced material ultimately leads to millennial scale sequestration of refractory DOM (RDOM), then one would expect a clear correlation between bacterial biomarkers and DOM radiocarbon (Δ14C) ages, in particular in the deep sea. Here we directly test this idea for the first time, by measuring D-AA abundance and distribution in isolated Δ14C young vs. old DOM from the central north pacific gyre. We used a coupled ultrafiltration/solid phase extraction approach to isolate semi-labile vs. RDOM, based on known molecular weight and Δ14C age correlations. The Δ14C ages of isolated material ranged from 205-275 ybp for surface semi-labile DOM, to 6680-6740 ybp for deep ocean RDOM. We measured enantiomeric (D/L) AA ratios, as well as AA molar percentages to estimate traditional degradation parameters (DI and RI), in semi-labile vs. RDOM fractions from the surface to deep ocean at HOT, Station ALOHA. We interpret our results in terms of the hypothesis of a microbial N pump, examining the similarity of microbial source signatures (D/L distributions) and calculated organic N contributions from heterotrophic bacteria, in the context of the Δ14C age of each fraction. Finally, we also evaluate these data vs. common AA molar percentage based indices of degradation.

[Effect of amino acid and glucose infusion on perioperative body temperature and postoperative infection in patients undergoing total knee arthroplasty].

PubMed

Fujita, Yasuki; Yamaguchi, Sayo; Nakamura, Kayo; Horiguchi, Yuu; Ikeda, Daisuke; Kaneko, Michiko; Tomioka, Keiko; Tokunaga, Chiharu; Iwakura, Takeo

2012-01-01

We investigated whether the perioperative amino acid infusion with glucose is effective for preventing perioperative hypothermia and postoperative infection in patients undregoing total knee arthroplasty (TKA). Forty patients undergoing TKA under general anesthesia were enrolled in this study. The patients were randomly allocated to two groups: AA group (n = 22), to which amino acid was infused, and AAGlu group (n = 18), to which amino acid and glucose were infused. The infusions were started before the anesthetic induction. Remifentanil was administered during the surgery, and the dose of remifentanil was adjusted to keep stable hemodynamics. The levels of blood glucose and body temperature were evaluated. We also recorded the frequency of additional use of nonsteroidal anti-inflammatory drugs, the days required until the wound closure, and complications in the post-operative period. The levels of blood glucose in AAGlu group were significantly higher than those of AA group (P < 0.05). However, no significant differences were found in perioperative body temperature, postoperative days required until the wound closure and the frequency of additional use of analgesics between the groups. These results suggest that in patients undergoing TKA receiveing amino acid infusion perioperatively, thermogenic effect and prevention of postoperative infection are similar whether exogenous glucose is infused or not.

Temporal dynamics of amino and fatty acid composition in the razor clam Ensis siliqua (Mollusca: Bivalvia)

NASA Astrophysics Data System (ADS)

Baptista, Miguel; Repolho, Tiago; Maulvault, Ana Luísa; Lopes, Vanessa M.; Narciso, Luis; Marques, António; Bandarra, Narcisa; Rosa, Rui

2014-12-01

Few studies have been conducted on the temporal dynamics of both amino acid (AA) and fatty acid (FA) profiles in marine bivalves. We investigated the seasonal variation of these compounds in the pod razor clam Ensis siliqua in relation to food availability, salinity, water temperature and reproductive cycle. AA content varied between 46.94 and 54.67 % dry weight (DW), and the AAs found in greater quantity were glutamic acid, glycine and aspartic acid. FA content varied between 34.02 and 87.94 mg g-1 DW and the FAs found in greater quantity were 16:0 and 22:6 n-3. Seasonal trends were observed for AAs and FAs. FAs increased with gametogenesis and decreased with spawning while AA content increased throughout spawning. The effect of increasing temperature and high food availability during the spawning season masked the loss of AAs resulting from gamete release. Still, a comparatively greater increase in the contents of glutamic acid and leucine with spawning indicate their possible involvement in a post-spawning gonad recovery mechanism. A post-spawning decrease in 14:0, 16:0, 16:1 n-7, 18:1 n-7 and 18:1 n-9 is indicative of the importance of these FAs in bivalve eggs. An increase in 18:3 n-3, 18:4 n-3, 20:1 n-9 and 20:2 n-6 during gametogenesis suggests their involvement in oocyte maturation. The FA 22:4 n-6, while increasing with spawning, appears to play a role in post-spawning gonad recovery. Salinity did not have an effect on the AA composition. None of the environmental parameters measured had an effect on FA composition.

40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

Code of Federal Regulations, 2014 CFR

2014-07-01

... (40 CFR Part 63, Subpart A) to Subpart AA A Appendix A to Subpart AA of Part 63 Protection of... Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to Subpart AA of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA 40 CFR...

40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

Code of Federal Regulations, 2010 CFR

2010-07-01

... (40 CFR Part 63, Subpart A) to Subpart AA A Appendix A to Subpart AA of Part 63 Protection of... Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to Subpart AA of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA 40 CFR...

Production of volatiles in fresh-cut apple: effect of applying alginate coatings containing linoleic acid or isoleucine.

PubMed

Maya-Meraz, Irma O; Espino-Díaz, Miguel; Molina-Corral, Francisco J; González-Aguilar, Gustavo A; Jacobo-Cuellar, Juan L; Sepulveda, David R; Olivas, Guadalupe I

2014-11-01

One of the main quality parameters in apples is aroma, its main precursors are fatty acids (FA) and amino acids (AA). In this study, alginate edible coatings were used as carriers of linoleic acid or isoleucine to serve as precursors for the production of aroma in cut apples. Apple wedges were immersed in a CaCl2 solution and coated with one of the following formulations: alginate solution (Alg-Ca), Alg-Ca-low-level linoleic acid (0.61 g/Lt), (LFA), Alg-Ca-high-level linoleic acid (2.44 g/L; HFA), Alg-Ca-low-level isoleucine (0.61 g/L; LAA), and Alg-Ca-high-level isoleucine (2.44 g/L; HAA). Apple wedges were stored at 3 °C and 85% relative humidity for 21 d and key volatiles were studied during storage. Addition of precursors, mainly isoleucine, showed to increase the production of some key volatiles on coated fresh-cut apples during storage. The concentration of 2-methyl-1-butanol was 4 times higher from day 12 to day 21 in HAA, while 2-methyl butyl acetate increased from day 12 to day 21 in HAA. After 21 d, HAA-apples presented a 40-fold value of 2-methyl-butyl acetate, compared to Alg-Ca cut apples. Values of hexanal increased during cut apple storage when the coating carried linoleic acid, mainly on HFA, from 3 to 12 d. The ability of apples to metabolize AA and FA depends on the concentration of precursors, but also depends on key enzymes, previous apple storage, among others. Further studies should be done to better clarify the behavior of fresh-cut apples as living tissue to metabolize precursors contained in edible coatings for the production of volatiles. © 2014 Institute of Food Technologists®

Novel Haloperoxidase from the Agaric Basidiomycete Agrocybe aegerita Oxidizes Aryl Alcohols and Aldehydes

PubMed Central

Ullrich, René; Nüske, Jörg; Scheibner, Katrin; Spantzel, Jörg; Hofrichter, Martin

2004-01-01

Agrocybe aegerita, a bark mulch- and wood-colonizing basidiomycete, was found to produce a peroxidase (AaP) that oxidizes aryl alcohols, such as veratryl and benzyl alcohols, into the corresponding aldehydes and then into benzoic acids. The enzyme also catalyzed the oxidation of typical peroxidase substrates, such as 2,6-dimethoxyphenol (DMP) or 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS). A. aegerita peroxidase production depended on the concentration of organic nitrogen in the medium, and highest enzyme levels were detected in the presence of soybean meal. Two fractions of the enzyme, AaP I and AaP II, which had identical molecular masses (46 kDa) and isoelectric points of 4.6 to 5.4 and 4.9 to 5.6, respectively (corresponding to six different isoforms), were identified after several steps of purification, including anion- and cation-exchange chromatography. The optimum pH for the oxidation of aryl alcohols was found to be around 7, and the enzyme required relatively high concentrations of H2O2 (2 mM) for optimum activity. The apparent Km values for ABTS, DMP, benzyl alcohol, veratryl alcohol, and H2O2 were 37, 298, 1,001, 2,367 and 1,313 μM, respectively. The N-terminal amino acid sequences of the main AaP II spots blotted after two-dimensional gel electrophoresis were almost identical and exhibited almost no homology to the sequences of other peroxidases from basidiomycetes, but they shared the first three amino acids, as well as two additional amino acids, with the heme chloroperoxidase (CPO) from the ascomycete Caldariomyces fumago. This finding is consistent with the fact that AaP halogenates monochlorodimedone, the specific substrate of CPO. The existence of haloperoxidases in basidiomycetous fungi may be of general significance for the natural formation of chlorinated organic compounds in forest soils. PMID:15294788

Acid-Group-Content-Dependent Proton Conductivity Mechanisms at the Interlayer of Poly(N-dodecylacrylamide-co-acrylic acid) Copolymer Multilayer Nanosheet Films.

PubMed

Sato, Takuma; Tsukamoto, Mayu; Yamamoto, Shunsuke; Mitsuishi, Masaya; Miyashita, Tokuji; Nagano, Shusaku; Matsui, Jun

2017-11-14

The effect of the content of acid groups on the proton conductivity at the interlayer of polymer-nanosheet assemblies was investigated. For that purpose, amphiphilic poly(N-dodecylacrylamide-co-acrylic acid) copolymers [p(DDA/AA)] with varying contents of AA were synthesized by free radical polymerization. Surface pressure (π)-area (A) isotherms of these copolymers indicated that stable polymer monolayers are formed at the air/water interface for AA mole fraction (n) ≤ 0.49. In all cases, a uniform dispersion of the AA groups in the polymer monolayer was observed. Subsequently, polymer monolayers were transferred onto solid substrates using the Langmuir-Blodgett (LB) technique. X-ray diffraction (XRD) analyses of the multilayer films showed strong Bragg diffraction peaks, suggesting a highly uniform lamellar structure for the multilayer films. The proton conductivity of the multilayer films parallel to the direction of the layer planes were measured by impedance spectroscopy, which revealed that the conductivity increased with increasing values of n. Activation energies for proton conduction of ∼0.3 and 0.42 eV were observed for n ≥ 0.32 and n = 0.07, respectively. Interestingly, the proton conductivity of a multilayer film with n = 0.19 did not follow the Arrhenius equation. These results were interpreted in terms of the average distance between the AA groups (l AA ), and it was concluded that, for n ≥ 0.32, an advanced 2D hydrogen bonding network was formed, while for n = 0.07, l AA is too long to form such hydrogen bonding networks. The l AA for n = 0.19 is intermediate to these extremes, resulting in the formation of hydrogen bonding networks at low temperatures, and disruption of these networks at high temperatures due to thermally induced motion. These results indicate that a high proton conductivity with low activation energy can be achieved, even under weakly acidic conditions, by arranging the acid groups at an optimal distance.

Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study

PubMed Central

Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

2015-01-01

Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism. PMID:25588215

Acetic acid can catalyze succinimide formation from aspartic acid residues by a concerted bond reorganization mechanism: a computational study.

PubMed

Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

2015-01-12

Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism.

Unique anthranilic acid chemistry facilitates profiling and characterization of Ser/Thr-linked sugar chains following hydrazinolysis.

PubMed

Anumula, Kalyan Rao

2008-02-01

A novel method for the analysis of Ser/Thr-linked sugar chains was made possible by the virtue of unique anthranilic acid (AA, 2-aminobenzoic acid [2AA]) chemistry for labeling carbohydrates in aqueous salt solutions (K. R. Anumula, Anal. Biochem. 350 (2006) 1-23). The protocol for profiling of Ser/Thr carbohydrates by hydrazinolysis was made simple by eliminating intermediary isolation steps involved in a sample preparation such as desalting and various chromatographic purification schemes. A 6-h hydrazinolysis was carried out at 60 degrees C for O-linked oligosaccharides and at 95 degrees C for total oligosaccharides (N-linked with some O-linked). Following evaporation of hydrazine (<10 min), the oligosaccharides were N-acetylated and derivatized with AA in the same reaction mixture containing salts. Presumably, the glycosyl-hydrazines/hydrazones present in the mixture did not interfere with AA labeling. Because AA is the most fluorescent and highly reactive tag for labeling carbohydrates, the procedures described are suitable for the analysis of a limited amount of samples ( approximately 5 microg) by the current high-resolution high-performance liquid chromatography (HPLC) methods. HPLC conditions developed for the separation of O-linked sugar chains based on size on an amide column were satisfactory for quantitative profiling and characterization. Common O-linked sugar chains found in fetuin, equine chorionic gonadotropin, and glycophorin can be analyzed in less than 50 min. In addition, these fast profiling methods were comparable to profiling by PNGase F (peptide N-glycosidase from Flavobacterium meningosepticum) digestion in terms of time, effort, and simplicity and also were highly reproducible for routine testing. The procedures for the release of sugar chains by hydrazinolysis at the microgram level, labeling with fluorescent tag AA, and profiling by HPLC should be useful in characterization of carbohydrates found in glycoproteins.

Formulation with ascorbic acid and sucrose modulates catechin bioavailability from green tea

PubMed Central

Peters, Catrina M.; Green, Rodney J.; Janle, Elsa M.; Ferruzzi, Mario G.

2009-01-01

In order to investigate the impact of common food ingredients on catechin absorption, green tea (GT) extract (50 mg) was formulated plain, with sucrose (GT+S), with ascorbic acid (GT+AA) and with sucrose and ascorbic acid (GT+S+AA). Bioavailability and bioaccessibility were assessed in Sprague Dawley rats and an in vitro digestion/Caco-2 cell model respectively. Absorption of epigallocatechin (EGC) and epigallocatechin gallate (EGCG) was significantly (P<0.05) enhanced in GT+S+AA formulations (AUC0-6h= 3237.0 and 181.8 pmol*h/L plasma respectively) relative to GT control (AUC0-6h = 1304.1 and 61.0 pmol*h/L plasma respectively). In vitro digestive recovery was higher for EGC and epicatechin (EC) (∼51-53%) relative to EGCG and epicatechin gallate (ECG) (< 20%) and was modestly enhanced in GT+S and GT+S+AA formulations. Accumulation of EGC, EGCG and ECG by Caco-2 cells was significantly (P<0.05) higher from GT+S+AA compared to other formulations while retention of catechins was enhanced in presence of ascorbic acid. These data suggest that formulation with sucrose and ascorbic acid may improve catechin bioavailability by enhancing bioaccessibility and intestinal uptake from tea. PMID:20161530

IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids.

PubMed

Chung, Si-Yin; Reed, Shawndrika

2015-01-01

The objective of this study was to determine if D-amino acids (D-aas) bind and inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and controls. Each sample was mixed with a pooled plasma from peanut-allergic donors, and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu] was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding to peanut allergens in vitro. Published by Elsevier Ltd.

Ascorbic acid, cognitive function, and Alzheimer’s disease: a current review and future direction

PubMed Central

Bowman, Gene L.

2013-01-01

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer’s disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging. PMID:22419527

The roles of AMY1 copies and protein expression in human salivary α-amylase activity.

PubMed

Yang, Ze-Min; Lin, Jing; Chen, Long-Hui; Zhang, Min; Chen, Wei-Wen; Yang, Xiao-Rong

2015-01-01

Salivary α-amylase (sAA) activity has been extensively investigated in nutrition and psychology. But few studies were performed to assess the role played by sAA gene (AMY1) copies and protein expression in basal and stimulus-induced sAA activity. The sAA activity, amount and AMY1 copy number were determined from 184 saliva samples pre- and post-citric acid stimulation. Our findings showed that citric acid could induce significant increase in sAA activity, total sAA amount, and glycosylated sAA amount, among which the glycosylated sAA amount had the largest response. The correlation analysis showed that AMY1 copy number, total sAA amount and AMY1 copy number×total sAA amount had significantly positive and successively increasing correlations with sAA activity in unstimulated and stimulated saliva, respectively, and furthermore, we observed higher correlations in unstimulated saliva when compared with the corresponding correlations in stimulated saliva. We also observed significant correlations between glycosylated sAA amount and sAA activity in unstimulated and stimulated saliva, respectively. Interestingly, the correlations were higher in stimulated saliva than in unstimulated saliva, and the correlations between glycosylated sAA amount and sAA activity were higher than that of between total sAA amount and sAA activity in stimulated saliva. Moreover, total sAA amount ratio and glycosylated sAA amount ratio showed significantly positive correlation with sAA activity ratio. AMY1 copy number had no correlation with sAA activity ratio. These findings suggested that AMY1 copy number and sAA amount played crucial roles in sAA activity; however, the roles were attenuated after stimulation due to fortified release of glycosylated sAA. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Molecular Compounds (Selected Articles).

DTIC Science & Technology

1987-08-24

Polymethacrylic Acid and Polyvinyl Alcohol, by I.F. Yefremov, E.B. D’yakonova, A.A. Spartakov, A.A. Trusov ._’ . Us’yarov...polyoctafluoroamyl methacrylate) was converted into polymethacrylic acid by hydrolysis in an alkaline medium. The poly acid was methylated by diazomethane...Institute im. Lensovet Submitted 25 Apr 66 In a low-concentrated aqueous solution of polymethacrylic acid (PHAK) and polyvinyl alcohol (PVS) mixed

Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

PubMed

Bassaganya-Riera, Josep; Guri, Amir J; Noble, Alexis M; Reynolds, Kathryn A; King, Jennifer; Wood, Cynthia M; Ashby, Michael; Rai, Deshanie; Hontecillas, Raquel

2007-03-01

Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

Changes of seed weight, fatty acid composition, oil and protein contents from different peanut FAD2 genotypes at different seed developmental and maturation stages

USDA-ARS?s Scientific Manuscript database

The level of oleic acid in peanut seed is one of the most important factors in determining seed quality and is controlled by two pairs of homeologous genes Fatty Acid Desaturase 2A and 2B (FAD2A and FAD2B). The genotypes of eight F8 breeding lines were determined as AABB, aaBB, AAbb, and aabb by rea...

Levels of Red Blood Cell Fatty Acids in Patients With Psychosis, Their Unaffected Siblings, and Healthy Controls.

PubMed

Medema, Suzanne; Mocking, Roel J T; Koeter, Maarten W J; Vaz, Frédéric M; Meijer, Carin; de Haan, Lieuwe; van Beveren, Nico J M; Kahn, René; de Haan, Lieuwe; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; Meijer, Carin; Myin-Germeys, Inez

2016-03-01

Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder. For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups. Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings. We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Glycomacropeptide in children with phenylketonuria: does its phenylalanine content affect blood phenylalanine control?

PubMed

Daly, A; Evans, S; Chahal, S; Santra, S; MacDonald, A

2017-08-01

In phenylketonuria (PKU), there are no data available for children with respect to evaluating casein glycomacropeptide (CGMP) as an alternative to phenylalanine-free protein substitutes [Phe-free L-amino acid (AA)]. CGMP contains a residual amount of phenylalanine, which may alter blood phenylalanine control. In a prospective 6-month pilot study, we investigated the effect on blood phenylalanine control of CGMP-amino acid (CGMP-AA) protein substitute in 22 PKU subjects (13 boys, nine girls), median age (range) 11 years (6-16 years). Twelve received CGMP-AA and nine received Phe-free L-AA, (1 CGMP-AA withdrawal). Subjects partially or wholly replaced Phe-free L-AA with CGMP-AA. If blood phenylalanine exceeded the target range, the CGMP-AA dose was reduced and replaced with Phe-free L-amino acids. The control group remained on Phe-free L-AAs. Phenylalanine, tyrosine and Phe : Tyr ratio concentrations were compared with the results for the previous year. In the CGMP-AA group, there was a significant increase in blood phenylalanine concentrations (pre-study, 275 μmol L -1 ; CGMP-AA, 317 μmol L -1 ; P = 0.02), a decrease in tyrosine concentrations (pre-study, 50 μmol L -1 ; CGMP-AA, 40 μmol L -1 ; P = 0.03) and an increase in Phe : Tyr ratios (pre-study, Phe : Tyr 4.9:1; CGMP-AA, Phe : Tyr 8:1; P = 0.02). In the control group there was a non-significant fall in phenylalanine concentrations (pre-study 325μmol/L: study 280μmol/L [p = 0.9], and no significant changes for tyrosine or phe/tyr ratios [p = 0.9]. Children taking the CGMP-AA found it more acceptable to L-AA. Blood phenylalanine control declined with CGMP-AA but, by titrating the dose of CGMP-AA, blood phenylalanine control remained within target range. The additional intake of phenylalanine may have contributed to the change in blood phenylalanine concentration. CGMP-AA use requires careful monitoring in children. © 2017 The British Dietetic Association Ltd.

Replacing dietary nonessential amino acids with ammonia nitrogen does not alter amino acid profile of deposited protein in the carcass of growing pigs fed a diet deficient in nonessential amino acid nitrogen.

PubMed

Mansilla, W D; Htoo, J K; de Lange, C F M

2017-10-01

Amino acid usage for protein retention, and, consequently, the AA profile of retained protein, is the main factor for determining AA requirements in growing animals. The objective of the present study was to determine the effect of supplementing ammonia N on whole-body N retention and the AA profile of retained protein in growing pigs fed a diet deficient in nonessential AA (NEAA) N. In total, 48 barrows with a mean initial BW of 13.6 kg (SD 0.7) were used. At the beginning of the study, 8 pigs were euthanized for determination of initial protein mass. The remaining animals were individually housed and fed 1 of 5 dietary treatments. A common basal diet (95% of experimental diets) was formulated to meet the requirements for all essential AA (EAA) but to be deficient in NEAA N (CP = 8.01%). The basal diet was supplemented (5%) with cornstarch (negative control) or 2 N sources (ammonia or NEAA) at 2 levels each to supply 1.35 or 2.70% extra CP. The final standardized ileal digestible (SID) NEAA content in the high-NEAA-supplemented diet (positive control) was based on the NEAA profile of whole-body protein of 20-kg pigs, and it was expected to reduce the endogenous synthesis of NEAA. Pigs were fed at 3.0 times maintenance energy requirements for ME in 3 equal meals daily. At the end of a 3-wk period, pigs were euthanized and the carcass and visceral organs were weighed, frozen, and ground for determination of protein mass. From pigs in the initial, negative control, high-ammonia, and high-NEAA groups, AA contents in the carcass and pooled visceral organs were analyzed to determine the total and deposited protein AA profile, dietary EAA efficiencies, and minimal de novo synthesis of NEAA. Carcass weight and whole-body N retention linearly increased ( < 0.05) with N supplementation. The AA profile of protein and deposited protein in the carcass was not different ( > 0.10) between N sources, but Cys content increased ( < 0.05) with NEAA compared with ammonia in visceral organ protein and deposited protein. The dietary SID EAA efficiency for increasing EAA deposition in whole-body protein increased ( < 0.05) with N supplementation, but it was not different ( > 0.10) between N sources. The de novo synthesis of NEAA increased ( < 0.05) for ammonia compared with NEAA supplementation. In conclusion, adding ammonia as a N source to diets deficient in NEAA N increases whole-body N retention without affecting the carcass AA profile.

Commensal bacteria and essential amino acids control food choice behavior and reproduction

PubMed Central

Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M.; Piper, Matthew D. W.

2017-01-01

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits. PMID:28441450

Commensal bacteria and essential amino acids control food choice behavior and reproduction.

PubMed

Leitão-Gonçalves, Ricardo; Carvalho-Santos, Zita; Francisco, Ana Patrícia; Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M; Piper, Matthew D W; Ribeiro, Carlos

2017-04-01

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits.

Early amino acid administration in very preterm infants: Too little, too late or too much, too soon?

PubMed

Morgan, Colin

2013-03-09

Early postnatal growth failure is well described in very preterm infants. It reflects the nutritional deficits in protein and energy intake that accumulate in the first few weeks after birth. This coincides with the period of maximum parenteral nutrition (PN) dependency, so that protein intake is largely determined by intravenous amino acid (AA) administration. The contribution of PN manufacture, supply, formulation, prescribing and administration to the early postnatal nutritional deficit is discussed, focusing on total AA intake. The implications of postnatal deficits in AA and energy intake for growth are reviewed, with particular emphasis on early head/brain growth and long-term neurodevelopmental outcome. The rationale for maximising AA acid intake as soon as possible after birth is explained. This includes the benefits for very early postnatal nutritional intake and metabolic adaptation after birth. These benefits relate to total AA intake and so have to be interpreted with some caution, given the very limited evidence base surrounding the balance of individual AAs in neonatal PN formulations. This work mostly predates current nutritional recommendations and therefore may not provide a true reflection of individual AA utilisation in current clinical practice. Copyright © 2013. Published by Elsevier Ltd.

Synthesis and Biomedical Applications of Poly((meth)acrylic acid) Brushes.

PubMed

Qu, Zhenyuan; Xu, Hong; Gu, Hongchen

2015-07-15

Poly((meth)acrylic acid) (P(M)AA) brushes possess a number of distinctive properties that are particularly attractive for biomedical applications. This minireview summarizes recent advances in the synthesis and biomedical applications of P(M)AA brushes and brushes containing P(M)AA segments. First, we review different surface-initiated polymerization (SIP) methods, with a focus on recent progress in the surface-initiated controlled/living radical polymerization (SI-CLRP) techniques used to generate P(M)AA brushes with a tailored structure. Next, we discuss biomolecule immobilization methods for P(M)AA brushes, including physical adsorption, covalent binding, and affinity interactions. Finally, typical biomedical applications of P(M)AA brushes are reviewed, and their performance is discussed based on their unique properties. We conclude that P(M)AA brushes are promising biomaterials, and more potential biomedical applications are expected to emerge with the further development of synthetic techniques and increased understanding of their interactions with biological systems.

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

PubMed Central

Maliszewski, Anne M.; Gadhia, Monika M.; O'Meara, Meghan C.; Thorn, Stephanie R.; Rozance, Paul J.

2012-01-01

Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n = 8) or saline [control (Con), n = 10] for ∼12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 ± 0.5 vs. 1.4 ± 0.6 μmol·min−1·kg−1, P < 0.05). Fetal protein accretion (2.6 ± 0.5 and 2.2 ± 0.6 μmol·min−1·kg−1 in AA and Con, respectively), synthesis (6.2 ± 0.8 and 7.0 ± 0.9 μmol·min−1·kg−1 in AA and Con, respectively), and degradation (3.6 ± 0.6 and 4.5 ± 1.0 μmol·min−1·kg−1 in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 ± 0.4 vs. 3.9 ± 0.1 mg·kg−1·min−1, P < 0.05). The glucose-O2 quotient also decreased over time in the AA group (P < 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 ± 24 vs. 59 ± 9 pg/ml, P < 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 ± 181 vs. 419 ± 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r2 = 0.38, P < 0.05), cortisol (r2 = 0.31, P < 0.05), and NE (r2 = 0.59, P < 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids. PMID:22454287

Versatility of acyl-acyl carrier protein synthetases

DOE PAGES

Beld, Joris; Finzel, Kara; Burkart, Michael D.

2014-10-09

The acyl carrier protein (ACP) requires posttranslational modification with a 4'-phosphopantetheine arm for activity, and this thiol-terminated modification carries cargo between enzymes in ACP-dependent metabolic pathways. In this paper, we show that acyl-ACP synthetases (AasSs) from different organisms are able to load even, odd, and unnatural fatty acids onto E. coli ACP in vitro. Vibrio harveyi AasS not only shows promiscuity for the acid substrate, but also is active upon various alternate carrier proteins. AasS activity also extends to functional activation in living organisms. We show that exogenously supplied carboxylic acids are loaded onto ACP and extended by the E.more » coli fatty acid synthase, including unnatural fatty acid analogs. These analogs are further integrated into cellular lipids. Finally, in vitro characterization of four different adenylate-forming enzymes allowed us to disambiguate CoA-ligases and AasSs, and further in vivo studies show the potential for functional application in other organisms.« less

Preparation and characterization of poly(acrylic acid)-hydroxyethyl cellulose graft copolymer.

PubMed

Abdel-Halim, E S

2012-10-01

Poly(acrylic acid) hydroxyethyl cellulose [poly(AA)-HEC] graft copolymer was prepared by polymerizing acrylic acid (AA) with hydroxyethyl cellulose (HEC) using potassium bromate/thiourea dioxide (KBrO(3)/TUD) as redox initiation system. The polymerization reaction was carried out under a variety of conditions including concentrations of AA, KBrO(3) and TUD, material to liquor ratio and polymerization temperature. The polymerization reaction was monitored by withdrawing samples from the reaction medium and measuring the total conversion. The rheological properties of the poly(AA)-HEC graft copolymer were investigated. The total conversion and rheological properties of the graft copolymer depended on the ratio of KBrO(3) to TUD and on acrylic acid concentration as well as temperature and material to liquor ratio. Optimum conditions of the graft copolymer preparation were 30 mmol KBrO(3) and 30 mmol TUD/100g HEC, 100% AA (based on weight of HEC), duration 2h at temperature 50 °C using a material to liquor ratio of 1:10. Copyright © 2012. Published by Elsevier Ltd.

Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

PubMed

Nagahara, Yasuomi; Motoyama, Sadako; Sarai, Masayoshi; Ito, Hajime; Kawai, Hideki; Takakuwa, Yoko; Miyagi, Meiko; Shibata, Daisuke; Takahashi, Hiroshi; Naruse, Hiroyuki; Ishii, Junichi; Ozaki, Yukio

2016-07-01

Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA and CCTA might be useful for risk stratification of CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Lowering rumen-degradable and rumen-undegradable protein improved amino acid metabolism and energy utilization in lactating dairy cows exposed to heat stress.

PubMed

Kaufman, J D; Pohler, K G; Mulliniks, J T; Ríus, A G

2018-01-01

The objective of this study was to evaluate the effects of reducing dietary rumen-degradable protein (RDP) and rumen-undegradable protein (RUP) on protein and energy metabolism in heat-stressed dairy cows. Eighteen primiparous and 30 multiparous mid-lactation Holstein cows were used in a completely randomized design arranged in a 2 × 2 factorial (n = 12/treatment). Cows were randomly assigned to 1 of 4 dietary treatments that included 2 levels of RDP (10 and 8%; D) and 2 levels of RUP (8 and 6%; U) of dry matter for 21 d as (1) 10D:8U, (2) 8D:8U, (3) 10D:6U, and (4) 8D:6U. Diets were isoenergetic and contained 50% forage and 50% concentrate (dry matter basis). Cows were housed in a freestall barn. Three weeks before start of treatments, all animals were fed the 10D:8U diet and received supplemental cooling to prevent heat stress. During the treatment period, cows experienced a daily increment in temperature-humidity index from 74 to 82 for 1000 to 2000 h. Blood samples were collected on d -1 and 21 of the treatment period to determine plasma concentrations of AA, glucose, insulin, fatty acids, and β-hydroxybutyrate. For primiparous cows, reducing from 10 to 8% RDP decreased insulin concentrations. For multiparous cows, we found significant RDP by RUP interactions for insulin, β-hydroxybutyrate, fatty acids, total essential AA, and 3-methylhistidine concentrations. Reducing from 10 to 8% RDP decreased insulin concentrations at 6% RUP, but concentrations did not change when reducing RDP at 8% RUP. Reducing from 10 to 8% RDP decreased β-hydroxybutyrate concentrations at 8% RUP, but concentrations did not change when reducing RDP at 6% RUP. Reducing from 10 to 8% RDP increased nonesterified fatty acid and total essential AA concentrations at 8% RUP, but concentrations did not change when reducing RDP at 6% RUP. Reducing from 8 to 6% RUP decreased 3-methylhistidine concentration at 8% RDP, but not at 10% RDP. Reducing from 8 to 6% RUP increased milk protein yield efficiency in primiparous and multiparous cows. These results indicate that reducing RDP and RUP lowers circulating insulin, which was associated with mobilization and utilization of fatty acids. Reduced RDP and RUP increases the use of AA to maintain milk protein synthesis and limit AA catabolism in cows exposed to warm climates. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of Bacillus subtilis and Bacillus licheniformis supplementation in diets with low- and high-protein content on ileal crude protein and amino acid digestibility and intestinal microbiota composition of growing pigs.

PubMed

Kaewtapee, Chanwit; Burbach, Katharina; Tomforde, Georgina; Hartinger, Thomas; Camarinha-Silva, Amélia; Heinritz, Sonja; Seifert, Jana; Wiltafsky, Markus; Mosenthin, Rainer; Rosenfelder-Kuon, Pia

2017-01-01

Bacillus spp. seem to be an alternative to antimicrobial growth promoters for improving animals' health and performance. However, there is little information on the effect of Bacillus spp. in combination with different dietary crude protein (CP) levels on the ileal digestibility and microbiota composition. Therefore, the objective of this study was to determine the effect of Bacillus spp. supplementation to low- (LP) and high-protein diets (HP) on ileal CP and amino acid (AA) digestibility and intestinal microbiota composition. Eight ileally cannulated pigs with an initial body weight of 28.5 kg were randomly allocated to a row-column design with 8 pigs and 3 periods of 16 d each. The assay diets were based on wheat-barley-soybean meal with two protein levels: LP (14% CP, as-fed) and HP diet (18% CP, as-fed). The LP and HP diets were supplemented with or without Bacillus spp. at a level of 0.04% (as-fed). The apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of CP and AA was determined. Bacterial community composition from ileal digesta was analyzed by Illumina amplicon sequencing and quantitative real-time PCR. Data were analyzed as a 2 × 2 factorial design using the GLIMMIX procedures of SAS. The supplementation with Bacillus spp. did not affect both AID and SID of CP and AA in growing pigs. Moreover, there was no difference in AID of CP and AA between HP and LP diets, but SID of cystine, glutamic acid, glycine, and proline was lower ( P  < 0.05) in pigs fed the HP diets. The HP diets increased abundance of Bifidobacterium spp. and Lactobacillus spp., ( P  < 0.05) and by amplicon sequencing the latter was identified as predominant genus in microbiota from HP with Bacillus spp., whereas dietary supplementation of Bacillus spp. increased ( P  < 0.05) abundance of Roseburia spp.. The HP diet increased abundance of Lactobacillus spp. and Bifidobacterium spp.. The supplementation of Bacillus spp. resulted in a higher abundance of healthy gut associated bacteria without affecting ileal CP and AA digestibility, whereas LP diet may reduce the flow of undigested protein to the large intestine of pigs.

Leucine and methionine deficiency induce catabolism through non-overlapping mechanisms in rainbow trout (Oncorhynchus mykiss) primary myoblasts

USDA-ARS?s Scientific Manuscript database

Amino acids (AA) have anabolic effects on protein accretion in muscle. In fish it is unknown if this anabolic response is directly attributed to a single AA or a specific AA profile. Therefore, our experimental objective was to determine if AAs or AA profiles regulate protein turnover and growth-r...

The role of amino acids in hydroxyapatite mineralization

PubMed Central

2016-01-01

Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone mineral density by stimulating growth hormone production. In vitro studies suggest that the role of AAs in controlling HA precipitation is affected by their mobility. While dissolved AAs are able to inhibit HA precipitation and growth by chelating Ca2+ and PO43− ions or binding to nuclei of calcium phosphate and preventing their further growth, AAs bound to surfaces can promote HA precipitation by attracting Ca2+ and PO43− ions and increasing the local supersaturation. Overall, the effect of AAs on HA precipitation is worth being investigated more, especially under conditions closer to the physiological ones, where the presence of other factors such as collagen, mineralization inhibitors, and cells heavily influences HA precipitation. A deeper understanding of the role of AAs in HA mineralization will increase our fundamental knowledge related to bone formation, and could lead to new therapies to improve bone regeneration in damaged tissues or cure pathological diseases caused by excessive mineralization in tissues such as cartilage, blood vessels and cardiac valves. PMID:27707904

Effects of a novel SNP of IGF2R gene on growth traits and expression rate of IGF2R and IGF2 genes in gluteus medius muscle of Egyptian buffalo.

PubMed

El-Magd, Mohammed Abu; Abo-Al-Ela, Haitham G; El-Nahas, Abeer; Saleh, Ayman A; Mansour, Ali A

2014-05-01

Insulin-like growth factor 2 receptor (IGF2R) is responsible for degradation of the muscle development initiator, IGF2, and thus it can be used as a marker for selection strategies in the farm animals. The aim of this study was to search for polymorphisms in three coding loci of IGF2R, and to analyze their effect on the growth traits and on the expression levels of IGF2R and IGF2 genes in the gluteus medius muscle of Egyptian buffaloes. A novel A266C SNP was detected in the coding sequences of the third IGF2R locus (at nucleotide number 51 of exon 23) among Egyptian water buffaloes. This SNP was non-synonymous mutation and led to replacement of Y (tyrosine) amino acid (aa) by D (aspartic acid) aa. Three different single-strand conformation polymorphism patterns were observed in the third IGF2R locus: AA, AC, and CC with frequencies of 0.555, 0.195, and 0.250, respectively. Statistical analysis showed that the homozygous AA genotype significantly associated with the average daily gain than AC and CC genotypes from birth to 9 mo of age. Expression analysis showed that the A266C SNP was correlated with IGF2, but not with IGF2R, mRNA levels in the gluteus medius muscle of Egyptian buffaloes. The highest IGF2 mRNA level was estimated in the muscle of animals with the AA homozygous genotype as compared to the AC heterozygotes and CC homozygotes. We conclude that A266C SNP at nucleotide number 51 of exon 23 of the IGF2R gene is associated with the ADG during the early stages of life (from birth to 9 mo of age) and this effect is accompanied by, and may be caused by, increased expression levels of the IGF2 gene. Copyright © 2014 Elsevier B.V. All rights reserved.

Functionalized-graphene modified graphite electrode for the selective determination of dopamine in presence of uric acid and ascorbic acid.

PubMed

Mallesha, Malledevaru; Manjunatha, Revanasiddappa; Nethravathi, C; Suresh, Gurukar Shivappa; Rajamathi, Michael; Melo, Jose Savio; Venkatesha, Thimmappa Venkatarangaiah

2011-06-01

Graphene is chemically synthesized by solvothermal reduction of colloidal dispersions of graphite oxide. Graphite electrode is modified with functionalized-graphene for electrochemical applications. Electrochemical characterization of functionalized-graphene modified graphite electrode (FGGE) is carried out by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The behavior of FGGE towards ascorbic acid (AA), dopamine (DA) and uric acid (UA) has been investigated by CV, differential pulse voltammetry (DPV) and chronoamperommetry (CA). The FGGE showed excellent catalytic activity towards electrochemical oxidation of AA, DA and UA compared to that of the bare graphite electrode. The electrochemical oxidation signals of AA, DA and UA are well separated into three distinct peaks with peak potential separation of 193mv, 172mv and 264mV between AA-DA, DA-UA and AA-UA respectively in CV studies and the corresponding peak potential separations in DPV mode are 204mv, 141mv and 345mv. The FGGE is successfully used for the simultaneous detection of AA, DA and UA in their ternary mixture and DA in serum and pharmaceutical samples. The excellent electrocatalytic behavior of FGGE may lead to new applications in electrochemical analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size of Amino Acid by Decreasing Expression of Specific Transporters in the Small Intestine

PubMed Central

Luo, Min; Zhang, Xin; Sun, Wen Juan; Jiao, Ning; Li, De Fa; Yin, Jing Dong

2016-01-01

Dietary protein restriction is not only beneficial to health and longevity in humans, but also protects against air pollution and minimizes feeding cost in livestock production. However, its impact on amino acid (AA) absorption and metabolism is not quite understood. Therefore, the study aimed to explore the effect of protein restriction on nitrogen balance, circulating AA pool size, and AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 ± 1.5 kg were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial. Growth (n = 24), nitrogen balance (n = 6), and the expression of small intestinal AA and peptide transporters (n = 6) were evaluated. In Exp.2, 12 barrows weighting 22.7 ± 1.3 kg were surgically fitted with catheters in the portal and jejunal veins as well as the carotid artery and assigned to a diet containing 14 or 18% CP. A series of blood samples were collected before and after feeding for determining the pool size of circulating AA and AA absorption in the portal vein, respectively. Protein restriction did not sacrifice body weight gain and protein retention, since nitrogen digestibility was increased as dietary protein content reduced. However, the pool size of circulating AA except for lysine and threonine, and most AA flux through the portal vein were reduced in pigs fed the low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1) was stimulated, but the expression of the neutral and cationic AA transporter systems was depressed. These results evidenced that protein restriction with essential AA-balanced diets, decreased AA absorption and reduced circulating AA pool size. Increased expression of small intestinal peptide transporter PepT-1 could not compensate for the depressed expression of jejunal AA transporters for AA absorption. PMID:27611307

A comparison study on flesh quality of large yellow croaker ( Larimichthys croceus) cultured with three different modes

NASA Astrophysics Data System (ADS)

Li, Xiaoqin; Li, Baian; Chen, Naisong; Huang, Xuxiong; Hua, Xuemin; Leng, Xiangjun

2017-12-01

To compare the flesh quality of large yellow croaker cultured with three different modes, enclosure culture (EC), cage culture with feeding trash fish (CCF) and cage culture with feeding formula diet (CCD), thirty six fish individuals of EC (484.6 ± 79.8 g), CCF (432.7 ± 87.9 g) and CCD (416.9 ± 49.5 g) were sampled to measure body color, flesh water holding capacity, flesh proximate composition, amino acids and fatty acids composition, and collagen and inosinic acid contents. The analysis showed that there was no significant difference in the yellowness of skin and the contents of crude protein and inosinic acid between CCD and EC (P >0.05), and the two modes showed higher values than CCF ( P < 0.05). Most of the amino acids (AA) in flesh were higher in EC than in CCF ( P < 0.05), but CCD showed no difference in AA composition from the other two modes ( P > 0.05). EC and CCD had higher contents of collagen, free AA and lower drip loss than CC ( P < 0.05). In polyunsaturated fatty acids, EC showed significantly higher levels of C20:5n-3 and C22:6n-3 than CCF and CCD ( P < 0.05), but CCD had significantly higher C18:2n-6 than CCF and EC ( P < 0.05). In conclusion, the flesh quality of CCD fish is similar to EC fish, and these two modes have better flesh quality than CCF.

Hydrocortisone selectively inhibits IgE-dependent arachidonic acid release from rat peritoneal mast cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heiman, A.S.; Crews, F.T.

Purified rat mst cells were used to study the effects of antiinflammatory steroids on the release of (1-14C)-arachidonic acid ((1-14C)AA) and metabolites. Mast cell were incubated overnight with glucocorticoids, (1-14C)AA incorporated into cellular phospholipids and the release of (1-14C)AA, and metabolites determined using a variety of secretagogues. Release of (1-14C)AA and metabolites by concanavalin A, the antigen ovalbumin and anti-immunoglobulin E antibody was markedly reduced by glucocorticoid treatment. Neither the total incorporation of (1-14C)AA nor the distribution into phospholipids was altered by hydrocortisone pretreatment. Glucocorticoid pretreatment did not alter (1-14C)AA release stimulated by somatostatin, compound 48/80, or the calcium ionophore,more » A23187. These data indicate that antiinflammatory steroids selectively inhibit immunoglobulin dependent release of arachidonic acid from rat mast cells. These findings question the role of lipomodulin and macrocortin as general phospholipase inhibitors and suggest that they may be restricted to immunoglobulin stimuli.« less

Acetic acid in aged vinegar affects molecular targets for thrombus disease management.

PubMed

Jing, Li; Yanyan, Zhang; Junfeng, Fan

2015-08-01

To elucidate the mechanism underlying the action of dietary vinegar on antithrombotic activity, acetic acid, the main acidic component of dietary vinegar, was used to determine antiplatelet and fibrinolytic activity. The results revealed that acetic acid significantly inhibits adenosine diphosphate (ADP)-, collagen-, thrombin-, and arachidonic acid (AA)-induced platelet aggregation. Acetic acid (2.00 mM) reduced AA-induced platelet aggregation to approximately 36.82 ± 1.31%, and vinegar (0.12 mL L(-1)) reduced the platelet aggregation induced by AA to 30.25 ± 1.34%. Further studies revealed that acetic acid exerts its effects by inhibiting cyclooxygenase-1 and the formation of thromboxane-A2. Organic acids including acetic acid, formic acid, lactic acid, citric acid, and malic acid also showed fibrinolytic activity; specifically, the fibrinolytic activity of acetic acid amounted to 1.866 IU urokinase per mL. Acetic acid exerted its fibrinolytic activity by activating plasminogen during fibrin crossing, thus leading to crosslinked fibrin degradation by the activated plasmin. These results suggest that organic acids in dietary vinegar play important roles in the prevention and cure of cardiovascular diseases.

A Novel Glucosylation Reaction on Anthocyanins Catalyzed by Acyl-Glucose–Dependent Glucosyltransferase in the Petals of Carnation and Delphinium[C][W

PubMed Central

Matsuba, Yuki; Sasaki, Nobuhiro; Tera, Masayuki; Okamura, Masachika; Abe, Yutaka; Okamoto, Emi; Nakamura, Haruka; Funabashi, Hisakage; Takatsu, Makoto; Saito, Mikako; Matsuoka, Hideaki; Nagasawa, Kazuo; Ozeki, Yoshihiro

2010-01-01

Glucosylation of anthocyanin in carnations (Dianthus caryophyllus) and delphiniums (Delphinium grandiflorum) involves novel sugar donors, aromatic acyl-glucoses, in a reaction catalyzed by the enzymes acyl-glucose–dependent anthocyanin 5(7)-O-glucosyltransferase (AA5GT and AA7GT). The AA5GT enzyme was purified from carnation petals, and cDNAs encoding carnation Dc AA5GT and the delphinium homolog Dg AA7GT were isolated. Recombinant Dc AA5GT and Dg AA7GT proteins showed AA5GT and AA7GT activities in vitro. Although expression of Dc AA5GT in developing carnation petals was highest at early stages, AA5GT activity and anthocyanin accumulation continued to increase during later stages. Neither Dc AA5GT expression nor AA5GT activity was observed in the petals of mutant carnations; these petals accumulated anthocyanin lacking the glucosyl moiety at the 5 position. Transient expression of Dc AA5GT in petal cells of mutant carnations is expected to result in the transfer of a glucose moiety to the 5 position of anthocyanin. The amino acid sequences of Dc AA5GT and Dg AA7GT showed high similarity to glycoside hydrolase family 1 proteins, which typically act as β-glycosidases. A phylogenetic analysis of the amino acid sequences suggested that other plant species are likely to have similar acyl-glucose–dependent glucosyltransferases. PMID:20971893

Toward mosquito control with a green alga: Expression of Cry toxins of Bacillus thuringiensis subsp. israelensis (Bti) in the chloroplast of Chlamydomonas

PubMed Central

Kang, Seongjoon; Odom, Obed W.; Thangamani, Saravanan; Herrin, David L.

2016-01-01

We are developing Chlamydomonas strains that can be used for safe and sustainable control of mosquitoes, because they produce proteins from Bacillus thuringiensis subsp. israelensis (Bti) in the chloroplast. Chlamydomonas has a number of advantages for this approach, including genetic controls that are not generally available with industrial algae. The Bti toxin has been used for mosquito control for > 30 years and does not engender resistance; it contains three Cry proteins, Cry4Aa (135 kDa), Cry4Ba (128 kDa) and Cry11Aa (72 kDa), and Cyt1Aa (25 kDa). To express the Cry proteins in the chloroplast, the three genes were resynthesized and cry4Aa was truncated to the first 700 amino acids (cry4Aa700); also, since they can be toxic to host cells, the inducible Cyc6:Nac2-psbD expression system was used. Western blots of total protein from the chloroplast transformants showed accumulation of the intact polypeptides, and the relative expression level was Cry11Aa > Cry4Aa700 > Cry4Ba. Quantitative western blots with purified Cry11Aa as a standard showed that Cry11Aa accumulated to 0.35% of total cell protein. Live cell bioassays in dH20 demonstrated toxicity of the cry4Aa700 and cry11Aa transformants to larvae of Aedes aegypti and Culex quinquefasciatus. These results demonstrate that the Cry proteins that are most toxic to Aedes and Culex mosquitoes, Cry4Aa and Cry11Aa, can be successfully expressed in the chloroplast of Chlamydomonas. PMID:28713202

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

PubMed Central

Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

2014-01-01

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117

Determination and stereochemistry of proteinogenic and non-proteinogenic amino acids in Saudi Arabian date fruits.

PubMed

Ali, Hatem Salama Mohamed; Alhaj, Omar Amin; Al-Khalifa, Abdulrahman Saleh; Brückner, Hans

2014-09-01

Whereas an abundance of literature is available on the occurrence of common proteinogenic amino acids (AAs) in edible fruits of the date palm (Phoenix dactylifera L.), recent reports on non-proteinogenic (non-coded) AAs and amino components are scarce. With emphasis on these components we have analyzed total hydrolysates of twelve cultivars of date fruits using automated ion-exchange chromatography, HPLC employing a fluorescent aminoquinolyl label, and GC-MS of total hydrolysates using the chiral stationary phases Chirasil(®)-L-Val and Lipodex(®) E. Besides common proteinogenic AAs, relatively large amounts of the following non-proteinogenic amino acids were detected: (2S,5R)-5-hydroxypipecolic acid (1.4-4.0 g/kg dry matter, DM), 1-aminocyclopropane-1-carboxylic acid (1.3-2.6 g/kg DM), γ-amino-n-butyric acid (0.5-1.2 g/kg DM), (2S,4R)-4-hydroxyproline (130-230 mg/kg DM), L-pipecolic acid (40-140 mg/kg DM), and 2-aminoethanol (40-160 mg/kg DM) as well as low or trace amounts (<70 mg/kg DM) of L-ornithine, 5-hydroxylysine, β-alanine, and in some samples (<20 mg/kg DM) of (S)-β-aminoisobutyric acid and (<10 mg/kg DM) L-allo-isoleucine. In one date fruit, traces of α-aminoadipic acid could be determined. Enantiomeric analysis of 6 M DCl/D2O hydrolysates of AAs using chiral capillary gas chromatography-mass spectrometry revealed the presence of very low amounts of D-Ala, D-Asp, D-Glu, D-Ser and D-Phe (1.2-0.4%, relative to the corresponding L-enantiomers), besides traces (0.2-1%) of other D-AAs. The possible relevance of non-proteinogenic amino acids in date fruits is briefly addressed.

Targeting 2.5 versus 4 g/kg/day of amino acids for extremely low birth weight infants: a randomized clinical trial.

PubMed

Burattini, Ilaria; Bellagamba, Maria Paola; Spagnoli, Cristina; D'Ascenzo, Rita; Mazzoni, Nadia; Peretti, Anna; Cogo, Paola E; Carnielli, Virgilio P

2013-11-01

To compare the effect of 2.5 vs 4 g/kg/d of amino acid (AA) in parenteral nutrition of extremely low birth weight infants on metabolic tolerance, short-term growth, and neurodevelopment. One hundred thirty-one infants with birth weight between 500 and 1249 g were randomized to 2.5 (standard AA [SAA] group) or 4 (high AA [HAA] group) g/kg/d AA intake, with equal nonprotein energy. The primary outcome was body size at 36 weeks. One hundred thirty-one patients were randomized and 114 analyzed (58 SAA group and 56 HAA group). Study groups had similar demographics and clinical characteristics. Elevated blood urea (BU >70 mg/dL = BU nitrogen >32.6 mg/dL) occurred in 24% vs 59% (P = .000) and hyperglycemia (>175 mg/dL) in 34% vs 11% (P = .003) of the SAA and HAA patients, respectively. Body weight, length, and head circumference at 36 weeks and 2 years were similar between groups. Bayley Scales of Infant and Toddler Development, Third Edition score was 94 ± 13 in the SAA group and 97 ± 15 in the HAA group (P = .35). The HAA group had higher BU levels and better glucose control. An extra 8 g/kg of AA over the first 10 days of life did not improve growth and neurodevelopment. Copyright © 2013 Mosby, Inc. All rights reserved.

A combination of additives can synergically decrease acrylamide content in gingerbread without compromising sensory quality.

PubMed

Komprda, Tomáš; Pridal, Antonin; Mikulíková, Renata; Svoboda, Zdeněk; Cwiková, Olga; Nedomová, Šárka; Sýkora, Vladimír

2017-02-01

The present study tested whether replacement of the leavening agent ammonium carbonate by sodium hydrogen carbonate in combination with calcium cation and acidifying agent will synergically decrease acrylamide (AA) content in gingerbread. The type of leavening agent and the presence of Ca 2+ and citric acid accounted for 33.6%, 13.2% and 53.2% of the explained variability of the AA content, respectively (P < 0.01). The AA content in gingerbread produced with (NH 4 ) 2 CO 3 alone was 186.5 µg kg -1 . Irrespective of other tested additives, NaHCO 3 decreased (P < 0.05) AA content to 42% compared to (NH 4 ) 2 CO 3 . Combination of NaHCO 3 + CaCl 2 + citric acid in dough reduced (P < 0.05) AA content below the limit of detection (25 µg kg -1 ). The AA content in gingerbread (y; µg kg -1 ) decreased with an increasing number of additives used (x) according to the equation y = 158.8 - 47.94x (r 2 = 0.42; P < 0.0001). A comprehensive sensory analysis did not indicate any significant deterioration (P > 0.05) in the organoleptic quality of gingerbread produced using calcium cation and citric acid. The present study demonstrates that the combination of additives NaHCO 3 /Ca 2+ /citric acid synergically decreases AA content in gingerbread without compromising the sensory quality. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Graft polymerization of acrylic acid onto chitin nanofiber to improve dispersibility in basic water.

PubMed

Ifuku, Shinsuke; Iwasaki, Masayoshi; Morimoto, Minoru; Saimoto, Hiroyuki

2012-09-01

Graft copolymerization of acrylic acid (AA) on chitin nanofibers was carried out with potassium persulfate as a free radical initiator in an aqueous medium. The molar ratio of grafted AA increased with the AA concentration. The grafted chitin nanofibers were characterized by FT-IR, FE-SEM, UV-vis, XRD, and TGA. After polymerization, the characteristic morphology of chitin nanofibers was maintained. Chitin nanofibers grafted with AA were efficiently dissociated and dispersed homogeneously in basic water because of the electrostatic repulsion effect between nanofibers. AA was grafted on the surface and amorphous part of chitin nanofibers, and the original crystalline structure of α-chitin was maintained. At 330 °C, the weight residue of the graft copolymer increased with the grafted AA content. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ligand-independent activation of EphA2 by arachidonic acid induces metastasis-like behaviour in prostate cancer cells

PubMed Central

Tawadros, T; Brown, M D; Hart, C A; Clarke, N W

2012-01-01

Background: High intake of omega-6 polyunsaturated fatty acids (PUFA) has been associated with clinical progression in prostate cancer (CaP). This study investigates the signalling mechanism by which the omega-6 PUFA arachidonic acid (AA) induces prostatic cellular migration to bone marrow stroma. Methods: Western blot analysis of the PC-3, PC3-GFP, DU 145 and LNCaP cells or their lipid raft (LR) components post AA stimulation was conducted in association with assays for adhesion and invasion through the bone marrow endothelial monolayers. Results: Arachidonic acid increased transendothelial migration of PC3-GFP cells (adhesion 37%±0.08, P=0.0124; transmigration 270%±0.145, P=0.0008). Akt, Src and focal adhesion kinase (FAK) pathways were induced by AA and integrally involved in transendothelial migration. LR were critical in AA uptake and induced Akt activity. Ephrin receptor A2 (EphA2), localised in LR, is expressed in DU 145 and PC-3 cells. Arachidonic acid induced a rapid increase of EphA2 Akt-dependent/ligand-independent activation, while knockdown of the EphrinA1 ligand decreased AA induced transendothelial migration, with an associated decrease in Src and FAK activity. Arachidonic acid activated Akt in EphA2− LNCaP cells but failed to induce BMEC transendothelial invasion. Conclusion: Arachidonic acid induced stimulation of EphA2 in vitro is associated fundamentally with CaP epithelial migration across the endothelial barrier. PMID:23037715

A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner

PubMed Central

Ramírez-López, María Teresa; Vázquez, Mariam; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemi; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Bindila, Laura

2017-01-01

Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight. PMID:28346523

A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner.

PubMed

Ramírez-López, María Teresa; Vázquez, Mariam; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemi; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Bindila, Laura; Rodríguez de Fonseca, Fernando

2017-01-01

Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight.

Different Fatty Acids Compete with Arachidonic Acid for Binding to the Allosteric or Catalytic Subunits of Cyclooxygenases to Regulate Prostanoid Synthesis*

PubMed Central

Dong, Liang; Zou, Hechang; Yuan, Chong; Hong, Yu H.; Kuklev, Dmitry V.; Smith, William L.

2016-01-01

Prostaglandin endoperoxide H synthases (PGHSs), also called cyclooxygenases (COXs), convert arachidonic acid (AA) to PGH2. PGHS-1 and PGHS-2 are conformational heterodimers, each composed of an (Eallo) and a catalytic (Ecat) monomer. Previous studies suggested that the binding to Eallo of saturated or monounsaturated fatty acids (FAs) that are not COX substrates differentially regulate PGHS-1 versus PGHS-2. Here, we substantiate and expand this concept to include polyunsaturated FAs known to modulate COX activities. Non-substrate FAs like palmitic acid bind Eallo of PGHSs stimulating human (hu) PGHS-2 but inhibiting huPGHS-1. We find the maximal effects of non-substrate FAs on both huPGHSs occurring at the same physiologically relevant FA/AA ratio of ∼20. This inverse allosteric regulation likely underlies the ability of PGHS-2 to operate at low AA concentrations, when PGHS-1 is effectively latent. Unlike FAs tested previously, we observe that C-22 FAs, including ω-3 fish oil FAs, have higher affinities for Ecat than Eallo subunits of PGHSs. Curiously, C-20 ω-3 eicosapentaenoate preferentially binds Ecat of huPGHS-1 but Eallo of huPGHS-2. PGE2 production decreases 50% when fish oil consumption produces tissue EPA/AA ratios of ≥0.2. However, 50% inhibition of huPGHS-1 itself is only seen with ω-3 FA/AA ratios of ≥5.0. This suggests that fish oil-enriched diets disfavor AA oxygenation by altering the composition of the FA pool in which PGHS-1 functions. The distinctive binding specificities of PGHS subunits permit different combinations of non-esterified FAs, which can be manipulated dietarily, to regulate AA binding to Eallo and/or Ecat thereby controlling COX activities. PMID:26703471

Morphological assessment of bone mineralization in tibial metaphyses of ascorbic acid-deficient ODS rats.

PubMed

Hasegawa, Tomoka; Li, Minqi; Hara, Kuniko; Sasaki, Muneteru; Tabata, Chihiro; de Freitas, Paulo Henrique Luiz; Hongo, Hiromi; Suzuki, Reiko; Kobayashi, Masatoshi; Inoue, Kiichiro; Yamamoto, Tsuneyuki; Oohata, Noboru; Oda, Kimimitsu; Akiyama, Yasuhiro; Amizuka, Norio

2011-08-01

Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone formation, we have examined the bone mineralization in this rat model. A fibrous tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def ODS rats, and this layer showed intense alkaline phosphatase activity and proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached from the bone surfaces and were characterized by round-shaped rough endoplasmic reticulum (rER), suggesting accumulation of malformed collagen inside the rER. Accordingly, fine, fragile fibrillar collagenous structures without evident striation were found in aa-def bones, which may result from misassembling of the triple helices of collagenous α-chains. Despite a marked reduction in bone formation, ascorbic acid deprivation seemed to have no effect on mineralization: while reduced in number, normal matrix vesicles and mineralized nodules could be seen in aa-def bones. Fine needle-like mineral crystals extended from these mineralized nodules, and were apparently bound to collagenous fibrillar structures. In summary, collagen mineralization seems unaffected by ascorbic acid deficiency in spite of the fine, fragile collagenous fibrils identified in the bones of our animal model.

Compound-specific amino acid δ15N patterns in marine algae: Tracer potential for cyanobacterial vs. eukaryotic organic nitrogen sources in the ocean

NASA Astrophysics Data System (ADS)

McCarthy, Matthew D.; Lehman, Jennifer; Kudela, Raphael

2013-02-01

Stable nitrogen isotopic analysis of individual amino acids (δ15N-AA) has unique potential to elucidate the complexities of food webs, track heterotrophic transformations, and understand diagenesis of organic nitrogen (ON). While δ15N-AA patterns of autotrophs have been shown to be generally similar, prior work has also suggested that differences may exist between cyanobacteria and eukaryotic algae. However, δ15N-AA patterns in differing oceanic algal groups have never been closely examined. The overarching goals of this study were first to establish a more quantitative understanding of algal δ15N-AA patterns, and second to examine whether δ15N-AA patterns have potential as a new tracer for distinguishing prokaryotic vs. eukaryotic N sources. We measured δ15N-AA from prokaryotic and eukaryotic phytoplankton cultures and used a complementary set of statistical approaches (simple normalization, regression-derived fractionation factors, and multivariate analyses) to test for variations. A generally similar δ15N-AA pattern was confirmed for all algae, however significant AA-specific variation was also consistently identified between the two groups. The relative δ15N fractionation of Glx (glutamine + glutamic acid combined) vs. total proteinaceous N appeared substantially different, which we hypothesize could be related to differing enzymatic forms. In addition, the several other AA (most notably glycine and leucine) appeared to have strong biomarker potential. Finally, we observed that overall patterns of δ15N values in algae correspond well with the Trophic vs. Source-AA division now commonly used to describe variable AA δ15N changes with trophic transfer, suggesting a common mechanistic basis. Overall, these results show that autotrophic δ15N-AA patterns can differ between major algal evolutionary groupings for many AA. The statistically significant multivariate results represent a first approach for testing ideas about relative eukaryotic vs. prokaryotic ON sources in the sea.

Risk of secondary lymphedema in breast cancer survivors is related to serum phospholipid fatty acid desaturation.

PubMed

Ryu, Eunjung; Yim, Seung Yun; Do, Hyun Ju; Lim, Jae-Young; Yang, Eun Joo; Shin, Min-Jeong; Lee, Seung-Min

2016-09-01

Secondary lymphedema is a common irreversible side effect of breast cancer surgery. We investigated if risk of secondary lymphedema in breast cancer survivors was related to changes in serum phospholipid fatty acid composition. Study subjects were voluntarily recruited into the following three groups: breast cancer survivors who had sentinel lymph node biopsy without lymphedema (SLNB), those who had auxillary lymph node dissection without lymphedema (ALND), and those who had ALND with lymphedema (ALND + LE). Body mass index (BMI), serum lipid profiles, bioimpedance data with single-frequency bioimpedance analysis (SFBIA), and serum phospholipid compositions were analyzed and compared among the groups. BMI, serum total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) and SFBIA ratios increased only in the ALND + LE. High polyunsaturated fatty acids (PUFAs) and high C20:4 to C18:2 n-6 PUFAs (arachidonic acid [AA]/linoleic acid [LA]) was detected in the ALND and ALND + LE groups compared to SLNB. The ALND + LE group showed increased activity indices for delta 6 desaturase (D6D) and D5D and increased ratio of AA to eicosapentaenoic acid (AA/EPA) compared to the ALND and SLNB groups. Correlation and regression analysis indicated that D6D, D5D, and AA/EPA were associated with SFBIA ratios. We demonstrated that breast cancer survivors with lymphedema had elevated total PUFAs, fatty acid desaturase activity indices, and AA/EPA in serum phospholipids. Our findings suggested that desaturation extent of fatty acid composition might be related to the risk of secondary lymphedema in breast cancer survivors.

Hydroxyapatite formation on graphene oxide modified with amino acids: arginine versus glutamic acid

PubMed Central

Tavafoghi, M.; Brodusch, N.; Gauvin, R.; Cerruti, M.

2016-01-01

Hydroxyapatite (HA, Ca5(PO4)3OH) is the main inorganic component of hard tissues, such as bone and dentine. HA nucleation involves a set of negatively charged phosphorylated proteins known as non-collagenous proteins (NCPs). These proteins attract Ca2+ and PO43− ions and increase the local supersaturation to a level required for HA precipitation. Polar and charged amino acids (AAs) are highly expressed in NCPs, and seem to be responsible for the mineralizing effect of NCPs; however, the individual effect of these AAs on HA mineralization is still unclear. In this work, we investigate the effect of a negatively charged (Glu) and positively charged (Arg) AA bound to carboxylated graphene oxide (CGO) on HA mineralization in simulated body fluids (SBF). Our results show that Arg induces HA precipitation faster and in larger amounts than Glu. We attribute this to the higher stability of the complexes formed between Arg and Ca2+ and PO43− ions, and also to the fact that Arg exposes both carboxyl and amino groups on the surface. These can electrostatically attract both Ca2+ and PO43− ions, thus increasing local supersaturation more than Glu, which exposes carboxyl groups only. PMID:26791001

Hydroxyapatite formation on graphene oxide modified with amino acids: arginine versus glutamic acid.

PubMed

Tavafoghi, M; Brodusch, N; Gauvin, R; Cerruti, M

2016-01-01

Hydroxyapatite (HA, Ca5(PO4)3OH) is the main inorganic component of hard tissues, such as bone and dentine. HA nucleation involves a set of negatively charged phosphorylated proteins known as non-collagenous proteins (NCPs). These proteins attract Ca(2+) and PO4(3-) ions and increase the local supersaturation to a level required for HA precipitation. Polar and charged amino acids (AAs) are highly expressed in NCPs, and seem to be responsible for the mineralizing effect of NCPs; however, the individual effect of these AAs on HA mineralization is still unclear. In this work, we investigate the effect of a negatively charged (Glu) and positively charged (Arg) AA bound to carboxylated graphene oxide (CGO) on HA mineralization in simulated body fluids (SBF). Our results show that Arg induces HA precipitation faster and in larger amounts than Glu. We attribute this to the higher stability of the complexes formed between Arg and Ca(2+) and PO4(3-) ions, and also to the fact that Arg exposes both carboxyl and amino groups on the surface. These can electrostatically attract both Ca(2+) and PO4(3-) ions, thus increasing local supersaturation more than Glu, which exposes carboxyl groups only. © 2016 The Author(s).

The gut microbiota modulates host amino acid and glutathione metabolism in mice

PubMed Central

Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias; Ghaffari, Pouyan; Zhang, Cheng; Larsson, Erik; Bäckhed, Fredrik; Nielsen, Jens

2015-01-01

The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N-acetylated AAs in the hepatic portal vein of CONV-R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV-R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice. PMID:26475342

Amino Acid Intakes Are Inversely Associated with Arterial Stiffness and Central Blood Pressure in Women.

PubMed

Jennings, Amy; MacGregor, Alex; Welch, Ailsa; Chowienczyk, Phil; Spector, Tim; Cassidy, Aedín

2015-09-01

Although data suggest that intakes of total protein and specific amino acids (AAs) reduce blood pressure, data on other cardiovascular disease risk factors are limited. We examined associations between intakes of AAs with known mechanistic links to cardiovascular health and direct measures of arterial stiffness, central blood pressure, and atherosclerosis. In a cross-sectional study of 1898 female twins aged 18-75 y from the TwinsUK registry, intakes of 7 cardioprotective AAs (arginine, cysteine, glutamic acid, glycine, histidine, leucine, and tyrosine) were calculated from food-frequency questionnaires. Direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (cSBP), mean arterial pressure (MAP), augmentation index (AI), pulse wave velocity (PWV), and intima-media thickness (IMT). ANCOVA was used to assess the associations between endpoints of arterial stiffness and intake (per quintile), adjusting for potential confounders. In multivariable analyses, higher intakes of total protein and 7 potentially cardioprotective AAs were associated with lower cSBP, MAP, and PWV. Higher intakes of glutamic acid, leucine, and tyrosine were most strongly associated with PWV, with respective differences of -0.4 ± 0.2 m/s (P-trend = 0.02), -0.4 ± 0.2 m/s (P-trend = 0.03), and -0.4 ± 0.2 m/s (P-trend = 0.03), comparing extreme quintiles. There was a significant interaction between AA intakes and protein source, and higher intakes of AAs from vegetable sources were associated with lower central blood pressure and AI. Higher intakes of glutamic acid, leucine, and tyrosine from animal sources were associated with lower PWV. These data provide evidence to suggest that intakes of several AAs are associated with cardiovascular benefits beyond blood pressure reduction in healthy women. The magnitude of the observed associations was similar to those previously reported for other lifestyle factors. Increasing intakes of these AAs could be an important and readily achievable way to reduce cardiovascular disease risk.

[Effect of phospholipids containing omega-3 fatty acids on structural changes of microsomal lipids in cell membranes of functionally different cells].

PubMed

Datsenko, Z M; Volkov, H L; Kryvenko, O M; Nechytaĭlo, L O; Shovkun, S A; Khmel', T O; Perederiĭ, O F

2002-01-01

As a result of the experimental researches conducted it has been shown that administration of some normal animal marine phospholipids (PL) including in their structure omega-3 polyunsaturated fatty acids (PUFA) provides for quantitative changes of individual PL, fatty acids (FA) content and quantity in general and individual PL of liver, heart, brain and gonads microsomes. While estimating general microsomal PL fraction FA content under the action of PL omega-3 PUFA FA concentration change, unsaturation index (omega 6/omega 3) and relation of arachidonic acid to docosahexenic (AA/DHA) decrease have been identified. The decrease of AA/DHA relationship occurs due to AA and DHA quantitative changes. In the case of AA increase in some tissues there is observed the decrease of docosapentaenic acid and increase of DHA and eucosapentaenic (EPA) acidds. As a result of studying FA content in the individual PL composition it has been identified that certain PL classes characteristic for some tissues respond by changes of some certain FA. The relationship omega 6/omega 3 has been shown as decreasing in phosphatidilcholine (PC) all tissues microsomes (liver, gonads, heart, brain), in phosphatidilethanolamine (PEA) of liver and cardiac microsomes, in phosphatidilserine (PS) this relationship relationship decreases in the liver, brain and heart, for phosphatidilinositole (PI) the changes take place in liver, gonads, brain. Simultaneously, the decrease of AA/DHA relationship in the individual PL decrease of AA and increase of EPA and DHA depend on the tested tissues. The marine phospholipids might be supposed to render their effect on AA metabolism resulting in AA/DHA relationship in PEA and PS relationship displays itself as specific and depends on the tissues functions. The preference of PEA and PS use by certain tissues microsomes could be explained by their membrane protective capability.

Selection of the Strain Lactobacillus acidophilus ATCC 43121 and Its Application to Brewers' Spent Grain Conversion into Lactic Acid

PubMed Central

Liguori, Rossana; Soccol, Carlos Ricardo; Vandenberghe, Luciana Porto de Souza; Woiciechowski, Adenise Lorenci; Ionata, Elena; Marcolongo, Loredana; Faraco, Vincenza

2015-01-01

Six Lactobacillus strains were analyzed to select a bacterium for conversion of brewers' spent grain (BSG) into lactic acid. Among the investigated strains, L. acidophilus ATCC 43121 showed the highest yield of lactic acid production (16.1 g/L after 48 hours) when grown in a synthetic medium. It was then analyzed for its ability to grow on the hydrolysates obtained from BSG after acid-alkaline (AAT) or aqueous ammonia soaking (AAS) pretreatment. The lactic acid production by L. acidophilus ATCC 43121 through fermentation of the hydrolysate from AAS treated BSG was 96% higher than that from the AAT treated one, although similar yields of lactic acid per consumed glucose were achieved due to a higher (46%) glucose consumption by L. acidophilus ATCC 43121 in the AAS BSG hydrolysate. It is worth noting that adding yeast extract to the BSG hydrolysates increased both the yield of lactic acid per substrate consumed and the volumetric productivity. The best results were obtained by fermentation of AAS BSG hydrolysate supplemented by yeast extract, in which the strain produced 22.16 g/L of lactic acid (yield of 0.61 g/g), 27% higher than the value (17.49 g/L) obtained in the absence of a nitrogen source. PMID:26640784

Impact of EPA ingestion on COX- and LOX-mediated eicosanoid synthesis in skin with and without a pro-inflammatory UVR challenge--report of a randomised controlled study in humans.

PubMed

Pilkington, Suzanne M; Rhodes, Lesley E; Al-Aasswad, Naser M I; Massey, Karen A; Nicolaou, Anna

2014-03-01

Eicosapentaenoic acid (EPA), abundant in oily fish, is reported to reduce skin inflammation and provide photoprotection, potential mechanisms include competition with arachidonic acid (AA) for metabolism by cyclooxygenases/lipoxygenases to less pro-inflammatory mediators. We thus examine impact of EPA intake on levels of AA, EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation (UVR) challenge. In a double-blind randomised controlled study, 79 females took 5 g EPA-rich or control lipid for 12 wk. Pre- and post-supplementation, red blood cell and skin polyunsaturated fatty acids were assessed by GC, and eicosanoids from unexposed and UVR-exposed skin by LC-MS/MS. Active supplementation increased red blood cell and dermal EPA versus control (both p < 0.001), lowering relative AA:EPA content (4:1 versus 15:1 and 5:1 versus 11:1, respectively; both p < 0.001). Pre-supplementation, UVR increased PGE2, 12-hydroxyeicosatetraenoic acids, 12-HEPE (all p < 0.001) and PGE3 (p < 0.05). Post-EPA, PGE2 was reduced in unchallenged skin (p < 0.05) while EPA-derived PGE3 (non-sign) and 12-HEPE (p < 0.01) were elevated post-UVR. Thus, post-EPA, PGE2 :PGE3 was lower in unchallenged (12:1 versus 28:1; p < 0.05) and UVR exposed (12:1 versus 54:1; p < 0.01) skin; 12-hydroxyeicosatetraenoic acids:12-HEPE was lower in UVR-exposed skin (3:1 versus 11:1; p < 0.001). Dietary EPA augments skin EPA:AA content, shifting eicosanoid synthesis towards less pro-inflammatory species, and promoting a regulatory milieu under basal conditions and in response to inflammatory insult. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution.

PubMed

Maida, Adriano; Chan, Jessica S K; Sjøberg, Kim A; Zota, Annika; Schmoll, Dieter; Kiens, Bente; Herzig, Stephan; Rose, Adam J

2017-08-01

Dietary protein dilution (PD) has been associated with metabolic advantages such as improved glucose homeostasis and increased energy expenditure. This phenotype involves liver-induced release of FGF21 in response to amino acid insufficiency; however, it has remained unclear whether dietary dilution of specific amino acids (AAs) is also required. Circulating branched chain amino acids (BCAAs) are sensitive to protein intake, elevated in the serum of obese humans and mice and thought to promote insulin resistance. We tested whether replenishment of dietary BCAAs to an AA-diluted (AAD) diet is sufficient to reverse the glucoregulatory benefits of dietary PD. We conducted AA profiling of serum from healthy humans and lean and high fat-fed or New Zealand obese (NZO) mice following dietary PD. We fed wildtype and NZO mice one of three amino acid defined diets: control, total AAD, or the same diet with complete levels of BCAAs (AAD + BCAA). We quantified serum AAs and characterized mice in terms of metabolic efficiency, body composition, glucose homeostasis, serum FGF21, and tissue markers of the integrated stress response (ISR) and mTORC1 signaling. Serum BCAAs, while elevated in serum from hyperphagic NZO, were consistently reduced by dietary PD in humans and murine models. Repletion of dietary BCAAs modestly attenuated insulin sensitivity and metabolic efficiency in wildtype mice but did not restore hyperglycemia in NZO mice. While hepatic markers of the ISR such as P-eIF2α and FGF21 were unabated by dietary BCAA repletion, hepatic and peripheral mTORC1 signaling were fully or partially restored, independent of changes in circulating glucose or insulin. Repletion of BCAAs in dietary PD is sufficient to oppose changes in somatic mTORC1 signaling but does not reverse the hepatic ISR nor induce insulin resistance in type 2 diabetes during dietary PD.

Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

PubMed Central

Kondo, Yoshitaka; Masutomi, Hirofumi; Noda, Yoshihiro; Ozawa, Yusuke; Takahashi, Keita; Handa, Setsuko; Maruyama, Naoki; Shimizu, Takahiko; Ishigami, Akihito

2014-01-01

Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30) is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA) biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO) mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1) higher plasma levels of triglyceride and aspartate aminotransferase; (2) severe accumulation of hepatic triglyceride and total cholesterol; (3) higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4) decreased mRNA and protein levels of Apolipoprotein B (ApoB) in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion. PMID:25003023

Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants.

PubMed

Nilsson, Anders K; Löfqvist, Chatarina; Najm, Svetlana; Hellgren, Gunnel; Sävman, Karin; Andersson, Mats X; Smith, Lois E H; Hellström, Ann

2018-04-21

Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC-PUFA profiles in extremely preterm infants during early perinatal life. Ninety infants born < 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω-3 LC-PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother's milk total lipids on postnatal day 7. Enteral and parenteral intake of LC-PUFAs was correlated with levels in infant serum. Infants administered parenteral ω-3 LC-PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks of life. Parenteral EPA but not DHA correlated with levels in infant serum. We found linear relationships between dietary EPA and DHA and infant serum levels in the Clinoleic (Baxter Medical AB) group. The volume of administered SMOFlipid (Fresenius Kabi) was inversely correlated with serum AA, whereas Clinoleic (Baxter Medical AB) inversely correlated with serum EPA and DHA. There appears to be no or low correlation between the amount of DHA administered parenterally and levels measured in serum. Whether this observation reflects serum phospholipid fraction only or truly represents the amount of accreted DHA needs to be investigated. None of the parenteral lipid emulsions satisfactorily maintained high levels of both ω-6 and ω-3 LC-PUFAs in infant serum. © 2018 The Authors. Journal of Parenteral and Enteral Nutrition published by American Society for Parenteral and Enteral Nutrition.

Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

PubMed

Wan, Xiaojuan; Wang, Songbo; Xu, Jingren; Zhuang, Lu; Xing, Kongping; Zhang, Mengyuan; Zhu, Xiaotong; Wang, Lina; Gao, Ping; Xi, Qianyun; Sun, Jiajie; Zhang, Yongliang; Li, Tiejun; Shu, Gang; Jiang, Qingyan

2017-01-01

Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms "oxidative phosphorylation", "ribosome", "gap junction", "PPAR signaling pathway", and "focal adhesion" were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

Hostility and Minimal Model of Glucose Kinetics in African American Women

PubMed Central

Surwit, Richard S.; Lane, James D.; Millington, David S.; Zhang, Haoyue; Feinglos, Mark N.; Minda, Sharon; Merwin, Rhonda; Kuhn, Cynthia M.; Boston, Raymond C.; Georgiades, Anastasia

2013-01-01

Objective To explore the underlying physiology of hostility (HOST) and to test the hypothesis that HOST has a greater impact on fasting glucose in African American (AA) women than it does on AA men or white men or women, using an intravenous glucose tolerance test (IVGTT) and the minimal model of glucose kinetics. Methods A total of 115 healthy subjects selected for high or low scores on the 27 item Cook Medley HOST Scale underwent an IVGTT. Fasting nonesterified fatty acids (NEFA) levels were measured before the IVGTT. Catecholamine levels were measured 10 minutes into the IVGTT. Results Moderation by group (AA women versus others) of HOST was found for glucose effectiveness (Sg, p = .02), acute insulin response (AIRg, p = .02), and disposition index (DI, p = .02). AA women showed a negative association between HOST and both Sg (β = −0.45, p = .04) and DI (β = −0.49, p = .02), controlling for age and body mass index. HOST was also associated with changes in epinephrine (β = 0.39, p = .05) and fasting NEFA (β = 0.44, p = .02) in the AA women. Controlling for fasting NEFA reduced the effect of HOST on both Sg and DI. Conclusions This study shows that HOST is related to decreased DI, a measure of pancreatic compensation for increased insulin resistance as well as decreased Sg, a measure of noninsulin-mediated glucose transport compared in AA women. These effects are partly mediated by the relationship of HOST to fasting NEFA. PMID:19561162

Enhancement of neurite outgrowth in PC12 cells stimulated with cyclic AMP and NGF by 6-acylated ascorbic acid 2-O-alpha-glucosides (6-Acyl-AA-2G), novel lipophilic ascorbate derivatives.

PubMed

Zhou, Xiaohua; Tai, Akihiro; Yamamoto, Itaru

2003-03-01

It has been shown that ascorbate (AsA) and its stable derivative, ascorbic acid 2-O-alpha-glucoside (AA-2G), do not elicit neurite outgrowth in PC12 cells. However, these ascorbates are synergistically enhanced by both dibutyryl cyclic AMP (Bt(2)cAMP)- and nerve growth factor (NGF)-induced neurite outgrowth in this model. In the present study, the effects of a series of novel lipophilic ascorbate derivatives, 6-acylated ascorbic acid 2-O-alpha-glucosides (6-Acyl-AA-2G), on neurite outgrowth induced by Bt(2)cAMP and NGF were examined in PC12 cells. We found that all the tested acylated ascorbate derivatives enhanced neurite formation induced by both agents in a dose-dependent manner. Of the 6-Acyl-AA-2G derivatives, 6-octanoyl ascorbic acid 2-O-alpha-glucoside (6-Octa-AA-2G) enhanced the Bt(2)cAMP-induced phosphorylated MAPK p44 and p42 expression. A alpha-glucosidase inhibitor, castanospermine, completely abrogated the promotion of neurite outgrowth and MAPK expression by 6-Octa-AA-2G. Addition of 6-Octa-AA-2G (0.5 mM) to PC12 cells caused a rapid and significant increase in intracellular AsA content, which reached a maximum and was maintained from 12 to 24 h after the culture. These findings suggest that 6-Acyl-AA-2G is rapidly hydrolyzed to AsA within the cell and enhances neurite differentiation through the interaction with the inducer-activated MAPK pathway.

Supplementing a ruminally undegradable protein supplement to maintain essential amino acid supply to the small intestine when forage intake is restricted in beef cattle.

PubMed

Scholljegerdes, E J; Weston, T R; Ludden, P A; Hess, B W

2005-09-01

Twelve Angus crossbred cattle (eight heifers and four steers; average initial BW = 594 +/- 44.4 kg) fitted with ruminal and duodenal cannulas and fed restricted amounts of forage plus a ruminally undegradable protein (RUP) supplement were used in a triplicated 4 x 4 Latin square design experiment to determine intestinal supply of essential AA. Cattle were fed four different levels of chopped (2.54 cm) bromegrass hay (11.4% CP, 57% NDF; OM basis): 30, 55, 80, or 105% of the forage intake required for maintenance. Cattle fed below maintenance were given specified quantities of a RUP supplement (6.8% porcine blood meal, 24.5% hydrolyzed feather meal, and 68.7% menhaden fish meal; DM basis) designed to provide duodenal essential AA flow equal to that of cattle fed forage at 105% of maintenance. Experimental periods lasted 21 d (17 d of adaptation and 4 d of sampling). Total OM intake and duodenal OM flow increased linearly (P < 0.001) as cattle consumed more forage; however, OM truly digested in the rumen (% of intake) did not change (P = 0.43) as intake increased. True ruminal N degradation (% of intake) tended (P = 0.07) to increase linearly, and true ruminal N degradation (g/d) decreased quadratically (P = 0.02) as intake increased from 30 to 105%. Duodenal N flow was equal (P = 0.33) across intake levels, even though microbial N flow increased linearly (P < 0.001) as forage OM intake increased. Total and individual essential AA intake decreased (cubic; P < 0.001) as forage intake increased because the supply of nonammonia, nonmicrobial N flow from RUP was decreased (linear; P < 0.001) by design. Total duodenal flow of essential AA did not differ (P = 0.39) across these levels of forage intake. Although the profile of essential AA reaching the duodenum differed (P < or = 0.02) for all 10 essential AA, the range of each essential AA as a proportion of total essential AA was low (11.1 to 11.2% of total essential AA for phenylalanine to 12.3 to 14.3% of total essential AA for lysine). Duodenal essential AA flow did not differ (P = 0.10 to 0.65) with forage intake level for eight of the 10 essential AA. Duodenal flow of arginine decreased linearly (P = 0.01), whereas duodenal flow of tryptophan increased linearly (P = 0.002) as forage intake increased from 30 to 105% of maintenance. Balancing intestinal essential AA supply in beef cattle can be accomplished by varying intake of a RUP supplement.

Arachidonic acid enhances intracellular [Ca2+]i increase and mitochondrial depolarization induced by glutamate in cerebellar granule cells.

PubMed

Surin, A M; Bolshakov, A P; Mikhailova, M M; Sorokina, E G; Senilova, Ya E; Pinelis, V G; Khodorov, B I

2006-08-01

Maturation of primary neuronal cultures is accompanied by an increase in the proportion of cells that exhibit biphasic increase in free cytoplasmic Ca2+ ([Ca2+]i) followed by synchronic decrease in electrical potential difference across the inner mitochondrial membrane (DeltaPsim) in response to stimulation of glutamate receptors. In the present study we have examined whether the appearance of the second phase of [Ca2+]i change can be attributed to arachidonic acid (AA) release in response to the effect of glutamate (Glu) on neurons. Using primary culture of rat cerebellar granule cells we have investigated the effect of AA (1-20 microM) on [Ca2+]i, DeltaPsim, and [ATP] and changes in these parameters induced by neurotoxic concentrations of Glu (100 microM, 10-40 min). At =10 microM, AA caused insignificant decrease in DeltaPsim without any influence on [Ca2+]i. The mitochondrial ATPase inhibitor oligomycin enhanced AA-induced decrease in DeltaPsim; this suggests that AA may inhibit mitochondrial respiration. Addition of AA during the treatment with Glu resulted in more pronounced augmentation of [Ca2+]i and the decrease in DeltaPsim than the changes in these parameters observed during independent action of AA; removal of Glu did not abolish these changes. An inhibitor of the cyclooxygenase and lipoxygenase pathways of AA metabolism, 5,8,11,14-eicosatetraynoic acid, increased the proportion of neurons characterized by Glu-induced biphasic increase in [Ca2+]i and the decrease in DeltaPsim. Palmitic acid (30 microM) did not increase the percentage of neurons exhibiting biphasic response to Glu. Co-administration of AA and Glu caused 2-3 times more pronounced decrease in ATP concentrations than that observed during the independent effect of AA and Glu. The data suggest that AA may influence the functional state of mitochondria, and these changes may promote biphasic [Ca2+]i and DeltaPsim responses of neurons to the neurotoxic effect of Glu.

Mechanical properties, biocompatibility, and biodegradation of cross-linked cellulose acetate-reinforced polyester composites.

PubMed

Wu, Chin-San

2014-05-25

Composites of treated (cross-linked) cellulose acetate (t-CA) and acrylic acid-grafted poly(hydroxyalkanoate) (PHA-g-AA/t-CA) exhibited noticeably superior mechanical properties compared with PHA/CA composites due to greater compatibility between the two components. The dispersion covering of t-CA in the PHA-g-AA matrix was highly homogeneous as a result of condensation reactions. Human lung fibroblasts (FBs) were seeded on these two series of composites to characterize the biocompatibility properties. In a time-dependent course, the FB proliferation results demonstrated higher performance from the PHA/CA series of composites than from the PHA-g-AA/t-CA composites. The water resistance of PHA-g-AA/t-CA was higher than that of PHA/CA, although the weight loss of both composites buried in Acetobacter pasteurianus (A. pasteurianus) indicated that they were both biodegradable, especially at higher levels of cellulose acetate substitution. The PHA/CA and PHA-g-AA/t-CA composites were more biodegradable than pure PHA, implying a strong connection between cellulose acetate content and biodegradability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Omega-3 and omega-6 Fatty acids in blood and breast tissue of high-risk women and association with atypical cytomorphology.

PubMed

Hidaka, Brandon H; Li, Shengqi; Harvey, Katherine E; Carlson, Susan E; Sullivan, Debra K; Kimler, Bruce F; Zalles, Carola M; Fabian, Carol J

2015-05-01

The ratio of omega-3 to omega-6 fatty acids, especially the long-chain eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, is inversely associated with breast cancer risk. We measured the association between cytologic atypia, a biomarker for short-term risk of breast cancer development, and omega-3 and omega-6 fatty acid intake and levels in blood and breast tissue. Blood and benign breast tissue, sampled by random periareolar fine-needle aspiration (RPFNA), was obtained from 70 women at elevated risk for breast cancer. Self-reported dietary intake was assessed by the NCI's Food Frequency Questionnaire. The fatty acid composition of five lipid compartments, red blood cell, plasma and breast phospholipids, and plasma and breast triaclyglycerides (TAG), was analyzed by gas chromatography as weight percent. Median daily intakes of EPA+DHA and total omega-3 fatty acids were 80 mg and 1.1 g, respectively. The median total omega-3:6 intake ratio was 1:10. Compared with women without atypia, those with cytologic atypia had lower total omega-3 fatty acids in red blood cell and plasma phospholipids and lower omega-3:6 ratios in plasma TAGs and breast TAGs (P < 0.05). The EPA+DHA:AA ratio in plasma TAGs was also lower among women with atypia. This is the first report of associations between tissue levels of omega-3 and omega-6 fatty acids and a reversible tissue biomarker of breast cancer risk. RPFNA cytomorphology could serve as a surrogate endpoint for breast cancer prevention trials of omega-3 fatty acid supplementation. ©2015 American Association for Cancer Research.

Ascorbyl coumarates as multifunctional cosmeceutical agents that inhibit melanogenesis and enhance collagen synthesis.

PubMed

Kwak, Jun Yup; Park, Soojin; Seok, Jin Kyung; Liu, Kwang-Hyeon; Boo, Yong Chool

2015-09-01

L-Ascorbic acid (AA) and p-coumaric acid (p-CA) are naturally occurring antioxidants that are known to enhance collagen synthesis and inhibit melanin synthesis, respectively. The purpose of this study was to examine hybrid compounds between AA and p-CA as multifunctional cosmeceutical agents. Ascorbyl 3-p-coumarate (A-3-p-C), ascorbyl 2-p-coumarate (A-2-p-C), and their parent compounds were tested for their effects on cellular melanin synthesis and collagen synthesis. At 100 μM, A-3-p-C and A-2-p-C decreased melanin content of human dermal melanocytes stimulated by L-tyrosine, by 65 and 59%, respectively, compared to 11% inhibition of AA and 70% inhibition of p-CA. A-3-p-C and A-2-p-C were less effective than p-CA but more effective than AA at inhibiting tyrosinase activity. A-3-p-C and A-2-p-C were more effective than p-CA at inhibiting the autoxidation of L-3,4-dihydroxyphenylalanine. At 100-300 μM, A-3-p-C and A-2-p-C augmented collagen release from human dermal fibroblasts by 120-144% and 125-191%, respectively, compared to 126-133% increase of AA and 120-146% increase of p-CA. They increased procollagen type I C-peptide release (A-3-p-C, and A-2-p-C) like AA, and decreased matrix metalloproteinase 1 level (A-2-p-C) like p-CA, implicating that they might regulate collagen metabolism by multiple mechanisms. This study suggests that A-3-p-C and A-2-p-C could be used as multifunctional cosmeceutical agents for the attenuation of certain aspects of skin aging.

A Novel Concept of Amino Acid Supplementation to Improve the Growth of Young Malnourished Male Rats.

PubMed

Furuta, Chie; Murakami, Hitoshi

2018-01-01

This study was aimed at understanding the relationship between plasma amino acids and protein malnutrition and at determining whether amino acid supplementation associated with malnutrition and growth improves linear growth in growing rats. Body length and plasma amino acids were measured in young male rats that were fed the following diet for 3 weeks, mimicking a low and imbalanced protein diets based on maize, a major staple consumed in developing countries: a 70% calorically restricted cornmeal-based diet (C), C + micronutrients (CM), CM + casein (CMC), CM + soy protein (CMS) or CMS + 0.3% lysine. A correlation analysis of linear growth and plasma amino acids indicated that lysine, tryptophan, branched-chain amino acids, methionine, and phenylalanine significantly correlated with body length. Supplementation with these 5 amino acids (AA1) significantly improved the body length in rats compared to CMC treatment whereas, nitrogen-balanced amino acid supplemented controls (AA2) did not (CM +1.2 ± 0.2, CMC +2.7 ± 0.3, CMS +2.1 ± 0.3, AA1 +2.8 ± 0.2, and AA2 +2.5 ± 0.3 cm). With securing proper amino acid balance, supplementing growth-related amino acids is more effective in improving linear growth in malnourished growing male rats. Analysis of the correlation between plasma amino acids and growth represents a powerful tool to determine candidate amino acids for supplementation to prevent malnutrition. This technology is adaptable to children in developing countries. © 2018 S. Karger AG, Basel.

Dose- and Glucose-Dependent Effects of Amino Acids on Insulin Secretion from Isolated Mouse Islets and Clonal INS-1E Beta-Cells

PubMed Central

Liu, Zhenping; Jeppesen, Per B.; Gregersen, Søren; Chen, Xiaoping; Hermansen, Kjeld

2008-01-01

BACKGROUND: The influence of glucose and fatty acids on beta-cell function is well established whereas little is known about the role of amino acids (AAs). METHODS: Islets isolated from NMRI mice were incubated overnight. After preincubation, isolated islets as well as clonal INS-1E beta-cells were incubated for 60 min in a modified Krebs Ringer buffer containing glucose and AAs. RESULTS: At 16.7 mmol/l (mM) glucose, L-arginine, L-lysine, L-alanine, L-proline, L-leucine, and L-glutamine potentiated glucose-stimulated insulin secretion dose-dependently, while DL-homocysteine inhibited insulin secretion. Maximal insulin stimulation was obtained at 20 mM L-proline, L-lysine, L-alanine, L-arginine (islets: 2.5 to 6.7 fold increase; INS-1E cells: 1.6 to 2.2 fold increase). L-glutamine and L-leucine only increased glucose-stimulated (16.7 mM) insulin secretion (INS-1E cells: 1.5 and 1.3 fold, respectively) at an AA concentration of 20 mM. Homocysteine inhibited insulin secretion both at 5.6 mM and 16.7 mM glucose. At glucose levels ranging from 1.1 to 25 mM, the equimolar concentration of 10 mM, L-proline, L-lysine, L-arginine increased insulin secretion from mouse islets and INS-1E cells at all glucose levels applied, with a maximal effect obtained at 25 mM glucose. At a concentration of 10 mM, L-arginine and L-lysine had the highest insulinotropic potency among the AAs investigated. CONCLUSION: L-arginine, L-lysine, L-alanine, L-proline, L-leucine and L-glutamine acutely stimulate insulin secretion from mouse islets and INS-1E cells in a dose- and glucose-dependent manner, whereas DL-homocysteine inhibits insulin release. PMID:19290384

Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.

PubMed

Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

2017-03-01

We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-α and antioxidants, lipid peroxides and nitric oxide were measured. Of all, arachidonic acid (AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Valine Supplementation in a Reduced Protein Diet Regulates Growth Performance Partially through Modulation of Plasma Amino Acids Profile, Metabolic Responses, Endocrine, and Neural Factors in Piglets.

PubMed

Zhang, Xiaoya; Liu, Xutong; Jia, Hongmin; He, Pingli; Mao, Xiangbing; Qiao, Shiyan; Zeng, Xiangfang

2018-03-28

The objective of this study was to investigate whether valine (Val) supplementation in a reduced protein (RP) diet regulates growth performance associated with the changes in plasma amino acids (AAs) profile, metabolism, endocrine, and neural system in piglets. Piglets or piglets with a catheter in the precaval vein were randomly assigned to two treatments, including two RP diets with standardized ileal digestible (SID) Val:Lysine (Lys) ratio of 0.45 and 0.65, respectively. The results indicated that piglets in the higher Val:Lys ratio treatment had higher average daily feed intake (ADFI) ( P < 0.001), average daily gain (ADG) ( P = 0.001), feed conversion ratio (FCR) ( P = 0.004), lower plasma urea nitrogen ( P = 0.032), expression of gastric cholecystokinin (CCK), and hypothalamic pro-opiomelanocortin (POMC). Plasma AAs profiles including postprandial plasma essential AAs (EAAs) profile and in serum, muscle, and liver involved in metabolism of AAs and fatty acids were significantly different between two treatments. In conclusion, Val influenced growth performance associated with metabolism of AAs and fatty acids and both endocrine and neural system in piglets.

Uptake and Accumulation of Nephrotoxic and Carcinogenic Aristolochic Acids in Food Crops Grown in Aristolochia clematitis-Contaminated Soil and Water.

PubMed

Li, Weiwei; Hu, Qin; Chan, Wan

2016-01-13

Emerging evidence has suggested aristolochic acids (AAs) are linked to the development of Balkan endemic nephropathy (BEN), a chronic renal disease affecting numerous farmers living in the Balkan peninsula. However, the pathway by which AAs enter the human food chain and cause kidney disease remains poorly understood. Using our previously developed analytical method with high sensitivity and selectivity (Chan, W.; Lee, K. C.; Liu, N.; Cai, Z. J. Chromatogr. A 2007, 1164, 113-119), we quantified AAs in lettuce, tomato, and spring onion grown in AA-contaminated soil and culture medium. Our study revealed that AAs were being taken up from the soil and bioaccumulated in food crops in a time- and dose-dependent manner. To the best of our knowledge, this study is the first to identify one of the possible pathways by which AAs enter our food chain to cause chronic food poisoning. Results also demonstrated that AAs were resistant to the microbial activity of the soil/water.

Gabapentin’s minimal action on markers of rat brain arachidonic acid metabolism agrees with its inefficacy against bipolar disorder

PubMed Central

Reese, Edmund A.; Cheon, Yewon; Ramadan, Epolia; Kim, Hyung-Wook; Chang, Lisa; Rao, Jagadeesh S.; Rapoport, Stanley I.; Taha, Ameer Y.

2012-01-01

In rats, FDA-approved mood stabilizers used for treating bipolar disorder (BD) selectively downregulate brain markers of the arachidonic acid (AA) cascade, which are upregulated in postmortem BD brain. Phase III clinical trials show that gabapentin (GBP) is ineffective in treating BD. We hypothesized that GBP would not alter the rat brain AA cascade. Chronic GBP (10 mg/kg body weight, injected i.p. for 30 days) compared to saline vehicle did not significantly alter brain expression or activity of AA-selective cytosolic phospholipase A2 (cPLA2) IVA or secretory (s) PLA2 IIA, activity of cyclooxygenase-2, or prostaglandin or thromboxane concentrations. Plasma AA concentration was unaffected. These results, taken with evidence of an upregulated AA cascade in the BD brain and that approved mood stabilizers downregulate rat brain AA cascade, support the hypothesis that effective anti-BD drugs act by targeting the AA cascade, and suggest that the rat model might be used for drug screening PMID:22841517

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women.

PubMed

Barbosa, P R; Stabler, S P; Machado, A L K; Braga, R C; Hirata, R D C; Hirata, M H; Sampaio-Neto, L F; Allen, R H; Guerra-Shinohara, E M

2008-08-01

To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula

USDA-ARS?s Scientific Manuscript database

Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA c...

Active biopolymer film based on carboxymethyl cellulose and ascorbic acid for food preservation

NASA Astrophysics Data System (ADS)

Halim, Al Luqman Abdul; Kamari, Azlan

2017-05-01

In the present study, an active biopolymer film based on carboxymethyl cellulose (CMC) and ascorbic acid (AA) was synthesised at an incorporation rate of 15% (w/w). Several analytical instruments such as Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetry Analyser (TGA), UV-Visible Spectrophotometer (UV-Vis), Scanning Electron Microscope (SEM) and Universal Testing Machine were used to characterise the physical and chemical properties of CMC-AA film. The addition of AA significantly reduced elongation at break (322%) and tensile strength (10 MPa) of CMC-AA film. However, CMC-AA film shows a better antimicrobial property against two bacteria, namely Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as compared to CMC film. The CMC-AA film was able to preserve cherry tomato with low weight loss and browning index. Overall, results from this study highlight the feasibility of CSAA film for food preservation.

Simultaneous determination of ascorbic acid, dopamine and uric acid based on tryptophan functionalized graphene.

PubMed

Lian, Qianwen; He, Zhifang; He, Qian; Luo, Ai; Yan, Kaiwang; Zhang, Dongxia; Lu, Xiaoquan; Zhou, Xibin

2014-05-01

A new type of tryptophan-functionalized graphene nanocomposite (Trp-GR) was synthesized by utilizing a facile ultrasonic method via π-π conjugate action between graphene (GR) and tryptophan (Trp) molecule. The material as prepared had well dispersivity in water and better conductivity than pure GR. The surface morphology of Trp-GR was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The electrochemical behaviors of ascorbic acid (AA), dopamine (DA), and uric acid (UA) were investigated by cyclic voltammetry (CV) on the surface of Trp-GR. The separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 182 mV, 125 mV and 307 mV, which allowed simultaneously determining AA, DA, and UA. Differential pulse voltammetery (DPV) was used for the determination of AA, DA, and UA in their mixture. Under optimum conditions, the linear response ranges for the determination of AA, DA, and UA were 0.2-12.9 mM, 0.5-110 μM, and 10-1000 μM, with the detection limits (S/N=3) of 10.09 μM, 0.29 μM and 1.24 μM, respectively. Furthermore, the modified electrode was investigated for real sample analysis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Influence of caffeine on allyl alcohol-induced hepatotoxicity in rats. I. In vivo study.

PubMed

Karas, M; Chakrabarti, S K

2001-01-01

Cotreatment of rats with a low hepatotoxic dose (30.7 mg/kg, i.p.) of allyl alcohol (AA) and a higher, but nontoxic, dose (150 mg/kg, oral) of caffeine (CF) potentiated the hepatotoxicity of AA. This was verified by significantly higher levels of plasma alanine aminotransferase (ALT) activity and histopathologically greater severity of lesions in the periportal hepatocytes than those due to AA alone. Treatment of rats with 4-methylpyrazole (4-MP) (0.5 mmol/kg, i.p.) (an inhibitor liver alcohol dehydrogenase) for 30 minutes, followed by similar cotreatment with AA and CF, completely prevented the elevation of plasma levels of ALT and histological damage induced by cotreatment with CF and AA 24 hours following their administration. Severe liver damage induced by cotreatment with CF and AA was further, markedly enhanced by phenobarbital pretreatment (80 mg/kg, i.p., 3 days). Thus, extensive necrosis of periportal hepatocytes was noted, as well as edema and accumulation of inflammatory cells in the necrotic foci caused by such pretreatment. The depression of hepatic nonprotein sulfhydryls resulting from CF plus AA was much more severe than that caused by AA or CF alone and appeared as early as 30 minutes after administration. However, much less marked depletion of protein thiols was observed following similar treatments. Significant increase in lipid peroxidation (as measured by melondialdehyde [MDA] formation) was also observed in rat liver but only 24 hours after administration. The production ofMDA in the rat liver was significantly higher after administration of AA plus CF than after administration of AA alone. Pretreatment of rats with phenobarbital further significantly enhanced the formation of 2,4-dinitrophenylhydrazine (DNP)-reactive metabolite(s) (measured as DNP-acrolein adduct equivalents) in rat liver induced by AA (30.7 mg/kg) plus CF (150 mg/kg) within 1 hour following such treatment. Cotreatment with AA and a higher dose of CF resulted in significantly higher excretion of urinary thioethers or mercapturic acids than in rats treated with AA alone. Thus, these data suggest that an increased bioactivation pathway of acrolein involving a P450 mixed-function oxidase system caused by CF may be involved in such potentiating effects of CF on AA-induced hepatotoxicity in rats.

Rapid microwave-assisted acid extraction of southern pine waste wood to remove metals from chromated copper arsenate (CCA) treatment

Treesearch

Chung-Yun Hse; Todd F. Shupe; Bin Yu

2013-01-01

Recovery of metals from chromated copper arsenate (CCA)-treated southern pine wood particles was investigated by extraction in a microwave reactor with binary combinations of acetic acid (AA), oxalic acid (OxA), and phosphoric acid (PhA). Use of OxA was not successful, as insoluble copper oxalate complexes impeded copper removal. The combination of OxA and AA also had...

Prediction protein structural classes with pseudo-amino acid composition: approximate entropy and hydrophobicity pattern.

PubMed

Zhang, Tong-Liang; Ding, Yong-Sheng; Chou, Kuo-Chen

2008-01-07

Compared with the conventional amino acid (AA) composition, the pseudo-amino acid (PseAA) composition as originally introduced for protein subcellular location prediction can incorporate much more information of a protein sequence, so as to remarkably enhance the power of using a discrete model to predict various attributes of a protein. In this study, based on the concept of PseAA composition, the approximate entropy and hydrophobicity pattern of a protein sequence are used to characterize the PseAA components. Also, the immune genetic algorithm (IGA) is applied to search the optimal weight factors in generating the PseAA composition. Thus, for a given protein sequence sample, a 27-D (dimensional) PseAA composition is generated as its descriptor. The fuzzy K nearest neighbors (FKNN) classifier is adopted as the prediction engine. The results thus obtained in predicting protein structural classification are quite encouraging, indicating that the current approach may also be used to improve the prediction quality of other protein attributes, or at least can play a complimentary role to the existing methods in the relevant areas. Our algorithm is written in Matlab that is available by contacting the corresponding author.

Chlamydia trachomatis Scavenges Host Fatty Acids for Phospholipid Synthesis via an Acyl-Acyl Carrier Protein Synthetase*

PubMed Central

Yao, Jiangwei; Dodson, V. Joshua; Frank, Matthew W.; Rock, Charles O.

2015-01-01

The obligate intracellular parasite Chlamydia trachomatis has a reduced genome but relies on de novo fatty acid and phospholipid biosynthesis to produce its membrane phospholipids. Lipidomic analyses showed that 8% of the phospholipid molecular species synthesized by C. trachomatis contained oleic acid, an abundant host fatty acid that cannot be made by the bacterium. Mass tracing experiments showed that isotopically labeled palmitic, myristic, and lauric acids added to the medium were incorporated into C. trachomatis-derived phospholipid molecular species. HeLa cells did not elongate lauric acid, but infected HeLa cell cultures elongated laurate to myristate and palmitate. The elongated fatty acids were incorporated exclusively into C. trachomatis-produced phospholipid molecular species. C. trachomatis has adjacent genes encoding the separate domains of the bifunctional acyl-acyl carrier protein (ACP) synthetase/2-acylglycerolphosphoethanolamine acyltransferase gene (aas) of Escherichia coli. The CT775 gene encodes an acyltransferase (LpaT) that selectively transfers fatty acids from acyl-ACP to the 1-position of 2-acyl-glycerophospholipids. The CT776 gene encodes an acyl-ACP synthetase (AasC) with a substrate preference for palmitic compared with oleic acid in vitro. Exogenous fatty acids were elongated and incorporated into phospholipids by Escherichia coli-expressing AasC, illustrating its function as an acyl-ACP synthetase in vivo. These data point to an AasC-dependent pathway in C. trachomatis that selectively scavenges host saturated fatty acids to be used for the de novo synthesis of its membrane constituents. PMID:26195634

Oxidative potential of ambient water-soluble PM2.5 in the southeastern United States: contrasts in sources and health associations between ascorbic acid (AA) and dithiothreitol (DTT) assays

NASA Astrophysics Data System (ADS)

Fang, Ting; Verma, Vishal; Bates, Josephine T.; Abrams, Joseph; Klein, Mitchel; Strickland, Matthew J.; Sarnat, Stefanie E.; Chang, Howard H.; Mulholland, James A.; Tolbert, Paige E.; Russell, Armistead G.; Weber, Rodney J.

2016-03-01

The ability of certain components of particulate matter to induce oxidative stress through the generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and report here the development of a similar semi-automated system for the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed for a host of aerosol species, along with AA and DTT activities. We present a detailed contrast in findings from these two assays. Water-soluble AA activity was higher in summer and fall than in winter, with highest levels near heavily trafficked highways, whereas DTT activity was higher in winter compared to summer and fall and more spatially homogeneous. AA activity was nearly exclusively correlated with water-soluble Cu (r = 0.70-0.94 at most sites), whereas DTT activity was correlated with organic and metal species. Source apportionment models, positive matrix factorization (PMF) and a chemical mass balance method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from traffic emissions and secondary processes (e.g., organic aerosol oxidation or metals mobilization by secondary acids) to both AA and DTT activities in urban Atlanta. In contrast, biomass burning was a large source for DTT activity, but insignificant for AA. AA activity was not correlated with PM2.5 mass, while DTT activity co-varied strongly with mass (r = 0.49-0.86 across sites and seasons). Various linear models were developed to estimate AA and DTT activities for the central Atlanta Jefferson Street site, based on the CMB-E sources. The models were then used to estimate daily oxidative potential at this site over the 1998-2009 period. Time series epidemiological analyses were conducted to assess daily emergency department (ED) visits data for the five-county Atlanta metropolitan area based on the estimated 10-year backcast oxidative potential. Estimated AA activity was not statistically associated with any tested health outcome, while DTT activity was associated with ED visits for both asthma or wheeze and congestive heart failure. The findings point to the importance of both organic components and transition metals from biomass burning and mobile sources to adverse health outcomes in this region.

Oxidative potential of ambient water-soluble PM2.5 measured by Dithiothreitol (DTT) and Ascorbic Acid (AA) assays in the southeastern United States: contrasts in sources and health associations

NASA Astrophysics Data System (ADS)

Fang, T.; Verma, V.; Bates, J. T.; Abrams, J.; Klein, M.; Strickland, M. J.; Sarnat, S. E.; Chang, H. H.; Mulholland, J. A.; Tolbert, P. E.; Russell, A. G.; Weber, R. J.

2015-11-01

The ability of certain components of particulate matter to induce oxidative stress through catalytic generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and have recently developed a similar semi-automated system using the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed using both assays. We found that water-soluble DTT activity on a per air volume basis was more spatially uniform than water-soluble AA activity. DTT activity was higher in winter than in summer/fall, whereas AA activity was higher in summer/fall compared to winter, with highest levels near highly trafficked highways. DTT activity was correlated with organic and metal species, whereas AA activity was correlated with water-soluble metals (especially water-soluble Cu, r=0.70-0.91 at most sites). Source apportionment models, Positive Matrix Factorization (PMF) and a Chemical Mass Balance Method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from secondary processes (e.g., organic aerosol oxidation or metal mobilization by formation of an aqueous particle with secondary acids) and traffic emissions to both DTT and AA activities in urban Atlanta. Biomass burning was a large source for DTT activity, but insignificant for AA. DTT activity was well correlated with PM2.5 mass (r=0.49-0.86 across sites/seasons), while AA activity did not co-vary strongly with mass. A linear model was developed to estimate DTT and AA activities for the central Atlanta Jefferson Street site, based on the CMB-E sources that are statistically significant with positive coefficients. The model was used to estimate oxidative potential at this site over the period 1998-2009. Time-series epidemiological analyses were conducted to assess daily emergency department (ED) visits data for the five-county Atlanta metropolitan area based on the estimated 10 year backcast oxidative potential. Results suggest that estimated DTT activity was associated with ED visits for both asthma/wheeze and congestive heart failure, while AA activity was not linked to any health outcomes. The findings point to the importance of both organic components and transition metals from biomass burning and mobile sources to adverse health outcomes in this region.

Ruminal bacteria and protozoa composition, digestibility, and amino acid profile determined by multiple hydrolysis times.

PubMed

Fessenden, S W; Hackmann, T J; Ross, D A; Foskolos, A; Van Amburgh, M E

2017-09-01

Microbial samples from 4 independent experiments in lactating dairy cattle were obtained and analyzed for nutrient composition, AA digestibility, and AA profile after multiple hydrolysis times ranging from 2 to 168 h. Similar bacterial and protozoal isolation techniques were used for all isolations. Omasal bacteria and protozoa samples were analyzed for AA digestibility using a new in vitro technique. Multiple time point hydrolysis and least squares nonlinear regression were used to determine the AA content of omasal bacteria and protozoa, and equivalency comparisons were made against single time point hydrolysis. Formalin was used in 1 experiment, which negatively affected AA digestibility and likely limited the complete release of AA during acid hydrolysis. The mean AA digestibility was 87.8 and 81.6% for non-formalin-treated bacteria and protozoa, respectively. Preservation of microbe samples in formalin likely decreased recovery of several individual AA. Results from the multiple time point hydrolysis indicated that Ile, Val, and Met hydrolyzed at a slower rate compared with other essential AA. Singe time point hydrolysis was found to be nonequivalent to multiple time point hydrolysis when considering biologically important changes in estimated microbial AA profiles. Several AA, including Met, Ile, and Val, were underpredicted using AA determination after a single 24-h hydrolysis. Models for predicting postruminal supply of AA might need to consider potential bias present in postruminal AA flow literature when AA determinations are performed after single time point hydrolysis and when using formalin as a preservative for microbial samples. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Risk control of traditional Chinese medicines containing aristolochis acids (AAs) based on influencing factors of content of AAs].

PubMed

Tian, Jing-Zhuo; Liang, Ai-Hua; Liu, Jing; Zhang, Bo-Li

2017-12-01

Aristolochic acids (AAs) widely exist in such plants as Aristolochia and Asarum. The renal toxicity of AAs as well as its carcinogenicity to urinary system have been widely known. In 2003 and 2004, China prohibited the use of Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolochiae Fangchi Radix, and required administering other AAs-containing medicines in accordance with the regulations for prescription drugs. In this paper, we retrieved literatures on the content determination of AAs in recent 10 years in China. It suggested that the AAs content is lower in Asarum herb, especially in its roots and rhizomes, and most of which do not show detectable amount of AA-I. Some of traditional Chinese medicines show fairly small amount of detectable AA-I. The AAs content in Aristolochia herb (including Fructus Aristolochiae, kaempfer dutchmanspipe root) is relatively high; however, there are fewer literatures for studying the content determination of AAs in Chinese patent medicines. There were many factors affecting AAs content, including the parts used, origins, processing methods, extraction process. It suggested that we should pay attention to the toxicity of Chinese medicines containing AAs and use these decoction pieces and traditional Chinese medicines cautiously. In addition, basic studies for the origins, processing methods and extraction process of Chinese patent medicines containing AAs, as well as supervision and detection of AAs content in traditional Chinese medicinal materials, decoction pieces and Chinese patent medicines shall be strengthened for reducing medication risk and guaranteeing clinical medication safety. Copyright© by the Chinese Pharmaceutical Association.

Anacardic acid from brazilian cashew nut trees reduces dentine erosion.

PubMed

Silveira, Cintia; Oliveira, Flávia; Dos Santos, Maria Lucilia; de Freitas, Thiago; Imparato, José Carlos; Magalhães, Ana Carolina

2014-01-01

The aim of this study was to analyze the effect of solutions containing saturated anacardic acid (AA) on dentine erosion in vitro. AA was chemically isolated from natural cashew nutshell liquid obtained by continuous extraction in a Soxhlet extractor and was fully saturated by catalytic hydrogenation. Matrix metalloproteinase 2 (MMP-2) activity, when exposed to buffers containing 100 µmol/l AA, was analyzed using zymography. Bovine root samples were subjected to erosive demineralization (Sprite Zero™, 4 × 90 s/day) and remineralization with artificial saliva between the erosive cycles for 5 days. The samples were treated as follows, after the first and the last acid exposure (1 min; n = 12/group): (1) 100 µmol/l epigallocatechin-3-gallate (EGCG) (positive control); (2) 0.05% NaF; (3) 100 µmol/l saturated AA; (4) saturated AA and EGCG; (5) saturated AA, EGCG and NaF; (6) untreated (negative control). Dentine erosion was measured using a contact profilometer. Two dentine samples from each group were analyzed using scanning electron microscopy. Saturated AA reduced the activity of MMP-2. ANOVA and Tukey's test revealed that all treatments significantly reduced dentine loss compared to the negative control (6.03 ± 0.98 µm). Solutions containing saturated AA (1.97 ± 1.02 µm) showed the greatest reduction in dentine erosion compared to the NaF (3.93 ± 1.54 µm) and EGCG (3.79 ± 0.83 µm) solutions. Therefore, it may be concluded that AA significantly reduces dentine erosion in vitro, possibly by acting as an MMP-2 inhibitor.

Analysis of Metal Contents in Portland Type V and MTA-Based Cements

PubMed Central

Dorileo, Maura Cristiane Gonçales Orçati; Bandeca, Matheus Coelho; Pedro, Fábio Luis Miranda; Volpato, Luiz Evaristo Ricci; Guedes, Orlando Aguirre; Villa, Ricardo Dalla; Tonetto, Mateus Rodrigues; Borges, Alvaro Henrique

2014-01-01

The aim of this study was to determine, by Atomic Absorption Spectrometry (AAS), the concentration levels of 11 metals in Type V gray and structural white PC, ProRoot MTA, and MTA Bio. Samples, containing one gram of each tested cement, were prepared and transferred to a 100 mL Teflon tube with a mixture of 7.0 mL of nitric acid and 21 mL of hydrochloric acid. After the reaction, the mixture was filtered and then volumed to 50 mL of distilled water. For each metal, specific patterns were determined from universal standards. Arsenic quantification was performed by hydride generator. The analysis was performed five times and the data were statistically analyzed at 5% level of significance. Only the cadmium presented concentration levels of values lower than the quantification limit of the device. The AAS analysis showed increased levels of calcium, nickel, and zinc in structural white PC. Type V PC presented the greatest concentration levels of arsenic, chromium, copper, iron, lead, and manganese (P < 0.05). Bismuth was found in all cements, and the lowest concentration levels were observed in Portland cements, while the highest were observed in ProRoot MTA. Both PC and MTA-based cements showed evidence of metals inclusion. PMID:25436238

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

PubMed

Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

2016-10-01

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arachidonic acid, but not its metabolites, is essential for FcγR-stimulated intracellular killing of Staphylococcus aureus by human monocytes

PubMed Central

Zheng, L; Zomerdijk, T P L; Van Den Barselaar, M T; Geertsma, M F; Van Furth, R; Nibbering, P H

1999-01-01

Since arachidonic acid (AA) production by phospholipase A2 (PLA2) is essential for the Fcγ receptor (FcγR)-mediated respiratory burst and phagocytosis of opsonized erythrocytes by monocytes and macrophages, we focused in this study on the role of AA and its metabolites in the FcγR-stimulated intracellular killing of Staphylococcus aureus by human monocytes. The results revealed that the PLA2 inhibitors, but not inhibitors of cyclo-oxygenase and lipoxygenase, markedly suppressed the FcγR-mediated killing process. The production of O−2 by monocytes upon FcγR cross-linking was inhibited by 4-bromophenacyl bromide in a dose-dependent fashion, indicating that inhibition of PLA2 activity impairs the oxygen-dependent bactericidal mechanisms of monocytes, which could be partially restored by addition of exogenous AA and docosahexaenoic acid, but not myristic acid. These polyunsaturated fatty acids, but not myristic acid, stimulated the intracellular killing of S. aureus by monocytes, although not as effectively as FcγR cross-linking. Furthermore, FcγR cross-linking stimulated the release of AA from monocytes. Studies with selective inhibitors revealed that the FcγR-mediated activation of PLA2 is dependent on Ca2+ and tyrosine kinase activity. Together these results indicate a key role for PLA2/AA, but not its major metabolites, in mediating the FcγR-stimulated intracellular killing of S. aureus by monocytes. PMID:10233682

Biomonitoring of Aristolactam-DNA Adducts in Human Tissues using Ultra-Performance Liquid Chromatography/Ion-Trap Mass Spectrometry

PubMed Central

Yun, Byeong Hwa; Rosenquist, Thomas; Sidorenko, Viktoriya; Iden, Charles; Chung-Hsin, Chen; Pu, Yeong-Shiau; Bonala, Radha; Johnson, Francis; Dickman, Kathleen G.; Grollman, Arthur P.; Turesky, Robert J.

2012-01-01

Aristolochic acids (AAs) are a structurally-related family of nephrotoxic and carcinogenic nitrophenanthrene compounds found in Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes. AAs have been implicated in the etiology of so-called Chinese herbs nephropathy and of Balkan endemic nephropathy. Both of these disease syndromes are associated with carcinomas of the upper urinary tract (UUC). 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I) is a principal component of Aristolochia herbs. Following metabolic activation, AA-I reacts with DNA to form aristolactam (AL-I)-DNA adducts. We have developed a sensitive analytical method, using ultra-performance liquid chromatography-electrospray ionization/multistage mass spectrometry (UPLC-ESI/MSn) with a linear quadrupole ion-trap mass spectrometer, to measure 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) and 7-(deoxyguanosin-N2-yl) aristolactam I (dG-AL-I) adducts. Using 10 μg of DNA for measurements, the lower limits of quantitation of dA-AL-I and dG-AL-I are, respectively, 0.3 and 1.0 adducts per 108 DNA bases. We have used UPLC-ESI/MSn to quantify AL-DNA adducts in tissues of rodents exposed to AA, and in the renal cortex of patients with UUC who reside in Taiwan, where the incidence of this uncommon cancer is the highest reported for any country in the world. In human tissues, dA-AL-I was detected at levels ranging from 9 to 338 adducts per 108 DNA bases, whereas dG-AL-I was not found. We conclude that UPLC-ESI/MSn is a highly sensitive, specific and robust analytical method, positioned to supplant 32P-postlabeling techniques currently used for biomonitoring of DNA adducts in human tissues. Importantly, UPLC-ESI/MSn could be used to document exposure to AA, the toxicant responsible for AA nephropathy and its associated UUC. PMID:22515372

β-Cell Lipotoxicity After an Overnight Intravenous Lipid Challenge and Free Fatty Acid Elevation in African American Versus American White Overweight/Obese Adolescents

PubMed Central

Hughan, Kara S.; Bonadonna, Riccardo C.; Lee, SoJung; Michaliszyn, Sara F.

2013-01-01

Objective: Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents. Research Design and Methods: Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively. Results: Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs. Conclusions: Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts. PMID:23526462

Quantitative determination of proteins at nanogram levels by the resonance light-scattering technique with macromolecules nanoparticles of PS-AA.

PubMed

Wang, Leyu; Chen, Hongqi; Li, Ling; Xia, Tingting; Dong, Ling; Wang, Lun

2004-03-01

The polystyrene-acrylic acid (PS-AA) nanoparticles have been prepared by ultrasonic polymerization, characterized by FT-IR and TEM. It is the first report on the determination of proteins with macromolecules nanoparticles of PS-AA by resonance light-scattering (RLS). At pH 6.9, the RLS of macromolecules nanoparticles of PS-AA can be enhanced by proteins. Based on this, a novel quantitative assay of proteins at the nanogram levels has been proposed. At pH 6.9, the RLS signals of PS-AA were greatly enhanced by proteins in the region of 250-700 nm characterized by the peak at 342 nm. Under optimal conditions, the linear ranges of the calibration curves were 0.02-11.0 microgml-1, 0.04-10.0 microgml-1 and 0.03-10.0 microgml-1 for gamma-globulin (gamma-IgG), bovine serum albumin (BSA) and human serum albumin (HSA), respectively. The detection limits were 16.0 ngml-1, 19.0 ngml-1, and 15.0 ngml-1 for gamma-IgG, BSA and HSA, respectively. The method has been applied to the analysis of total proteins in human serum samples collected from the hospital and the results were in good agreement with those reported by the hospital, which indicates that the method presented here is not only sensitive, simple, but also reliable and suitable for practical application.

Characteristics and mechanisms of acrylate polymer damage to maize seedlings.

PubMed

Chen, Xian; Mao, Xiaoyun; Lu, Qin; Liao, Zongwen; He, Zhenli

2016-07-01

Superabsorbent acrylate polymers (SAPs) have been widely used to maintain soil moisture in agricultural management, but they may cause damage to plants, and the mechanisms are not well understood. In this study, seed germination, soil pot culture, hydroponic experiments, and SAPs degradation were conducted to investigate damage characteristics and mechanisms associated with SAPs application. The Results showed that SAPs inhibited maize growth and altered root morphology (irregular and loose arrangement of cells and breakage of cortex parenchyma), and the inhibitory effects were enhanced at higher SAPs rates. After 1h SAP hydrogels treatment, root malondialdehyde (MDA) content was significantly increased, while superoxide dismutase (SOD) and catalase (CAT) content were significantly decreased. Hydroponics experiment indicated that root and shoot growth was inhibited at 2.5mgL(-1) acrylic acid (AA), and the inhibition was enhanced with increasing AA rates. This effect was exacerbated by the presence of Na(+) at a high concentration in the hydrogels. Release and degradation of AA were enhanced at higher soil moisture levels. A complete degradation of AA occurred between 15 and 20 days after incubation (DAI), but it took longer for Na(+) concentration to decrease to a safe level. These results indicate that high concentration of both AA and Na(+) present in the SAPs inhibits plant growth. The finding of this study may provide a guideline for appropriate application of SAPs in agriculture. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulating the gut flora alters amino acid metabolism in neonatal pigs

USDA-ARS?s Scientific Manuscript database

Intestinal microbes consume and produce amino acids (AA). This may impact intestinal threonine (THR) metabolism necessary for adequate gut function. We hypothesized that modulating the gut flora results in an alteration of intestinal THR utilization and hence whole body AA metabolism. Neonatal pigs ...

Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma.

PubMed

Fischer, Adam P; Miles, Sarah L

2017-02-01

Accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in malignant tissue is known to contribute to oncogenic progression and is inversely associated with patient survival. Ascorbic acid (AA) depletion in malignant tissue may contribute to aberrant normoxic activity of HIF-1α. While AA supplementation has been shown to attenuate HIF-1α function in malignant melanoma, the use of dehydroascorbic acid (DHA) as a therapeutic means to increase intracellular AA and modulate HIF-1α function is yet to be evaluated. Here we compared the ability of AA and DHA to increase intracellular vitamin C content and decrease the malignant potential of human melanoma by reducing the activity of HIF-1α. HIF-1α protein accumulation was evaluated by western blot and transcriptional activity was evaluated by reporter gene assay using a HIF-1 HRE-luciferase plasmid. Protein expressions and subcellular localizations of vitamin C transporters were evaluated by western blot and confocal imaging. Intracellular vitamin C content following AA, ascorbate 2-phosphate (A2P), or DHA supplementation was determined using a vitamin C assay. Malignant potential was accessed using a 3D spheroid Matrigel invasion assay. Data was analyzed by One or Two-way ANOVA with Tukey's multiple comparisons test as appropriate with p<0.05 considered significant. Melanoma cells expressed both sodium dependent vitamin C (SVCT) and glucose (GLUT) transporters for AA and DHA transport respectively, however advanced melanomas responded favorably to AA, but not DHA. Physiological glucose conditions significantly impaired intracellular vitamin C accumulation following DHA treatment. Consequently, A2P and AA, but not DHA treated cells demonstrated lower HIF-1α protein expression and activity, and reduced malignant potential. The ability of AA to regulate HIF-1α was dependent on SVCT2 function and SVCT2 was not significantly inhibited at pH representative of the tumor microenvironment. The use of ascorbic acid as an adjuvant cancer therapy remains under investigated. While AA and A2P were capable of modulating HIF-1α protein accumulation/activity, DHA supplementation resulted in minimal intracellular vitamin C activity with decreased ability to inhibit HIF-1α activity and malignant potential in advanced melanoma. Restoring AA dependent regulation of HIF-1α in malignant cells may prove beneficial in reducing chemotherapy resistance and improving treatment outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Earwax metabolomics: An innovative pilot metabolic profiling study for assessing metabolic changes in ewes during periparturition period

PubMed Central

Pereira, Julião; Marques Júnior, Jair Gonzalez; da Cunha, Paulo Henrique Jorge; Noronha Filho, Antônio Dionísio Feitosa; da Silva, Jessica Alves; Fioravanti, Maria Clorinda Soares; de Oliveira, Anselmo Elcana

2017-01-01

Important metabolic changes occur during transition period of late pregnancy and early lactation to meet increasing energy demands of the growing fetus and for milk production. The aim of this investigation is to present an innovative and non-invasive tool using ewe earwax sample analysis to assess the metabolic profile in ewes during late pregnancy and early lactation. In this work, earwax samples were collected from 28 healthy Brazilian Santa Inês ewes divided into 3 sub-groups: 9 non-pregnant ewes, 6 pregnant ewes in the last 30 days of gestation, and 13 lactating ewes ≤ 30 days postpartum. Then, a range of metabolites including volatile organic compounds (VOC), amino acids (AA), and minerals were profiled and quantified in the samples by applying headspace gas chromatography/mass spectrometry, high performance liquid chromatography/tandem mass spectrometry, and inductively coupled plasma-optical emission spectrometry, respectively. As evident in our results, significant changes were observed in the metabolite profile of earwax between the studied groups where a remarkable elevation was detected in the levels of non-esterified fatty acids, alcohols, ketones, and hydroxy urea in the VOC profile of samples obtained from pregnant and lactating ewes. Meanwhile, a significant decrease was detected in the levels of 9 minerals and 14 AA including essential AA (leucine, phenyl alanine, lysine, isoleucine, threonine, valine), conditionally essential AA (arginine, glycine, tyrosine, proline, serine), and a non-essential AA (alanine). Multivariate analysis using robust principal component analysis and hierarchical cluster analysis was successfully applied to discriminate the three study groups using the variations of metabolites in the two stress states (pregnancy and lactation) from the healthy non-stress condition. The innovative developed method was successful in evaluating pre- and post-parturient metabolic changes using earwax and can in the future be applied to recognize markers for diagnosis, prevention, and intervention of pregnancy complications in ewes. PMID:28841695

Earwax metabolomics: An innovative pilot metabolic profiling study for assessing metabolic changes in ewes during periparturition period.

PubMed

Shokry, Engy; Pereira, Julião; Marques Júnior, Jair Gonzalez; da Cunha, Paulo Henrique Jorge; Noronha Filho, Antônio Dionísio Feitosa; da Silva, Jessica Alves; Fioravanti, Maria Clorinda Soares; de Oliveira, Anselmo Elcana; Antoniosi Filho, Nelson Roberto

2017-01-01

Important metabolic changes occur during transition period of late pregnancy and early lactation to meet increasing energy demands of the growing fetus and for milk production. The aim of this investigation is to present an innovative and non-invasive tool using ewe earwax sample analysis to assess the metabolic profile in ewes during late pregnancy and early lactation. In this work, earwax samples were collected from 28 healthy Brazilian Santa Inês ewes divided into 3 sub-groups: 9 non-pregnant ewes, 6 pregnant ewes in the last 30 days of gestation, and 13 lactating ewes ≤ 30 days postpartum. Then, a range of metabolites including volatile organic compounds (VOC), amino acids (AA), and minerals were profiled and quantified in the samples by applying headspace gas chromatography/mass spectrometry, high performance liquid chromatography/tandem mass spectrometry, and inductively coupled plasma-optical emission spectrometry, respectively. As evident in our results, significant changes were observed in the metabolite profile of earwax between the studied groups where a remarkable elevation was detected in the levels of non-esterified fatty acids, alcohols, ketones, and hydroxy urea in the VOC profile of samples obtained from pregnant and lactating ewes. Meanwhile, a significant decrease was detected in the levels of 9 minerals and 14 AA including essential AA (leucine, phenyl alanine, lysine, isoleucine, threonine, valine), conditionally essential AA (arginine, glycine, tyrosine, proline, serine), and a non-essential AA (alanine). Multivariate analysis using robust principal component analysis and hierarchical cluster analysis was successfully applied to discriminate the three study groups using the variations of metabolites in the two stress states (pregnancy and lactation) from the healthy non-stress condition. The innovative developed method was successful in evaluating pre- and post-parturient metabolic changes using earwax and can in the future be applied to recognize markers for diagnosis, prevention, and intervention of pregnancy complications in ewes.

Achiral-chiral two-dimensional chromatography of free amino acids in milk: A promising tool for detecting different levels of mastitis in cows.

PubMed

Ianni, Federica; Sardella, Roccaldo; Lisanti, Antonella; Gioiello, Antimo; Cenci Goga, Beniamino Terzo; Lindner, Wolfgang; Natalini, Benedetto

2015-12-10

In two-dimensional HPLC (2D-HPLC) "heart-cut" applications, two columns are connected in series via a switching valve and volume fractions from the "primary" column are re-injected on the "secondary" column. The heart-cut 2D-HPLC system here described was implemented by connecting a reversed-phase (RP) column (first dimension) to a chiral column (second dimension) containing a quinidine-based chiral stationary phase. The system was used to evaluate the change in the enantiomeric excess value of dansylated (Dns) amino acids (AAs) in milk samples from two cows with different "California Mastitis Test" scores: negative test for sample 1, positive for sample 2. Apart from the co-elution of Dns-Arg/Dns-Gly and the reduced chemoselectivity for Dns-Leu/Dns-allo-Ile, the optimized achiral RP method distinguished the remaining standard Dns-AAs. Dns-AAs were identified in the chromatograms of the real samples, and in higher concentration Dns-Ala, Dns-Arg, Dns-Asp, Dns-Glu, Dns-Ile, Dns-Leu, Dns-Phe and Dns-Val. Except Dns-Arg, the chiral column enabled the RP enantioseparation of all the other compounds (α and RS values up to 1.65 and 8.63, respectively, for Dns-Phe). In sample 2, the amounts of Dns-d-AAs were rather elevated, in particular for Dns-Ala and Dns-Asp. Instead, for sample 1, D-isomers were detected for Dns-Ala, Dns-Glu and Dns-Leu. The proposed 2D-HPLC method could be useful for the identification of clinical mastitis difficult to be diagnosed. Moreover, the eventual progressive reduction of D-AAs levels with the degree of sub-clinical mastitis could allow the building of mathematical models to use for the diagnosis of early stages of mastitis. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognition, dopamine and bioactive lipids in schizophrenia

PubMed Central

Condray, Ruth; Yao, Jeffrey K.

2011-01-01

Schizophrenia is a remarkably complex disorder with a multitude of behavioral and biological perturbations. Cognitive deficits are a core feature of this disorder, and involve abnormalities across multiple domains, including memory, attention, and perception. The complexity of this debilitating illness has led to a view that the key to unraveling its pathophysiology lies in deconstructing the clinically-defined syndrome into pathophysiologically distinct intermediate phenotypes. Accumulating evidence suggests that one of these intermediate phenotypes may involve phospholipid signaling abnormalities, particularly in relation to arachidonic acid (AA). Our data show relationships between levels of AA and performance on tests of cognition for schizophrenia patients, with defects in AA signaling associated with deficits in cognition. Moreover, dopamine may moderate these relationships between AA and cognition. Taken together, cognitive deficits, dopaminergic neurotransmission, and bioactive lipids have emerged as related features of schizophrenia. Existing treatment options for cognitive deficits in schizophrenia do not specifically target lipid-derived signaling pathways; understanding these processes could inform efforts to identify novel targets for treatment innovation. PMID:21196378

Modulatory effects of steroid hormones, oxytocin, arachidonic acid, forskolin and cyclic AMP on the expression of aquaporin 1 and aquaporin 5 in the porcine uterus during placentation.

PubMed

Skowronska, A; Mlotkowska, P; Okrasa, S; Nielsen, S; Skowronski, M T

2016-04-01

Aquaporins (AQPs) are proteins forming trans-membrane channels responsible for water transport. AQP1 and AQP5 are present in structures of the female reproductive system. In the uterus, these AQPs are involved in water movement between the intraluminal, interstitial and capillary compartments and their uterine expression is essential throughout the pregnancy, including its early stages. Thus, the study aimed to assess the influence of P4 (progesterone), E2 (estradiol), OT (oxytocin), AA (arachidonic acid), cAMP and FSK (forskolin) on the AQP1 and AQP5 mRNA and protein expression in the uterine tissue of gilts on Days 30 - 32 of gestation (the placentation period), following short (3 h) and long (24 h) incubations. Steroid hormones influenced the expression of AQP1 and AQP5; E2 up-regulated, but P4 down-regulated mRNAs of these AQPs, whereas the protein level of studied AQPs was increased by both steroids. OT treatment decreased AQP1 (after 24 h), but increased AQP5 (after 3 h) mRNA expression. Treatment with AA significantly reduced the AQP1 expression at the mRNA level, but stimulated at the protein level. The expression of AQP5 mRNA and protein was stimulated by AA. FSK markedly decreased AQP1 mRNA, but increased of AQP5 after 3-h incubation. In turn, cAMP stimulated and inhibited transcription of AQP5 after 3- and 24-h incubations, respectively. Immunohistochemical analysis confirmed the uterine localization of AQP1 in the apical and basal membranes of endothelial cells and AQP5 in the apical membranes of epithelial cells under control condition. Treatments with P4, E2, AA, cAMP or FSK have caused additional appearance of AQP5 labeling in the basolateral membranes of epithelial cells. These results suggest a participation of steroid hormones (P4 and E2), AA derivatives and cAMP in controlling the expression of AQP1 and AQP5 as well as the distribution of AQP5 in the uterine tissue of pregnant gilts during placentation (Days 30 - 32 of gestation).

The multiplicity of spinal AA-5-HT anti-nociceptive action in a rat model of neuropathic pain.

PubMed

Malek, Natalia; Kostrzewa, Magdalena; Makuch, Wioletta; Pajak, Agnieszka; Kucharczyk, Mateusz; Piscitelli, Fabiana; Przewlocka, Barbara; Di Marzo, Vincenzo; Starowicz, Katarzyna

2016-09-01

There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPV1) has been the most investigated. Both, inhibition of AEA breakdown by fatty acid amide hydrolase (FAAH) and blockage of TRPV1 have been shown to produce anti-nociceptive effects. Recent research suggests the usefulness of dual-action compounds, which may afford greater anti-allodynic efficacy. Therefore, in the present study, we examined the effect of N-arachidonoyl-serotonin (AA-5-HT), a blocker of FAAH and TRPV1, in a rat model of neuropathic pain after intrathecal administration. We found that treatment with AA-5-HT increased the pain threshold to mechanical and thermal stimuli, with highest effect at the dose of 500nM, which was most strongly attenuated by AM-630, CB2 antagonist, administration. The single action blockers PF-3845 (1000nM, for FAAH) and I-RTX (1nM, for TRPV1) showed lower efficacy than AA-5-HT. Moreover AA-5-HT (500nM) elevated AEA and palmitoylethanolamide (PEA) levels. Among the possible targets of these mediators, only the mRNA levels of CB2, GPR18 and GPR55, which are believed to be novel cannabinoid receptors, were upregulated in the spinal cord and/or DRG of CCI rats. It was previously reported that AA-5-HT acts in CB1 and TRPV1-dependent manner after systemic administration, but here for the first time we show that AA-5-HT action at the spinal level involves CB2, with potential contributions from GRP18 and/or GPR55 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acetaldehyde Stimulates FANCD2 Monoubiquitination, H2AX Phosphorylation, and BRCA1 Phosphorylation in Human Cells in Vitro: Implications for Alcohol-Related Carcinogenesis

PubMed Central

Marietta, Cheryl; Thompson, Larry H.; Lamerdin, Jane E.; Brooks, P.J.

2009-01-01

According to a recent IARC Working Group report, alcohol consumption is causally related to an increased risk of cancer of the upper aerodigestive tract, liver, colorectum, and female breast (Lancet Oncol. 2007 8:292–3). Several lines of evidence indicate that acetaldehyde (AA), the first product of alcohol metabolism, plays a very important role in alcohol-related carcinogenesis, particularly in the esophagus. We previously proposed a model for alcohol-related carcinogenesis in which AA, generated from alcohol metabolism, reacts in cells to generate DNA lesions that form interstrand crosslinks (ICLs) (Nucleic Acids Res. 2005 33:3513–20). Since the Fanconi anemia-breast cancer associated (FANC-BRCA) DNA damage response network plays a crucial role in protecting cells against ICLs, in the present work we tested this hypothesis by exposing cells to AA and monitoring activation of this network. We found that AA exposure results in a concentration-dependent increase in FANCD2 monoubiquitination, which is dependent upon the FANC core complex. AA also stimulated BRCA1 phosphorylation at Ser1524 and increased the level of γH2AX, with both modifications occurring in a dose-dependent manner. However, AA did not detectably increase the levels of hyperphosphorylated RPA34, a marker of single-stranded DNA exposure at replication forks. These results provide the initial description of the AA-DNA damage response, which is qualitatively similar to the cellular response to mitomycin C, a known DNA crosslinking agent. We discuss the mechanistic implications of these results, as well as their possible relationship to alcohol-related carcinogenesis in different human tissues. PMID:19428384

[A novel gene (Aa-accA ) encoding acetyl-CoA carboxyltransferase alpha-subunit of Alkalimonas amylolytica N10 enhances salt and alkali tolerance of Escherichia coli and tobacco BY-2 cells].

PubMed

Xian, Mingjie; Zhai, Lei; Zhong, Naiqin; Ma, Yiwei; Xue, Yanfen; Ma, Yanhe

2013-08-04

Acetyl-CoA carboxylase (ACC) catalyzes the first step of fatty acid synthesis. In most bacteria, ACC is composed of four subunits encoded by accA, accB, accC, and accD. Of them, accA encodes acetyl-CoA carboxyltransferase alpha-subunit. Our prior work on proteomics of Alkalimonas amylolytica N10 showed that the expression of the Aa-accA has a remarkable response to salt and alkali stress. This research aimed to find out the Aa-accA gene contributing to salt and alkali tolerance. The Aa-accA was amplified by PCR from A. amylolytica N10 and expressed in E. coli K12 host. The effects of Aa-accA expression on the growth of transgenic strains were examined under different NaCl concentration and pH conditions. Transgenic tobacco BY-2 cells harboring Aa-accA were also generated via Agrobacterium-mediated transformation. The viability of BY-2 cells was determined with FDA staining method after salt and alkali shock. The Aa-accA gene product has 318 amino acids and is homologous to the carboxyl transferase domain of acyl-CoA carboxylases. It showed 76% identity with AccA (acetyl-CoA carboxylase carboxyltransferase subunit alpha) from E. coli. Compared to the wild-type strains, transgenic E. coli K12 strain containing Aa-accA showed remarkable growth superiority when grown in increased NaCl concentrations and pH levels. The final cell density of the transgenic strains was 2.6 and 3.5 times higher than that of the control type when they were cultivated in LB medium containing 6% (W/V) NaCl and at pH 9, respectively. Complementary expression of Aa-accA in an accA-depletion E. coli can recover the tolerance of K12 delta accA to salt and alkali stresses to some extent. Similar to the transgenic E. coli, transgenic tobacco BY-2 cells showed higher percentages of viability compared to the wild BY-2 cells under the salt or alkali stress condition. We found that Aa-accA from A. amylolytica N10 overexpression enhances the tolerance of both transgenic E. coli and tobacco BY-2 cells to NaCl and alkali stresses.

Determination of trace amino acids in human serum by a selective and sensitive pre-column derivatization method using HPLC-FLD-MS/MS and derivatization optimization by response surface methodology.

PubMed

Li, Guoliang; Cui, Yanyan; You, Jinmao; Zhao, Xianen; Sun, Zhiwei; Xia, Lian; Suo, Yourui; Wang, Xiao

2011-04-01

Analysis of trace amino acids (AA) in physiological fluids has received more attention, because the analysis of these compounds could provide fundamental and important information for medical, biological, and clinical researches. More accurate method for the determination of those compounds is highly desirable and valuable. In the present study, we developed a selective and sensitive method for trace AA determination in biological samples using 2-[2-(7H-dibenzo [a,g]carbazol-7-yl)-ethoxy] ethyl chloroformate (DBCEC) as labeling reagent by HPLC-FLD-MS/MS. Response surface methodology (RSM) was first employed to optimize the derivatization reaction between DBCEC and AA. Compared with traditional single-factor design, RSM was capable of lessening laborious, time and reagents consumption. The complete derivatization can be achieved within 6.3 min at room temperature. In conjunction with a gradient elution, a baseline resolution of 20 AA containing acidic, neutral, and basic AA was achieved on a reversed-phase Hypersil BDS C(18) column. This method showed excellent reproducibility and correlation coefficient, and offered the exciting detection limits of 0.19-1.17 fmol/μL. The developed method was successfully applied to determinate AA in human serum. The sensitive and prognostic index of serum AA for liver diseases has also been discussed.

Sulfite Oxidase Activity Is Essential for Normal Sulfur, Nitrogen and Carbon Metabolism in Tomato Leaves

PubMed Central

Brychkova, Galina; Yarmolinsky, Dmitry; Batushansky, Albert; Grishkevich, Vladislav; Khozin-Goldberg, Inna; Fait, Aaron; Amir, Rachel; Fluhr, Robert; Sagi, Moshe

2015-01-01

Plant sulfite oxidase [SO; E.C.1.8.3.1] has been shown to be a key player in protecting plants against exogenous toxic sulfite. Recently we showed that SO activity is essential to cope with rising dark-induced endogenous sulfite levels in tomato plants (Lycopersicon esculentum/Solanum lycopersicum Mill. cv. Rheinlands Ruhm). Here we uncover the ramifications of SO impairment on carbon, nitrogen and sulfur (S) metabolites. Current analysis of the wild-type and SO-impaired plants revealed that under controlled conditions, the imbalanced sulfite level resulting from SO impairment conferred a metabolic shift towards elevated reduced S-compounds, namely sulfide, S-amino acids (S-AA), Co-A and acetyl-CoA, followed by non-S-AA, nitrogen and carbon metabolite enhancement, including polar lipids. Exposing plants to dark-induced carbon starvation resulted in a higher degradation of S-compounds, total AA, carbohydrates, polar lipids and total RNA in the mutant plants. Significantly, a failure to balance the carbon backbones was evident in the mutants, indicated by an increase in tricarboxylic acid cycle (TCA) cycle intermediates, whereas a decrease was shown in stressed wild-type plants. These results indicate that the role of SO is not limited to a rescue reaction under elevated sulfite, but SO is a key player in maintaining optimal carbon, nitrogen and sulfur metabolism in tomato plants. PMID:27135342

The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model.

PubMed

Ren, Xiaobin; Zhang, Mingzhu; Chen, Lingxiang; Zhang, Wanli; Huang, Yu; Luo, Huazhen; Li, Ling; He, Hongbing

2017-10-01

The traditional Chinese medicine Yunnan Baiyao (YNB) has been reported to possess anti‑inflammatory properties, however its mechanism of action remains unclear. It was previously reported that YNB ameliorated depression of arachidonic acid (AA) levels in a rat model of collagen-induced arthritis. In the current study, the capacity of YNB to ameliorate inflammation was compared in carrageenan‑induced and AA‑induced acute inflammation of the rat paw with celecoxib and mizolastine, respectively (n=24 per group). The capacity of YNB to affect the phospholipase A2 (PLA2)/AA pathway (using reverse transcription‑quantitative polymerase chain reaction) and release of inflammatory lipid mediators (by ELISA) were investigated. Celecoxib ameliorated carrageenan‑induced paw edema, and mizolastine ameliorated AA‑induced rat paw edema. YNB alleviated paw edema and inhibited inflammatory cell infiltration in the two models. YNB inhibited production of 5‑LOX AA metabolite leukotriene B4 (LTB4), and suppressed expression of 5‑LOX, cytosolic PLA2 (cPLA2), 5‑LOX‑activating protein, and LTB4 receptor mRNA in the AA‑induced inflammation model (P<0.05). YNB Inhibited the production of the COX‑2 AA metabolite prostaglandin E2 (PGE2) and suppressed expression of COX‑2, cPLA2, PGE2 mRNA in the carrageenan‑induced inflammation mode (P<0.05). Taken together, the data suggest that modulation of COX and LOX pathways in AA metabolism represent a novel anti-inflammatory mechanism of YNB.

Colonization by Phloem-Feeding Herbivore Overrides Effects of Plant Virus on Amino Acid Composition in Phloem of Chili Plants.

PubMed

Ángeles-López, Yesenia Ithaí; Rivera-Bustamante, Rafael F; Heil, Martin

2016-10-01

The 'adaptive host manipulation' hypothesis predicts that parasites can enhance their transmission rates via manipulation of their host's phenotype. For example, many plant pathogens alter the nutritional quality of their host for herbivores that serve as their vectors. However, herbivores, including non-vectors, might cause additional alterations in the plant phenotype. Here, we studied changes in the amino acid (AA) content in the phloem of chilli (Capsicum annuum) plants infected with Pepper golden mosaic virus (PepGMV) upon subsequent colonization with a non-vector, the phloem-feeding whitefly (Trialeurodes vaporariorum). Virus infection alone caused an almost 30-fold increase in overall phloem AAs, but colonization by T. vaporariorum completely reversed this effect. At the level of individual AAs, contents of proline, tyrosine, and valine increased, and histidine and alanine decreased in PepGMV -infected as compared to control plants, whereas colonization by T. vaporariorum caused decreased contents of proline, tyrosine, and valine, and increased contents of histidine and alanine. Overall, the colonization by the whitefly had much stronger effects on phloem AA composition than virus infection. We conclude that the phloem composition of a virus-infected host plant can rapidly change upon arrival of an herbivore and that these changes need to be monitored to predict the nutritional quality of the plant in the long run.

Stepwise microhydration of aromatic amide cations: water solvation networks revealed by the infrared spectra of acetanilide+-(H2O)n clusters (n ≤ 3).

PubMed

Klyne, Johanna; Schmies, Matthias; Miyazaki, Mitsuhiko; Fujii, Masaaki; Dopfer, Otto

2018-01-31

The structure and activity of peptides and proteins strongly rely on their charge state and the interaction with their hydration environment. Here, infrared photodissociation (IRPD) spectra of size-selected microhydrated clusters of cationic acetanilide (AA + , N-phenylacetamide), AA + -(H 2 O) n with n ≤ 3, are analysed by dispersion-corrected density functional theory calculations at the ωB97X-D/aug-cc-pVTZ level to determine the stepwise microhydration process of this aromatic peptide model. The IRPD spectra are recorded in the informative X-H stretch (ν OH , ν NH , ν CH , amide A, 2800-3800 cm -1 ) and fingerprint (amide I-II, 1000-1900 cm -1 ) ranges to probe the preferred hydration motifs and the cluster growth. In the most stable AA + -(H 2 O) n structures, the H 2 O ligands solvate the acidic NH proton of the amide by forming a hydrogen-bonded solvent network, which strongly benefits from cooperative effects arising from the excess positive charge. Comparison with neutral AA-H 2 O reveals the strong impact of ionization on the acidity of the NH proton and the topology of the interaction potential. Comparison with related hydrated formanilide clusters demonstrates the influence of methylation of the amide group (H → CH 3 ) on the shape of the intermolecular potential and the structure of the hydration shell.

Metabolomic profiling of amino acids and beta-cell function relative to insulin sensitivity in youth

USDA-ARS?s Scientific Manuscript database

In longitudinal studies of adults, elevated amino acid (AA) concentrations predicted future type 2 diabetes mellitus (T2DM). The aim of the present investigation was to examine whether increased plasma AA concentrations are associated with impaired beta-cell function relative to insulin sensitivity ...

Amino acids, independent of insulin, attenuate skeletal muscle autophagy in neonatal pigs during endotoxemia

USDA-ARS?s Scientific Manuscript database

Sepsis induces loss of skeletal muscle mass by activating the ubiquitin proteasome (UPS) and autophagy systems. Although muscle protein synthesis in healthy neonatal piglets is responsive to amino acids (AA) stimulation, it is not known if AA can prevent the activation of muscle protein degradation ...

Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms.

PubMed

Palla, Amber Hanif; Iqbal, Najeeha Talat; Minhas, Khurram; Gilani, Anwarul-Hassan

2016-09-01

New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-α, IFN-γ and IL-17, at 6, 12 and 24h by ELISA. Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24h as compared to the AA group. These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-γ and TNF-α and increasing IL-17 levels. Copyright © 2016. Published by Elsevier B.V.

Study of new ways of supplementary and combinatory therapy of rheumatoid arthritis with immunomodulators. Glucomannan and Imunoglukán in adjuvant arthritis.

PubMed

Bauerová, K; Paulovicová, E; Mihalová, D; Svík, K; Ponist, S

2009-01-01

We studied the anti-arthritic activity of glucomannan (GM) isolated from Candida utilis and of Imunoglukán, a beta-(1,3/1,6)-D-glucan (IMG) isolated from Pleurotus ostreatus. Adjuvant arthritis (AA) was induced intradermally by the injection of Mycobacterium butyricum in incomplete Freund's adjuvant to Lewis rats. Blood for biochemical and immunological analysis was collected on experimental days 1, 14, 21, and 28. A clinical parameter--hind paw volume (HPV)--was also measured. The detection of IL-1 alpha, IL-4, TNF alpha, and MCP-1 was done by immunoflowcytometry. On day 28--the end of the experiment--we determined spectrophotometrically: the total anti-oxidant status (TAS) of plasma samples along with thiobarbituric acid-reacting substances (TBARS) levels in plasma and we assessed the activity of gamma-glutamyl transferase (GGT) in hind paw joint homogenate. The experiments included healthy animals, arthritic animals without treatment, and arthritic animals with administration of glucomannan (GM-AA) in the oral daily dose of 15 mg/kg b.w. and of IMG (IMG-AA) in the oral daily dose of 2 mg/kg b.w. The progress of AA was manifested by all parameters monitored. Both substances had beneficial effects on HPV, TBARS levels, GGT activity, and TAS levels. For cytokine assessment, only IMG-AA samples were selected, considering the significant HPV improvement accompanied with the observed anti-oxidant action. IMG administration had a positive immunomodulating effect on all cytokine plasma levels measured, changed markedly due to arthritis progression. Thus, IMG may be considered as a candidate for combinatorial therapy of rheumatoid arthritis.

A 100-Year Review: Protein and amino acid nutrition in dairy cows.

PubMed

Schwab, Charles G; Broderick, Glen A

2017-12-01

Considerable progress has been made in understanding the protein and amino acid (AA) nutrition of dairy cows. The chemistry of feed crude protein (CP) appears to be well understood, as is the mechanism of ruminal protein degradation by rumen bacteria and protozoa. It has been shown that ammonia released from AA degradation in the rumen is used for bacterial protein formation and that urea can be a useful N supplement when lower protein diets are fed. It is now well documented that adequate rumen ammonia levels must be maintained for maximal synthesis of microbial protein and that a deficiency of rumen-degradable protein can decrease microbial protein synthesis, fiber digestibility, and feed intake. Rumen-synthesized microbial protein accounts for most of the CP flowing to the small intestine and is considered a high-quality protein for dairy cows because of apparent high digestibility and good AA composition. Much attention has been given to evaluating different methods to quantify ruminal protein degradation and escape and for measuring ruminal outflows of microbial protein and rumen-undegraded feed protein. The methods and accompanying results are used to determine the nutritional value of protein supplements and to develop nutritional models and evaluate their predictive ability. Lysine, methionine, and histidine have been identified most often as the most-limiting amino acids, with rumen-protected forms of lysine and methionine available for ration supplementation. Guidelines for protein feeding have evolved from simple feeding standards for dietary CP to more complex nutrition models that are designed to predict supplies and requirements for rumen ammonia and peptides and intestinally absorbable AA. The industry awaits more robust and mechanistic models for predicting supplies and requirements of rumen-available N and absorbed AA. Such models will be useful in allowing for feeding lower protein diets and increased efficiency of microbial protein synthesis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

PubMed Central

Rink, Cameron

2011-01-01

Abstract The significance of the hypoxia component of stroke injury is highlighted by hypermetabolic brain tissue enriched with arachidonic acid (AA), a 22:6n-3 polyunsaturated fatty acid. In an ischemic stroke environment in which cerebral blood flow is arrested, oxygen-starved brain tissue initiates the rapid cleavage of AA from the membrane phospholipid bilayer. Once free, AA undergoes both enzyme-independent and enzyme-mediated oxidative metabolism, resulting in the formation of number of biologically active metabolites which themselves contribute to pathological stroke outcomes. This review is intended to examine two divergent roles of molecular dioxygen in brain tissue as (1) a substrate for life-sustaining homeostatic metabolism of glucose and (2) a substrate for pathogenic metabolism of AA under conditions of stroke. Recent developments in research concerning supplemental oxygen therapy as an intervention to correct the hypoxic component of stroke injury are discussed. Antioxid. Redox Signal. 14, 1889–1903. PMID:20673202

Prescription profile of potentially aristolochic acid containing Chinese herbal products: an analysis of National Health Insurance data in Taiwan between 1997 and 2003.

PubMed

Hsieh, Shu-Ching; Lin, I-Hsin; Tseng, Wei-Lum; Lee, Chang-Hsing; Wang, Jung-Der

2008-10-23

Some Chinese herbal products (CHPs) may contain aristolochic acid (AA) or may be adulterated by the herbs suspected of containing AA which is nephrotoxic and carcinogenic. This study aims to identify the risk and the prescription profile of AA-containing CHPs (AA-CHPs) in Taiwan. A longitudinal analysis was conducted on a randomly sampled cohort of 200,000 patients using the data from the National Health Insurance (NHI) in Taiwan between 1997 and 2003. During the 7-year study period, 78,644 patients were prescribed with AA-CHPs; most patients were females, or middle-aged, or both. A total of 526,867 prescriptions were made to use 1,218 licensed AA-CHPs. Over 85% of the AA-exposed patients took less than 60 g of AA-herbs; however, about 7% were exposed to a cumulated dose of over 100 g of Radix et Rhizoma Asari (Xixin), Caulis Akebiae (Mutong) or Fructus Aristolochiae (Madouling). Patients of respiratory and musculoskeletal diseases received most of the AA-CHP prescriptions. The most frequently prescribed AA-CHPs Shujing Huoxie Tang, Chuanqiong Chadiao San and Longdan Xiegan Tang, containing Radix Stephaniae Tetrandrae, Radix et Rhizoma Asari and Caulis Akebiae, respectively. About one-third of people in Taiwan have been prescribed with AA-CHPs between 1997 and 2003. Although the cumulated doses were not large, further actions should be carried out to ensure the safe use of AA-CHPs.

Prescription profile of potentially aristolochic acid containing Chinese herbal products: an analysis of National Health Insurance data in Taiwan between 1997 and 2003

PubMed Central

Hsieh, Shu-Ching; Lin, I-Hsin; Tseng, Wei-Lum; Lee, Chang-Hsing; Wang, Jung-Der

2008-01-01

Background Some Chinese herbal products (CHPs) may contain aristolochic acid (AA) or may be adulterated by the herbs suspected of containing AA which is nephrotoxic and carcinogenic. This study aims to identify the risk and the prescription profile of AA-containing CHPs (AA-CHPs) in Taiwan. Methods A longitudinal analysis was conducted on a randomly sampled cohort of 200,000 patients using the data from the National Health Insurance (NHI) in Taiwan between 1997 and 2003. Results During the 7-year study period, 78,644 patients were prescribed with AA-CHPs; most patients were females, or middle-aged, or both. A total of 526,867 prescriptions were made to use 1,218 licensed AA-CHPs. Over 85% of the AA-exposed patients took less than 60 g of AA-herbs; however, about 7% were exposed to a cumulated dose of over 100 g of Radix et Rhizoma Asari (Xixin), Caulis Akebiae (Mutong) or Fructus Aristolochiae (Madouling). Patients of respiratory and musculoskeletal diseases received most of the AA-CHP prescriptions. The most frequently prescribed AA-CHPs Shujing Huoxie Tang, Chuanqiong Chadiao San and Longdan Xiegan Tang, containing Radix Stephaniae Tetrandrae, Radix et Rhizoma Asari and Caulis Akebiae, respectively. Conclusion About one-third of people in Taiwan have been prescribed with AA-CHPs between 1997 and 2003. Although the cumulated doses were not large, further actions should be carried out to ensure the safe use of AA-CHPs. PMID:18945373

Effects of arachidonic acid intake on inflammatory reactions in dextran sodium sulphate-induced colitis in rats.

PubMed

Naito, Yukiko; Ji, Xu; Tachibana, Shigehiro; Aoki, Satoko; Furuya, Mami; Tazura, Yoshiyuki; Miyazawa, Daisuke; Harauma, Akiko; Moriguchi, Toru; Nagata, Tomoko; Iwai, Naoharu; Ohara, Naoki

2015-09-14

The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease.

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.

PubMed

O'Connor, D L; Hall, R; Adamkin, D; Auestad, N; Castillo, M; Connor, W E; Connor, S L; Fitzgerald, K; Groh-Wargo, S; Hartmann, E E; Jacobs, J; Janowsky, J; Lucas, A; Margeson, D; Mena, P; Neuringer, M; Nesin, M; Singer, L; Stephenson, T; Szabo, J; Zemon, V

2001-08-01

A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development. Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants

Activity of Aristolochia bracteolata against Moraxella catarrhalis

PubMed Central

Khedr, Amgad I. M.; Abd AlGadir, Haidar; Takeshita, Satoshi; Shah, Mohammad Monir; Ichinose, Yoshio; Maki, Toshihide

2014-01-01

A bioassay-guided fractionation of methanol extract of Aristolochia bracteolata whole plant was carried out in order to evaluate its antimicrobial activity and to identify the active compounds in this extract. Antibacterial and antifungal activities of methanol extract against gram-positive, gram-negative, and fungal strains were investigated by the agar disk diffusion method. Among the strains tested, Moraxella catarrhalis and sea urchin-derived Bacillus sp. showed the highest sensitivity towards the methanol extract and hence they are used as test organisms for the bioassay-guided fractionation. From this extract, aristolochic acid 1 (AA-1) has been isolated and has showed the greatest antibacterial activity against both standard strain and clinical isolates of Moraxella catarrhalis with equal minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 25 and 50 μg/mL. Modification of the AA-1 to AA-1 methyl ester completely abolished the antibacterial activity of the compound and the piperonylic acid moiety of AA-1 which suggested that the coexistence of phenanthrene ring and free carboxylic acid is essential for AA-1 antibacterial activity. PMID:26904734

Chronic inflammation modulates ghrelin levels in humans and rats.

PubMed

Otero, M; Nogueiras, R; Lago, F; Dieguez, C; Gomez-Reino, J J; Gualillo, O

2004-03-01

The aim of this work was to investigate whether changes in plasma ghrelin, the recently discovered 28-amino acid gastric hormone that regulates growth hormone (GH) secretion and energy homeostasis, occur during inflammation in adjuvant-induced arthritis (AA) in rats. For completeness, ghrelin plasma levels were measured in rheumatoid arthritis (RA) patients. AA was induced in male Lewis rats using Freund's complete adjuvant. Animals were monitored for weight and food intake, every 2 or 3 days, along all time-course experiments. Plasma ghrelin concentrations in 31 RA patients and 18 healthy controls, as well as in rats, were determined by a specific double-antibody radioimmunoassay. Gastric ghrelin mRNA expression was evaluated by northern blot analysis. Human GH and insulin-like growth factor (IGF)-1 were determined by quantitative chemiluminescence assay. Compared with controls, arthritic rats gained significantly (P < 0.01) less body weight than controls until the end of the study, when a partial recovery occurred. Ghrelin plasma levels were significantly lower at day 7 after arthritis induction than in controls (AA 7 = 91.2 +/- 5.6 pg/ml vs controls = 124.75 +/- 5.9 pg/ml), but they recovered to control levels by day 15. RA patients had ghrelin plasma levels significantly lower than healthy controls (RA = 24.54 +/- 2.57 pg/ml vs 39.01 +/- 4.47 pg/ml of healthy controls; P = 0.0041). In AA, there is a compensatory variation of ghrelin levels that relates to body weight adjustments. Recovery of ghrelin levels in the latter stage suggests an adaptive response and may represent a compensatory mechanism under catabolic conditions. In RA patients, chronic imbalance in ghrelin levels suggests that this gastric hormone may participate, together with other factors, in alterations of metabolic status during inflammatory stress.

Organic N cycling in Arctic ecosystems: Quantifying root uptake kinetics and temporal variability of soil amino acids.

NASA Astrophysics Data System (ADS)

Homyak, P. M.; Iverson, S. L.; Slessarev, E.; Marchus, K.; Schimel, J.

2017-12-01

Arctic ecosystems are undergoing shifts in plant community composition with increased warming. How these changes may alter ecosystem function is not well constrained, owing in part to uncertainties on how plant-soil feedbacks influence nutrient cycling. For nitrogen (N), in particular, understanding how these feedbacks may alter cycling rates is challenging because i) Arctic plants take up organic N (i.e., amino acids; AA) when inorganic N is limiting, yet ii) it has never been quantified, for any plant species growing in the wild, how much of its N demand is actually met by taking up AA. To advance fundamental understanding of plant-soil feedbacks as the Arctic warms, we are integrating field measurements of AA availability in N-limited tussock tundra (E. vaginatum) and a comparably less N-limited birch shrub tundra (Betula nana and Salix spp.) with a root uptake model. We used soil microdialysis to determine available AA concentrations in the soil solution and potential rates of AA diffusion and mass flow to roots at the Toolik Field Station in Alaska. These measurements are being combined with AA root uptake kinetic experiments using E. vaginatum to establish actual AA root uptake rates. We found that in the early growing season (June), total AA concentrations in the soil solution averaged 104 µg N L-1 and were similar to NH4+ across sites. In the late growing season (August), AA were the dominant form of N averaging 75 µg N L-1 while NH4+ decreased to 13 µg N L-1. In the early growing season AA diffusion rates in the soil averaged 200 ng N cm-2 s-1 and declined to 150 ng N cm-2 s-1 in the late growing season. Lysine, serine, and arginine were the most abundant AA and differences in the N status of sites did not affect total AA concentrations. Amino acids made up at least half of the N diffusing through the soil solution, suggesting they can subsidize the N demand of arctic plants. Ongoing field experiments at Toolik will be used to constrain actual AA root uptake rates.

Removal of Pb(II) from aqueous solutions using waste textiles/poly(acrylic acid) composite synthesized by radical polymerization technique.

PubMed

Zhou, Tao; Xia, Fafa; Deng, Yue; Zhao, Youcai

2018-05-01

Waste textiles (WTs) are the inevitable outcome of human activity and should be separated and recycled in view of sustainable development. In this work, WT was modified through grafting with acrylic acid (AA) via radical polymerization process using ceric ammonium nitrate (CAN) as an initiator and microwave and/or UV irradiation as energy supply. The acrylic acid-grafted waste textiles (WT-g-AA) thus obtained was then used as an adsorbent to remove Pb(II) from Pb(II)-containing wastewater. The effects of pH, initial concentrations of Pb(II) and adsorbent dose were investigated, and around 95% Pb(II) can be removed from the aqueous solution containing 10mg/L at pH6.0-8.0. The experimental adsorption isotherm data was fitted to the Langmuir model with maximum adsorption capacity of 35.7mg Pb/g WT-g-AA. The Pb-absorbed WT-g-AA was stripped using dilute nitric acid solution and the adsorption capacity of Pb-free material decreased from 95.4% (cycle 1) to 91.1% (cycle 3). It was considered that the WT-g-AA adsorption for Pb(II) may be realized through the ion-exchange mechanism between COOH and Pb(II). The promising results manifested that WT-g-AA powder was an efficient, eco-friendly and reusable adsorbent for the removal of Pb(II) from wastewater. Copyright © 2017. Published by Elsevier B.V.

Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites.

PubMed

Jiang, Jingjing; Du, Xuezhong

2014-10-07

Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.

Novel graphene flowers modified carbon fibers for simultaneous determination of ascorbic acid, dopamine and uric acid.

PubMed

Du, Jiao; Yue, Ruirui; Ren, Fangfang; Yao, Zhangquan; Jiang, Fengxing; Yang, Ping; Du, Yukou

2014-03-15

A novel and sensitive carbon fiber electrode (CFE) modified by graphene flowers was prepared and used to simultaneously determine ascorbic acid (AA), dopamine (DA) and uric acid (UA). SEM images showed that beautiful and layer-petal graphene flowers homogeneously bloomed on the surface of CFE. Moreover, sharp and obvious oxidation peaks were found at the obtained electrode when compared with CFE and glassy carbon electrode (GCE) for the oxidation of AA, DA and UA. Also, the linear calibration plots for AA, DA and UA were observed, respectively, in the ranges of 45.4-1489.23 μM, 0.7-45.21 μM and 3.78-183.87 μM in the individual detection of each component. By simultaneously changing the concentrations of AA, DA and UA, their oxidation peaks appeared at -0.05 V, 0.16 V and 2.6 V, and the good linear responses ranges were 73.52-2305.53 μM, 1.36-125.69 μM and 3.98-371.49 μM, respectively. In addition, the obtained electrode showed satisfactory results when applied to the determination of AA, DA and UA in urine and serum samples. © 2013 Elsevier B.V. All rights reserved.

Overoxidized polyimidazole/graphene oxide copolymer modified electrode for the simultaneous determination of ascorbic acid, dopamine, uric acid, guanine and adenine.

PubMed

Liu, Xiaofang; Zhang, Ling; Wei, Shaping; Chen, Shihong; Ou, Xin; Lu, Qiyi

2014-07-15

In the present work, a novel strategy based on overoxidized polyimidazole (PImox) and graphene oxide (GO) copolymer modified electrode was proposed for the simultaneous determination of ascorbic acid (AA), dopamine (DA), uric acid (UA), guanine (G) and adenine (A). The copolymer was characterized by the scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Due to the synergistic effects between PImox and GO, the proposed electrode exhibited excellent electrochemical catalytic activities and high selectivity and sensitivity toward the oxidation of AA, DA, UA, G and A. The peak separations between AA and DA, AA and UA, UA and G, and G and A were 140 mV, 200 mV, 380 mV and 300 mV, respectively. The linear response ranges for AA, DA, UA, G and A were 75-2275 μM, 12-278 μM, 3.6-249.6 μM, 3.3-103.3 μM and 9.6-215 μM, respectively, and corresponding detection limits were 18 μM, 0.63 μM, 0.59 μM, 0.48 μM and 1.28 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous determination of ascorbic acid, dopamine and uric acid by a novel electrochemical sensor based on N2/Ar RF plasma assisted graphene nanosheets/graphene nanoribbons.

PubMed

Jothi, Lavanya; Neogi, Sudarsan; Jaganathan, Saravana Kumar; Nageswaran, Gomathi

2018-05-15

A novel nitrogen/argon (N 2 /Ar) radio frequency (RF) plasma functionalized graphene nanosheet/graphene nanoribbon (GS/GNR) hybrid material (N 2 /Ar/GS/GNR) was developed for simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid (UA). Various nitrogen mites introduced into GS/GNR hybrid structure was evidenced by a detailed microscopic, spectroscopic and surface area analysis. Owing to the unique structure and properties originating from the enhanced surface area, nitrogen functional groups and defects introduced on both the basal and edges, N 2 /Ar/GS/GNR/GCE showed high electrocatalytic activity for the electrochemical oxidations of AA, DA, and UA with the respective lowest detection limits of 5.3, 2.5 and 5.7 nM and peak-to-peak separation potential (ΔE P ) (vs Ag/AgCl) in DPV of 220, 152 and 372 mV for AA/DA, DA/UA and AA/UA respectively. Moreover, the selectivity, stability, repeatability and excellent performance in real time application of the fabricated N 2 /Ar/GS/GNR/GCE electrode suggests that it can be considered as a potential electrode material for simultaneous detection of AA, DA, and UA. Copyright © 2018 Elsevier B.V. All rights reserved.

Ascorbic Acid Intake and Oxalate Synthesis

PubMed Central

Knight, John; Madduma-Liyanage, Kumudu; Mobley, James A.; Assimos, Dean G.; Holmes, Ross P.

2016-01-01

In humans approximately 60 mg of ascorbic acid (AA) breaks down in the body each day and has to be replaced by a dietary intake of 70 mg in females and 90 mg in males to maintain optimal health and AA homeostasis. The breakdown of AA is non-enzymatic and results in oxalate formation. The exact amount of oxalate formed has been difficult to ascertain primarily due to the limited availability of healthy human tissue for such research and the difficulty in measuring AA and its breakdown products. The breakdown of 60 mg of AA to oxalate could potentially result in the formation of up to 30 mg oxalate per day. This exceeds our estimates of the endogenous production of 10 – 25 mg oxalate per day, indicating that degradative pathways that do not form oxalate exist. In this review we examine what is known about the pathways of AA metabolism and how oxalate forms. We further identify how gaps in our knowledge may be filled to more precisely determine the contribution of AA breakdown to oxalate production in humans. The use of stable isotopes of AA to directly assess the conversion of vitamin to oxalate should help fill this void. PMID:27002809

Combination of azelaic acid 5% and erythromycin 2% in the treatment of acne vulgaris.

PubMed

Pazoki-Toroudi, Hamidreza; Nassiri-Kashani, Mansour; Tabatabaie, Hossein; Ajami, Marjan; Habibey, Rouhollah; Shizarpour, Mohammad; Babakoohi, Shahab; Rahshenas, Makan; Firooz, Alireza

2010-05-01

Acne vulgaris is a common problem, particularly among adolescents, which is usually resistant to monotherapy. We evaluated the efficacy and safety of a combination of azelaic acid (AA) 5% and erythromycin 2% gel (AzE) compared with AA 20% or erythromycin 2% gels in facial acne vulgaris. We conducted a 12-week, multicenter, randomized double-blind study on 147 patients with mild-to-moderate acne vulgaris. Four treatment group were determined (placebo, erythromycin, AA and AzE) and followed in 4-week intervals for 12 weeks, except the placebo group which was changed to routine treatment after 4 weeks. The combination of AA 5% and erythromycin 2% gel significantly reduced the number of papules, pustules and comedones compared with placebo (p < 0.001), erythromycin 2% (p < 0.01) or AA 20% (p < 0.05). The incidence of adverse effects observed in patients treated with AzE (27%) was less than that with erythromycin 2% (54%) and AA 20% (45%). The combination of AA 5% and erythromycin 2% produced more potent therapeutic effects in comparison with erythromycin 2% or AA 20% alone, and with fewer side effects.

Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

PubMed Central

Fang, Pengfei; Guo, Min

2015-01-01

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. PMID:26670257

Evaluation of the antioxidant effect of ganghwayakssuk (Artemisia princeps Pamp.) extract alone and in combination with ascorbic acid in raw chicken patties.

PubMed

Hwang, K E; Kim, H W; Choi, Y S; Lee, S Y; Yeo, E J; Ham, Y K; Choi, S M; Lee, M A; Kim, C J

2013-12-01

We investigated the inhibition of lipid oxidation of raw chicken patties by the antioxidants ascorbic acid (Aa), ganghwayakssuk extracts (GE), and their combination (Aa + GE). All antioxidant combinations were effective at delaying lipid oxidation compared with the control or Aa. A combination of Aa + GE (0.05% Aa + 0.2% GE) was the most effective for delaying lipid oxidation (TBA reactive substances, conjugated dienes, and peroxide formation). The color values of all samples were significantly affected by adding GE. Additionally, the redness, color difference, and hue values of all treatments, except for Aa, were lower than those of the control as the amount of GE increased. The total viable bacterial counts of samples with GE 0.2 and Aa + GE 0.2 were significantly affected during storage (P < 0.05). The results suggest that adding an antioxidant combination reduced the oxidative stress and microbial growth of raw chicken patties stored for 12 d under normal refrigeration temperature, which may extend the shelf life of chicken patties.

Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid.

PubMed

Ghasemi, Simagol; Hosseini, Mahmoud; Feizpour, Azadeh; Alipour, Fatemeh; Sadeghi, Akram; Vafaee, Farzaneh; Mohammadpour, Toktam; Soukhtanloo, Mohammad; Ebrahimzadeh Bideskan, Alireza; Beheshti, Farimah

2017-04-01

The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4)  Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.

Arachidonic acid induces macrophage cell cycle arrest through the JNK signaling pathway.

PubMed

Shen, Ziying; Ma, Yunqing; Ji, Zhonghao; Hao, Yang; Yan, Xuan; Zhong, Yuan; Tang, Xiaochun; Ren, Wenzhi

2018-02-09

Arachidonic acid (AA) has potent pro-apoptotic effects on cancer cells at a low concentration and on macrophages at a very high concentration. However, the effects of AA on the macrophage cell cycle and related signaling pathways have not been fully investigated. Herein we aim to observe the effect of AA on macrophages cell cycle. AA exposure reduced the viability and number of macrophages in a dose- and time-dependent manner. The reduction in RAW264.7 cell viability was not caused by apoptosis, as indicated by caspase-3 and activated caspase-3 detection. Further research illustrated that AA exposure induced RAW264.7 cell cycle arrested at S phase, and some cell cycle-regulated proteins were altered accordingly. Moreover, JNK signaling was stimulated by AA, and the stimulation was partially reversed by a JNK signaling inhibitor in accordance with cell cycle-related factors. In addition, nuclear and total Foxo1/3a and phosphorylated Foxo1/3a were elevated by AA in a dose- and time-dependent manner, and this elevation was suppressed by the JNK signaling inhibitor. Our study demonstrated that AA inhibits macrophage viability by inducing S phase cell cycle arrest. The JNK signaling pathway and the downstream FoxO transcription factors are involved in AA-induced RAW264.7 cell cycle arrest.

Values for digestible indispensable amino acid scores (DIAAS) for some dairy and plant proteins may better describe protein quality than values calculated using the concept for protein digestibility-corrected amino acid scores (PDCAAS).

PubMed

Mathai, John K; Liu, Yanhong; Stein, Hans H

2017-02-01

An experiment was conducted to compare values for digestible indispensable amino acid scores (DIAAS) for four animal proteins and four plant proteins with values calculated as recommended for protein digestibility-corrected amino acid scores (PDCAAS), but determined in pigs instead of in rats. Values for standardised total tract digestibility (STTD) of crude protein (CP) and standardised ileal digestibility (SID) of amino acids (AA) were calculated for whey protein isolate (WPI), whey protein concentrate (WPC), milk protein concentrate (MPC), skimmed milk powder (SMP), pea protein concentrate (PPC), soya protein isolate (SPI), soya flour and whole-grain wheat. The PDCAAS-like values were calculated using the STTD of CP to estimate AA digestibility and values for DIAAS were calculated from values for SID of AA. Results indicated that values for SID of most indispensable AA in WPI, WPC and MPC were greater (P<0·05) than for SMP, PPC, SPI, soya flour and wheat. With the exception of arginine and tryptophan, the SID of all indispensable AA in SPI was greater (P<0·05) than in soya flour, and with the exception of threonine, the SID of all indispensable AA in wheat was less (P<0·05) than in all other ingredients. If the same scoring pattern for children between 6 and 36 months was used to calculate PDCAAS-like values and DIAAS, PDCAAS-like values were greater (P<0·05) than DIAAS values for SMP, PPC, SPI, soya flour and wheat indicating that PDCAAS-like values estimated in pigs may overestimate the quality of these proteins.

Raman spectroscopy and capillary zone electrophoresis for the analysis of degradation processes in commercial effervescent tablets containing acetylsalicylic acid and ascorbic acid.

PubMed

Neuberger, Sabine; Jooß, Kevin; Flottmann, Dirk; Scriba, Gerhard; Neusüß, Christian

2017-02-05

In order to ensure the stability of pharmaceutical products appropriate manufacturing and storage conditions are required. In general, the degradation of active pharmaceutical ingredients (APIs) and subsequent formation of degradation products affect the pharmaceutical quality. Thus, a fast and effective detection and characterization of these substances is mandatory. Here, the applicability of Raman spectroscopy and CZE for the characterization of the degradation of effervescent tablets containing acetylsalicylic acid (ASA) and ascorbic acid (AA) was evaluated. Therefore, a degradation study was performed analyzing tablets from two different manufacturers at varying conditions (relative humidity (RH) 33%, 52% and 75% at 30°C). Raman spectroscopy combined with principal component analysis could be successfully applied for the fast and easy discrimination of non-degraded and degraded effervescent tablets after a storage period of approximately 24h (RH 52%). Nevertheless, a clear identification or quantification of APIs and degradation products within the analyzed tablets was not possible, i.a. due to missing reference materials. CZE-UV enabled the quantification of the APIs (ASA, AA) and related degradation products (salicylic acid (SA); semi-quantitative also mono- and diacetylated AA) within the complex tablet mixtures. The higher the RH, the faster the degradation of ASA and AA as well as the formation of the degradation products. Mono- and diacetylated AA are major primary degradation products of AA for the applied effervescent tablets. A significant degradation of the APIs was detected earlier by CZE (6-12h, RH 52%) than by Raman spectroscopy. Summarized, Raman spectroscopy is well-suited as quick test to detect degradation of these tablets and CZE can be utilized for further detailed characterization and quantification of specific APIs and related degradation products. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites

NASA Astrophysics Data System (ADS)

Jiang, Jingjing; Du, Xuezhong

2014-09-01

Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing. Electronic supplementary information (ESI) available: pH optimization, comparison of sensor performances, interference experiments, and detection in urine samples. See DOI: 10.1039/c4nr01774a

The selective conversion of glutamic acid in amino acid mixtures using glutamate decarboxylase--a means of separating amino acids for synthesizing biobased chemicals.

PubMed

Teng, Yinglai; Scott, Elinor L; Sanders, Johan P M

2014-01-01

Amino acids (AAs) derived from hydrolysis of protein rest streams are interesting feedstocks for the chemical industry due to their functionality. However, separation of AAs is required before they can be used for further applications. Electrodialysis may be applied to separate AAs, but its efficiency is limited when separating AAs with similar isoelectric points. To aid the separation, specific conversion of an AA to a useful product with different charge behavior to the remaining compounds is desired. Here the separation of L-aspartic acid (Asp) and L-glutamic acid (Glu) was studied. L-Glutamate α-decarboxylase (GAD, Type I, EC 4.1.1.15) was applied to specifically convert Glu into γ-aminobutyric acid (GABA). GABA has a different charge behavior from Asp therefore allowing a potential separation by electrodialysis. Competitive inhibition and reduced operational stability caused by Asp could be eliminated by maintaining a sufficiently high concentration of Glu. Immobilization of GAD does not reduce the enzyme's initial activity. However, the operational stability was slightly reduced. An initial study on the reaction operating in a continuous mode was performed using a column reactor packed with immobilized GAD. As the reaction mixture was only passed once through the reactor, the conversion of Glu was lower than expected. To complete the conversion of Glu, the stream containing Asp and unreacted Glu might be recirculated back to the reactor after GABA has been removed. Overall, the reaction by GAD is specific to Glu and can be applied to aid the electrodialysis separation of Asp and Glu. © 2014 American Institute of Chemical Engineers.

Omega-3 and omega-6 polyunsaturated fatty acids enhance arsenic trioxide efficacy in arsenic trioxide-resistant leukemic and solid tumor cells.

PubMed

Wirtitsch, Melanie; Roth, Erich; Bachleitner-Hofmann, Thomas; Wessner, Barbara; Sturlan, Sanda

2009-01-01

Recently we showed that the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) sensitizes arsenic trioxide (As2O3)-resistant tumor cells to a clinically achievable concentration (1 microM) of As2O3 via a reactive oxygen species (ROS)-dependent mechanism. The aim of the present study was to evaluate, whether this combined effect of As2O3 and DHA is also applicable to other PUFAs [i.e., eicospentaenoic acid (EPA), arachidonic acid (AA), and gamma-linolenic acid (GLA)]. Fourteen tumor cell lines were incubated with As2O3 (1 microM), PUFA (25-100 microM), or the combination thereof (+/- vitamin E). Cell viability (colorimetric), apoptosis (bivariate annexin V/propidium iodide staining, detection of hypodiploid DNA), and thiobarbituric acid reactive substances (TBARS) were evaluated. Twelve of 14 As2O3-resistant cell lines tested were resistant to PUFA monotherapy. However, combined treatment with As2O3 and either PUFA significantly reduced cell viability in a dose-dependent manner with AA being the most potent As2O3 enhancer. The combined cytotoxic effect of As2O3/AA treatment was due to induction of apoptosis, preceded by increased intracellular TBARS and was abolished by the antioxidant vitamin E. Importantly, the combined effect of As2O3 and AA was selectively toxic for malignant cells because no cytotoxic effect was observed in normal skin fibroblasts and human microvascular endothelial cells. In conclusion, our study shows that also other PUFAs than DHA-and in particular the omega-6-PUFA AA--can be used as effective modulators of tumor cell chemosensitivity to clinically achievable concentrations of As2O3. Enhanced lipid peroxidation most likely constitutes the key mechanism for the combined effect.

Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

PubMed Central

Elshenawy, Osama H.; Shoieb, Sherif M.; Mohamed, Anwar; El-Kadi, Ayman O.S.

2017-01-01

Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future. PMID:28230738

Effects of Histidine Supplementation on Global Serum and Urine 1H NMR-based Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized Controlled Study.

PubMed

Du, Shanshan; Sun, Shuhong; Liu, Liyan; Zhang, Qiao; Guo, Fuchuan; Li, Chunlong; Feng, Rennan; Sun, Changhao

2017-06-02

The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine 1 H NMR-based metabolomics and serum AA profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum 1 H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/β-glucose were exhibited after histidine supplement. In urine 1 H NMR metabolic profiles, citrate, creatinine/creatine, methylguanidine, and betaine + TMAO were higher, while hippurate was lower in histidine supplement group. In serum AA profiles, 10 AAs changed after histidine supplementation, including increased histidine, glycine, alanine, lysine, asparagine, and tyrosine and decreased leucine, isoleucine, ornithine, and citrulline. The study showed a systemic metabolic response in serum and urine metabolomics and AA profiles to histidine supplementation, showing significantly changed metabolism in AAs, lipid, and glucose in obese women with MetS.

Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life.

PubMed

Alessandri, Jean-Marc; Guesnet, Philippe; Vancassel, Sylvie; Astorg, Pierre; Denis, Isabelle; Langelier, Bénédicte; Aïd, Sabah; Poumès-Ballihaut, Carine; Champeil-Potokar, Gaëlle; Lavialle, Monique

2004-01-01

Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the only treatment--in several psychiatric disorders. The mechanisms by which polyunsaturated fatty acids have an impact on neuronal functions will be reviewed: the modulation of membrane biophysical properties, regulation of neurotransmitter release, synthesis of biologically active oxygenated derivatives, and nuclear receptor-mediated transcription of genes responsive to fatty acids or to their derivatives.

Protection of ascorbic acid from copper(II)-catalyzed oxidative degradation in the presence of flavonoids: quercetin, catechin and morin.

PubMed

Beker, Bilge Yildoğan; Sönmezoğlu, Inci; Imer, Filiz; Apak, Reşat

2011-08-01

Protection of ascorbic acid (AA) (vitamin C) from Cu(II)-catalyzed autoxidation is an important aspect of antioxidant chemistry. The autoxidation of AA in the absence and presence of Cu(II) ions was investigated in aerated solution at room temperature and I = 0.1 ionic strength (KNO(3)); the effects of three different flavonoids of similar structure (quercetin, morin and catechin) and their mixtures on the AA system were studied. The concentration of unoxidized AA remaining in solution was measured with the modified cupric ion reducing antioxidant capacity spectrophotometric method. The Cu(II)-catalyzed oxidation at pH 4.5 followed first-order kinetics with respect to AA concentration. Catalytic autoxidation of AA was inhibited to a greater extent by stable quercetin and morin complexes of Cu(II) than by catechin complex. The inhibitive effectiveness order of mixtures gives information about possible synergistic or antagonistic combinations of flavonoid antioxidants, which should be further confirmed with other antioxidant tests.

Comparison of the nucleotide and amino acid sequences of the RsrI and EcoRI restriction endonucleases.

PubMed

Stephenson, F H; Ballard, B T; Boyer, H W; Rosenberg, J M; Greene, P J

1989-12-21

The RsrI endonuclease, a type-II restriction endonuclease (ENase) found in Rhodobacter sphaeroides, is an isoschizomer of the EcoRI ENase. A clone containing an 11-kb BamHI fragment was isolated from an R. sphaeroides genomic DNA library by hybridization with synthetic oligodeoxyribonucleotide probes based on the N-terminal amino acid (aa) sequence of RsrI. Extracts of E. coli containing a subclone of the 11-kb fragment display RsrI activity. Nucleotide sequence analysis reveals an 831-bp open reading frame encoding a polypeptide of 277 aa. A 50% identity exists within a 266-aa overlap between the deduced aa sequences of RsrI and EcoRI. Regions of 75-100% aa sequence identity correspond to key structural and functional regions of EcoRI. The type-II ENases have many common properties, and a common origin might have been expected. Nevertheless, this is the first demonstration of aa sequence similarity between ENases produced by different organisms.

Functional amino acids in nutrition and health.

PubMed

Wu, Guoyao

2013-09-01

The recent years have witnessed growing interest in biochemistry, physiology and nutrition of amino acids (AA) in growth, health and disease of humans and other animals. This results from the discoveries of AA in cell signaling involving protein kinases, G protein-coupled receptors, and gaseous molecules (i.e., NO, CO and H2S). In addition, nutritional studies have shown that dietary supplementation with several AA (e.g., arginine, glutamine, glutamate, leucine, and proline) modulates gene expression, enhances growth of the small intestine and skeletal muscle, or reduces excessive body fat. These seminal findings led to the new concept of functional AA, which are defined as those AA that participate in and regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of the organisms. Functional AA hold great promise in prevention and treatment of metabolic diseases (e.g., obesity, diabetes, and cardiovascular disorders), intrauterine growth restriction, infertility, intestinal and neurological dysfunction, and infectious disease (including viral infections).

Methionine and Choline Supply during the Periparturient Period Alter Plasma Amino Acid and One-Carbon Metabolism Profiles to Various Extents: Potential Role in Hepatic Metabolism and Antioxidant Status.

PubMed

Zhou, Zheng; Vailati-Riboni, Mario; Luchini, Daniel N; Loor, Juan J

2016-12-29

The objective of this study was to profile plasma amino acids (AA) and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET) or rumen-protected choline (CHOL). Forty cows were fed from -21 through 30 days around parturition in a 2 × 2 factorial design a diet containing MET or CHOL. MET supply led to greater circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also was greater in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) were greater in MET-fed cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA and total AA concentrations were greater in cows supplied MET due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, CHOL supply had no effect on essential AA or total AA, and only tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower in response to CHOL supply, suggesting less tissue protein mobilization in these cows. Overall, the data revealed that enhanced periparturient supply of MET has positive effects on plasma AA profiles and overall antioxidant status.

Expression of Renal Aquaporins in Aristolochic Acid I and Aristolactam I-Induced Nephrotoxicity.

PubMed

Li, Ji; Zhang, Liang; Jiang, ZhenZhou; He, XiuQin; Zhang, LuYong; Xu, Ming

2016-01-01

Exposure to aristolochic acid (AA) can cause AA nephropathy, which is characterized by extensive proximal tubular damage and polyuria. To test the hypothesis that polyuria might be induced by altered regulation of aquaporins (AQPs) in the kidney, different doses of AA-I or aristolactam I (AL-I) were administered intraperitoneally to Sprague-Dawley rats, and urine, blood, and kidney samples were analyzed. In addition, AQP1, AQP2, AQP4 and AQP6 expression in the kidney were determined. The results showed dose-dependent proximal tubular damage and polyuria in the AA-I- and AL-I-treated groups, and the nephrotoxicity of AL-I was higher than that of AA-I. The expression of renal AQP1, AQP2 and AQP4, but not AQP6 were significantly inhibited by AA-I and AL-I. Comparison of the inhibition potencies of AA-I and AL-I showed that AL-I was a stronger inhibitor of AQP1 expression than AA-I, while there was no difference in their effects on AQP2 and AQP4. These results suggested that AA induced renal damage and polyuria were associated with a specific decrease in the expression of renal AQP1 AQP2 and AQP4, and AL-I showed higher nephrotoxicity than AA-I, which might be attributable to the differences in their inhibition of AQP1. © 2016 S. Karger AG, Basel.

Methionine and Choline Supply during the Periparturient Period Alter Plasma Amino Acid and One-Carbon Metabolism Profiles to Various Extents: Potential Role in Hepatic Metabolism and Antioxidant Status

PubMed Central

Zhou, Zheng; Vailati-Riboni, Mario; Luchini, Daniel N.; Loor, Juan J.

2016-01-01

The objective of this study was to profile plasma amino acids (AA) and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET) or rumen-protected choline (CHOL). Forty cows were fed from −21 through 30 days around parturition in a 2 × 2 factorial design a diet containing MET or CHOL. MET supply led to greater circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also was greater in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) were greater in MET-fed cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA and total AA concentrations were greater in cows supplied MET due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, CHOL supply had no effect on essential AA or total AA, and only tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower in response to CHOL supply, suggesting less tissue protein mobilization in these cows. Overall, the data revealed that enhanced periparturient supply of MET has positive effects on plasma AA profiles and overall antioxidant status. PMID:28036059

AaCAT1 of the Yellow Fever Mosquito, Aedes aegypti

PubMed Central

Hansen, Immo A.; Boudko, Dmitri Y.; Shiao, Shin-Hong; Voronov, Dmitri A.; Meleshkevitch, Ella A.; Drake, Lisa L.; Aguirre, Sarah E.; Fox, Jeffrey M.; Attardo, Geoffrey M.; Raikhel, Alexander S.

2011-01-01

Insect yolk protein precursor gene expression is regulated by nutritional and endocrine signals. A surge of amino acids in the hemolymph of blood-fed female mosquitoes activates a nutrient signaling system in the fat bodies, which subsequently derepresses yolk protein precursor genes and makes them responsive to activation by steroid hormones. Orphan transporters of the SLC7 family were identified as essential upstream components of the nutrient signaling system in the fat body of fruit flies and the yellow fever mosquito, Aedes aegypti. However, the transport function of these proteins was unknown. We report expression and functional characterization of AaCAT1, cloned from the fat body of A. aegypti. Expression of AaCAT1 transcript and protein undergoes dynamic changes during postembryonic development of the mosquito. Transcript expression was especially high in the third and fourth larval stages; however, the AaCAT1 protein was detected only in pupa and adult stages. Functional expression and analysis of AaCAT1 in Xenopus oocytes revealed that it acts as a sodium-independent cationic amino acid transporter, with unique selectivity to l-histidine at neutral pH (K0.5l-His = 0.34 ± 0.07 mm, pH 7.2). Acidification to pH 6.2 dramatically increases AaCAT1-specific His+-induced current. RNAi-mediated silencing of AaCAT1 reduces egg yield of subsequent ovipositions. Our data show that AaCAT1 has notable differences in its transport mechanism when compared with related mammalian cationic amino acid transporters. It may execute histidine-specific transport and signaling in mosquito tissues. PMID:21262963

Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release kinetics in a 3D microparticle-hydrogel drug delivery system.

PubMed

Pinezich, Meghan R; Russell, Lauren N; Murphy, Nicholas P; Lampe, Kyle J

2018-04-16

Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol-based hydrogel. The goal of this DDS was to better understand the relationship between PDGF-AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF-AA under seven different delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCs in vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF-AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs.

PubMed

Radhakrishnakartha, Harikrishnan; Appu, Abhilash Puthuvelvippel; Madambath, Indira

2014-02-01

Chronic ethanol exposure causes hyperlipidemia. The present study was designed to investigate the impact of ascorbic acid supplementation on ethanol induced hyperlipidemia in testis and to compare it with that of abstinence from taking alcohol. Thirty-six male guinea pigs were divided into two groups and were maintained for 90 days as follows (1) control (C) (2) ethanol treated group (E) (4 g/kg body wt/day). Ethanol was administered for 90 days and on 90th day, alanine amino transaminase (ALT), aspartate amino transaminase (AST) and γ-glutamyltransferase (GGT) in serum was assayed. The animals in the ethanol group were further divided into an ascorbic acid supplemented group (25 mg/100 g body wt/day) (E+AA) and an ethanol abstention group (EAG) and those in the control group were divided into a control group and a control+ascorbic acid group (C+AA). There was significant increase in levels of testicular cholesterol, free fatty acid, phospholipids and triglycerides in the ethanol group. There was also a significant increase in the activity of HMG CoA reductase and decrease in activity of testicular glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme in ethanol-ingested animals that further led to decreased levels of serum testosterone. Alcohol administration also enhanced the activity of testicular alcohol dehydrogenase (ADH). Ascorbic acid supplementation and abstention altered all these parameters induced by chronic alcohol administration. Histological studies were also in line with the above results. Ascorbic acid was able to reinstate the cholesterol homeostasis in testis which could have further restored the testicular steroidogenesis. The present study demonstrated that ascorbic acid is effective in reducing the hyperlipidemia induced by chronic alcohol administration and produced a better recovery than abstention.

Effect of water soluble vitamins on Zn transport of Caco-2 cells and their implications under oxidative stress conditions.

PubMed

Tupe, Rashmi Santosh; Agte, Vaishali Vilas

2010-02-01

The role of different water soluble vitamins in Zn metabolism beyond intestinal Zn absorption is poorly explored. Using Caco-2 cells, effects of different vitamins on intestinal Zn transport and their implications under oxidative stress (OS) were investigated. Cells were apically treated with Zn (25 muM) and vitamins (Folic acid (FA), Nicotinic acid (NA), Ascorbic acid (AA), riboflavin, thiamine, pyridoxine) for 60 min. The effect of most promising vitamins on zinc transport, antioxidant enzymes (Catalase, Glutathione peroxidase, and superoxide dismutase), and intracellular OS status (ROS generation and mitochondrial transmembrane potential) were investigated. OS was generated by tert-butyl hydro peroxide and results for each vitamin were compared with respective Zn containing controls with and without OS. Without OS, Zn transport was slightly enhanced in presence of NA, while it was significantly reduced by thiamine, riboflavin, and pyridoxine. Under OS, NA significantly (P < 0.01) enhanced Zn transport in dose-dependent manner, while, pyridoxine and AA moderately improved it. Under both conditions, Zn transport exhibited decreasing trend with increase of FA. The antioxidant enzyme and OS markers levels varied significantly in Zn + vitamins. With Zn + FA + OS, enzyme activities decreased maximally, with twofold increase in 2',7'-dichlorofluorescin diacetate (DCF-DA) (P < 0.01) and lowering of rhodamine fluorescence (P < 0.05). In Zn + AA + OS, DCF-DA fluorescence increased (P < 0.05) but with NA, cellular enzymes, and antioxidant profile were improved. Results for the first time demonstrate advantageous effects of NA and deleterious consequences of FA with no effect by AA on Zn transport, especially under OS. These observed changes in the transport of Zn seem to have an impact on OS markers.

Contribution of Fermentation Yeast to Final Amino Acid Profile in DDGS

USDA-ARS?s Scientific Manuscript database

One major factor affecting DDGS quality and market values is amino acid (AA) composition. DDGS proteins come from corn and yeast. Yet, the effect of fermentation yeast on DDGS protein quantity and quality (AA profile) has not been well documented. Based on literature review, there are at least 4 met...

77 FR 63813 - Agency Information Collection Activities: Request for Comments on Thirty-Seven Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-17

... Phosphoric Acid Manufacturing and Phosphate Fertilizers Production (40 CFR Part 63, Subparts AA and BB). ICR... September 30, 2013. (33) Docket ID Number: EPA-HQ-OECA-2012-0686. Title: NESHAP for Organic Liquids... Acid Manufacturing and Phosphate Fertilizers Production (40 CFR Part 63, Subparts AA and BB); Learia...

Advances in the application of amino acid nitrogen isotopic analysis in ecological and biogeochemical studies

USDA-ARS?s Scientific Manuscript database

Compound-specific isotopic analysis of amino acids (CSIA-AA) has emerged in the last decade as a powerful approach for tracing the origins and fate of nitrogen in ecological and biogeochemical studies. This approach is based on the empirical knowledge that source AAs (i.e., phenylalanine), fractiona...

Eicosapentaenoic Acid Enhances Heat Stress-Impaired Intestinal Epithelial Barrier Function in Caco-2 Cells

PubMed Central

Xiao, Guizhen; Tang, Liqun; Yuan, Fangfang; Zhu, Wei; Zhang, Shaoheng; Liu, Zhifeng; Geng, Yan; Qiu, Xiaowen

2013-01-01

Objective Dysfunction of the intestinal epithelial tight junction (TJ) barrier is known to have an important etiologic role in the pathophysiology of heat stroke. N-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in maintaining and protecting the TJ structure and function. This study is aimed at investigating whether n-3 PUFAs could alleviate heat stress-induced dysfunction of intestinal tight junction. Methods Human intestinal epithelial Caco-2 cells were pre-incubated with EPA, DHA or arachidonic acid (AA) and then exposed to heat stress. Transepithelial electrical resistance (TEER) and Horseradish Peroxidase (HRP) permeability were measured to analyze barrier integrity. Levels of TJ proteins, including occludin, ZO-1 and claudin-2, were analyzed by Western blot and localized by immunofluorescence microscopy. Messenger RNA levels were determined by quantitative real time polymerase chain reaction (Q-PCR). TJ morphology was observed by transmission electron microscopy. Results EPA effectively attenuated the decrease in TEER and impairment of intestinal permeability in HRP flux induced by heat exposure. EPA significantly elevated the expression of occludin and ZO-1, while DHA was less effective and AA was not at all effective. The distortion and redistribution of TJ proteins, and disruption of morphology were also effectively prevented by pretreatment with EPA. Conclusion This study indicates for the first time that EPA is more potent than DHA in protecting against heat-induced permeability dysfunction and epithelial barrier damage of tight junction. PMID:24066055

Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review

PubMed Central

Borow, Kenneth M.; Mason, R. Preston; Vijayaraghavan, Krishnaswami

2017-01-01

Background Patients with end-stage renal disease on hemodialysis have excess cardiovascular disease (CVD) burden with substantially increased CV event rates compared with the general population. Summary Traditional interventions that, according to standard clinical guidelines, reduce CV risk such as antihypertensive therapy, diet, exercise, and statins are not similarly effective in the hemodialysis population. This raises the question of whether additional risk factors, such as enhanced inflammation and oxidative stress, may drive the increased CVD burden in hemodialysis patients. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into the atherosclerotic plaque as well as membrane phospholipid bilayers and produces beneficial effects on inflammatory and oxidative mechanisms involved in atherosclerotic plaque formation and progression. EPA levels and the ratio of EPA to the omega-6 polyunsaturated fatty acid arachidonic acid (AA) are reduced in hemodialysis patients. Serum EPA levels have been inversely correlated with proinflammatory cytokines, and the EPA/AA ratio has been inversely associated with CV events in hemodialysis cohorts. Three recent studies involving over 800 hemodialysis patients and follow-up of 2–3 years suggest that EPA therapy may improve clinical outcomes in this patient population as evidenced by significant reductions in cardiovascular mortality, all-cause mortality, and/or CV events. Key Messages Further studies with high-purity EPA are warranted in patients on hemodialysis, especially given the fact that other interventions including antihypertensives, diet, exercise, and statins have not provided meaningful benefit. PMID:29344023

Preparation of poly(acrylamide-co-acrylic acid)-grafted gum and its flocculation and biodegradation studies.

PubMed

Mittal, H; Mishra, Shivani B; Mishra, A K; Kaith, B S; Jindal, R; Kalia, S

2013-10-15

Biodegradation studies of Gum ghatti (Gg) and acrylamide-co-acrylic acid based flocculants [Gg-cl-poly(AAm-co-AA)] have been reported using the soil composting method. Gg-cl-poly(AAm-co-AA) was found to degrade 89.76% within 60 days. The progress of biodegradation at each stage was monitored through FT-IR and SEM. Polymer was synthesized under pressure using potassium persulphate-ascorbic acid as a redox initiator and N,N'-methylene-bis-acrylamide as a crosslinker. Synthesized polymer was found to show pH, temperature and ionic strength of the cations dependent swelling behavior. Gg-cl-poly(AAm-co-AA) was utilized for the selective absorption of saline from different petroleum fraction-saline emulsions. The flocculation efficiency of the polymer was studied as a function of polymer dose, temperature and pH of the solution. Gg-cl-poly(AAm-co-AA) showed maximum flocculation efficiency with 20 mol L(-1) polymer dose in acidic medium at 50 °C. Copyright © 2013. Published by Elsevier Ltd.

Bolus oral or continuous intestinal amino acids reduce hypothermia during anesthesia in rats.

PubMed

Imoto, Akinobu; Yokoyama, Takeshi; Suwa, Kunio; Yamasaki, Fumiyasu; Yatabe, Tomoaki; Yokoyama, Reiko; Yamashita, Koichi; Selldén, Eva

2010-01-01

We hypothesized that, with oral or intestinal administration of amino acids (AA), we may reduce hypothermia during general anesthesia as effectively as with intravenous AA. We, therefore, examined the effect of bolus oral and continuous intestinal AA in preventing hypothermia in rats. Male Wistar rats were anesthetized with sevoflurane for induction and with propofol for maintenance. In the first experiment, 30 min before anesthesia, rats received one bolus 42 mL/kg of AA solution (100 g/L) or saline orally. Then for the next 3 h during anesthesia, they received 14 mL/kg/h of AA and/or saline intravenously. They were in 4 groups: I-A/A, both AA; I-A/S, oral AA and intravenous saline; I-S/A, oral saline and intravenous AA; I-S/S, both saline. In the second experiment, rats received 14 mL/kg/h duodenal AA and/or saline for 2 h. They were in 3 groups: II-A/S, duodenal AA and intravenous saline; II-S/A, duodenal saline and intravenous AA; II-S/S, both saline. Core body temperature was measured rectally. After the second experiment, serum electrolytes were examined. In both experiments, rectal temperature decreased in all groups during anesthesia. However, the decrease in rectal temperature was significantly less in groups receiving AA than in groups receiving only saline. In the second experiment, although there was no significant difference in the decrease in body temperature between II-A/S and II-S/A, Na(+) concentration was significantly lower in II-S/A. In conclusion, AA, administered orally or intestinally, tended to keep the body temperature stable during anesthesia without disturbing electrolyte balance. These results suggest that oral or enteral AA may be useful for prevention of hypothermia in patients.

Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma.

PubMed

Ishikawa, Toru

2012-05-07

The prognosis of hepatocellular carcinoma (HCC) depends on tumor extension as well as hepatic function. Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC; the Child-Pugh classification system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease, using serum albumin level to achieve accurate assessment of the status of protein metabolism. However, insufficient attention has been given to the status of amino acid (AA) metabolism in chronic liver disease and HCC. Fischer's ratio is the molar ratio of branched-chain AAs (BCAAs: leucine, valine, isoleucine) to aromatic AAs (phenylalanine, tyrosine) and is important for assessing liver metabolism, hepatic functional reserve and the severity of liver dysfunction. Although this ratio is difficult to determine in clinical situations, BCAAs/tyrosine molar concentration ratio (BTR) has been proposed as a simpler substitute. BTR correlates with various liver function examinations, including markers of hepatic fibrosis, hepatic blood flow and hepatocyte function, and can thus be considered as reflecting the degree of hepatic impairment. This manuscript examines the literature to clarify whether BTR can serve as a prognostic factor for treatment of HCC.

Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations.

PubMed

Chen, Tianlu; Ni, Yan; Ma, Xiaojing; Bao, Yuqian; Liu, Jiajian; Huang, Fengjie; Hu, Cheng; Xie, Guoxiang; Zhao, Aihua; Jia, Weiping; Jia, Wei

2016-02-05

Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 Chinese participants at different stages of diabetes development, using an ultra-performance liquid chromatography triple quadruple mass spectrometry platform. The alterations of the five AAs in Chinese populations are well in accordance with previous reports. Early elevation of the five AAs and their combined score was closely associated with future development of diabetes, suggesting an important role of these metabolites as early markers of diabetes. On the other hand, the five AAs were not as good as existing clinical markers in differentiating diabetic patients from their healthy counterparts. Our findings verified the close correlation of BCAAs and AAAs with insulin resistance and future development of diabetes in Chinese populations and highlighted the predictive value of these markers for future development of diabetes.

Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations

PubMed Central

Chen, Tianlu; Ni, Yan; Ma, Xiaojing; Bao, Yuqian; Liu, Jiajian; Huang, Fengjie; Hu, Cheng; Xie, Guoxiang; Zhao, Aihua; Jia, Weiping; Jia, Wei

2016-01-01

Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 Chinese participants at different stages of diabetes development, using an ultra-performance liquid chromatography triple quadruple mass spectrometry platform. The alterations of the five AAs in Chinese populations are well in accordance with previous reports. Early elevation of the five AAs and their combined score was closely associated with future development of diabetes, suggesting an important role of these metabolites as early markers of diabetes. On the other hand, the five AAs were not as good as existing clinical markers in differentiating diabetic patients from their healthy counterparts. Our findings verified the close correlation of BCAAs and AAAs with insulin resistance and future development of diabetes in Chinese populations and highlighted the predictive value of these markers for future development of diabetes. PMID:26846565

β-Cell lipotoxicity in response to free fatty acid elevation in prepubertal youth: African American versus Caucasian contrast.

PubMed

Michaliszyn, Sara F; Bonadonna, Riccardo C; Sjaarda, Lindsey A; Lee, Sojung; Farchoukh, Lama; Arslanian, Silva A

2013-08-01

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition × race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion, consistent with our theory.

Rapid quantification of underivatized amino acids in plasma by hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass-spectrometry.

PubMed

Prinsen, Hubertus C M T; Schiebergen-Bronkhorst, B G M; Roeleveld, M W; Jans, J J M; de Sain-van der Velden, M G M; Visser, G; van Hasselt, P M; Verhoeven-Duif, N M

2016-09-01

Amino acidopathies are a class of inborn errors of metabolism (IEM) that can be diagnosed by analysis of amino acids (AA) in plasma. Current strategies for AA analysis include cation exchange HPLC with post-column ninhydrin derivatization, GC-MS, and LC-MS/MS-related methods. Major drawbacks of the current methods are time-consuming procedures, derivative problems, problems with retention, and MS-sensitivity. The use of hydrophilic interaction liquid chromatography (HILIC) columns is an ideal separation mode for hydrophilic compounds like AA. Here we report a HILIC-method for analysis of 36 underivatized AA in plasma to detect defects in AA metabolism that overcomes the major drawbacks of other methods. A rapid, sensitive, and specific method was developed for the analysis of AA in plasma without derivatization using HILIC coupled with tandem mass-spectrometry (Xevo TQ, Waters). Excellent separation of 36 AA (24 quantitative/12 qualitative) in plasma was achieved on an Acquity BEH Amide column (2.1×100 mm, 1.7 μm) in a single MS run of 18 min. Plasma of patients with a known IEM in AA metabolism was analyzed and all patients were correctly identified. The reported method analyzes 36 AA in plasma within 18 min and provides baseline separation of isomeric AA such as leucine and isoleucine. No separation was obtained for isoleucine and allo-isoleucine. The method is applicable to study defects in AA metabolism in plasma.

Effect of cultivar and variety on phenolic compounds and antioxidant activity of cherry wine.

PubMed

Xiao, Zuobing; Fang, Lingling; Niu, Yunwei; Yu, Haiyan

2015-11-01

To compare the influence of cultivar and variety on the phenolic compounds and antioxidant activity (AA) of cherry wines, total phenolic (TP), total flavonoid (TF), total anthocyanin (TA), total tannin (TT), five individual phenolic acids, and AA were determined. An ultra-performance liquid chromatography tandem mass spectrometry (HPLC-DAD/ESI-MS) method was developed for the determination of gallic acid (GAE), p-hydroxybenzoic acid (PHB), chlorogenic acid (CHL), vanillic acid (VAN), and caffeic acid (CAF). A principal component analysis (PCA) and a cluster analysis (CA) were used to analyze differences related to cultivar and variety. The TP, TF, TA, TT, and AA of samples sourced from the Shandong province of China were higher than those from the Jiangsu province. The PCA and CA results showed that phenolic compounds in cherry wines were closely related to cultivar and variety and that cultivar had more influence on the phenolic compounds of cherry wines than variety. Copyright © 2015 Elsevier Ltd. All rights reserved.

Free radical grafting of gallic acid (GA) on cellulose nanocrystals (CNCS) and evaluation of antioxidant reinforced gellan gum films

NASA Astrophysics Data System (ADS)

Criado, P.; Fraschini, C.; Salmieri, S.; Becher, D.; Safrany, A.; Lacroix, M.

2016-01-01

Antiradical properties were introduced on cellulose nanocrystals (CNCs) by redox pair (RP) initiator and γ-radiation treatments. Different procedures were tested on CNC, first a 2 h reaction of hydrogen peroxide (H2O2)/ascorbic acid (AA) was performed on CNC solution. γ-Radiation treatment at 20 kGy dose was then applied and immediately after GA was reacted during 24 h with the pretreated CNCs, giving CNC-H2O2-AA-γ-GA. The formation of new carboxylic acids and carbonyl groups were characterized by FT-IR at 1650 and 1730 cm-1 respectively. Carboxylic acid functionalities were also analyzed by conductometric titration where an increase from 49 to 134 mmol COOH kg-1 was found from native to irradiated CNCs. A similar increase in the carboxylic acid content (132 mmol kg-1) was observed for CNC-H2O2-AA-γ-GA, showing the highest radical scavenging properties (8 mM Trolox eq/mg CNC). Thermogravimetric analysis confirmed the structural changes onto CNC. Film packaging containing 20% of CNC-H2O2-AA-γ-GA was then added to a gellan-based film packaging. A significant improvement (p<0.05) of the tensile strength (TS), the tensile modulus (TM) and the elongation at break (EB) and water vapor permeability reduction was observed when CNC-H2O2-AA-γ-GA was added to the film packaging formulation.

Sufficient protein quality of food aid varies with the physiologic status of recipients

USDA-ARS?s Scientific Manuscript database

Protein quality scores use the amino acid (AA) requirements of a healthy North American child. AA requirements vary with physiologic status. We estimated AA requirements for healthy North American children, children with environmental enteric dysfunction, children recovering from wasting, and childr...

Expression of Selected Ginkgo biloba Heat Shock Protein Genes After Cold Treatment Could Be Induced by Other Abiotic Stress

PubMed Central

Cao, Fuliang; Cheng, Hua; Cheng, Shuiyuan; Li, Linling; Xu, Feng; Yu, Wanwen; Yuan, Honghui

2012-01-01

Heat shock proteins (HSPs) play various stress-protective roles in plants. In this study, three HSP genes were isolated from a suppression subtractive hybridization (SSH) cDNA library of Ginkgo biloba leaves treated with cold stress. Based on the molecular weight, the three genes were designated GbHSP16.8, GbHSP17 and GbHSP70. The full length of the three genes were predicted to encode three polypeptide chains containing 149 amino acids (Aa), 152 Aa, and 657 Aa, and their corresponding molecular weights were predicted as follows: 16.67 kDa, 17.39 kDa, and 71.81 kDa respectively. The three genes exhibited distinctive expression patterns in different organs or development stages. GbHSP16.8 and GbHSP70 showed high expression levels in leaves and a low level in gynoecia, GbHSP17 showed a higher transcription in stamens and lower level in fruit. This result indicates that GbHSP16.8 and GbHSP70 may play important roles in Ginkgo leaf development and photosynthesis, and GbHSP17 may play a positive role in pollen maturation. All three GbHSPs were up-regulated under cold stress, whereas extreme heat stress only caused up-regulation of GbHSP70, UV-B treatment resulted in up-regulation of GbHSP16.8 and GbHSP17, wounding treatment resulted in up-regulation of GbHSP16.8 and GbHSP70, and abscisic acid (ABA) treatment caused up-regulation of GbHSP70 primarily. PMID:22754330

Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease, asthma-COPD overlap syndrome and bronchial asthma.

PubMed

Kodama, Yuzo; Kishimoto, Yuki; Muramatsu, Yoko; Tatebe, Junko; Yamamoto, Yu; Hirota, Nao; Itoigawa, Yukinari; Atsuta, Ryo; Koike, Kengo; Sato, Tadashi; Aizawa, Koich; Takahashi, Kazuhisa; Morita, Toshisuke; Homma, Sakae; Seyama, Kuniaki; Ishigami, Akihito

2017-11-01

Few studies to date have investigated the antioxidant nutrients such as vitamin C (ascorbic acid), vitamin E (α-tocopherol), retinol and carotenoids in plasma from patients with pulmonary disease in Japan. To clarify the role of antioxidant nutrients such as vitamin C, vitamin E, retinol and various carotenoids in plasma of Japanese patients with chronic obstructive lung diseases (COPD), asthma-COPD overlap syndrome (ACOS) and/or bronchial asthma (BA), we compared to healthy elderly controls. Ascorbic acid (AA), carotenoids (lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene and lycopene), retinol and α-tocopherol levels in plasma were determined by using a high performance liquid chromatography. Reduced glutathione (GSH), oxidised glutathione (GSSG) in whole blood and urinary 8-OHdG were also determined. Plasma AA level of COPD subjects was significantly lower than that of healthy elderly people. Conversely, ACOS and BA subjects showed no significant difference from healthy elderly people. Moreover, plasma lycopene and total carotenoid levels and GSH content in blood were significantly lower in COPD subjects than these in healthy elderly people. However, other redox markers such as GSSG, GSH/GSSG ratio and urinary 8-OHdG found no significant differences between COPD, ACOS and BA compared to healthy elderly people. These results suggested that COPD of Japanese patients may develop partly because of oxidative stress derived from a shortage of antioxidant nutrients, especially of AA and lycopene, as well as GSH while this may not be the case in both ACOS and BA. © 2016 John Wiley & Sons Ltd.

Sex Differences in Omega-3 and -6 Fatty Acids and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO Study.

PubMed

Lu, Yuan; Ding, Qinglan; Xu, Xiao; Spatz, Erica S; Dreyer, Rachel P; D'Onofrio, Gail; Caulfield, Michael; Nasir, Khurram; Spertus, John A; Krumholz, Harlan M

2018-05-30

Young women (aged ≤55 years) with acute myocardial infarction (AMI) have poorer health status outcomes than similarly aged men. Low omega-3 fatty acids (FAs) have been implicated as risk factors for cardiovascular outcomes in AMI patients, but it is not clear whether young women have similar or different post-AMI omega-3 FA profiles compared with young men. We assessed the sex differences in post-AMI omega-3 FAs and the associations of these biomarkers with patient-reported outcomes (symptom, functioning status, and quality of life) at 12-month follow-up, using data from 2985 US adults with AMI aged 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study. Biomarkers including eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid (AA), eicosapentaenoic acid/AA ratio, omega-3/omega-6 ratio, and omega-3 index were measured 1 month after AMI. Overall, the omega-3 FAs and AA were similar in young men and women with AMI. In both unadjusted and adjusted analysis (controlling for age, sex, race, smoking, hypertension, diabetes mellitus, body mass index, and health status score at 1 month), omega-3 FAs and AA were not significantly associated with 12-month health status scores using the Bonferroni corrected statistical threshold. We found no evidence of sex differences in omega-3 FAs and AA in young men and women 1 month after AMI. Omega-3 FAs and AA at 1-month after AMI were generally not associated with 12-month patient-reported health status after adjusting for patient demographic, clinical characteristics, and the corresponding 1-month health status score. © 2018 The Authors and Quest Diagnostics Inc. Published on behalf of the American Heart Association, Inc., by Wiley.

Vitamin-C delivery from CoCr alloy surfaces using polymer-free and polymer-based platforms for cardiovascular stent applications.

PubMed

Thiruppathi, Eagappanath; Mani, Gopinath

2014-06-03

Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (l-ascorbic acid, l-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of l-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly(lactic-co-glycolic acid) (PLGA) platform were used for coating l-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of l-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of l-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that l-AA (276 μg/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the l-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that l-AA was incorporated into the bulk of the PLGA film. DSC showed that the l-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that l-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of l-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of l-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells.

PubMed

Liu, G; Bibus, D M; Bode, A M; Ma, W Y; Holman, R T; Dong, Z

2001-06-19

Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (omega3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (omega6) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the omega3 fatty acids EPA and DHA and of the omega6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of omega3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of omega6 to omega3 fatty acids may be a significant factor in mediating tumor development.

The gene road to royalty--differential expression of hydroxylating genes in the mandibular glands of the honeybee.

PubMed

Malka, Osnat; Karunker, Iris; Yeheskel, Adva; Morin, Shai; Hefetz, Abraham

2009-10-01

The advances in honeybee sociogenomics have paved the way for the study of social communication processes at the gene level, in particular the expression of caste-specific pheromones. The queen honeybee mandibular pheromone provides an excellent model system, in that biosynthesis of the hydroxylating fatty acid caste-specific pheromone appears to be reduced to a single chemical hydroxylation step of stearic acid. Queens are typified by omega-1-hydroxylation, as opposed to the worker-typical omega-hydroxylation. We hypothesized that this bifurcation is the consequence of differential expression of caste-specific genes that code for fatty acid-hydroxylating enzymes from the cytochrome P450 (CYP) family. Bioinformatics studies disclosed two candidate proteins CYP4AA1 and CYP18A1. We thus investigated the expression of these genes in the mandibular glands of queens, and of queenright (QR) and queenless (QL) workers. The real-time PCR results revealed that CYP4AA1 (omega-hydroxylation) was expressed at high levels in both QR and QL workers, whereas in queens its expression was negligible. The expression of CYP18A1 (omega-1-hydroxylation), on the other hand, was high in the queen's glands and negligible in those of QR workers. In QL workers, however, the expression of CYP18A1 was considerably elevated and significantly greater than in QR workers. Three-dimensional structural models constructed for these enzymes demonstrate differences in the active site between CYP18A1 and CYP4AA1, in line with their differential catalytic specificity. The fact that queen pheromone plasticity can be tracked all the way to gene expression provides a new insight into the process of caste differentiation and the accompanying social communication.