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Sample records for a-lipoic acid increases

  1. Stability, cutaneous delivery and antioxidant potential of a lipoic acid and α-tocopherol co-drug incorporated in microemulsions

    PubMed Central

    Thomas, Siji; Vieira, Camila S.; Hass, Martha A.; Lopes, Luciana B.

    2014-01-01

    The aim of this study was to assess the skin penetration, stability and antioxidant effects of a α-tocopherol-lipoic acid co-drug. To enhance penetration, we evaluated three microemulsions varying in water content and composition of the oil phase (isopropyl myristate with either monocaprylin or oleic acid). The co-drug was incorporated at 1% (w/w). Co-drug hydrolysis in the microemulsion increased with increases in time (up to 48 h) and formulation water content (10–30%, w/w). Microemulsions increased the co-drug delivery into viable layers of porcine ear skin by 2.9–7.8–fold compared to a control formulation (20% monocaprylin in isopropyl myristate) after 24 h. Penetration enhancement was influenced by the oil phase, with the formulation containing monocaprylin displaying the most pronounced effect. Antioxidant activity, assessed in skin bioequivalents using the thiobarbituric acid-reactive substances (TBARS) assay, demonstrated that TBARS levels decreased by 39% after treatment with the co-drug-containing microemulsion compared to the unloaded formulation. In addition to the co-drug, tocopherol (8.2 ± 0.6 μg/cm2) was detected in the viable bioequivalent tissues, suggesting that the co-drug was partly hydrolyzed after 12 h. Taken together, these results support the potential of nanodispersed formulations containing a tocopherol-lipoic acid co-drug to improve skin antioxidant activity. PMID:24961388

  2. Aspirin increases mitochondrial fatty acid oxidation.

    PubMed

    Uppala, Radha; Dudiak, Brianne; Beck, Megan E; Bharathi, Sivakama S; Zhang, Yuxun; Stolz, Donna B; Goetzman, Eric S

    2017-01-08

    The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders.

  3. Method of increasing conversion of a fatty acid to its corresponding dicarboxylic acid

    DOEpatents

    Craft, David L.; Wilson, C. Ron; Eirich, Dudley; Zhang, Yeyan

    2004-09-14

    A nucleic acid sequence including a CYP promoter operably linked to nucleic acid encoding a heterologous protein is provided to increase transcription of the nucleic acid. Expression vectors and host cells containing the nucleic acid sequence are also provided. The methods and compositions described herein are especially useful in the production of polycarboxylic acids by yeast cells.

  4. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.

    PubMed

    Simopoulos, Artemis P

    2016-03-02

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

  5. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

    PubMed Central

    Simopoulos, Artemis P.

    2016-01-01

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

  6. Cinnamic Acid Increases Lignin Production and Inhibits Soybean Root Growth

    PubMed Central

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

  7. Acid mine drainage and subsidence: effects of increased coal utilization.

    PubMed

    Hill, R D; Bates, E R

    1979-12-01

    The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence.

  8. Acid mine drainage and subsidence: effects of increased coal utilization.

    PubMed Central

    Hill, R D; Bates, E R

    1979-01-01

    The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence. PMID:540617

  9. Phytic acid increases mucin and endogenous amino acid losses from the gastrointestinal tract of chickens.

    PubMed

    Onyango, Edward M; Asem, Elikplimi K; Adeola, Olayiwola

    2009-03-01

    The influence of the form of phytic acid on the regulation of mucin and endogenous losses of amino acids, nitrogen and energy in chickens was investigated. Forty-eight 10-week-old male broilers were grouped by weight into eight blocks of six cages with one bird per cage. Birds received by intubation six dextrose-based combinations of phytic acid and phytase arranged in a 3 x 2 factorial consisting of phytic acid form (no phytic acid, 1.0 g free phytic acid or 1.3 g magnesium-potassium phytate) and phytase (0 or 1000 units). Each bird received the assigned combination added to 25 g dextrose at each of the two feedings on the first day of experimentation. All excreta were collected continuously for 54 h following feeding and frozen until analysed. Frozen excreta were thawed, pooled for each bird, lyophilised, ground, and analysed for DM, energy, nitrogen, amino acids, mucin, and sialic and uric acids. Chickens fed either magnesium-potassium phytate or free phytic acid showed increased (P < 0.05) loss of crude mucin and sialic acid. The amount of crude mucin lost was significantly greater (P < 0.05) with magnesium-potassium phytate than with free phytic acid treatment. Both phytic acid treatments also increased (P < 0.05) endogenous loss of threonine, proline and serine. In conclusion, the form of phytic acid fed to chickens affects the extent of mucin and endogenous amino acid losses from the gastrointestinal tract.

  10. Uric acid increases erythrocyte aggregation: Implications for cardiovascular disease.

    PubMed

    Sloop, Gregory D; Bialczak, Jessica K; Weidman, Joseph J; St Cyr, J A

    2016-10-05

    Uric acid may be a risk factor for atherosclerotic cardiovascular disease, although the data conflict and the mechanism by which it may cause cardiovascular disease is uncertain. This study was performed to test the hypothesis that uric acid, an anion at physiologic pH, can cause erythrocyte aggregation, which itself is associated with cardiovascular disease. Normal erythrocytes and erythrocytes with a positive direct antiglobulin test for surface IgG were incubated for 15 minutes in 14.8 mg/dL uric acid. Erythrocytes without added uric acid were used as controls. Erythrocytes were then examined microscopically for aggregation. Aggregates of up to 30 erythrocytes were noted when normal erythrocytes were incubated in uric acid. Larger aggregates were noted when erythrocytes with surface IgG were incubated in uric acid. Aggregation was negligible in controls. These data show that uric acid causes erythrocyte aggregation. The most likely mechanism is decreased erythrocyte zeta potential. Erythrocyte aggregates will increase blood viscosity at low shear rates and increase the risk of atherothrombosis. In this manner, hyperuricemia and decreased zeta potential may be risk factors for atherosclerotic cardiovascular disease.

  11. Conjugated fatty acids increase energy expenditure in part by increasing voluntary movement in mice.

    PubMed

    Park, Yooheon; Park, Yeonhwa

    2012-07-15

    Conjugated linoleic acid (CLA) and conjugated nonadecadienoic acid (CNA) have been previously shown to effectively reduce body fat. However, it is not clear if these effects persist with extended feeding, including potential mechanisms of increased energy expenditure. Thus the current investigation was conducted to determine the influence of dietary conjugated fatty acids on non-exercise form of voluntary movement and lipid and glucose metabolisms for 4-12 week feeding of male mice. CLA and CNA significantly reduced body weight and fat mass by increasing energy expenditure, in part by increasing voluntary movement. CLA and CNA significantly reduced serum leptin and tumour necrosis factor-α, while modulating the mRNA levels of genes associated with lipid and glucose metabolisms. The current results of increased physical activity along with modulation of lipid and glucose metabolisms by conjugated fatty acids will help contribute to future applications of these toward controlling obesity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  13. Accumulation of Phosphatidic Acid Increases Vancomycin Resistance in Escherichia coli

    PubMed Central

    Sutterlin, Holly A.; Zhang, Sisi

    2014-01-01

    In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall. PMID:24957626

  14. Aurintricarboxylic acid increases yield of HSV-1 vectors

    PubMed Central

    Pechan, Peter; Ardinger, Jeffery; Ketavarapu, Jyothi; Rubin, Hillard; Wadsworth, Samuel C; Scaria, Abraham

    2014-01-01

    Production of large quantities of viral vectors is crucial for the success of gene therapy in the clinic. There is a need for higher titers of herpes simplex virus-1 (HSV-1) vectors both for therapeutic use as well as in the manufacturing of clinical grade adeno-associated virus (AAV) vectors. HSV-1 yield increased when primary human fibroblasts were treated with anti-inflammatory drugs like dexamethasone or valproic acid. In our search for compounds that would increase HSV-1 yield, we investigated another anti-inflammatory compound, aurintricarboxylic acid (ATA). Although ATA has been previously shown to have antiviral effects, we find that low (micromolar) concentrations of ATA increased HSV-1 vector production yields. Our results showing the use of ATA to increase HSV-1 titers have important implications for the production of certain HSV-1 vectors as well as recombinant AAV vectors. PMID:26015945

  15. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  16. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, M.; Millard, C.S.; Stols, L.

    1998-06-23

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria. 2 figs.

  17. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  18. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2002-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  19. Acidic beverages increase the risk of in vitro tooth erosion.

    PubMed

    Ehlen, Leslie A; Marshall, Teresa A; Qian, Fang; Wefel, James S; Warren, John J

    2008-05-01

    Acidic beverages are thought to increase the potential for dental erosion. We report pH and titratable acidities (ie, quantity of base required to bring a solution to neutral pH) of beverages popular in the United States and lesion depths in enamel and root surfaces after beverage exposure, and we describe associations among pH, titratable acidity, and both enamel and root erosive lesion depths. The pH of 100% juices, regular sodas, diet sodas, and sports drinks upon opening and the titratable acidity both upon opening and after 60 minutes of stirring were measured. Enamel and root surfaces of healthy permanent molars and premolars were exposed to individual beverages (4 enamel and 4 root surfaces per beverage) for 25 hours, and erosion was measured. Statistical analyses included 2-sample t tests, analyses of variance with post hoc Tukey studentized range test; and Spearman rank correlation coefficients. All beverages were acidic; the titratable acidity of energy drinks was greater than that of regular and diet sodas that were greater than that of 100% juices and sports drinks (P < .05). Enamel lesion depths after beverage exposures were greatest for Gatorade, followed by those for Red Bull and Coke that were greater than those for Diet Coke and 100% apple juice (P < .05). Root lesion depths were greatest for Gatorade, followed by Red Bull, Coke, 100% apple juice, and Diet Coke (P < .05). Lesion depths were not associated with pH or titratable acidity. Beverages popular in the United States can produce dental erosion.

  20. Acidic beverages increase the risk of in vitro tooth erosion

    PubMed Central

    Ehlen, Leslie A.; Marshall, Teresa A.; Qian, Fang; Wefel, James S.; Warren, John J.

    2008-01-01

    Acidic beverages are thought to increase the potential for dental erosion. We report pH and titratable acidities (i.e., quantity of base required to bring a solution to neutral pH) of beverages popular in the United States and lesion depths in enamel and root surfaces following beverage exposure, and we describe associations among pH, titratable acidity and both enamel and root erosive lesion depths. The pH of 100% juices, regular sodas, diet sodas and sports drinks upon opening, and the titratable acidity both upon opening and after 60 minutes of stirring were measured. Enamel and root surfaces of healthy permanent molars and premolars were exposed to individual beverages (4 enamel and 4 root surfaces per beverage) for 25 hours and erosion was measured. Statistical analyses included two-sample t-tests, analyses of variance with post hoc Tukey’s studentized range test; and Spearman rank correlation coefficients. All beverages were acidic; the titratable acidity of energy drinks was greater than regular sodas and diet sodas which were greater than 100% juices and sports drinks (P<0.05). Enamel lesion depths following beverage exposures were greatest for Gatorade® followed by Red Bull® and Coke® which were greater than Diet Coke® and 100% apple juice (P <0.05). Root lesion depths were greatest for Gatorade® followed by Red Bull®, Coke®, 100% apple juice and Diet Coke® (P<0.05). Lesion depths were not associated with pH or titratable acidity. Beverages popular in the United States can produce dental erosion. PMID:19083423

  1. Acute acid exposure increases rabbit esophageal cell proliferation.

    PubMed

    Carpizo, D R; Reaka, A J; Glaws, W R; Pooley, N; Schmidt, L; Halline, A G; Goldstein, J L; Layden, T J

    1998-02-01

    In the present study we examined whether an acute infusion of HCl into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCl or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division. Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H+ infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H+ infusion (31%+/-6%) as compared with that in control animals infused with NSS (15%+/-4%). This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H+ infusion. Rete pegs were infrequent in control tissues (4+/-4 rete pegs per 100 microm of esophageal length) or in animals examined 24 hours after acid exposure (4+/-2 rete pegs per 100 microm). However, rete pegs were very prominent 48 hours after acid infusion (22+/-6 rete pegs per 100 microm). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.

  2. DIETARY N-6 POLYUNSATURATED FATTY ACID DEPRIVATION INCREASES DOCOSAHEXAENOIC ACID METABOLISM IN RAT BRAIN

    PubMed Central

    Kim, Hyung-Wook; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.

    2011-01-01

    Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A2 (cPLA2-IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective Ca2+-independent iPLA2-VIA expression. We hypothesized that these changes are accompanied by upregulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA “adequate” (31.4 wt% linoleic acid) or “deficient” (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-14C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acidn-3 (DPAn-3, 22:5n-3) and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid. Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promote neuroprotection. (199 words) PMID:22117540

  3. Increased amplification success from forensic samples with locked nucleic acids.

    PubMed

    Ballantyne, Kaye N; van Oorschot, Roland A H; Mitchell, R John

    2011-08-01

    Inadequate sample quantities and qualities can commonly result in poor DNA amplification success rates for forensic case samples. In some instances, modifying the PCR protocol or components may assist profiling by overcoming inhibition, or reducing the threshold required for successful amplification and detection. Incorporation of locked nucleic acids (LNAs) into PCR primers has previously been shown to increase amplification success for a range of non-forensic sample types and applications. To investigate their use in a forensic context, the PCR primers for four commonly used STR loci have been redesigned to include LNA bases. The modified LNA primers provided significantly increased amplification success when compared to standard DNA primers, with both high-quality buccal samples and simulated forensic casework samples. Peak heights increased by as much as 5.75× for the singleplex amplifications. When incorporated into multiplexes, the LNA primers continued to outperform standard DNA primers, with increased ease of optimisation, and increased amplification success. The use of LNAs in PCR primers can greatly assist the profiling of a range of samples, and increase success rates from challenging forensic samples.

  4. Free fatty acids do not acutely increase asymmetrical dimethylarginine concentrations.

    PubMed

    Namiranian, K; Mittermayer, F; Artwohl, M; Pleiner, J; Schaller, G; Mayer, B X; Bayerle-Eder, M; Roden, M; Baumgartner-Parzer, S; Wolzt, M

    2005-12-01

    Concentrations of asymmetrical dimethylarginine (ADMA) and free fatty acids (FFAs) are elevated in insulin resistance which is associated with impaired vascular function. We hypothesized that FFAs could alter vascular tone by affecting ADMA concentrations. Plasma FFA levels were increased in seventeen healthy male volunteers by Intralipid/heparin infusion; hemodynamic and biochemical parameters were measured after 90 minutes. Plasma collected before and during Intralipid/heparin or equivalent synthetic FFAs was incubated with human umbilical vein endothelial cells (HUVECs) in vitro. Intralipid/heparin infusion resulted in an approximately seven-fold increase in plasma FFA levels to 1861 +/- 139 micromol/l, which was paralleled by increased systemic blood pressure and forearm blood flow. Intralipid/heparin did not affect ADMA (baseline mean 0.59 [95 % confidence interval [CI]: 0.54; 0.64] and 0.56 [CI: 0.51; 0.59] after 90 minutes), but slightly decreased SDMA (from 0.76, [CI: 0.70; 0.83] to 0.71 [CI: 0.64; 0.74], p < 0.05), and had no effect on ADMA/SDMA ratio. There was no correlation between ADMA and FFA concentrations or forearm blood flow. Incubation of HUVECs with FFA-rich plasma or synthetic FFAs induced an ADMA release after 24 hours, but not after 90 minutes. Acutely increased FFA levels caused hemodynamic effects but did not affect ADMA. Prolonged elevation of FFA levels might influence vascular function by increasing ADMA levels.

  5. Internal waves as a proposed mechanism for increasing ambient noise in an increasingly acidic ocean.

    PubMed

    Rouseff, Daniel; Tang, Dajun

    2010-06-01

    The effect on the ambient noise level in shallow water of the ocean growing more acidic is modeled. Because most noise sources are near the surface, high-order acoustic modes are preferentially excited. Linear internal waves, however, can scatter the noise into the low-order, low-loss modes most affected by the changes in acidity. The model uses transport theory to couple the modes and assumes an isotropic distribution for the noise sources. For a scenario typical of the East China Sea, the noise at 3 kHz is predicted to increase by 30%, about one decibel, as the pH decreases from 8.0 to 7.4.

  6. Increasing dietary crude protein does not increase the essential amino acid requirements of kittens.

    PubMed

    Strieker, M J; Morris, J G; Rogers, Q R

    2006-08-01

    Essential amino acid (EAA) requirements of omnivores and herbivores (e.g. chicks, lambs, pigs and rats) are directly related to the concentration of dietary crude protein (CP). When an EAA is limiting in the diet, addition of a mixture of EAA lacking the limiting one (which increases dietary CP) results in a decrease in food intake and weight gain. This interaction has been referred to as an AA imbalance and has not been studied in depth in strict carnivores. The objectives of these experiments were to examine the effects on growing kittens (2-week periods) of the addition to diets of a mixture of AA lacking the limiting one. The control diets were at the requirement of the respective limiting EAA (or about 85% of the 1986 National Research Council requirement). In experiment 1, with the dietary EAAs at the minimally determined requirements, the concentration of the essential or dispensable amino acids was increased to determine if CP or an EAA was limiting. Results of growth rates (n = 12) and plasma AA concentrations indicated that tryptophan was limiting, but increased body weight gain also occurred when the concentration of CP was increased as dispensable amino acids without additional tryptophan. Experiment 1 was repeated in experiment 2 using a crossover design. Again, when tryptophan was limiting additional concentrations of dispensable AAs increased body weight gain. This response is the opposite of that in herbivores and omnivores. Experiment 3 consisted of 10 separate crossover trials, one for each of the 10 EAA and examined the effect of two concentrations of dietary CP (200 and 300 g CP/kg diet) on body weight gain of kittens (n = 8) offered diets limiting in each respective EAA. Body weight gain was numerically greater when diets contained 300 g CP/kg than 200 g CP/kg for eight of 10 EAAs (p < 0.05 for only isoleucine and threonine) when each amino acid was limiting. This response is the reverse of that which occurs in chicks, lambs, pigs and rats when

  7. Factors Which Increase Acid Production in Milk by Lactobacilli

    PubMed Central

    Huhtanen, C. N.; Williams, W. L.

    1963-01-01

    The stimulation by yeast extract of acid production in milk by various lactobacilli was studied. It was found that supplementing milk with purine and pyrimidine bases and amino acids allowed nearly maximal acid production by Lactobacillus bulgaricus strain 7994, L. acidophilus 4796, 4356, and 4357, and L. leichmannii 326 and 327. Further supplementation with deoxyribotides allowed maximal acid production by L. acidophilus 204, but L. acidophilus 207 required adenosine or adenylic acid. L. casei strain 7469 showed no appreciable response to the amino acids or purine and pyrimidine bases, and is presumed to require an unidentified factor in corn steep liquor. PMID:13955610

  8. Wall teichoic acids mediate increased virulence in Staphylococcus aureus.

    PubMed

    Wanner, Stefanie; Schade, Jessica; Keinhörster, Daniela; Weller, Nicola; George, Shilpa E; Kull, Larissa; Bauer, Jochen; Grau, Timo; Winstel, Volker; Stoy, Henriette; Kretschmer, Dorothee; Kolata, Julia; Wolz, Christiane; Bröker, Barbara M; Weidenmaier, Christopher

    2017-01-23

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are the cause of a severe pandemic consisting primarily of skin and soft tissue infections. The underlying pathomechanisms have not been fully understood and we report here a mechanism that plays an important role for the elevated virulence of CA-MRSA. Surprisingly, skin abscess induction in an animal model was correlated with the amount of a major cell wall component of S. aureus, termed wall teichoic acid (WTA). CA-MRSA exhibited increased cell-wall-associated WTA content (WTA(high)) and thus were more active in inducing abscess formation via a WTA-dependent and T-cell-mediated mechanism than S. aureus strains with a WTA(low) phenotype. We show here that WTA is directly involved in S. aureus strain-specific virulence and provide insight into the underlying molecular mechanisms that could guide the development of novel anti-infective strategies.

  9. Dietary guanidinoacetic acid increases brain creatine levels in healthy men.

    PubMed

    Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan; Jovanov, Pavle

    2017-01-01

    Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention. Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention. Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Eicosapentaenoic and docosahexaenoic acids increase insulin sensitivity in growing steers.

    PubMed

    Cartiff, S E; Fellner, V; Eisemann, J H

    2013-05-01

    An experiment was conducted to determine the effect of dietary n-3 long chain PUFA on insulin sensitivity in growing steers. Steers (n = 12, initial BW = 336.3 kg, SEM = 7.7) were adapted to a basal diet that was 70% concentrate mix and 30% orchardgrass hay. Steers were fed a daily amount of 0.26 Mcal ME per kg BW (0.75). After 3 wk steers were transitioned to 1 of 2 treatment (Trt) diets (n = 6 per diet) containing added Ca salts of fatty acids at 4% of DM using a source of fat that was enriched in n-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid (FOFA), or a source of fat without n-3 fatty acids and a greater percentage of C16:0 and C18:1 (LCFA). Three intravenous (i.v.) glucose tolerance tests (IVGTT) were conducted, 1 during the basal diet, and 2 after transition to treatment diets at time 1 (T1; d 4 Trt) and time 2 (T2; d 39 Trt). Three i.v. insulin challenge tests (IC) were conducted the day after each IVGTT. Measurements on the basal diet were used as covariates. For IVGTT, there was a diet by time interaction (P < 0.05) for glucose area under the response curve (AUC). The AUC50 (mM glucose × 50 min) at T1 was less (P = 0.02) for LCFA (126.2) than FOFA (151.8), AUC50 at T2 tended to be greater (P = 0.07) for LCFA (165.9) than FOFA (146.0). Preinfusion insulin concentration was greater (P < 0.001) before the IVGTT and IC for steers fed LCFA (40.4 and 40.2 µIU/mL) than for steers fed FOFA (23.7 and 27.1 µIU/mL), respectively. Glucose clearance did not differ between treatments. For IC, minimum glucose concentration was greater (P = 0.02) and glucose AUC150 was less (P < 0.01) for steers fed LCFA than for steers fed FOFA. Values for glucose concentration were 1.8 mM and 1.5 mM and for AUC150 (mM glucose × 150 min) were 203.1 and 263.6 for steers fed LCFA and FOFA, respectively. Insulin clearance (fraction/min) was greater (P < 0.01) for steers fed LCFA (0.121) than FOFA (0.101). The insulin AUC60 (µIU/mL × 60 min) postinfusion was

  11. Free fatty acids increase androgen precursors in vivo.

    PubMed

    Mai, K; Bobbert, T; Kullmann, V; Andres, J; Rochlitz, H; Osterhoff, M; Weickert, M O; Bähr, V; Möhlig, M; Pfeiffer, A F H; Diederich, S; Spranger, J

    2006-04-01

    There is considerable evidence that metabolic factors such as insulin resistance may induce hyperandrogenemia in polycystic ovary syndrome. However, other metabolic factors such as free fatty acids (FFAs) may also contribute to androgen excess. The objective was to study effects of FFAs on adrenal production of androgen precursors in vivo. We investigated eight healthy young men, because male individuals produce the androgen precursors dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione predominantly in the adrenal gland. A randomized controlled crossover trial was performed. After a 10-h overnight fast, 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 ml/min. Four hours after start of lipid infusion, a euglycemic hyperinsulinemic clamp was performed. DHEA, androstenedione, 17-OH-progesterone, testosterone, estrone, LH, FSH, ACTH, and cortisol were measured. The adrenal androgen precursors DHEA and androstenedione showed a circadian decline during saline/heparin infusion (P < 0.05 vs. baseline, respectively), whereas no significant changes were observed during lipid/heparin infusion (P = not significant vs. baseline, respectively). Correspondingly, DHEA and androstenedione values were significantly elevated during lipid compared with saline infusion (P < 0.05, respectively), and areas under curve of both androgen precursors were significantly increased with lipid compared with saline infusion. Notably, all changes were detected before induction of insulin resistance. This study demonstrates that FFAs increase production of androgen precursors in vivo in men. These data tentatively suggest that hyperandrogenemia in polycystic ovary syndrome may be induced, at least in part, by elevated FFAs.

  12. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils.

  13. Increased mutagenicity of chromium compounds by nitrilotriacetic acid

    SciTech Connect

    Loprieno, N.; Boncristiani, G.; Venier, P.; Montaldi, A.; Majone, F.; Bianchi, V.; Paglialunga, S.; Levis, A.G.

    1985-01-01

    Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA and NIDA independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary (CHO) line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr/sub 2/(SO/sub 4/)/sub 3/) and the direct mutagenicity of soluble Cr(VI) (Na/sub 2/CrO/sub 4/, K/sub 2/Cr/sub 2/O/sub 7/) compounds. The very insoluble Cr(VI) compounds PbCrO/sub 4/ and PbCrO/sub 4/ x PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The chromosome-damaging activity of PbCrO/sub 4/ is significantly increased by NTA but not by NaOH.

  14. Uric acid excretion predicts increased aggression in urban adolescents.

    PubMed

    Mrug, Sylvie; Mrug, Michal

    2016-09-01

    Elevated levels of uric acid have been linked with impulsive and disinhibited behavior in clinical and community populations of adults, but no studies have examined uric acid in relation to adolescent aggression. This study examined the prospective role of uric acid in aggressive behavior among urban, low income adolescents, and whether this relationship varies by gender. A total of 84 adolescents (M age 13.36years; 50% male; 95% African American) self-reported on their physical aggression at baseline and 1.5years later. At baseline, the youth also completed a 12-h (overnight) urine collection at home which was used to measure uric acid excretion. After adjusting for baseline aggression and age, greater uric acid excretion predicted more frequent aggressive behavior at follow up, with no significant gender differences. The results suggest that lowering uric acid levels may help reduce youth aggression. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V

    2013-04-30

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  16. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian [East Lansing, MI; Kleff, Susanne [East Lansing, MI; Guettler, Michael V [Holt, MI

    2012-02-21

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  17. Substitution of aspartic acid with glutamic acid increases the unfolding transition temperature of a protein.

    PubMed

    Lee, Duck Yeon; Kim, Kyeong-Ae; Yu, Yeon Gyu; Kim, Key-Sun

    2004-07-30

    Proteins from thermophiles are more stable than those from mesophiles. Several factors have been suggested as causes for this greater stability, but no general rule has been found. The amino acid composition of thermophile proteins indicates that the content of polar amino acids such as Asn, Gln, Ser, and Thr is lower, and that of charged amino acids such as Arg, Glu, and Lys is higher than in mesophile proteins. Among charged amino acids, however, the content of Asp is even lower in thermophile proteins than in mesophile proteins. To investigate the reasons for the lower occurrence of Asp compared to Glu in thermophile proteins, Glu was substituted with Asp in a hyperthermophile protein, MjTRX, and Asp was substituted with Glu in a mesophile protein, ETRX. Each substitution of Glu with Asp decreased the Tm of MjTRX by about 2 degrees C, while each substitution of Asp with Glu increased the Tm of ETRX by about 1.5 degrees C. The change of Tm destabilizes the MjTRX by 0.55 kcal/mol and stabilizes the ETRX by 0.45 kcal/mol in free energy.

  18. Hyaluronic acid levels are increased in complicated parapneumonic pleural effusions.

    PubMed

    Zaga, T; Makris, D; Tsilioni, I; Kiropoulos, T; Oikonomidi, S; Damianos, A; Gourgoulianis, K I

    2011-09-01

    Hyaluronic acid (HA) is a component of extracellular matrix and may play a role in the pleural inflammation which is implicated in parapneumonic effusions.The aim of the current study was to investigate HA levels in serum and pleura in patients with parapneumonic effusions. We prospectively studied pleural and serum levels of HA in 58 patients with pleural effusions due to infection (complicated and uncomplicated parapneumonic effusions), malignant effusions and transudative effusions due to congestive heart failure. In addition to HA, TNF-alpha and IL-beta levels were determined in pleural fluid and serum by ELISA. The median +/- SD HA levels (pg/ml) in pleural fluid of patients with complicated effusions (39.058 +/- 11.208) were significantly increased (p < 0.005), compared to those with uncomplicated parapneumonic effusions (11.230 +/- 1.969), malignant effusions (10.837 +/- 4.803) or congestive heart failure (5.392 +/- 3.133). There was no correlation between pleural fluid and serum HA values. Pleural fluid TNF-alpha levels (146 +/- 127 pg/mL) and IL-1beta levels (133.4 +/- 156 pg/mL) were significantly higher in patients with complicated parapneumonic effusions compared to patients with other types of effusion (p < 0.05). No significant association between HA and TNF-alpha or IL-1beta was found. CONCLUSIONS. HA may play a significant role in the inflammatory process which characterises exudative infectious pleuritis. Further investigation might reveal whether HA is a useful marker in the management of parapneumonic effusions.

  19. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review

    PubMed Central

    2011-01-01

    Background Linoleic acid, with a DRI of 12-17 g/d, is the most highly consumed polyunsaturated fatty acid in the Western diet and is found in virtually all commonly consumed foods. The concern with dietary linoleic acid, being the metabolic precursor of arachidonic acid, is its consumption may enrich tissues with arachidonic acid and contribute to chronic and overproduction of bioactive eicosanoids. However, no systematic review of human trials regarding linoleic acid consumption and subsequent changes in tissue levels of arachidonic acid has been undertaken. Objective In this study, we reviewed the human literature that reported changes in dietary linoleic acid and its subsequent impact on changing tissue arachidonic acid in erythrocytes and plasma/serum phospholipids. Design We identified, reviewed, and evaluated all peer-reviewed published literature presenting data outlining changes in dietary linoleic acid in adult human clinical trials that reported changes in phospholipid fatty acid composition (specifically arachidonic acid) in plasma/serum and erythrocytes within the parameters of our inclusion/exclusion criteria. Results Decreasing dietary linoleic acid by up to 90% was not significantly correlated with changes in arachidonic acid levels in the phospholipid pool of plasma/serum (p = 0.39). Similarly, when dietary linoleic acid levels were increased up to six fold, no significant correlations with arachidonic acid levels were observed (p = 0.72). However, there was a positive relationship between dietary gamma-linolenic acid and dietary arachidonic acid on changes in arachidonic levels in plasma/serum phospholipids. Conclusions Our results do not support the concept that modifying current intakes of dietary linoleic acid has an effect on changing levels of arachidonic acid in plasma/serum or erythrocytes in adults consuming Western-type diets. PMID:21663641

  20. An Increase Incidence in Uric Acid Nephrolithiasis: Changing Patterns

    PubMed Central

    Kumari, Asha; Mittal, Pawan; Kumar, Rajender; Goel, Richa; Bansal, Piyush; Kumar, Himanshu Devender; Bhutani, Jaikrit

    2016-01-01

    Introduction Nephrolithiasis is a complex disease affecting all age groups globally. As the causative factors for nephrolithiasis rises significantly, its incidence, prevalence and recurrence continues to baffle clinicians and patients. Aim To study the prevalence of different types of renal stones extracted by Percutaneous Nephrolithotomy (PCNL) and open surgical procedures. Materials and Methods Renal stones from 50 patients were retrieved by Percutaneous Nephrolithotomy (PCNL), Ureterorenoscopy (URS) and open surgical techniques for qualitative tests for detection of calcium, oxalate, uric acid, phosphate, ammonium ion, carbonate, cystine and xanthine. Results Three patients had stone removed by open surgery and rest had undergone PCNL. Nine of the stones were pure of calcium oxalate, 9 were of pure uric acid and 32 were mixed stones. Forty one stones had calcium. Among the mixed stones, oxalate was present in 25 samples (39 of total), uric acid was seen in 17 (25 of total stones), phosphate was present in 23 (23 of total) and carbonate was present in 4 stones (4 of total). Only 1 patient had triple phosphate stone. 12 were of staghorn appearance of which 6 were of struvite type, 6 were pure uric acid and remaining were mixed oxalate-phosphate stones. Conclusion Our study, though in a small number of hospital based patients, found much higher prevalence of uric acid stones and mixed stones than reported by previous hospital based studies in north India (oxalate stones~90%, uric acid~1% and mixed stones~3%). Biochemical analysis of renal stones is warranted in all cases. PMID:27630833

  1. Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation.

    PubMed

    Rozance, Paul J; Crispo, Michelle M; Barry, James S; O'Meara, Meghan C; Frost, Mackenzie S; Hansen, Kent C; Hay, William W; Brown, Laura D

    2009-09-01

    Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005), and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16 vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29 micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C), release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(-1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x min(-1) x kg(-1)) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.

  2. Increased ophthalmic acid production is supported by amino acid catabolism under fasting conditions in mice.

    PubMed

    Kobayashi, Sho; Lee, Jaeyong; Takao, Toshifumi; Fujii, Junichi

    2017-09-23

    Glutathione (GSH) plays pivotal roles in antioxidation and detoxification. The transsulfuration pathway, in conjunction with methionine metabolism, produces equimolar amounts of cysteine (Cys) and 2-oxobutyric acid (2OB). The resulting 2OB is then converted into 2-aminobutyric acid (2AB) by a transaminase and is utilized as a substitute for Cys by the GSH-synthesizing machinery to produce ophthalmic acid (OPT). By establishing a method for simultaneously measuring Cys, GSH, and OPT by liquid chromatography-mass spectrometry, we found that fasting causes an elevation in OPT levels in the liver and blood plasma, even though the levels of Cys and GSH are decreased. Autophagy was activated, but the levels of GSH/OPT-synthesizing enzymes remained unchanged. After 6 h of fasting, the mice were given 1% 2AB and/or 5% glucose in the drinking water for an additional 24 h and the above metabolites analyzed. 2AB administration caused an increase in OPT levels, and, when glucose was co-administered with 2AB, the levels of OPT were elevated further but GSH levels were decreased somewhat. These results suggest that, while Cys is utilized for glyconeogenesis under fasting conditions, reaching levels that were insufficient for the synthesis of GSH, 2OB was preferentially converted to 2AB via amino acid catabolism and was utilized as a building block for OPT. Thus the consumption of Cys and the parallel elevation of 2AB under fasting conditions appeared to force γ-glutamylcysteine synthetase to form γ-glutamyl-2AB, despite the fact that the enzyme has a higher Km value for 2AB than Cys. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

    PubMed

    Nüsken, Eva; Gellhaus, Alexandra; Kühnel, Elisabeth; Swoboda, Isabelle; Wohlfarth, Maria; Vohlen, Christina; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

    2016-07-01

    Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc.

  4. Transcript and metabolite alterations increase ganoderic acid content in Ganoderma lucidum using acetic acid as an inducer.

    PubMed

    Ren, Ang; Li, Xiong-Biao; Miao, Zhi-Gang; Shi, Liang; Jaing, Ai-Liang; Zhao, Ming-Wen

    2014-12-01

    Acetic acid at 5-8 mM increased ganoderic acid (GA) accumulation in Ganoderma lucidum. After optimization by the response surface methodology, the GA content reached 5.5/100 mg dry weight, an increase of 105% compared with the control. The intermediate metabolites of GA biosynthesis, lanosterol and squalene also increased to 47 and 15.8 μg/g dry weight, respectively, in response to acetic acid. Acetic acid significantly induced transcription levels of sqs, lano, hmgs and cyp51 in the GA biosynthesis pathway. An acetic acid-unregulated acetyl coenzyme A synthase (acs) gene was selected from ten candidate homologous acs genes. The results indicate that acetic acid alters the expression of genes related to acetic acid assimilation and increases GA biosynthesis and the metabolic levels of lanosterol, squalene and GA-a, thereby resulting in GA accumulation.

  5. N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

    PubMed

    Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

    2017-09-01

    The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

  6. Acetic acid enhances endurance capacity of exercise-trained mice by increasing skeletal muscle oxidative properties.

    PubMed

    Pan, Jeong Hoon; Kim, Jun Ho; Kim, Hyung Min; Lee, Eui Seop; Shin, Dong-Hoon; Kim, Seongpil; Shin, Minkyeong; Kim, Sang Ho; Lee, Jin Hyup; Kim, Young Jun

    2015-01-01

    Acetic acid has been shown to promote glycogen replenishment in skeletal muscle during exercise training. In this study, we investigated the effects of acetic acid on endurance capacity and muscle oxidative metabolism in the exercise training using in vivo mice model. In exercised mice, acetic acid induced a significant increase in endurance capacity accompanying a reduction in visceral adipose depots. Serum levels of non-esterified fatty acid and urea nitrogen were significantly lower in acetic acid-fed mice in the exercised mice. Importantly, in the mice, acetic acid significantly increased the muscle expression of key enzymes involved in fatty acid oxidation and glycolytic-to-oxidative fiber-type transformation. Taken together, these findings suggest that acetic acid improves endurance exercise capacity by promoting muscle oxidative properties, in part through the AMPK-mediated fatty acid oxidation and provide an important basis for the application of acetic acid as a major component of novel ergogenic aids.

  7. Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

    SciTech Connect

    Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.; Culley, David E.; Deng, Shuang; Collett, James R.; Umemura, Myco; Koike, Hideaki; Baker, Scott E.; Machida, Masa

    2013-01-01

    Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes we successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.

  8. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  9. Ocean acidification increases fatty acids levels of larval fish

    PubMed Central

    Díaz-Gil, Carlos; Catalán, Ignacio A.; Palmer, Miquel; Faulk, Cynthia K.; Fuiman, Lee A.

    2015-01-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  10. Adipic acid increases plasma lysine but does not improve the efficiency of lysine utilization in swine.

    PubMed

    van Kempen, T A; van Heugten, E; Trottier, N L

    2001-09-01

    Adipic acid, upon catabolism, results in intermediates that bear a structural similarity to lysine degradation products. The objectives of this research were to determine whether adipic acid affects lysine concentrations in plasma and to evaluate whether adipic acid improves the efficiency of lysine utilization in pigs. In Exp. 1, nursery pigs (n = 14) were fed (for a period of 7 d) either a standard nursery diet or the same diet supplemented with 1% adipic acid to assess effects on plasma amino acid concentrations (plasma collected on d 7). In Exp. 2, nursery pigs (n = 56) were fed (for a period of 15 d) either a control diet or the same diet but deficient in either lysine, threonine, or tryptophan with or without supplemental adipic acid to assess the effects of adipic acid on the efficiency of amino acid utilization. The results from Exp. 1 showed that adipic acid increased plasma lysine (by 18%) but not alpha-amino adipic acid, an intermediate in lysine degradation. Experiment 2 demonstrated that adipic acid did not increase the efficiency of utilization of lysine, threonine, or tryptophan. The lack of effects on alpha-amino adipic acid in Exp. 1 and the lack of a positive effect on the efficiency of utilization of lysine, threonine, and tryptophan suggest that adipic acid does not inhibit the mitochondrial uptake of lysine and(or) its degradation in the mitochondrion. It is concluded that feeding adipic acid increases plasma lysine but does not improve the efficiency of lysine utilization.

  11. Increased universality of Lepidopteran elicitor compounds across insects: Identification of fatty acid amino acid conjugates (FACs)

    USDA-ARS?s Scientific Manuscript database

    Fatty acid amino acid conjugates (FACs) are known elicitors of induced release of volatile compounds in plants that, in turn, attract foraging parasitoids. Since the discovery of volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] in the regurgitant of larval Spodoptera exigua1, a series of related FAC...

  12. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

    PubMed

    Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

    2014-05-01

    Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

  13. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance.

    PubMed

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H; Patton-Vogt, Jana; Bakalinsky, Alan T

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification.

  14. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance

    PubMed Central

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H.; Patton-Vogt, Jana; Bakalinsky, Alan T.

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. PMID:25673654

  15. Effects of Increased Free Fatty Acid Availability on Adipose Tissue Fatty Acid Storage in Men

    PubMed Central

    Mundi, Manpreet S.; Koutsari, Chistina

    2014-01-01

    Context: A portion of free fatty acids (FFA) released from adipose tissue lipolysis are re-stored in adipocytes via direct uptake. Rates of direct adipose tissue FFA storage are much greater in women than men, but women also have greater systemic FFA flux and more body fat. Objective: We tested the hypotheses that experimental increases in FFA in men would equalize the rates of direct adipose tissue FFA storage in men and women. Design: We used a lipid emulsion infusion to raise FFA in men to levels seen in post-absorptive women. Direct FFA storage (μmol·kg fat−1·min−1) rates in abdominal and femoral fat was assessed using stable isotope tracer infusions to measure FFA disappearance rates and an iv FFA radiotracer bolus/timed biopsy. Setting: These studies were performed in a Clinical Research Center. Participants: Data from 13 non-obese women was compared with that from eight obese and eight non-obese men. Intervention: The men received a lipid emulsion infusion to raise FFA. Main Outcome Measures: We measured the rates of direct FFA storage in abdominal and femoral adipose tissue. Results: The three groups were similar in age and FFA flux by design; obese men had similar body fat percentage as non-obese women. Despite matching for FFA concentrations and flux, FFA storage per kg abdominal (P < .01) and femoral (P < .001) fat was less in both lean and obese men than in non-obese women. Abdominal FFA storage rates were correlated with proteins/enzymes in the FFA uptake/triglyceride synthesis pathway in men. Conclusion: The lesser rates of direct FFA adipose tissue in men compared with women cannot be explained by reduced FFA availability. PMID:25192251

  16. Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating fructose alone or with aspartic acid at two pH levels.

    PubMed

    Zhang, Zhenhua; Zou, Yueyu; Wu, Taigang; Huang, Caihuan; Pei, Kehan; Zhang, Guangwen; Lin, Xiaohua; Bai, Weibin; Ou, Shiyi

    2016-01-01

    Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits. This work aims to investigate whether and how CGA influences HMF formation during heating fructose alone, or with an amino acid. The results showed that that CGA increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the addition of 5.0 μmol/ml CGA increased HMF formation by 49.4% and 25.2%, respectively when heating fructose alone, and by 9.0% and 16.7%, respectively when heating fructose with aspartic acid. CGA significantly increased HMF formation by promoting 3-deoxosone formation, and its conversion to HMF by inhibiting HMF elimination, especially in the Maillard reaction system. A comparison of the catalytic capacity of CGA with its six analogous compounds showed that both its di-hydroxyphenyl and carboxyl groups function in increasing HMF formation.

  17. Phosphorus limitation strategy to increase propionic acid flux towards 3-hydroxyvaleric acid monomers in Cupriavidus necator.

    PubMed

    Grousseau, Estelle; Blanchet, Elise; Déléris, Stéphane; Albuquerque, Maria G E; Paul, Etienne; Uribelarrea, Jean-Louis

    2014-02-01

    Properties of polyhydroxybutyrate-co-hydroxyvalerate (P(3HB-co-3HV)) depend on their 3HV content. 3HV can be produced by Cupriavidus necator from propionic acid. Few studies explored carbon distribution and dynamics of 3HV and 3HB monomers production, and none of them have been done with phosphorus as limiting nutrient. In this study, fed-batch cultures of C. necator with propionic acid, as sole carbon source or mixed with butyric acid, were performed. Phosphorus deficiency allowed sustaining 3HV production rate and decreasing 3HB production rate, leading to an instant production of up to 100% of 3HV. When a residual growth is sustained by a phosphorus feeding, the maximum 3HV percentage produced from propionic acid is limited to 33% (Mole.Mole(-1)). The association of a second carbon source like butyric acid lead to higher conversion of propionic acid into 3HV. This study showed the importance of the limiting nutrient and of the culture strategy to get the appropriate product. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Microwave Energy Increases Fatty Acid Methyl Ester Yield in Human Whole Blood Due to Increased Sphingomyelin Transesterification.

    PubMed

    Metherel, Adam H; Aristizabal Henao, Juan J; Ciobanu, Flaviu; Taha, Ameer Y; Stark, Ken D

    2015-09-01

    Dried blood spots (DBS) by fingertip prick collection for fatty acid profiling are becoming increasingly popular due to ease of collection, minimal invasiveness and its amenability to high-throughput analyses. Herein, we assess a microwave-assisted direct transesterification method for the production of fatty acid methyl esters (FAME) from DBS. Technical replicates of human whole blood were collected and 25-μL aliquots were applied to chromatography strips prior to analysis by a standard 3-h transesterification method or microwave-assisted direct transesterification method under various power (variable vs constant), time (1-5 min) and reagent (1-10% H2SO4 in methanol) conditions. In addition, a standard method was compared to a 5-min, 30-W power microwave in 1% H2SO4 method for FAME yield from whole blood sphingomyelin, and sphingomyelin standards alone and spiked in whole blood. Microwave-assisted direct transesterification yielded no significant differences in both quantitative (nmol/100 µL) and qualitative (mol%) fatty acid assessments after as little as 1.5- and 1-min reaction times, respectively, using the variable power method and 5% H2SO4 in methanol. However, 30-W power for 5 min increased total FAME yield of the technical replicates by 14%. This increase appears largely due to higher sphingomyelin-derived FAME yield of up to 109 and 399% compared to the standard method when determined from whole blood or pure standards, respectively. In conclusion, microwave-assisted direct transesterification of DBS achieved in as little as 1-min, and 5-min reaction times increase total fatty acids primarily by significantly improving sphingomyelin-derived fatty acid yield.

  20. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions.

    PubMed

    López-Morales, Dolores; Reyes-Leyva, Julio; Santos-López, Gerardo; Zenteno, Edgar; Vallejo-Ruiz, Verónica

    2010-11-22

    Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation.

  1. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  2. Type IV resistant starch increases cecum short chain fatty acids level in rats.

    PubMed

    Le Thanh-Blicharz, Joanna; Anioła, Jacek; Kowalczewski, Przemysław; Przygoński, Krzysztof; Zaborowska, Zofia; Lewandowicz, Grażyna

    2014-01-01

    Resistant starches are type of dietary fibers. However, their physiological effects depend on the way they resist digestion in the gastrointestinal tract. The objective of this study was to examine the hypothesis that new type of RS4 preparations, of in vitro digestibility of about 50%, obtained by cross-linking and acetylation, acts as a prebiotic by increasing short chain fatty acids content in cecum digesta. The rats were fed with diet containing pregelatinized, cross-linked and acetylated starches as a main carbohydrate source. Pregelatinized, but not chemically modified, potato starch was used in the composition of the control diet. After two weeks of experiment the increase of short chain fatty acids contents in ceceum digesta was observed. The intake of starch A, cross-linked only with adipic acid, resulted in increase of about 40% of short chain fatty acids content, whereas starch PA cross-linked with sodium trimetaphosphate and adipic acid of about 50%. The utmost twofold increase was observed in the case of the production of propionic acid. In contrast, the content of butyric acid increased (12%) only as an effect of consumption of starch PA and even decreased (about 30%) in case of starch A. Both RS4 starches caused an increase of the production of acetic acid by more than 40%. No changes in serum biochemistry, liver cholesterol and organ weights of rats were stated.

  3. Dietary oleic acid increases m2 macrophages in the mesenteric adipose tissue.

    PubMed

    Camell, Christina; Smith, C Wayne

    2013-01-01

    Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding increases adipose tissue (AT) leukocytes and alters the inflammatory profile of AT macrophages. We have seen that short term high fat feeding to C57BL/6J male mice increases palmitic and oleic acid within AT depots, but oleic acid increase is highest in the mesenteric AT (MAT). In vitro, oleic acid increases M2 macrophage markers (CD206, MGL1, and ARG1) in a murine macrophage cell line, while addition of palmitic acid is able to inhibit that increase. Three day supplementation of a chow diet, with oleic acid, induced an increase in M2 macrophage markers in the MAT, but not in the epididymal AT. We tested whether increases in M2 macrophages occur during short term ad lib feeding of a high fat diet, containing oleic acid. Experiments revealed two distinct populations of macrophages were altered by a three day high milk-fat diet. One population, phenotypically intermediate for F4/80, showed diet-induced increases in CD206, an anti-inflammatory marker characteristic of M2 macrophages intrinsic to the AT. Evidence for a second population, phenotypically F4/80(HI)CD11b(HI) macrophages, showed increased association with the MAT following short term feeding that is dependent on the adhesion molecule, ICAM-1. Collectively, we have shown that short term feeding of a high-fat diet changes two population of macrophages, and that dietary oleic acid is responsible for increases in M2 macrophage polarization.

  4. Does acid rain increase human exposure to mercury? A review and analysis of recent literature

    SciTech Connect

    Richardson, G.M. |; Egyed, M.; Currie, D.J.

    1995-05-01

    The literature suggests that acid deposition may lead to increased mercury (Hg) contamination of fish. Employing published empirical relationships, the authors have estimated the change in associated Hg contamination with an increase in sulfate deposition from 0.25 to 1.25 g sulfur/m{sup 2}/year. In seepage lakes, one can predict that Hg in walleye from these lakes, and subsequent human exposure due to consumption of these fish, would be elevated at the higher rate of sulfate deposition. However, for drainage lakes, increasing acidic deposition was predicted to reduce Hg accumulation in lake trout and northern pike. Subsequent human exposure to Hg due to consumption of these species from drainage lakes was therefore also predicted to be lower at the higher rate of acidic deposition. They concluded that the hypothesis that acidic deposition increases mercury (Hg) contamination in fish, and thereby mercury exposure in humans via fish consumption, is only true for acidic deposition onto seepage lakes.

  5. Natural phenolic acids may increase serum estradiol level in ovariectomized rats.

    PubMed

    Zych, Maria; Folwarczna, Joanna; Trzeciak, Henryk I

    2009-01-01

    Natural phenolic acids are commonly present in plants consumed in the diet. Recently we have observed that different natural phenolic acids exert differential effects on the body mass gain in ovariectomized and non-ovariectomized female rats. The aim of the present study was to investigate the effects of ferulic, caffeic, p-coumaric and chlorogenic acids on serum estradiol and total cholesterol levels in ovariectomized and non-ovariectomized rats. The experiments were carried out on 3-month old female Wistar Cmd:(WI)WU rats, divided into following groups (n=8 in each group): non-ovariectomized control rats and non-ovariectomized rats receiving ferulic, caffeic, p-coumaric or chlorogenic acids, sham-operated control rats, ovariectomized control rats and ovariectomized rats receiving the same phenolic acids. The phenolic acids were administered at a dose of 10 mg/kg p.o. daily for 4 weeks. Serum estradiol and total cholesterol levels on the next day after the last administration of the phenolic acids were examined. The phenolic acids did not affect serum estradiol or total cholesterol levels in non-ovariectomized rats. In ovariectomized rats, caffeic acid and to a lesser extent p-coumaric acid increased serum estradiol level, which effect correlated with a decreased body mass gain. All the phenolic acids decreased serum cholesterol level in ovariectomized rats. Concluding, the anti-obesity activity of some phenolic acids may be, at least partially, connected with estrogenic pathways.

  6. Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice.

    PubMed

    Aspenström-Fagerlund, Bitte; Tallkvist, Jonas; Ilbäck, Nils-Gunnar; Glynn, Anders W

    2015-09-02

    The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120min after exposure, or were exposed to 0.6, 2.4 or 4.8g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

  7. Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids

    PubMed Central

    Khairallah, Ramzi J.; Kim, Junhwan; O'Shea, Karen M.; O'Connell, Kelly A.; Brown, Bethany H.; Galvao, Tatiana; Daneault, Caroline; Rosiers, Christine Des; Polster, Brian M.; Hoppel, Charles L.; Stanley, William C.

    2012-01-01

    Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs. PMID:22479624

  8. Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects.

    PubMed

    Rios, Laurent Y; Gonthier, Marie-Paule; Rémésy, Christian; Mila, Isabelle; Lapierre, Catherine; Lazarus, Sheryl A; Williamson, Gary; Scalbert, Augustin

    2003-04-01

    Proanthocyanidins, the most abundant polyphenols in chocolate, are not depolymerized in the stomach and reach the small intestine intact, where they are hardly absorbed because of their high molecular weight. In vitro and in vivo studies using pure compounds as substrates suggest that proanthocyanidins and the related catechin monomers may be degraded into more bioavailable low-molecular-weight phenolic acids by the microflora in the colon. The aim of the study was to estimate the amounts of phenolic acids formed by the microflora and excreted in the urine of human subjects after consumption of polyphenol-rich chocolate. After consumption of a polyphenol-free diet for 2 d and a subsequent overnight fast, 11 healthy subjects (7 men and 4 women) consumed 80 g chocolate containing 439 mg proanthocyanidins and 147 mg catechin monomers. All urine was collected during the 24 h before chocolate consumption and at 3, 6, 9, 24, and 48 h after chocolate consumption. Aromatic acids were identified in urine by gas chromatography-mass spectrometry and were quantified by HPLC-electrospray ionization tandem mass spectrometry. Chocolate intake increased the urinary excretion of the 6 following phenolic acids: m-hydroxyphenylpropionic acid, ferulic acid, 3,4-dihydroxyphenylacetic acid, m-hydroxyphenylacetic acid, vanillic acid, and m-hydroxybenzoic acid. The antioxidant and biological effects of chocolate may be explained not solely by the established absorption of catechin monomers but also by the absorption of microbial phenolic acid metabolites.

  9. Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep.

    PubMed

    Brown, Laura D; Rozance, Paul J; Thorn, Stephanie R; Friedman, Jacob E; Hay, William W

    2012-08-01

    Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion.

  10. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    PubMed Central

    2012-01-01

    Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA) or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was quantified by measuring extracellular acidification and oxygen consumption rates. Results Omega 3 significantly induced metabolic genes as well as oxidative metabolism (oxygen consumption), glycolytic capacity (extracellular acidification), and metabolic rate compared with control. Both treatments significantly increased mitochondrial content. Conclusion Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control. PMID:23107305

  11. Dietary oleic acid increases M2 macrophages in the mesenteric adipose

    USDA-ARS?s Scientific Manuscript database

    Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding in...

  12. Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

    PubMed Central

    Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

  13. Mechanisms by which ascorbic acid increases ferritin levels in cultured lens epithelial cells.

    PubMed

    Goralska, M; Harned, J; Grimes, A M; Fleisher, L N; McGahan, M C

    1997-03-01

    A previous study demonstrated that ascorbic acid increased the concentration of the iron storage protein, ferritin. In cultured lens epithelial cells. The current study was designed to determine the mechanism by which ascorbic acid exerts this effect. Ascorbic acid increased both ferritin mRNA levels (by about 30%) and translation of ferritin (de novo synthesis was increased up to 15-fold) within 6 hr. Cycloheximide completely abolished the ability of ascorbic acid to increase ferritin levels, whereas actinomycin D only decreased it by about 30%. Therefore, the ascorbic-acid induced increase in ferritin concentration is due mainly to an increase in ferritin synthesis at the translational levels. This is a novel role for ascorbic acid. Addition of iron with ascorbic acid further increased de novo synthesis of ferritin, but this additive effect was only noted at a later time point (20 hr). Factors which decrease ferritin mRNA translation, such as the reducing agent dithiothreitol or the iron chelator desferrioxamine, reduced the ascorbic acid effect on de novo ferritin synthesis. The effects of ascorbic acid on ferritin mRNA levels may be mediated by its oxidation product, H2O2, since, like ascorbic acid, H2O2 increased ferritin mRNA levels by 30%. However, in contrast to the ascorbic acid-induced increase in translation of ferritin, H2O2 substantially decreased de novo ferritin synthesis. This effect of H2O2 could have physiological significance in eyes where concentrations of H2O2 in the aqueous humor are elevated. High levels of H2O2 could decrease the concentration of ferritin within the lens. Since ferritin sequesters iron and has been shown to decrease oxidative damage by limiting the availability of iron to catalyse free radical reactions, H2O2-induced reduction in ferritin concentration in the lens could have deleterious effects. The ability of ascorbic acid to increase ferritin concentration in lens epithelial cells could provide an additional protective

  14. Valproic Acid Increases the Hepatic Differentiation Potential of Salivary Gland Cells

    PubMed Central

    Petrakova, O. S.; Ashapkin, V. V.; Shtratnikova, V. Y.; Kutueva, L. I.; Vorotelyak, E. A.; Borisov, M. A.; Terskikh, V. V.; Gvazava, I. G.; Vasiliev, A. V.

    2015-01-01

    The studies of cell plasticity and differentiation abilities are important problems in modern cellular biology. The use of histone deacetylase inhibitor - valproic acid is a promising approach to increasing the differentiation efficiency of various cell types. In this paper we investigate the ability of mouse submandibular salivary gland cells to differentiate into the hepatic direction and the effect of valproic acid on the efficiency of this differentiation. It was shown that the gene expression levels of hepatocyte markers (Aat, Afp, G6p, Pepck, Tat, Cyp3a13) and liver-enriched transcription factors (Hnf-3α, Hnf-3β, Hnf-4α, Hnf-6) were increased after differentiation in salivary gland cells. Valproic acid increases the specificity of hepatic differentiation, reducing the expression levels of the ductal (Krt19, Hhex1, Cyp7a1) and acinar (Ptf1a) markers. After valproic acid exposure, the efficiency of hepatic differentiation also increases, as evidenced by the increase in the gene expression level of Alb and Tdo, and increase in urea production by differentiated cells. No change was found in DNA methylation of the promoter regions of the genes; however, valproic acid treatment and subsequent hepatic differentiation largely affected the histone H3 methylation of liver-enriched genes. Thus, mouse submandibular salivary gland cells are capable of effective differentiation in the hepatic direction. Valproic acid increases the specificity and efficiency of the hepatic differentiation of these cells. PMID:26798494

  15. Low phytic acid lentils (Lens culinaris L.): a potential solution for increased micronutrient bioavailability.

    PubMed

    Thavarajah, Pushparajah; Thavarajah, Dil; Vandenberg, Albert

    2009-10-14

    Phytic acid is an antinutrient present mainly in seeds of grain crops such as legumes and cereals. It has the potential to bind mineral micronutrients in food and reduce their bioavailability. This study analyzed the phytic acid concentration in seeds of 19 lentil ( Lens culinaris L.) genotypes grown at two locations for two years in Saskatchewan, Canada. The objectives of this study were to determine (1) the levels of phytic acid in commercial lentil genotypes and (2) the impact of postharvest processing and (3) the effect of boiling on the stability of phytic aid in selected lentil genotypes. The phytic acid was analyzed by high-performance anion exchange separation followed by conductivity detection. The Saskatchewan-grown lentils were naturally low in phytic acid (phytic acid = 2.5-4.4 mg g(-1); phytic acid phosphorus = 0.7-1.2 mg g(-1)), with concentrations lower than those reported for low phytic acid mutants of corn, wheat, common bean, and soybean. Decortication prior to cooking further reduced total phytic acid by >50%. As lowering phytic acid intake can lead to increased mineral bioavailability, dietary inclusion of Canadian lentils may have significant benefits in regions with widespread micronutrient malnutrition.

  16. Forage breeding and management to increase the beneficial fatty acid content of ruminant products.

    PubMed

    Dewhurst, R J; Scollan, N D; Lee, M R F; Ougham, H J; Humphreys, M O

    2003-05-01

    The declining consumption of ruminant products has been partly associated with their high proportion (but not necessarily content) of saturated fatty acids. Recent studies have focused on the less prominent fact that they are also important sources of beneficial fatty acids, including n-3 fatty acids and conjugated linoleic acids. alpha-Linolenic acid (18 : 3n-3) is of particular interest because it also contributes to improved flavour of beef and lamb. Many recent studies showed large effects of special concentrates on levels of fatty acids in milk and meat. However, the 'rumen protection' treatments, needed to ensure a worthwhile level of fatty acid in products, are expensive. Herbage lipids are the cheapest and safest source of these fatty acids and so breeding to increase delivery of fatty acids from plants into ruminant products is an important long-term strategy. Plant lipids usually contain high levels of polyunsaturated fatty acids, particularly 18 : 2n-6 and 18 : 3n-3 which are the precursors of beneficial fatty acids. Whilst some plants are particularly rich in individual fatty acids (e.g. 18 : 3n-3 in linseed), there are also useful levels in grass and clover (Trifolium Spp.). Levels of fatty acids in forages in relation to species and varieties are considered, as well as management and conservation methods. Relationships between levels of fatty acids and existing traits and genetic markers are identified. The effects of forage treatments on the fatty acid content of ruminant products are reviewed. The higher levels of polyunsaturated fatty acids in milk from cows fed clover silages show that the level of fatty acids in herbage is not the only factor affecting levels of fatty acids in ruminant products. Further effort is needed to characterise susceptibility of unsaturated fatty acids to oxidative loss during field wilting and biohydrogenation losses in the rumen, and the relative importance of plant and microbial processes in these losses. The pathways

  17. Folate administration increases n-3 polyunsaturated fatty acids in rat plasma and tissue lipids.

    PubMed

    Pita, M L; Delgado, M J

    2000-09-01

    It has been shown that folic acid deficiency can modify polyunsaturated fatty acid (PUFA) metabolism and thus could contribute to the development of cardiovascular diseases. We have studied the effect of folate administration on fatty acid composition of plasma, platelet, erythrocyte, intestinal and liver lipids. Two groups of rats were daily injected with either saline solution (control group) or 5-methyl-tetrahydrofolate (MTHF) solution (MTHF group) for 15 days. Changes induced by folate treatment on n-6 PUFA were not very significant. Linoleic acid only decreased in liver and intestinal phospholipids of MTHF rats whereas arachidonic acid was unaffected by folate administration. However, n-3 PUFA significantly increased in plasma lipid fractions and in platelet, erythrocyte and intestinal phospholipids. It is well known that n-3 PUFA show antithrombotic properties. Thus, the increase of n-3 PUFA observed after MTHF administration might contribute to the prevention of vascular disorders.

  18. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    SciTech Connect

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A. )

    1990-03-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. (3H) gamma-aminobutyric acid, (14C) butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of (3H) gamma-aminobutyric acid and (113mIn) transferrin were calculated using (14C) butanol as the highly extracted reference compound. The (113mIn) transferrin data were also used to correct the brain uptake index of (3H) gamma-aminobutyric acid for intravascular retention of (3H) gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid (3H) gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy.

  19. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

  20. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli

    PubMed Central

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M.; Baerga-Ortiz, Abel

    2014-01-01

    Increasing the production of fatty acids by microbial fermentation remains an important step towards the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations towards accessible biodiesel precursors. PMID:24411456

  1. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli.

    PubMed

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2014-02-05

    Increasing the production of fatty acids by microbial fermentation remains an important step toward the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations toward accessible biodiesel precursors.

  2. Endothelial connexin43 mediates acid-induced increases in pulmonary microvascular permeability

    PubMed Central

    2012-01-01

    Acid aspiration, a common cause of acute lung injury, leads to alveolar edema. Increase in lung vascular permeability underlies this pathology. To define mechanisms, isolated rat lungs were perfused with autologous blood. Hydrochloric acid and rhodamine-dextran 70 kDa (RDx70) were coinstilled into an alveolus by micropuncture. RDx70 fluorescence was used to establish the spatial distribution of acid. Subsequently, FITC-dextran 20 kDa (FDx20) was infused into microvessels for 60 min followed by a 10-min HEPES-buffered saline wash. During the infusion, FITC fluorescence changes were recorded to quantify the ratio of peak to postwash fluorescence. The ratio, termed normalized fluorescence, was low for acid compared with buffer instillation both in microvessels abutting acid-treated alveoli and those located more than 700 μm away. In contrast, the normalized fluorescence was similar to buffer controls when a higher molecular weight tracer (FITC-dextran 70 kDa) was infused instead of FDx20, suggesting that normalized FDx20 fluorescence faithfully represented microvascular permeability. Inhibiting endothelial connexin43 (Cx43) gap junction communication with Gap27 blunted the acid-induced reduction in normalized fluorescence, although scrambled Gap27 did not have any effect. The blunting was evident not only in microvessels away from the site of injury, but also in those abutting directly injured alveoli. Thus the new fluorescence-based method reveals that acid increases microvascular permeability both at acid-instilled and away sites. Inhibiting endothelial Cx43 blocked the permeability increase even at the direct injury sites. These data indicate for the first time that Cx43-dependent mechanisms mediate acid-induced increases in microvascular permeability. Cx43 may be a therapeutic target in acid injury. PMID:22561459

  3. Increased beta-aminoisobutyric acid in rat liver with 6-azauracil and its enantiomer.

    PubMed

    Tamaki, N; Fujimoto, S; Mizutani, N; Mizota, C

    1985-10-21

    When 6-azauracil was subcutaneously injected, beta-aminoisobutyric acid and beta-alanine contents were increased 22 and 61-fold, respectively, in rat liver. Incorporation of [methyl-14C]thymine into beta-aminoisobutyric acid was increased to 42-fold by 6-azauracil treatment. The absolute configuration of this amino acid was proved to be the (R)-form by means of a gas-chromatographic technique. 6-Azauracil inhibited beta-alanine-pyruvate aminotransferase activity with an I50 of approx. 2.5 mM.

  4. Malic acid or orthophosphoric acid-heat treatments for protecting sunflower (Helianthus annuus) meal proteins against ruminal degradation and increasing intestinal amino acid supply.

    PubMed

    Arroyo, J M; González, J; Ouarti, M; Silván, J M; Ruiz del Castillo, M L; de la Peña Moreno, F

    2013-02-01

    The protection of sunflower meal (SFM) proteins by treatments with solutions of malic acid (1 M) or orthophosphoric acid (0.67 M) and heat was studied in a 3 × 3 Latin-square design using three diets and three rumen and duodenum cannulated wethers. Acid solutions were applied to SFM at a rate of 400 ml/kg under continuous mixing. Subsequently, treated meals were dried in an oven at 150°C for 6 h. Diets (ingested at 75 g/kg BW0.75) were isoproteic and included 40% Italian ryegrass hay and 60% concentrate. The ratio of untreated to treated SFM in the concentrate was 100 : 0 in the control diet and around 40 : 60 in diets including acid-treated meals. The use of acid-treated meals did not alter either ruminal fermentation or composition of rumen contents and led to moderate reductions of the rumen outflow rates of untreated SFM particles, whereas it did not affect their comminution and mixing rate. In situ effective estimates of by-pass (BP) and its intestinal effective digestibility (IED) of dry matter (DM), CP and amino acids (AAs) were obtained considering both rates and correcting the particle microbial contamination in the rumen using 15N infusion techniques. Estimates of BP and IED decreased applying microbial correction, but these variations were low in agreement with the small contamination level. Protective treatments increased on average the BP of DM (48.5%) and CP (267%), mainly decreasing both the soluble fraction and the degradation rate but also increasing the undegradable fraction, which was higher using orthophosphoric acid. Protective treatments increased the IED of DM (108%) and CP, but this increase was lower using orthophosphoric acid (11.8%) than malic acid (20.7%). Concentrations of AA were similar among all meals, except for a reduction in lysine concentrations using malic acid (16.3%) or orthophosphoric acid (20.5%). Protective treatments also increased on average the BP of all AA, as well as the IED of most of them. Evidence of higher

  5. Increased plasma d-lactic acid associated with impaired memory in rats.

    PubMed

    Hanstock, T L; Mallet, P E; Clayton, E H

    2010-12-02

    d-Lactic acidosis is associated with memory impairment in humans. Recent research indicates that d-lactic acid may inhibit the supply of energy from astrocytes to neurons involved with memory formation. However, little is known about the effects of increased hind-gut fermentation due to changes in diet on circulating lactic acid concentrations and memory. Thirty-six male Wistar rats were fed three dietary treatments: a commercial rat and mouse chow, a soluble carbohydrate based diet or a fermentable carbohydrate based diet. The parameters estimating memory were examined by employing the object recognition test. Physical parameters of fermentation including hind-gut and plasma lactic acid concentrations were examined after sacrifice, either 3 or 21h after feeding. Increased fermentation in the hind-gut of rats, indicated by lower caecum pH, was associated with increased plasma l-lactic acid (r=-0.41, p=0.020) and d-lactic acid (r=-0.33, p=0.087). Memory, being able to discriminate between a familiar and a novel object during the object recognition test, was reduced with increasing plasma d-lactic acid (r=-0.51, p=0.021). Memory impairment was associated with alterations in plasma d-lactic acid following the fermentation of carbohydrate in the hind-gut. Further work is still required to determine whether these effects are mediated centrally or via direct connections through the enteric nervous system. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis

    PubMed Central

    Heaton, Nicholas S.; Perera, Rushika; Berger, Kristi L.; Khadka, Sudip; LaCount, Douglas J.; Kuhn, Richard J.; Randall, Glenn

    2010-01-01

    Dengue virus (DENV) modifies cellular membranes to establish its sites of replication. Although the 3D architecture of these structures has recently been described, little is known about the cellular pathways required for their formation and expansion. In this report, we examine the host requirements for DENV replication using a focused RNAi analysis combined with validation studies using pharmacological inhibitors. This approach identified three cellular pathways required for DENV replication: autophagy, actin polymerization, and fatty acid biosynthesis. Further characterization of the viral modulation of fatty acid biosynthesis revealed that a key enzyme in this pathway, fatty acid synthase (FASN), is relocalized to sites of DENV replication. DENV nonstructural protein 3 (NS3) is responsible for FASN recruitment, inasmuch as (i) NS3 expressed in the absence of other viral proteins colocalizes with FASN and (ii) NS3 interacts with FASN in a two-hybrid assay. There is an associated increase in the rate of fatty acid biosynthesis in DENV-infected cells, and de novo synthesized lipids preferentially cofractionate with DENV RNA. Finally, purified recombinant NS3 stimulates the activity of FASN in vitro. Taken together, these experiments suggest that DENV co-opts the fatty acid biosynthetic pathway to establish its replication complexes. This study provides mechanistic insight into DENV membrane remodeling and highlights the potential for the development of therapeutics that inhibit DENV replication by targeting the fatty acid biosynthetic pathway. PMID:20855599

  7. Chlorogenic acid increased acrylamide formation through promotion of HMF formation and 3-aminopropionamide deamination.

    PubMed

    Cai, Yun; Zhang, Zhenhua; Jiang, Shanshan; Yu, Miao; Huang, Caihuan; Qiu, Ruixia; Zou, Yueyu; Zhang, Qirui; Ou, Shiyi; Zhou, Hua; Wang, Yong; Bai, Weibing; Li, Yiqun

    2014-03-15

    This research was aimed to investigate why chlorogenic acid, presents at high concentrations in some food raw material, influences acrylamide formation. In the asparagine/glucose Maillard reaction system (pH=6.8), addition of chlorogenic acid significantly increased acrylamide formation and inhibited its elimination. In contrast, the quinone derivative of chlorogenic acid decreased acrylamide formation. Three mechanisms may be involved for increasing acrylamide formation by chlorogenic acid. Firstly, it increased the formation of HMF, which acts as a more efficient precursor than glucose to form acrylamide. Secondly, it decreased activation energy for conversion of 3-aminopropionamide (3-APA) to acrylamide (from 173.2 to 136.6kJ/mol), and enhances deamination from 3-APA. And thirdly, it prevented attack of the produced acrylamide from free radicals by keeping high redox potential during the Maillard reaction.

  8. Organic Acid Excretion in Penicillium ochrochloron Increases with Ambient pH

    PubMed Central

    Vrabl, Pamela; Fuchs, Viktoria; Pichler, Barbara; Schinagl, Christoph W.; Burgstaller, Wolfgang

    2012-01-01

    Despite being of high biotechnological relevance, many aspects of organic acid excretion in filamentous fungi like the influence of ambient pH are still insufficiently understood. While the excretion of an individual organic acid may peak at a certain pH value, the few available studies investigating a broader range of organic acids indicate that total organic acid excretion rises with increasing external pH. We hypothesized that this phenomenon might be a general response of filamentous fungi to increased ambient pH. If this is the case, the observation should be widely independent of the organism, growth conditions, or experimental design and might therefore be a crucial key point in understanding the function and mechanisms of organic acid excretion in filamentous fungi. In this study we explored this hypothesis using ammonium-limited chemostat cultivations (pH 2–7), and ammonium or phosphate-limited bioreactor batch cultivations (pH 5 and 7). Two strains of Penicillium ochrochloron were investigated differing in the spectrum of excreted organic acids. Confirming our hypothesis, the main result demonstrated that organic acid excretion in P. ochrochloron was enhanced at high external pH levels compared to low pH levels independent of the tested strain, nutrient limitation, and cultivation method. We discuss these findings against the background of three hypotheses explaining organic acid excretion in filamentous fungi, i.e., overflow metabolism, charge balance, and aggressive acidification hypothesis. PMID:22493592

  9. Polyunsaturated fats attenuate the dietary phytol-induced increase in hepatic fatty acid oxidation in mice.

    PubMed

    Hashimoto, Toru; Shimizu, Naoto; Kimura, Toshinori; Takahashi, Yoko; Ide, Takashi

    2006-04-01

    The effects of dietary phytol and the type of dietary fat on hepatic fatty acid oxidation were examined in male ICR mice. Mice were fed diets containing 0 or 5 g/kg phytol and 100 g/kg palm, safflower, or fish oil for 21 d. Among the groups fed phytol-free diets, the activities and mRNA abundance of various enzymes involved in fatty acid oxidation were greater in mice fed fish oil than in those fed palm or safflower oil. Dietary phytol profoundly increased the activities and mRNA abundance of hepatic fatty acid oxidation enzymes in mice fed palm oil. However, safflower and fish oils, especially the latter, greatly attenuated the phytol-dependent increase in hepatic fatty acid oxidation. The hepatic concentration of phytanic acid, a metabolite of phytol that is the ligand and activator of retinoid X receptors and peroxisome proliferator-activated receptors, was higher in mice fed fish oil than safflower or palm oil, and in those administered safflower oil than palm oil. The hepatic mRNA abundance of sterol carrier protein-2, a lipid-binding protein involved in phytol metabolism, was inversely correlated with the hepatic concentration of phytanic acid. We demonstrated that polyunsaturated fats attenuate the enhancing effect of dietary phytol on hepatic fatty acid oxidation. Dietary fat-dependent changes in the hepatic phytanic acid concentration cannot account for this phenomenon.

  10. Chemical Changes Associated with Increased Acid Resistance of Er:YAG Laser Irradiated Enamel

    PubMed Central

    Olea-Mejía, Oscar Fernando; García-Fabila, María Magdalena; Rodríguez-Vilchis, Laura Emma; Sánchez-Flores, Ignacio; Centeno-Pedraza, Claudia

    2014-01-01

    Background. An increase in the acid resistance of dental enamel, as well as morphological and structural changes produced by Er:YAG laser irradiation, has been reported. Purpose. To evaluate the chemical changes associated with acid resistance of enamel treated with Er:YAG laser. Methods. Forty-eight enamel samples were divided into 4 groups (n = 12). Group I (control); Groups II, III, and IV were irradiated with Er:YAG at 100 mJ (12.7 J/cm2), 200 mJ (25.5 J/cm2), and 300 mJ (38.2 J/cm2), respectively. Results. There were significant differences in composition of irradiated groups (with the exception of chlorine) and in the amount of calcium released. Conclusions. Chemical changes associated with an increase in acid resistance of enamel treated with Er:YAG laser showed a clear postirradiation pattern characterized by a decrease in C at.% and an increase in O, P, and Ca at.% and no changes in Cl at.%. An increased Ca/P ratio after Er:YAG laser irradiation was associated with the use of higher laser energy densities. Chemical changes produced by acid dissolution showed a similar trend among experimental groups. Stable or increased Ca/P ratio after acid dissolution was observed in the irradiated groups, with reduction of Ca released into the acid solution. PMID:24600327

  11. Chemical changes associated with increased acid resistance of Er:YAG laser irradiated enamel.

    PubMed

    Díaz-Monroy, Jennifer Manuela; Contreras-Bulnes, Rosalía; Olea-Mejía, Oscar Fernando; García-Fabila, María Magdalena; Rodríguez-Vilchis, Laura Emma; Sánchez-Flores, Ignacio; Centeno-Pedraza, Claudia

    2014-01-01

    An increase in the acid resistance of dental enamel, as well as morphological and structural changes produced by Er:YAG laser irradiation, has been reported. To evaluate the chemical changes associated with acid resistance of enamel treated with Er:YAG laser. Methods. Forty-eight enamel samples were divided into 4 groups (n = 12). Group I (control); Groups II, III, and IV were irradiated with Er:YAG at 100 mJ (12.7 J/cm(2)), 200 mJ (25.5 J/cm(2)), and 300 mJ (38.2 J/cm(2)), respectively. There were significant differences in composition of irradiated groups (with the exception of chlorine) and in the amount of calcium released. Chemical changes associated with an increase in acid resistance of enamel treated with Er:YAG laser showed a clear postirradiation pattern characterized by a decrease in C at.% and an increase in O, P, and Ca at.% and no changes in Cl at.%. An increased Ca/P ratio after Er:YAG laser irradiation was associated with the use of higher laser energy densities. Chemical changes produced by acid dissolution showed a similar trend among experimental groups. Stable or increased Ca/P ratio after acid dissolution was observed in the irradiated groups, with reduction of Ca released into the acid solution.

  12. Fasting rapidly increases fatty acid oxidation in white adipose tissue of young broiler chickens.

    PubMed

    Torchon, Emmanuelle; Ray, Rodney; Hulver, Matthew W; McMillan, Ryan P; Voy, Brynn H

    2017-01-02

    Upregulating the fatty acid oxidation capacity of white adipose tissue in mice protects against diet-induced obesity, inflammation and insulin resistance. Part of this capacity results from induction of brown-like adipocytes within classical white depots, making it difficult to determine the oxidative contribution of the more abundant white adipocytes. Avian genomes lack a gene for uncoupling protein 1 and are devoid of brown adipose cells, making them a useful model in which to study white adipocyte metabolism in vivo. We recently reported that a brief (5 hour) period of fasting significantly upregulated many genes involved in mitochondrial and peroxisomal fatty acid oxidation pathways in white adipose tissue of young broiler chickens. The objective of this study was to determine if the effects on gene expression manifested in increased rates of fatty acid oxidation. Abdominal adipose tissue was collected from 21 day-old broiler chicks that were fasted for 3, 5 or 7 hours or fed ad libitum (controls). Fatty acid oxidation was determined by measuring and summing (14)CO2 production and (14)C-labeled acid-soluble metabolites from the oxidation of [1-(14)C] palmitic acid. Fasting induced a progressive increase in complete fatty acid oxidation and citrate synthase activity relative to controls. These results confirm that fatty acid oxidation in white adipose tissue is dynamically controlled by nutritional status. Identifying the underlying mechanism may provide new therapeutic targets through which to increase fatty acid oxidation in situ and protect against the detrimental effects of excess free fatty acids on adipocyte insulin sensitivity.

  13. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  14. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling

    PubMed Central

    Alrob, Osama Abo; Sankaralingam, Sowndramalingam; Ma, Cary; Wagg, Cory S.; Fillmore, Natasha; Jaswal, Jagdip S.; Sack, Michael N.; Lehner, Richard; Gupta, Mahesh P.; Michelakis, Evangelos D.; Padwal, Raj S.; Johnstone, David E.; Sharma, Arya M.; Lopaschuk, Gary D.

    2014-01-01

    Aims Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acid and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice. Methods and results C57BL/6 mice were placed on either a HFD (60% fat) or a low-fat diet (LFD; 4% fat) for 16 or 18 weeks. Cardiac fatty acid oxidation rates were significantly increased in HFD vs. LFD mice (845 ± 76 vs. 551 ± 87 nmol/g dry wt min, P < 0.05). Activities of the fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD), and β-hydroxyacyl-CoA dehydrogenase (β-HAD) were increased in hearts from HFD vs. LFD mice, and were associated with LCAD and β-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD-fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1), did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared with wild-type (WT) mice (422 ± 29 vs. 291 ± 17 nmol/g dry wt min, P < 0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared with WT mice, including increased acetylation and activity of LCAD and β-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity. Conclusion We conclude that increased cardiac fatty acid oxidation in response to high-fat feeding is controlled, in part, via the down-regulation of SIRT3 and concomitant increased acetylation of mitochondrial β-oxidation enzymes. PMID:24966184

  15. [Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia].

    PubMed

    Figueroa, Catalina; Droppelmann, Katherine; Quiñones, Verónica; Amigo, Ludwig; Mendoza, Camila; Serrano, Valentina; Véjar, Margarita; Maiz, Alberto; Rigotti, Attilio

    2015-09-01

    Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

  16. Phosphatidic acid increases in response to noradrenaline and endothelin-1 in adult rabbit ventricular myocytes.

    PubMed

    Ye, H; Wolf, R A; Kurz, T; Corr, P B

    1994-12-01

    The aim was to assess whether noradrenaline and endothelin-1 can stimulate endogenous production of phosphatidic acid in adult ventricular myocytes. After stimulation of rabbit ventricular myocytes with noradrenaline and endothelin-1, total lipids were extracted using the Bligh and Dyer procedure and separated by thin layer chromatography, and phosphatidic acid was quantified using photodensitometric analysis of visualised lipids with CuSO4/H3PO4. Noradrenaline (10(-5) M) elicited a rapid increase in phosphatidic acid at 2 min, followed by a decrease at 5 min. A second delayed and sustained increase in phosphatidic acid occurred at 10 min. The response to noradrenaline (10(-9) to 10(-5) M) was concentration dependent with a half maximum response (EC50) of 3.1 x 10(-8) M and the maximum effect at 10(-6) M. The increase in phosphatidic acid production in response to noradrenaline was abolished by an alpha 1 adrenergic receptor blocking agent (2-[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone) but unaffected by the beta adrenergic blocking agent L-propranolol. An increase in phosphatidic acid was also elicited in rabbit ventricular myocytes in response to endothelin-1. The response was time and concentration dependent with the maximal increase at 12 min, EC50 5.3 x 10(-9) M, and maximum effect at 10(-6) M. Both noradrenalin and endothelin-1 stimulated phosphatidylbutanol production in the presence of butanol (100 mM), indicating that both agonists activate phospholipase D. Noradrenaline at physiological concentrations elicits both a rapid and a delayed increase in phosphatidic acid in adult rabbit ventricular myocytes. Endothelial-1, at physiological concentrations, also stimulates an increase in the mass of phosphatidic acid in myocytes, but the increase induced by endothelin-1 is monophasic, in contrast to the biphasic response seen during stimulation with noradrenaline. Activation of phospholipase D contributes to the increase in phosphatidic acid seen during

  17. In vivo blockade of thalamic GABA(B) receptors increases excitatory amino-acid levels.

    PubMed

    Nyitrai, G; Emri, Z; Crunelli, V; Kékesi, K A; Dobolyi, A; Juhász, G

    1996-12-30

    The effect of intrathalamic application of GABA(B) receptor antagonists on the basal excitatory amino-acid levels was studied using microdialysis probes implanted in the dorsal lateral geniculate nucleus and in the ventrobasal complex. In both nuclei, continuous perfusion of the GABA(B) receptor antagonist 3-aminopropyl-(diethoxymethyl)-phosphinic acid (CGP 35348) produced an increase in the extracellular concentration of aspartate and (to a lesser extent) glutamate, but no change was observed in the level of taurine, the main amino acid involved in the regulation of brain osmolarity processes. In contrast, 3-amino-2-hydroxy-2-(4-chlorophenyl)-propanesulphonic acid (2-hydroxy-saclofen), another GABA(B) receptor antagonist, failed to affect the extracellular concentration of aspartate, glutamate and taurine. Thus, the basal level of excitatory amino acids in the thalamus in vivo is under the control of CGP 35348-sensitive GABA(B) receptors.

  18. Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity.

    PubMed

    Ohashi, Toshimitsu; Akazawa, Takashi; Aoki, Mitsuhiro; Kuze, Bunya; Mizuta, Keisuke; Ito, Yatsuji; Inoue, Norimitsu

    2013-09-01

    The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well-known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL-23/IL-17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid-pretreated macrophages inhibited CD8+ T-cell proliferation, but CD8+ T-cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell- and NK cell-sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy. Copyright © 2013 UICC.

  19. Bile acids promote diethylnitrosamine-induced hepatocellular carcinoma via increased inflammatory signaling.

    PubMed

    Sun, Lina; Beggs, Kevin; Borude, Prachi; Edwards, Genea; Bhushan, Bharat; Walesky, Chad; Roy, Nairita; Manley, Michael W; Gunewardena, Sumedha; O'Neil, Maura; Li, Hua; Apte, Udayan

    2016-07-01

    Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC, but the mechanisms are not known. We investigated the mechanisms of HCC tumor promotion by bile acids the diethylnitrosamine (DEN)-initiation-cholic acid (CA)-induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in threefold increase in number and size of DEN-induced liver tumors. All tumors observed in DEN-treated mice were well-differentiated HCCs. The HCCs observed in DEN-treated CA-fed mice exhibited extensive CD3-, CD20-, and CD45-positive inflammatory cell aggregates. Microarray-based global gene expression studies combined with Ingenuity Pathway Analysis revealed significant activation of NF-κB and Nanog in the DEN-treated 0.2% CA-fed livers. Further studies showed significantly higher TNF-α and IL-1β mRNA, a marked increase in total and phosphorylated-p65 and phosphorylated IκBα (degradation form) in livers of DEN-treated 0.2% CA-fed mice. Treatment of primary mouse hepatocytes with various bile acids showed significant induction of stemness genes including Nanog, KLF4, Sox2, and Oct4. Quantification of total and 20 specific bile acids in liver, and serum revealed a tumor-associated bile acid signature. Finally, quantification of total serum bile acids in normal, cirrhotic, and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling. Copyright © 2016 the American Physiological Society.

  20. Lens epithelial cell apoptosis and intracellular Ca2+ increase in the presence of xanthurenic acid

    PubMed Central

    Malina, Halina; Richter, Christoph; Frueh, Beatrice; Hess, Otto M

    2002-01-01

    Background Xanthurenic acid is an endogenous product of tryptophan degradation by indoleamine 2,3-dioxygenase (IDO). We have previously reported that IDO is present in mammalian lenses, and xanthurenic acid is accumulated in the lenses with aging. Here, we studied the involvement of xanthurenic acid in the human lens epithelial cell physiology. Methods Human lens epithelial cells primary cultures were used. Control cells, and cells in the presence of xanthurenic acid grow in the dark. Western blot analysis and immunofluorescence studies were performed. Results In the presence of xanthurenic acid human lens epithelial cells undergo apoptosis-like cell death. In the control cells gelsolin stained the perinuclear region, whereas in the presence of 10 μM xanthurenic acid gelsolin is translocated to the cytoskeleton, but does not lead to cytoskeleton breakdown. In the same condition caspase-3 activation, and DNA fragmentation was observed. At low (5 to 10 μM) of xanthurenic acid concentration, the elongation of the cytoskeleton was associated with migration of mitochondria and cytochrome c release. At higher concentrations xanthurenic acid (20 μM and 40 μM) damaged mitochondria were observed in the perinuclear region, and nuclear DNA cleavage was observed. We observed an induction of calpain Lp 82 and an increase of free Ca2+ in the cells in a xanthurenic acid concentration-dependent manner. Conclusions The results show that xanthurenic acid accumulation in human lens epithelial cells disturbs the normal cell physiology and leads to a cascade of pathological events. Xanthurenic acid induces calpain Lp82 and caspases in the cells growing in the dark and can be involved in senile cataract development. PMID:11934353

  1. Increased intake of water and NaCl solutions in omega-3 fatty acid deficient monkeys.

    PubMed

    Reisbick, S; Neuringer, M; Connor, W E; Iliff-Sizemore, S

    1991-06-01

    We previously reported that long-term omega-3 fatty acid deficiency is associated with increased water intake in rhesus monkeys. To determine whether the increase was specific to water, intakes of salt solutions were measured in 15-minute single-bottle tests. Deficient monkeys drank at least twice as much of all NaCl concentrations as controls. Overall intake decreased as salt concentration increased. In 2-bottle preference tests, deficient monkeys again drank more total fluid but neither preferred nor avoided normal saline compared to controls. When deprived of water, deficient monkeys concentrated urine as well as controls, demonstrating that the increased intake was not a result of renal failure or diabetes insipidus. Omega-3 fatty acids have roles both in neural membrane function and in metabolism of prostaglandins and other eicosanoids. Omega-3 fatty acid deficiency may affect drinking through changes in one or both of these functions.

  2. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking.

    PubMed

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-10-24

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Mechanisms increasing n-3 highly unsaturated fatty acids in the heart.

    PubMed

    Glück, Tobias; Rupp, Heinz; Alter, Peter

    2016-03-01

    Due to ambiguous findings on cardiovascular benefits of systemic omega-3 fatty acid therapy, endogenous mechanisms contributing to local organ-specific concentrations of highly unsaturated fatty acids (HUFA) were examined. Using gas chromatography, 43 fatty acids were analyzed in atrial and ventricular myocardium and in pericardial fluid of male Wistar rats. To examine the endogenous fatty acid metabolism, precursors were administered into the pericardial sac. Pro- and anti-inflammatory actions were induced by talc or fenofibrate, respectively. Physical exercise and a sedentary obese state were used for increased beta-oxidation. DHA (22:6n-3) was increased in ventricular when compared with atrial myocardium (9.0 ± 2.1% vs. 4.7 ± 1.0%, p < 0.001). Intrapericardial EPA (20:5n-3) application lead to an increase of the succeeding tetracosapentaenoic acid (24:5n-3) in atrial myocardium, which is a key precursor of DHA. In contrast, proinflammatory stimulation of the n-6 HUFA pathway did not influence the n-3 metabolism. Exercise- and obesity-induced increased beta-oxidation, the finalizing step of DHA synthesis, was associated with increased ventricular DHA concentrations (6.7 ± 1.0% vs. 8.4 ± 1.2%, p < 0.01). It is concluded that the endogenous metabolism contributes markedly to myocardial HUFA concentrations. The findings are supposed to influence the efficacy of oral HUFA treatment and provide a rationale for divergent findings of previous trials on omega-3 therapy.

  4. Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

    PubMed Central

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

  5. Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

    PubMed

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox) phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox) mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts.

  6. Arachidonic acid metabolites mediate the radiation-induced increase in glomerular albumin permeability.

    PubMed

    Sharma, Mukut; McCarthy, Ellen T; Sharma, Ram; Fish, Brian L; Savin, Virginia J; Cohen, Eric P; Moulder, John E

    2006-01-01

    Radiation-induced renal injury is characterized by proteinuria, hypertension, and progressive decline in renal function. We have previously shown that in vivo or in vitro irradiation of glomeruli with a single dose of radiation (9.5 Gy) increases glomerular albumin permeability (P(alb)) within 1 hr. The current studies tested the hypothesis that this early radiation-induced increase in P(alb) is caused by the release of arachidonic acid and by the generation of specific arachidonic acid metabolites. Glomeruli obtained from WAG/Rij/MCW rats and cultured rat glomerular epithelial and mesangial cells were studied after irradiation (9.5 Gy, single dose). Arachidonic acid release and eicosanoid synthesis by glomeruli or cultured glomerular cells were measured after irradiation, and the effect of inhibitors of phospholipase A2 (PLA2) and cyclooxygenase (COX) on the irradiation-induced increase in P(alb) was assessed. Arachidonic acid release was demonstrated within 10 mins of irradiation of isolated glomeruli and monolayer cultures of glomerular epithelial and mesangial cells. Prostaglandin F(2alpha) (PGF(2alpha)) and PGE2 release was increased after irradiation of isolated glomeruli. Blocking arachidonic acid release or COX activity before irradiation completely prevented the increase in P(alb). COX inhibition immediately after irradiation also diminished the radiation-induced increase in P(alb). We conclude that arachidonic acid and its COX metabolites play an essential role in the early cellular changes that lead to the radiation-induced increase in P(alb). Understanding of the early epigenetic effects of irradiation may lead to new intervention strategies against radiation-induced injury of normal tissues.

  7. C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.

    PubMed

    Olson, Aaron K; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly Priddy, Colleen; Isern, Nancy; Portman, Michael A

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  8. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    PubMed Central

    OLSON, AARON K.; LEDEE, DOLENA; IWAMOTO, KATE; KAJIMOTO, MASAKI; PRIDDY, COLLEEN O’KELLY; ISERN, NANCY; PORTMAN, MICHAEL A.

    2012-01-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4–6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and 13Carbon (13C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  9. Fish meal supplementation increases bovine plasma and luteal tissue omega-3 fatty acid composition.

    PubMed

    White, N R; Burns, P D; Cheatham, R D; Romero, R M; Nozykowski, J P; Bruemmer, J E; Engle, T E

    2012-03-01

    The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.

  10. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  11. Acid and organic aerosol coatings on magnetic nanoparticles increase iron concentrations in human airway epithelial cells.

    PubMed

    Ghio, Andrew J; Dailey, Lisa A; Richards, Judy H; Jang, Myoseon

    2009-07-01

    Numerous industrial applications for man-made nanoparticles have been proposed. Interactions of nanoparticles with agents in the atmosphere may impact human health. We tested the postulate that in vitro exposures of respiratory epithelial cells to airborne magnetic nanoparticles (MNP; Fe(3)O(4)) with and without a secondary organic aerosol (SOA) and an inorganic acid could affect iron homeostasis, oxidative stress, and interleukin (IL)-8 release. Cell iron concentrations were increased after exposures to MNP and values were further elevated with co-exposures to either SOA or inorganic acid. Increased expression of ferritin and elevated levels of RNA for DMT1, proteins for iron storage and transport respectively, followed MNP exposures, but values were significant for only those with co-exposures to inorganic acid and organic aerosols. Cell iron concentration corresponded to a measure of oxidative stress in the airway epithelial cells; MNP with co-exposures to SOA and inorganic acid increased both available metal and indices of oxidant generation. Finally, the release of a proinflammatory cytokine (i.e. IL-8) by the exposed cells similarly increased with cell iron concentration. We conclude that MNP can interact with a SOA and an inorganic acid to present metal in a catalytically reactive state to cultured respiratory cells. This produces an oxidative stress to affect a release of IL-8.

  12. Consumption of a structured triacylglycerol containing behenic and oleic acids increases fecal fat excretion in humans.

    PubMed

    Kojima, Makiko; Arishima, Toshiharu; Shimizu, Ryoma; Kohno, Mitsutaka; Kida, Haruyasu; Hirotsuka, Motohiko; Ikeda, Ikuo

    2013-01-01

    We examined the fecal fat excretion of mildly hypertriacylglycerolemic subjects who ingested soft cookies containing 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) for 7 days. The subjects included 14 healthy men (average age; 44.9 ± 1.7) whose fasting plasma triacylglycerol level ranged from 150 to 250 mg/dL. Every day for 7 days, the subjects ate 5 soft cookies containing margarine with the BOO-rich experimental oil (BOO intake, 2.46 g/day). The placebo group ate soft cookies containing margarine without BOO. This study was a randomized double-blind, placebo-controlled, crossover study. Feces were collected for 3 days prior to the end of the treatment period, and fecal fat and fatty acid composition were determined. The fecal wet weight was significantly increased in BOO group compared with that in the placebo group. Moreover, fecal fat and fatty acid level were significantly higher in the BOO group than in the placebo group. There were no significant differences in the fecal fatty acid composition of the BOO and placebo groups. These results suggest that dietary BOO increases fecal excretion of dietary fat in humans. However, BOO does not increase the excretion of specific fatty acids; it increases the excretion of all fatty acids of dietary origin, which may lead to lower and delay intestinal absorption of dietary fat.

  13. Acute and chronic increases in osmolality increase excitatory amino acid drive of the rostral ventrolateral medulla in rats.

    PubMed

    Brooks, Virginia L; Freeman, Korrina L; O'Donaughy, Theresa L

    2004-12-01

    Water deprivation is associated with increased excitatory amino acid (EAA) drive of the rostral ventrolateral medulla (RVLM), but the mechanism is unknown. This study tested the hypotheses that the increased EAA activity is mediated by decreased blood volume and/or increased osmolality. This was first tested in urethane-anesthetized rats by determining whether bilateral microinjection of kynurenate (KYN, 2.7 nmol) into the RVLM decreases arterial pressure less in water-deprived rats after normalization of blood volume by intravenous infusion of isotonic saline or after normalization of plasma osmolality by intravenous infusion of 5% dextrose in water (5DW). Water-deprived rats exhibited decreased plasma volume and elevated plasma osmolality, hematocrit, and plasma sodium, chloride, and protein levels (all P < 0.05). KYN microinjection decreased arterial pressure by 24 +/- 2 mmHg (P < 0.05; n = 17). The depressor response was not altered following isotonic saline infusion but, while still present (P < 0.05), was reduced (P < 0.05) to -13 +/- 2 mmHg soon after 5DW infusion. These data suggest that the high osmolality, but not low blood volume, contributes to the KYN depressor response. To further investigate the action of increased osmolality on EAA input to RVLM, water-replete rats were also studied after hypertonic saline infusion. Whereas KYN microinjection did not decrease pressure immediately following the infusion, a depressor response gradually developed over the next 3 h. Lumbar sympathetic nerve activity also gradually increased to up to 167 +/- 19% of control (P < 0.05) 3 h after hypertonic saline infusion. In conclusion, acute and chronic increases in osmolality appear to increase EAA drive of the RVLM.

  14. Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

    PubMed

    Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

    2015-10-01

    Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant.

  15. Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis

    PubMed Central

    Hu, Youtian; Liu, Zhenyu; Yu, Xiaoyun; Pasricha, Pankaj J.; Undem, Bradley J.

    2014-01-01

    Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE. PMID:24875100

  16. Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis.

    PubMed

    Farese, R V; Konda, T S; Davis, J S; Standaert, M L; Pollet, R J; Cooper, D R

    1987-05-01

    The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances.

  17. Adaptation to multiday ozone exposure is associated with a sustained increase of bronchoalveolar uric acid.

    PubMed

    Kirschvink, Nathalie; Fiévez, Laurence; Bureau, Fabrice; Degand, Guy; Maghuin-Rogister, Guy; Smith, Nicola; Art, Tatiana; Lekeux, Pierre

    2002-01-01

    The phenomenon of ozone tolerance is described, but the underlying mechanisms remain unknown. We tested whether adaptation to multiday ozone exposure was related to an upregulated pulmonary antioxidant defence. Six calves were exposed to 0.75 ppm ozone, 12 h day(-1) for seven consecutive days. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed before, after the first (D1), third (D3) and seventh (D7) exposure. Differential cell count, total proteins, 8-epi-PGF2alpha, glutathione and uric acid were determined in BAL. Dynamic lung compliance and arterial oxygen tension were significantly decreased and lung oedema impaired pulmonary function on D1. By repeating ozone exposures, progressive functional adaptation occurred. Ozone induced a significant increase of BAL neutrophil percentage on D1. On D3 and D7, neutrophil percentage was progressively decreased, but remained significantly elevated. BAL total proteins were significantly increased on D1 and decreased progressively until D7. 8-Epi-PGF2alpha was significantly increased on D1 and was returned to baseline on D3 and D7, whilst glutathione significantly increased on D3 and returned to baseline on D7. Uric acid was increased ten-fold on D1. On D3, uric acid was increased six-fold and was persistently elevated at D7. This study suggests that ozone adaptation of functional and inflammatory variables is accompanied with sustained BAL uric acid elevation.

  18. Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

    PubMed

    Nolan, C J; Leahy, J L; Delghingaro-Augusto, V; Moibi, J; Soni, K; Peyot, M-L; Fortier, M; Guay, C; Lamontagne, J; Barbeau, A; Przybytkowski, E; Joly, E; Masiello, P; Wang, S; Mitchell, G A; Prentki, M

    2006-09-01

    The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.

  19. Significant increase of oleic acid level in the wild species Lepidium campestre through direct gene silencing.

    PubMed

    Ivarson, Emelie; Ahlman, Annelie; Lager, Ida; Zhu, Li-Hua

    2016-10-01

    Simultaneous RNAi silencing of the FAD2 and FAE1 genes in the wild species Lepidium campestre improved the oil quality with 80 % oleic acid content compared to 11 % in wildtype. Field cress (Lepidium campestre) is a wild biennial species within the Brassicaceae family with desirable agronomic traits, thus being a good candidate for domestication into a new oilseed and catch crop. However, it has agronomic traits that need to be improved before it can become an economically viable species. One of such traits is the seed oil composition, which is not desirable either for food use or for industrial applications. In this study, we have, through metabolic engineering, altered the seed oil composition in field cress into a premium oil for food processing, industrial, or chemical industrial applications. Through seed-specific RNAi silencing of the field cress fatty acid desaturase 2 (FAD2) and fatty acid elongase 1 (FAE1) genes, we have obtained transgenic lines with an oleic acid content increased from 11 % in the wildtype to over 80 %. Moreover, the oxidatively unstable linolenic acid was decreased from 40.4 to 2.6 %, and the unhealthy erucic acid was reduced from 20.3 to 0.1 %. The high oleic acid trait has been kept stable for three generations. This shows the possibility to use field cress as a platform for genetic engineering of oil compositions tailor-made for its end uses.

  20. Production of Siderophores Increases Resistance to Fusaric Acid in Pseudomonas protegens Pf-5

    PubMed Central

    Ruiz, Jimena A.; Bernar, Evangelina M.; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  1. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide.

    PubMed

    Yao, Chien-An; Chen, Chin-Chu; Wang, Nai-Phog; Chien, Chiang-Ting

    2016-04-01

    The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids' oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis.

  2. Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr−/− transgenic mice

    PubMed Central

    Zaman, Munir M.; Martin, Camilia R.; Andersson, Charlotte; Bhutta, Abdul Q.; Cluette-Brown, Joanne E.; Laposata, Michael

    2010-01-01

    Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2α secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/− Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators. PMID:20656894

  3. [Cardiovascular effects of omega-3-fatty acids and alternatives to increase their intake].

    PubMed

    Carrero, J J; Martín-Bautista, E; Baró, L; Fonollá, J; Jiménez, J; Boza, J J; López-Huertas, E

    2005-01-01

    Cardiovascular diseases are the main mortality cause in Europe, the USA and a great extent of Asia. There are several risk factors associated with cardiovascular diseases, such as increased total cholesterol, homocysteine and triglycerides, hypertension, diabetes, and reduced levels of HDL-cholesterol. Many of these risk factors are diet influenced. In spite of the great amount of foods enriched with n-3 fatty acids available at the market, the knowledge about the effects produced by regular intake of these foods still is a challenge in the majority of cases. It appears that intake of foods enriches with n-3 polyunsatured fatty acids is an option that may be effective in reducing risk factors for diseases, by substituting supplements without modifying consumer's alimentary habits. Also shown are the outcomes from a nutritional study undergone with a functional milk-bases food that contains n-3 fatty acids, oleic acid and vitamins.

  4. Methylprednisolone administration in primary biliary cirrhosis increases cholic acid turnover, synthesis, and deoxycholate concentration in bile.

    PubMed

    Mazzella, G; Fusaroli, P; Pezzoli, A; Azzaroli, F; Mazzeo, C; Zambonin, L; Simoni, P; Festi, D; Roda, E

    1999-12-01

    As immunosuppressive agents, corticosteroids may be considered an appropriate treatment for primary biliary cirrhosis, even if bone loss and other side effects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologically proven primary biliary cirrhosis (stage I-IV). We administered methylprednisolone (24 mg daily) for 30 days to ascertain its effects on biliary lipid metabolism, which are largely still unknown. All patients underwent a 30-day drug-washout period before entering the trial. The following parameters were studied before and after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kinetics and synthesis; biliary lipid secretion; biliary bile acid pattern; biliary lipid molar percentage; and cholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon rank test) increase in cholic acid turnover (from 0.26+/-0.04 to 0.50+/-0.05 K/day, P = 0.005) and synthesis (from 0.42+/-0.12 to 0.78+/-0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molar percentage (from 19.4+/-2.7 to 30.6+/-4.4% molar, P = 0.01). On the other hand, a significant decrease in biliary cholesterol molar percentage (from 7.9+/-0.7 to 6.4+/-0.5% molar, P = 0.005), cholesterol saturation index (from 1.11+/-0.11 to 0.95+/-0.07, P = 0.05), and biliary cholesterol secretion (from 64.7+/-5.4 to 53.0+/-4.5 micromol/hr, P = 0.005) was observed. These findings show that short-term administration of methylprednisolone in patients with primary biliary cirrhosis does not induce expansion of the cholic acid pool but increases cholic acid synthesis and turnover, as well as intestinal production of deoxycholic acid. If long-term treatment is considered, the beneficial immunosuppressive effects of corticosteroids have to be weighed against the hepatotoxic properties of deoxycholic acid.

  5. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    SciTech Connect

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  6. Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

    PubMed

    Horowitz, J F; Klein, S

    2000-12-01

    We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.

  7. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein.

    PubMed

    Miyata, Masaaki; Hayashi, Kenjiro; Yamakawa, Hiroki; Yamazoe, Yasushi; Yoshinari, Kouichi

    2015-01-01

    Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

  8. Abscisic Acid and Ethylene Increase in Heterodera avenae-infected Tolerant or Intolerant Oat Cultivars

    PubMed Central

    Volkmar, K. M.

    1991-01-01

    The relationship between root stunting caused by the cereal cyst nematode and levels of two root growth inhibiting hormones, abscisic acid and ethylene, was investigated in aseptically cultured root segments and in intact roots of two oat cultivars differing in tolerance to the nematode. Cultured root segments of oat cultivars New Zealand Cape (tolerant) and Sual (intolerant) were inoculated with sterilized Heterodera avenae second-stage juveniles. Suppressed growth of root axes and emerged laterals following nematode penetration corresponded to an increase in abscisic acid and ethylene in roots of both intolerant and tolerant cultivars. When the experiment was repeated on intact root systems, nematodes retarded root growth of Sual more than New Zealand Cape despite an increase in ABA and ethylene in both cultivars. Abscisic acid and (or) ethylene may be involved in growth inhibition of H. avenae-infected roots but appear to play no direct role in determining tolerance. PMID:19283149

  9. Palmitic acid feeding increases ceramide supply in association with increased milk yield, circulating nonesterified fatty acids, and adipose tissue responsiveness to a glucose challenge.

    PubMed

    Rico, J E; Mathews, A T; Lovett, J; Haughey, N J; McFadden, J W

    2016-11-01

    Reduced insulin action is a key adaptation that facilitates glucose partitioning to the mammary gland for milk synthesis and enhances adipose tissue lipolysis during early lactation. The progressive recovery of insulin sensitivity as cows advance toward late lactation is accompanied by reductions in circulating nonesterified fatty acids (NEFA) and milk yield. Because palmitic acid can promote insulin resistance in monogastrics through sphingolipid ceramide-dependent mechanisms, palmitic acid (C16:0) feeding may enhance milk production by restoring homeorhetic responses. We hypothesized that feeding C16:0 to mid-lactation cows would enhance ceramide supply and ceramide would be positively associated with milk yield. Twenty multiparous mid-lactation Holstein cows were enrolled in a study consisting of a 5-d covariate, 49-d treatment, and 14-d posttreatment period. All cows were randomly assigned to a sorghum silage-based diet containing no supplemental fat (control; n=10; 138±45 d in milk) or C16:0 at 4% of ration dry matter (PALM; 98% C16:0; n=10; 136±44 d in milk). Blood and milk were collected at routine intervals. Liver and skeletal muscle tissue were biopsied at d 47 of treatment. Intravenous glucose tolerance tests (300mg/kg of body weight) were performed at d -1, 24, and 49 relative to start of treatment. The plasma and tissue concentrations of ceramide and glycosylated ceramide were determined using liquid chromatography coupled with tandem mass spectrometry. Data were analyzed as repeated measures using a mixed model with fixed effects of treatment and time, and milk yield served as a covariate. The PALM treatment increased milk yield, energy-corrected milk, and milk fat yield. The most abundant plasma and tissue sphingolipids detected were C24:0-ceramide, C24:0-monohexosylceramide (GlcCer), and C16:0-lactosylceramide. Plasma concentrations of total ceramide and GlcCer decreased as lactation advanced, and ceramide and GlcCer were elevated in cows fed PALM

  10. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling.

    PubMed

    Alrob, Osama Abo; Sankaralingam, Sowndramalingam; Ma, Cary; Wagg, Cory S; Fillmore, Natasha; Jaswal, Jagdip S; Sack, Michael N; Lehner, Richard; Gupta, Mahesh P; Michelakis, Evangelos D; Padwal, Raj S; Johnstone, David E; Sharma, Arya M; Lopaschuk, Gary D

    2014-09-01

    Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acid and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice. C57BL/6 mice were placed on either a HFD (60% fat) or a low-fat diet (LFD; 4% fat) for 16 or 18 weeks. Cardiac fatty acid oxidation rates were significantly increased in HFD vs. LFD mice (845 ± 76 vs. 551 ± 87 nmol/g dry wt min, P < 0.05). Activities of the fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD), and β-hydroxyacyl-CoA dehydrogenase (β-HAD) were increased in hearts from HFD vs. LFD mice, and were associated with LCAD and β-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD-fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1), did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared with wild-type (WT) mice (422 ± 29 vs. 291 ± 17 nmol/g dry wt min, P < 0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared with WT mice, including increased acetylation and activity of LCAD and β-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity. We conclude that increased cardiac fatty acid oxidation in response to high-fat feeding is controlled, in part, via the down-regulation of SIRT3 and concomitant increased acetylation of mitochondrial β-oxidation enzymes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  11. Potential role for nonesterified fatty acids in beta-adrenoceptor-induced increases in brain tryptophan.

    PubMed

    Lenard, Natalie R; Dunn, Adrian J

    2005-01-01

    We tested the hypothesis that beta2- and beta3-adrenergic receptor-mediated increases in brain tryptophan are due to the liberation of fatty acids, which in turn displace tryptophan from its albumin-binding site and thus facilitate its entry into the brain. Male CD-1 mice were injected with subtype-selective beta-adrenergic agonists 1h before brain samples were collected for analysis of tryptophan content by HPLC with electrochemical detection, and blood samples were collected for analysis of total and free tryptophan and nonesterified fatty acid (NEFA) concentrations. The beta2-selective agonist, clenbuterol (0.1 mg/kg), increased concentrations of tryptophan in all brain regions studied and decreased plasma total tryptophan, but had no effect on plasma free tryptophan or NEFAs. The beta3-selective agonists, BRL 37344 (0.2 mg/kg) or CL 316243 (0.01 mg/kg), increased brain tryptophan, plasma NEFAs and free tryptophan. Pretreatment with nicotinic acid (500 mg/kg), an inhibitor of lipolysis, almost completely prevented the increase in plasma free tryptophan and NEFAs, and attenuated the increase in brain tryptophan induced by CL 316243. These results suggest that beta2- and beta3-adrenergic agonists increase brain tryptophan by a mechanism other than the liberation of NEFAs. Nonetheless, beta3-adrenergic agonists appear to increase brain tryptophan by a mechanism that may depend partially on elevations of plasma NEFAs.

  12. Overexpression of a Gene Involved in Phytic Acid Biosynthesis Substantially Increases Phytic Acid and Total Phosphorus in Rice Seeds.

    PubMed

    Tagashira, Yusuke; Shimizu, Tomoe; Miyamoto, Masanobu; Nishida, Sho; Yoshida, Kaoru T

    2015-04-24

    The manipulation of seed phosphorus is important for seedling growth and environmental P sustainability in agriculture. The mechanism of regulating P content in seed, however, is poorly understood. To study regulation of total P, we focused on phytic acid (inositol hexakisphosphate; InsP₆) biosynthesis-related genes, as InsP₆ is a major storage form of P in seeds. The rice (Oryza sativa L.) low phytic acid mutant lpa1-1 has been identified as a homolog of archael 2-phosphoglycerate kinase. The homolog might act as an inositol monophosphate kinase, which catalyzes a key step in InsP₆ biosynthesis. Overexpression of the homolog in transgenic rice resulted in a significant increase in total P content in seed, due to increases in InsP₆ and inorganic phosphates. On the other hand, overexpression of genes that catalyze the first and last steps of InsP₆ biosynthesis could not increase total P levels. From the experiments using developing seeds, it is suggested that the activation of InsP₆ biosynthesis in both very early and very late periods of seed development increases the influx of P from vegetative organs into seeds. This is the first report from a study attempting to elevate the P levels of seed through a transgenic approach.

  13. Pros and cons of increasing folic acid and vitamin B12 intake by fortification.

    PubMed

    Allen, Lindsay H

    2012-01-01

    There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects. The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes briefly data on neural tube defect reduction and other benefits of folic acid fortification as these have been reviewed in more detail elsewhere. More attention is drawn to questions that have been raised about the possible adverse effects of folic acid fortification including the incidence of colorectal cancer and immune function. The main question addressed here is whether folic acid fortification can exacerbate the adverse effects of vitamin B12 deficiency. Most analyses of this question have been conducted in wealthier countries based on data from elderly populations - which have the highest prevalence of vitamin B12 deficiency. However, of potentially greater concern is the increasingly common practice of folic acid fortification in developing countries, where folate status is probably often adequate even prior to fortification, and vitamin B12 depletion or deficiency is common. To add to this information, data from a group of Chilean elderly with a range of vitamin B12 status and exposed to high levels of folic acid fortification will be presented.

  14. Polyunsaturated fatty acid content is increased in the milk of women with pregnancy associated breast cancer

    USDA-ARS?s Scientific Manuscript database

    Background: Pregnancy associated breast cancer (PABC) is aggressive and difficult to diagnose. High intake of most types of dietary fat is thought to increase breast cancer risk, however results in humans supporting this premise remain equivocal. Fatty acid (FA) concentrations in the body comprise b...

  15. Increased muscle fatty acid oxidation in dairy cows with intensive body fat mobilization during early lactation.

    PubMed

    Schäff, C; Börner, S; Hacke, S; Kautzsch, U; Sauerwein, H; Spachmann, S K; Schweigel-Röntgen, M; Hammon, H M; Kuhla, B

    2013-10-01

    The beginning of lactation requires huge metabolic adaptations to meet increased energy demands for milk production of dairy cows. One of the adaptations is the mobilization of body reserves mainly from adipose tissue as reflected by increased plasma nonesterified fatty acid (NEFA) concentrations. The capacity of the liver for complete oxidation of NEFA is limited, leading to an increased formation of ketone bodies, reesterification, and accumulation of triglycerides in the liver. As the skeletal muscle also may oxidize fatty acids, it may help to decrease the fatty acid load on the liver. To test this hypothesis, 19 German Holstein cows were weekly blood sampled from 7 wk before until 5 wk after parturition to analyze plasma NEFA concentrations. Liver biopsies were obtained at d 3, 18, and 30 after parturition and, based on the mean liver fat content, cows were grouped to the 10 highest (HI) and 9 lowest (LO). In addition, muscle biopsies were obtained at d -17, 3, and 30 relative to parturition and used to quantify mRNA abundance of genes involved in fatty acid degradation. Plasma NEFA concentrations peaked after parturition and were 1.5-fold higher in HI than LO cows. Muscle carnitine palmitoyltransferase 1α and β mRNA was upregulated in early lactation. The mRNA abundance of muscle peroxisome proliferator-activated receptor γ (PPARG) increased in early lactation and was higher in HI than in LO cows, whereas the abundance of PPARA continuously decreased after parturition. The mRNA abundance of muscle PPARD, uncoupling protein 3, and the β-oxidative enzymes 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, very long-chain acyl-CoA dehydrogenase, and 3-ketoacyl-CoA was greatest at d 3 after parturition, whereas the abundance of PPARγ coactivator 1α decreased after parturition. Our results indicate that around parturition, oxidation of fatty acids in skeletal muscle is highly activated, which may contribute to diminish the fatty acid load on the liver. The

  16. The Biofilm Lifestyle Involves an Increase in Bacterial Membrane Saturated Fatty Acids

    PubMed Central

    Dubois-Brissonnet, Florence; Trotier, Elsa; Briandet, Romain

    2016-01-01

    Biofilm formation on contact surfaces contributes to persistence of foodborne pathogens all along the food and feed chain. The specific physiological features of bacterial cells embedded in biofilms contribute to their high tolerance to environmental stresses, including the action of antimicrobial compounds. As membrane lipid adaptation is a vital facet of bacterial response when cells are submitted to harsh or unstable conditions, we focused here on membrane fatty acid composition of biofilm cells as compared to their free-growing counterparts. Pathogenic bacteria (Staphylococcus aureus, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella Typhimurium) were cultivated in planktonic or biofilm states and membrane fatty acid analyses were performed on whole cells in both conditions. The percentage of saturated fatty acids increases in biofilm cells in all cases, with a concomitant decrease of branched-chain fatty acids for Gram-positive bacteria, or with a decrease in the sum of other fatty acids for Gram-negative bacteria. We propose that increased membrane saturation in biofilm cells is an adaptive stress response that allows bacteria to limit exchanges, save energy, and survive. Reprogramming of membrane fluidity in biofilm cells might explain specific biofilm behavior including bacterial recalcitrance to biocide action. PMID:27840623

  17. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    SciTech Connect

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W. )

    1991-05-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.

  18. The Biofilm Lifestyle Involves an Increase in Bacterial Membrane Saturated Fatty Acids.

    PubMed

    Dubois-Brissonnet, Florence; Trotier, Elsa; Briandet, Romain

    2016-01-01

    Biofilm formation on contact surfaces contributes to persistence of foodborne pathogens all along the food and feed chain. The specific physiological features of bacterial cells embedded in biofilms contribute to their high tolerance to environmental stresses, including the action of antimicrobial compounds. As membrane lipid adaptation is a vital facet of bacterial response when cells are submitted to harsh or unstable conditions, we focused here on membrane fatty acid composition of biofilm cells as compared to their free-growing counterparts. Pathogenic bacteria (Staphylococcus aureus, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella Typhimurium) were cultivated in planktonic or biofilm states and membrane fatty acid analyses were performed on whole cells in both conditions. The percentage of saturated fatty acids increases in biofilm cells in all cases, with a concomitant decrease of branched-chain fatty acids for Gram-positive bacteria, or with a decrease in the sum of other fatty acids for Gram-negative bacteria. We propose that increased membrane saturation in biofilm cells is an adaptive stress response that allows bacteria to limit exchanges, save energy, and survive. Reprogramming of membrane fluidity in biofilm cells might explain specific biofilm behavior including bacterial recalcitrance to biocide action.

  19. Use of ascorbic and citric acids to increase dialyzable iron from vinal (Prosopis ruscifolia) pulp.

    PubMed

    Bernardi, C; Freyre, M; Sambucetti, M E; Pirovani, M E

    2004-01-01

    Vinal (Prosopis ruscifolia) is an ecologically important wild leguminous tree that grows spontaneously in Argentine deforested lands, the fruit of which is consumed by humans and animals. Because considerable iron content with low to intermediate availability has been previously reported in vinal pulps, its enhancement would be of interest. Iron availability was determined as iron dialyzability using an in vitro technique. Response surface methodology was used to evaluate iron availability increase after adding ascorbic and/or citric acids to vinal pulp at different mM acid/mM Fe ratios. Those ratios ranged from 0.05:1 to 9.95:1 and from 0.5:1 to 99.5:1 for ascorbic acid/Fe (AA:Fe) and citric acid/Fe (CA:Fe), respectively. The obtained second- and first-order polynomial equations showed that AA:Fe and CA:Fe molar ratios linear terms had a significant effect on iron dialyzability increase (P < or = 0.05). It was possible to enhance iron availability to a maximum of 4.6 times. Additional confirmatory experiments were made adding the same organic acids to different vinal pulps and to a traditional cake prepared with vinal pulp called "patay." There were no significant differences (p > 0.05) between predicted values obtained by the model and experimental results.

  20. Increased saccharification yields from aspen biomass upon treatment with enzymatically generated peracetic acid.

    PubMed

    Duncan, Shona; Jing, Qing; Katona, Adrian; Kazlauskas, Romas J; Schilling, Jonathan; Tschirner, Ulrike; Aldajani, Waleed Wafa

    2010-03-01

    The recalcitrance of lignocellulosic biomass to enzymatic release of sugars (saccharification) currently limits its use as feedstock for biofuels. Enzymatic hydrolysis of untreated aspen wood releases only 21.8% of the available sugars due primarily to the lignin barrier. Nature uses oxidative enzymes to selectively degrade lignin in lignocellulosic biomass, but thus far, natural enzymes have been too slow for industrial use. In this study, oxidative pretreatment with commercial peracetic acid (470 mM) removed 40% of the lignin (from 19.9 to 12.0 wt.% lignin) from aspen and enhanced the sugar yields in subsequent enzymatic hydrolysis to about 90%. Increasing the amount of lignin removed correlated with increasing yields of sugar release. Unfortunately, peracetic acid is expensive, and concentrated forms can be hazardous. To reduce costs and hazards associated with using commercial peracetic acid, we used a hydrolase to catalyze the perhydrolysis of ethyl acetate generating 60-70 mM peracetic acid in situ as a pretreatment to remove lignin from aspen wood. A single pretreatment was insufficient, but multiple cycles (up to eight) removed up to 61.7% of the lignin enabling release of >90% of the sugars during saccharification. This value corresponds to a predicted 581 g of fermentable sugars from 1 kg of aspen wood. Improvements in the enzyme stability are needed before the enzymatically generated peracetic acid is a commercially viable alternative.

  1. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide

    PubMed Central

    Yao, Chien-An; Chen, Chin-Chu; Wang, Nai-Phog; Chien, Chiang-Ting

    2016-01-01

    The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids’ oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis. PMID:27043621

  2. Zoledronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis.

    PubMed

    Catalano, Antonino; Morabito, Nancy; Basile, Giorgio; Brancatelli, Santa; Cucinotta, Domenico; Lasco, Antonino

    2013-05-01

    Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown. The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers. We conducted a prospective intervention study in an ambulatory care setting. Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo. At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured. Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group. Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.

  3. Sluggish small bowel motility is involved in determining increased biliary deoxycholic acid in cholesterol gallstone patients.

    PubMed

    Azzaroli, F; Mazzella, G; Mazzeo, C; Simoni, P; Festi, D; Colecchia, A; Montagnani, M; Martino, C; Villanova, N; Roda, A; Roda, E

    1999-09-01

    Our aim was to establish whether small intestine transit time is defective in subjects with cholesterol gallstones. We enrolled 10 patients (eight women, two men; mean age, 48.7 yr; mean body mass index [BMI], 22.4 Kg/m2) with recently diagnosed cholelithiasis, with no liver pathology, who were not taking any drugs, and 11 comparable healthy volunteers (eight women, three men; mean age, 46.2 yr; mean BMI, 22.7 Kg/m2), who served as controls. All subjects underwent orocecal (by starch breath test technique and serum assays of salazopyrin), oroileal (by serum assays of tauroursodeoxycholic acid), and duodenoileal (by serum assays of taurocholic acid) transit times; cholesterol saturation index; and bile acid composition and gallbladder motility studies (by ultrasound). For serum assays, blood samples were collected over a period of 7 h. Gallbladder motility and orocecal transit time were evaluated simultaneously. All four means of assessing transit time gave longer times in cholesterol gallstone patients than in controls: orocecal transit time (salazopyrin) = 366 +/- 13 vs 258 +/- 16 min, p < 0.0005; orocecal transit time (starch breath test) = 415 +/- 139 vs 290 +/- 15 min, p < 0.01; duodenoileal transit time: 272 +/- 23 vs 205 +/- 23 min, p < 0.03; and oroileal transit time: 308 +/- 18 vs 230 +/- 19 min, p < 0.009. Cholesterol gallstone patients showed an increase in percent molar biliary deoxycholic acid (30% +/- 4.5% vs 16% +/- 1.3%, p < 0.02) and a decrease in percent molar cholic acid 32% +/- 2.2% vs 40% +/- 1.3%, p < 0.03) and chenodeoxycholic acid (34% +/- 3% vs 41% +/- 1.8%, p < 0.03), compared with controls; patients also had greater percent molar biliary cholesterol. A linear relationship (r2 = 0.6324, p = 0.0012) between biliary deoxycholic acid and small bowel transit time was found. Residual gallbladder volumes were larger in cholesterol gallstone patients (11.38 +/- 1.27 vs 7.55 +/- 0.39 ml, p < 0.04), whereas basal gallbladder volumes, although higher

  4. Homologous electron transport components fail to increase fatty acid hydroxylation in transgenic Arabidopsis thaliana

    PubMed Central

    Wayne, Laura L.; Browse, John

    2013-01-01

    Ricinoleic acid, a hydroxylated fatty acid (HFA) present in castor ( Ricinus communis) seeds, is an important industrial commodity used in products ranging from inks and paints to polymers and fuels. However, due to the deadly toxin ricin and allergens also present in castor, it would be advantageous to produce ricinoleic acid in a different agricultural crop. Unfortunately, repeated efforts at heterologous expression of the castor fatty acid hydroxylase (RcFAH12) in the model plant Arabidopsis thaliana have produced only 17-19% HFA in the seed triacylglycerols (TAG), whereas castor seeds accumulate up to 90% ricinoleic acid in the endosperm TAG. RcFAH12 requires an electron supply from NADH:cytochrome b5 reductase (CBR1) and cytochrome b5 (Cb5) to synthesize ricinoleic acid. Previously, our laboratory found a mutation in the Arabidopsis CBR1 gene, cbr1-1, that caused an 85% decrease in HFA levels in the RcFAH12 Arabidopsis line. These results raise the possibility that electron supply to the heterologous RcFAH12 may limit the production of HFA. Therefore, we hypothesized that by heterologously expressing RcCb5, the reductant supply to RcFAH12 would be improved and lead to increased HFA accumulation in Arabidopsis seeds. Contrary to this proposal, heterologous expression of the top three RcCb5 candidates did not increase HFA accumulation. Furthermore, coexpression of RcCBR1 and RcCb5 in RcFAH12 Arabidopsis also did not increase in HFA levels compared to the parental lines. These results demonstrate that the Arabidopsis electron transfer system is supplying sufficient reductant to RcFAH12 and that there must be other bottlenecks limiting the accumulation of HFA. PMID:24555099

  5. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    PubMed

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Intra-articular hyaluronic acid increases cartilage breakdown biomarker in patients with knee osteoarthritis.

    PubMed

    Gonzalez-Fuentes, Alexandra M; Green, David M; Rossen, Roger D; Ng, Bernard

    2010-06-01

    Intra-articular hyaluronic acid has been used in treatment of patients with knee osteoarthritis. Though its effect on pain has been well studied, it is not clear how it affects the articular cartilage. This is a preliminary study to evaluate the kinetics of urinary collagen type-II C-telopeptide (CTX-II) as a biomarker of collagen breakdown in response to intra-articular hyaluronic acid injection in patients with symptomatic knee osteoarthritis. Intra-articular injections of hyaluronan were administered to ten patients with symptomatic knee osteoarthritis. Urine collection for urinary CTX-II was obtained at baseline, before each injection and once every other week for a total of 6 months. Urine CTX-II was measured using a CartiLaps(c) ELISA kit. There was a statistically significant increase (p = 0.0136) in CTX-II a week after the third intra-articular injection of hyaluronic acid (6,216 ng/mmol +/- 4,428) compared with baseline (2,233 ng/mmol +/- 1,220). This increase in CTX-II was sustained throughout the entire 6 months follow-up period (repeated measures ANOVA, p < 0.015). This is the first study of changes in an osteoarthritis biomarker after intra-articular hyaluronic acid injections in patients with symptomatic knee osteoarthritis. Contrary to our initial hypothesis that CTX-II levels should decrease after intra-articular hyaluronic acid injections, we found a significant increase in urinary CTX-II levels that was sustained throughout the study. These observations suggest that intra-articular hyaluronic acid injections may accelerate cartilage breakdown in patients with symptomatic knee osteoarthritis. The responsible mechanisms are unknown and warrant further study.

  7. Increased thermal stability of proteins in the presence of amino acids.

    PubMed Central

    Taneja, S; Ahmad, F

    1994-01-01

    This study is a systematic attempt to understand the roles of osmolytes in protecting proteins against denaturing stress. Thermal denaturation of cytochrome c has been studied in the presence of various concentrations of all L-amino acids that are more hydrophobic than glycine and have a solubility of 0.1 M or higher in water at 25 degrees C. The basic observations are as follows. (1) Arginine and histidine destabilize the native protein; both Tm (the midpoint of thermal transition) and delta GDH2O (25 degrees C) (the Gibbs energy of stabilization) decrease with increasing amino acid concentration. (2) Isoleucine, leucine and phenylalanine have no effect on Tm and deltaGDH2O (25 degrees C). (3) Valine and less hydrophobic amino acids stabilize the protein in terms of Tm but deltaGDH2O (25 degrees C) is unchanged. This observation was confirmed by the study of isothermal denaturation of cytochrome c by guanidinium chloride which suggested that delta GDH2O is independent of osmolyte concentration, but Cm (the midpoint of transition) is increased in their presence. (4) In the case of stabilizers, change in Tm/mol of amino acid decreases with increasing hydrophobicity of these osmolytes. PMID:7945233

  8. Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury.

    PubMed

    Wesson, Donald E; Pruszynski, Jessica; Cai, Wendy; Simoni, Jan

    2017-04-01

    Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-β-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues.

  9. Organic reactions increasing the absorption index of atmospheric sulfuric acid aerosols

    NASA Astrophysics Data System (ADS)

    Nozière, B.; Esteve, W.

    2005-02-01

    Unlike most environments present at Earth's surface atmospheric aerosols can be favorable to organic reactions. Among them, the acid-catalyzed aldol condensation of aldehydes and ketones produces light-absorbing compounds. In this work the increase of the absorption index of sulfuric acid solutions 50-96 wt. % resulting from the uptake of gas-phase acetaldehyde, acetone, and 2-butanone (methyl ethyl ketone), has been measured in the near UV and visible range. Our results indicate that the absorption index between 200 and 500 nm for stratospheric sulfuric aerosols exposed to 100 pptV of acetaldehyde (1 pptV = 10-12 v/v) would increase by four orders of magnitude over a two-year lifetime. Rough estimates based on previous radiative calculations suggest that this reaction could result in an increase of the radiative forcing of sulfate aerosols of the order of 0.01 W m-2, and that these processes are worth further investigation.

  10. Folic acid supplementation increases cutaneous vasodilator sensitivity to sympathetic nerve activity in older adults.

    PubMed

    Stanhewicz, Anna E; Greaney, Jody L; Alexander, Lacy M; Kenney, W Larry

    2017-05-01

    During heat stress, blunted increases in skin sympathetic nervous system activity (SSNA) and reductions in end-organ vascular responsiveness contribute to the age-related reduction in reflex cutaneous vasodilation. In older adults, folic acid supplementation improves the cutaneous vascular conductance (CVC) response to passive heating; however, the influence of folic acid supplementation on SSNA:CVC transduction is unknown. Fourteen older adults (66 ± 1 yr, 8 male/6 female) ingested folic acid (5 mg/day) or placebo for 6 wk in a randomized, double-blind, crossover design. In protocol 1, esophageal temperature (Tes) was increased by 1.0°C (water-perfused suit) while SSNA (peroneal microneurography) and red cell flux in the innervated dermatome (laser Doppler flowmetry; dorsum of the foot) were continuously measured. In protocol 2, two intradermal microdialysis fibers were placed in the skin of the lateral calf for graded infusions of acetylcholine (ACh; 10(-10) to 10(-1) M) with and without nitric oxide synthase (NOS) blockade (20 mM nitro-l-arginine methyl ester). Folic acid improved reflex vasodilation (46 ± 4% vs. 31 ± 3% CVCmax for placebo; P < 0.001) without affecting the increase in SSNA (Δ506 ± 104% vs. Δ415 ± 73% for placebo; NS). Folic acid increased the slope of the SSNA-to-CVC relation (0.08 ± 0.02 vs. 0.05 ± 0.01 for placebo; P < 0.05) and extended the response range. Folic acid augmented ACh-induced vasodilation (83 ± 3% vs. 66 ± 4% CVCmax for placebo; P = 0.002); however, there was no difference between treatments at the NOS-inhibited site (53 ± 4% vs. 52 ± 4% CVCmax for placebo; NS). These data demonstrate that folic acid supplementation enhances reflex vasodilation by increasing the sensitivity of skin arterioles to central sympathetic nerve outflow during hyperthermia in aged human subjects. Copyright © 2017 the American Physiological Society.

  11. 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

  12. Infantile citrullinemia caused by citrin deficiency with increased dibasic amino acids.

    PubMed

    Ben-Shalom, Efrat; Kobayashi, Keiko; Shaag, Avraham; Yasuda, Tomotsugu; Gao, Hong-Zhi; Saheki, Takeyori; Bachmann, Claude; Elpeleg, Orly

    2002-11-01

    In an infant who suffered from prolonged icterus and hepatocellular dysfunction we detected an increase of citrulline and dibasic amino acids in plasma and urine. The amino acid levels along with all the abnormal liver tests normalized upon replacing breast-milk by formula feeding; there was no relapse after human milk was tentatively reintroduced. A novel mutation, a approximately 9.5-kb genomic duplication, was identified in the citrin gene (SLC25A13) resulting in the insertion of exon 15. No mutation was detected in the CAT2A specific exon of the SLC7A2 gene which encodes for the liver transporter of cationic amino acids. This is the first report of infantile citrin deficiency in non-Asian patients.

  13. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria.

    PubMed

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-10-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE(UA)) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE(UA), suggesting that SUA decreased as a result of the increase in the UE(UA). The increase in UE(UA) was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE(UA) is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. It was observed that the efflux of [(14) C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mm D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE(UA) could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose.

  14. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    PubMed Central

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  15. Bile acid increases expression of the histamine-producing enzyme, histidine decarboxylase, in gastric cells.

    PubMed

    Ku, Hye Jin; Kim, Hye Young; Kim, Hyeong Hoe; Park, Hee Ju; Cheong, Jae Hun

    2014-01-07

    To investigate the effect of bile acid on the expression of histidine decarboxylase (HDC), which is a major enzyme involved in histamine production, and gene expression of gastric transcription factors upon cooperative activation. HDC expression was examined by immunohistochemistry, reverse transcriptase polymerase chain reaction, and promoter assay in human gastric precancerous tissues, normal stomach tissue, and gastric cancer cell lines. The relationship between gastric precancerous state and HDC expression induced by bile acid was determined. The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated. MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor (FXR), small heterodimer partner (SHP), and caudal-type homeodomain transcription factor (CDX)1 expression plasmids. The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay. Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases. Here, we show that bile acid increased the expression of HDC, which is a rate-limiting enzyme of the histamine production pathway. FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression. In addition, the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression. We confirmed similar expression patterns for HDC, CDX1, and SHP in patient tissues. HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1.

  16. Conjugated linoleic acid increases in milk from cows fed condensed corn distillers solubles and fish oil.

    PubMed

    Bharathan, M; Schingoethe, D J; Hippen, A R; Kalscheur, K F; Gibson, M L; Karges, K

    2008-07-01

    Twelve lactating Holstein cows were randomly assigned to 1 of 4 experimental diets in a replicated 4 x 4 Latin square design with 4-wk periods to ascertain the lactational response to feeding fish oil (FO), condensed corn distillers solubles (CDS) as a source of extra linoleic acid, or both. Diets contained either no FO or 0.5% FO and either no CDS or 10% CDS in a 2 x 2 factorial arrangement of treatments. Diets were fed as total mixed rations for ad libitum consumption. The forage to concentrate ratio was 55:45 on a dry matter basis for all diets and the diets contained 16.2% crude protein. The ether extract concentrations were 2.86, 3.22, 4.77, and 5.02% for control, FO, CDS, and FOCDS diets, respectively. Inclusion of FO or CDS or both had no effect on dry matter intake, feed efficiency, body weight, and body condition scores compared with diets without FO and CDS, respectively. Yields of milk (33.3 kg/d), energy-corrected milk, protein, lactose, and milk urea N were similar for all diets. Feeding FO and CDS decreased milk fat percentages (3.85, 3.39, 3.33, and 3.12%) and yields compared with diets without FO and CDS. Proportions of trans-11 C18:1 (vaccenic acid), cis-9 trans-11 conjugated linoleic acid (CLA; 0.52, 0.90, 1.11, and 1.52 g/100 g of fatty acids), and trans-10 cis-12 CLA (0.07, 0.14, 0.13, and 0.16 g/100 g of fatty acids) in milk fat were increased by FO and CDS. No interactions were observed between FO and CDS on cis-9 trans-11 CLA although vaccenic acid tended to be higher with the interaction. The addition of CDS to diets increased trans-10 C18:1. Greater ratios of vaccenic acid to cis-9 trans-11 CLA in plasma than in milk fat indicate tissue synthesis of cis-9 trans-11 CLA in the mammary gland from vaccenic acid in cows fed FO or CDS. Feeding fish oil at 0.5% of diet dry matter with a C18:2 n-6 rich source such as CDS increased the milk CLA content but decreased milk fat percentages.

  17. Tetradecylthiopropionic acid induces hepatic mitochondrial dysfunction and steatosis, accompanied by increased plasma homocysteine in mice.

    PubMed

    Berge, Rolf K; Bjørndal, Bodil; Strand, Elin; Bohov, Pavol; Lindquist, Carine; Nordrehaug, Jan Erik; Svardal, Asbjørn; Skorve, Jon; Nygård, Ottar

    2016-02-05

    Hepatic mitochondrial dysfunction plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methyl donor supplementation has been shown to alleviate NAFLD, connecting the condition to the one-carbon metabolism. Thus, the objective was to investigate regulation of homocysteine (Hcy) and metabolites along the choline oxidation pathway during induction of hepatic steatosis by the fatty acid analogue tetradecylthiopropionic acid (TTP), an inhibitor of mitochondrial fatty acid oxidation. Mice were fed a control diet, or diets containing 0.3 %, 0.6 %, or 0.9 % (w/w) TTP for 14 days. Blood and liver samples were collected, enzyme activities and gene expression were analyzed in liver, lipid and fatty acid composition in liver and plasma, one-carbon metabolites, B-vitamin status, carnitine and acylcarnitines were analyzed in plasma. Liver mitochondrial fatty acid oxidation decreased by 40 % and steatosis was induced in a dose dependent manner; total lipids increased 1.6-fold in animals treated with 0.3 % TTP, 2-fold with 0.6 % TTP and 2.1 fold with 0.9 % TTP compared to control. The higher hepatic concentration of fatty acids was associated with shortening of carbon-length. Furthermore, the inhibited fatty acid oxidation led to a 30-fold decrease in plasma carnitine and 9.3-fold decrease in acetylcarnitine at the highest dose of TTP, whereas an accumulation of palmitoylcarnitine resulted. Compared to the control diet, TTP administration was associated with elevated plasma total Hcy (control: 7.2 ± 0.3 umol/L, 0.9 % TTP: 30.5 ± 5.9 umol/L) and 1.4-1.6 fold increase in the one-carbon metabolites betaine, dimethylglycine, sarcosine and glycine, accompanied by changes in gene expression of the different B-vitamin dependent pathways of Hcy and choline metabolism. A positive correlation between total Hcy and hepatic triacylglycerol resulted. The TTP-induced inhibition of mitochondrial fatty acid oxidation was not associated with increased hepatic

  18. Gibberellic acid increases secondary metabolite production in Echinacea purpurea hairy roots.

    PubMed

    Abbasi, Bilal H; Stiles, Amanda R; Saxena, Praveen K; Liu, Chun-Zhao

    2012-12-01

    Gibberellic acid (GA(3)) is reported to have diverse effects on hairy root cultures of many plant species; therefore, the effects of GA(3) on the growth, secondary metabolite production (caffeic acid derivatives and lignin), phenylalanine ammonia lyase (PAL) activity, and free radical scavenging activity of light-grown Echinacea purpurea L. hairy roots were investigated. Eight concentrations of GA(3), ranging from 0.005 to 1.0 μM, were added to shake flask cultures. The moderate GA(3) concentration, 0.025 μM, resulted in the highest concentrations of cichoric acid, caftaric acid, and chlorogenic acid, as well as increased PAL activity, cell viability, and free radical scavenging activity, while higher and lower GA(3) concentrations resulted in reduced levels compared to the control (lacking GA(3)). The moderate GA(3) concentration also affected root morphogenesis; supplementation with 0.025 μM GA(3) resulted in the development of thick, dense, purple-colored roots, while roots exposed to the higher and lower concentrations of GA(3) were thin and off-white. This study demonstrates that supplementation with GA(3) may be an excellent strategy to optimize the production of secondary metabolites from E. purpurea hairy root cultures; however, the GA(3) concentration is a critical factor.

  19. Ionic liquid pretreatment to increase succinic acid production from lignocellulosic biomass.

    PubMed

    Wang, Caixia; Yan, Daojiang; Li, Qiang; Sun, Wei; Xing, Jianmin

    2014-11-01

    In this study, pinewood and corn stover pretreated with the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AmimCl) were used as a feedstock for succinic acid production. Results reveal that 5% (v/v) AmimCl inhibited bacterial growth, whereas 0.01% (v/v) AmimCl inhibited succinic acid production. AmimCl was effective in extracting cellulose from pinewood and in degrading pinewood into a uniform pulp, as revealed by scanning electron microscopy (SEM). The rate of enzymatic hydrolysis of pinewood extract reached 72.16%. The combinations of AmimCl pretreatment with steam explosion or with hot compressed water were effective in treating corn stover, whereas AmimCl treatment alone did not result in a significant improvement. Pinewood extract produced 20.7g/L succinic acid with an average yield of 0.37g per gram of biomass. Workflow calculations indicated pine wood pretreated with IL has a theoretical yield of succinic acid of 57.1%. IL pretreatment led to increase in succinic acid yields. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Oxidation in fish oil enriched mayonnaise: ascorbic acid and low pH increase oxidative deterioration.

    PubMed

    Jacobsen, C; Timm, M; Meyer, A S

    2001-08-01

    The effect of ascorbic acid (0-4000 ppm) and pH (3.8-6.2) on oxidation and levels of iron and copper in various fractions of mayonnaise enriched with 16% fish oil was investigated. Ascorbic acid induced release of iron from the assumed oil-water interface into the aqueous phase at all pH levels, but this effect of ascorbic acid was strongest at low pH (pH 3.8-4.2). Ascorbic acid generally promoted formation of volatile oxidation compounds and reduced the peroxide value in mayonnaises. Peroxide values and total volatiles generally increased with decreasing pH values, suggesting that low pH promoted oxidation. It is proposed that iron bridges between the egg yolk proteins low-density lipoproteins, lipovitellin, and phosvitin at the oil-water interface are broken at low pH values, whereby iron ions become accessible as oxidation initiators. In the presence of ascorbic acid, oxidation is further enhanced due to the reduction of Fe(3+) to Fe(2+) that rapidly catalyzes lipid oxidation via lipid hydroperoxide decomposition at the oil-water interface in mayonnaise.

  1. Association between Increased Gastric Juice Acidity and Sliding Hiatal Hernia Development in Humans

    PubMed Central

    Kishikawa, Hiroshi; Kimura, Kayoko; Ito, Asako; Arahata, Kyoko; Takarabe, Sakiko; Kaida, Shogo; Kanai, Takanori; Miura, Soichiro; Nishida, Jiro

    2017-01-01

    Objectives Several clinical factors; overweight, male gender and increasing age, have been implicated as the etiology of hiatal hernia. Esophageal shortening due to acid perfusion in the lower esophagus has been suggested as the etiological mechanism. However, little is known about the correlation between gastric acidity and sliding hiatus hernia formation. This study examined whether increased gastric acid secretion is associated with an endoscopic diagnosis of hiatal hernia. Methods A total of 286 consecutive asymptomatic patients (64 were diagnosed as having a hiatal hernia) who underwent upper gastrointestinal endoscopy were studied. Clinical findings including fasting gastric juice pH as an indicator of acid secretion, age, sex, body mass index, and Helicobacter pylori infection status determined by both Helicobacter pylori serology and pepsinogen status, were evaluated to identify predictors in subjects with hiatal hernia. Results Male gender, obesity with a body mass index >25, and fasting gastric juice pH were significantly different between subjects with and without hiatal hernia. The cut-off point of fasting gastric juice pH determined by receiver operating curve analysis was 2.1. Multivariate regression analyses using these variables, and age, which is known to be associated with hiatal hernia, revealed that increased gastric acid secretion with fasting gastric juice pH <2.1 (OR = 2.60, 95% CI: 1.38–4.90) was independently associated with hiatal hernia. Moreover, previously reported risk factors including male gender (OR = 2.32, 95% CI: 1.23–4.35), body mass index >25 (OR = 3.49, 95% CI: 1.77–6.91) and age >65 years (OR = 1.86, 95% CI: 1.00–3.45), were also significantly associated with hiatal hernia. Conclusions This study suggests that increased gastric acid secretion independently induces the development of hiatal hernia in humans. These results are in accordance with the previously reported hypothesis that high gastric acid itself induces

  2. Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice.

    PubMed

    Choi, You-Jin; Lee, Chae-Hyeon; Lee, Kang-Yo; Jung, Seung-Hwan; Lee, Byung-Hoon

    2015-06-01

    Tetracycline induces microvesicular steatosis, which has a poor long-term prognosis and a higher risk of steatohepatitis development compared with macrovesicular steatosis. Recent gene expression studies indicated that tetracycline treatment affects the expression of many genes associated with fatty acid transport and esterification. In this study, we investigated the role of fatty acid transport and esterification in tetracycline-induced steatosis. Intracellular lipid accumulation and the protein expression of fatty acid translocase (FAT or CD36) and diacylglycerol acyltransferase (DGAT) 2 were increased in both mouse liver and HepG2 cells treated with tetracycline at 50 mg/kg (intraperitoneal injection, i.p.) and 100 μM, respectively. Tetracycline increased the cellular uptake of boron-dipyrromethene-labeled C16 fatty acid, which was abolished by CD36 RNA interference. Oleate-induced cellular lipid accumulation was further enhanced by co-incubation with tetracycline. Tetracycline downregulated extracellular signal-regulated kinase (ERK) phosphorylation, which negatively regulated DGAT2 expression. U0126, a specific ERK inhibitor, also increased DGAT2 expression and cellular lipid accumulation. DGAT1 and 2 knock-down with specific small interfering (si)-RNA completely abrogated the steatogenic effect of tetracycline in HepG2 cells. Taken together, our data showed that tetracycline induces lipid accumulation by facilitating fatty acid transport and triglyceride esterification by upregulating CD36 and DGAT2, respectively. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Long-term melatonin administration increases polyunsaturated fatty acid percentage in plasma lipids of hypercholesterolemic rats.

    PubMed

    Pita, Maria L; Hoyos, Marta; Martin-Lacave, Inés; Osuna, Carmen; Fernández-Santos, Jose M; Guerrero, Juan M

    2002-04-01

    This study was designed to investigate the effect of melatonin on the fatty acid composition of plasma and tissue lipids. Melatonin administration to rats fed with a standard diet only increased long-chain n-6 polyunsaturated fatty acids (PUFA) in total plasma lipids and liver phospholipids but induced significant changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses changes were reversed by melatonin administration. The analysis of lipid fractions revealed that only the cholesteryl ester fraction was affected by melatonin. Histological studies of the carotid artery intima revealed the appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of foam cells covered by the endothelium and by a thin layer of mononucleated cells. These changes were prevented by melatonin. We conclude that long-term melatonin administration modifies the fatty acid composition of rat plasma and liver lipids and ameliorates the arterial fatty infiltration induced by cholesterol.

  4. Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans.

    PubMed

    Hadjighassem, Mahmoudreza; Kamalidehghan, Behnam; Shekarriz, Nima; Baseerat, Argavan; Molavi, Nima; Mehrpour, Masoud; Joghataei, Mohammad Taghi; Tondar, Mahdi; Ahmadipour, Fatemeh; Meng, Goh Yong

    2015-02-26

    Dietary omega-6 and omega-3 fatty acids have remarkable impacts on the levels of DHA in the brain and retina. Low levels of DHA in plasma and blood hamper visual and neural development in children and cause dementia and cognitive decline in adults. The level of brain-derived neurotrophic factors (BDNF) changes with dietary omega-3 fatty acid intake. BDNF is known for its effects on promoting neurogenesis and neuronal survival. In this study, we examined the effect of the oral consumption of α-Linolenic acid (ALA) on blood levels of BDNF and Malondialdehyde (MDA) in healthy adult humans. 30 healthy volunteers, 15 men and 15 women, were selected randomly. Each individual served as his or her own control. Before consuming the Flaxseed oil capsules, 5cc blood from each individual was sampled in order to measure the plasma levels of BDNF and MDA as baseline controls. During the experiment, each individual was given 3 oral capsules of flaxseed oil, containing 500mg of alpha linolenic acid, daily for one week. Then, plasma levels of BDNF and MDA were tested. The plasma levels of BDNF and MDA significantly (P < 0.05) increased in individuals who received the oral capsules of ALA. Plasma levels of BDNF increased more in the women in comparison with the men. ALA treatment could be a feasible approach to reduce size of infarcts in stroke patients. Thus, ALA could be used in adjunction with routine stroke therapies to minimize brain lesions caused by stroke.

  5. Metabolic engineering of Aspergillus oryzae NRRL 3488 for increased production of L-malic acid.

    PubMed

    Brown, Stephen H; Bashkirova, Lena; Berka, Randy; Chandler, Tyler; Doty, Tammy; McCall, Keith; McCulloch, Michael; McFarland, Sarah; Thompson, Sheryl; Yaver, Debbie; Berry, Alan

    2013-10-01

    Malic acid, a petroleum-derived C4-dicarboxylic acid that is used in the food and beverage industries, is also produced by a number of microorganisms that follow a variety of metabolic routes. Several members of the genus Aspergillus utilize a two-step cytosolic pathway from pyruvate to malate known as the reductive tricarboxylic acid (rTCA) pathway. This simple and efficient pathway has a maximum theoretical yield of 2 mol malate/mol glucose when the starting pyruvate originates from glycolysis. Production of malic acid by Aspergillus oryzae NRRL 3488 was first improved by overexpression of a native C4-dicarboxylate transporter, leading to a greater than twofold increase in the rate of malate production. Overexpression of the native cytosolic alleles of pyruvate carboxylase and malate dehydrogenase, comprising the rTCA pathway, in conjunction with the transporter resulted in an additional 27 % increase in malate production rate. A strain overexpressing all three genes achieved a malate titer of 154 g/L in 164 h, corresponding to a production rate of 0.94 g/L/h, with an associated yield on glucose of 1.38 mol/mol (69 % of the theoretical maximum). This rate of malate production is the highest reported for any microbial system.

  6. Ceramides increase the activity of the secretory phospholipase A2 and alter its fatty acid specificity.

    PubMed Central

    Koumanov, Kamen S; Momchilova, Albena B; Quinn, Peter J; Wolf, Claude

    2002-01-01

    Modulation of human recombinant secretory type II phospholipase A(2) activity by ceramide and cholesterol was investigated using model glycerophospholipid substrates composed of phosphatidylethanolamine and phosphatidylserine dispersed in aqueous medium. Enzyme activity was monitored by measurement of released fatty acids using capillary GC-MS. Fatty acids from the sn-2 position of the phospholipids were hydrolysed by the enzyme in proportion to the relative abundance of the phospholipid in the substrate. Addition of increasing amounts of ceramide to the substrate progressively enhanced phospholipase activity. The increased activity was accomplished largely by preferential hydrolysis of polyunsaturated fatty acids, particularly arachidonic acid, derived from phosphatidylethanolamine. The addition of sphingomyelin to the substrate glycerophospholipids inhibited phospholipase activity but its progressive substitution by ceramide, so as to mimic sphingomyelinase activity, counteracted the inhibition. The presence of cholesterol in dispersions of glycerophospholipid-substrate-containing ceramides suppressed activation of the enzyme resulting from the presence of ceramide. The molecular basis of enzyme modulation was investigated by analysis of the phase structure of the dispersed lipid substrate during temperature scans from 46 to 20 degrees C using small-angle synchrotron X-ray diffraction. These studies indicated that intermediate structures created after ceramide-dependent phase separation of hexagonal and lamellar phases represent the most susceptible form of the substrate for enzyme hydrolysis. PMID:11903045

  7. Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster.

    PubMed

    Mora, Marylhi; Medina-Leendertz, Shirley J; Bonilla, Ernesto; Terán, Raikelin E; Paz, Milagros C; Arcaya, José Luis

    2013-06-01

    In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 +/- 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

  8. Uric acid increases cellular and humoral alloimmunity in primary human peripheral blood mononuclear cells.

    PubMed

    Eleftheriadis, Theodoros; Pissas, Georgios; Sounidaki, Maria; Antoniadi, Georgia; Antoniadis, Nikolaos; Liakopoulos, Vassilios; Stefanidis, Ioannis

    2017-05-05

    Hyperuricemia is common among kidney transplant recipients and has been associated with worse graft outcome. Since episodes of acute cellular rejection and chronic humoral rejection contribute to decreased graft survival, in this study the effect of uric acid on cellular and humoral alloimmunity was evaluated. Cellular alloimmunity was assessed by cell proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method in which humoral alloimmunity was induced in one-way MLR. Then the de novo production of alloantibodies was measured with an antibody-mediated complement-dependent cytotoxicity assay, in which supernatants from the above MRLs were used against resting PBMC similar to the stimulator cells of the above MLRs. Uric acid at a concentration above its crystallization threshold increased cellular proliferation in two-way MLRs. Supernatants from one-way MLRs performed in the presence of uric acid were more cytotoxic against PBMC from individuals that had conferred the stimulator cells for the above MLRs. Uric acid increases both cellular and humoral alloimmunity in human PBMC. These results offer a possible pathogenetic mechanism for the observed relation between hyperuricemia and worse kidney allograft survival. This article is protected by copyright. All rights reserved.

  9. Artichoke extract lowered plasma cholesterol and increased fecal bile acids in Golden Syrian hamsters.

    PubMed

    Qiang, Zhiyi; Lee, Sun-Ok; Ye, Zhong; Wu, Xianai; Hendrich, Suzanne

    2012-07-01

    A study was conducted in hamsters to determine if artichoke leaf extract (ALE) could lower plasma total and non-HDL cholesterol by increasing fecal excretion of neutral bile acids and sterols. Sixty-four Golden Syrian hamsters (8 week old) were fed control diet or a similar diet containing ALE (4.5 g/kg diet) for 6 weeks. No significant changes for total cholesterol, HDL, non-HDL cholesterol triglycerides or fecal neutral sterols and bile acids were found after 21 days for ALE-fed animals compared with controls. But after 42 days, ALE-fed male hamsters had significantly lower total cholesterol (15%), non-HDL cholesterol (30%) and triglycerides (22%) and female hamsters fed ALE showed reductions of 15% for total cholesterol, 29% for non-HDL cholesterol and 29% for triglycerides compared with controls. Total neutral sterol and bile acids concentrations increased significantly by 50% and 53% in fecal samples of ALE fed males, and 82.4% and 25% in ALE fed females compared with controls. The ALE lowered hamster plasma cholesterol levels by a mechanism involving the greater excretion of fecal bile acids and neutral sterols after feeding for 42 days. Copyright © 2011 John Wiley & Sons, Ltd.

  10. Purification of the Major Soybean Leaf Acid Phosphatase That Is Increased by Seed-Pod Removal.

    PubMed Central

    Staswick, P. E.; Papa, C.; Huang, J. F.; Rhee, Y.

    1994-01-01

    Fruit removal for 5 weeks after flowering increased acid phosphatase activity 10-fold in soybean (Glycine max L. Merr. Var Hobbit) leaves compared with normal seed-pod-bearing plants. The major acid phosphatase activity in leaves was purified over 2700-fold, yielding a single polypeptide of 51 kD with a specific activity of 1353 units/mg protein using p-nitrophenylphosphate as the substrate. Isoelectric focusing demonstrated that the purified protein co-migrated with a majority of the activity that increased in leaves following seed-pod removal. Immunoblot analysis demonstrated that at least part of the increased activity was due to an increased abundance of the phosphatase protein. In situ enzyme activity staining localized most of the total phosphatase activity to vascular tissues, the leaf paraveinal mesophyll cell layer, and the lower epidermis. This distribution and the response to seed-pod removal paralleled previous results for soybean vegetative storage protein (VSP) [alpha] and [beta]. However, in a native polyacrylamide gel the VSP detected by immunological staining of electrophoretically transferred protein did not migrate with the majority of the phosphatase activity. Fractionation of crude leaf protein on concanavalin A-Sepharose yielded a fraction containing 97% of the total VSP but only 0.1% of the total acid phosphatase activity. PMID:12232060

  11. Increasing ursodeoxycholic acid in the enterohepatic circulation of pigs through the administration of living bacteria.

    PubMed

    Lepercq, Pascale; Hermier, Dominique; David, Olivier; Michelin, Rachel; Gibard, Clotilde; Beguet, Fabienne; Relano, Purification; Cayuela, Chantal; Juste, Catherine

    2005-04-01

    We investigated the feasibility of increasing ursodeoxycholic acid (UDCA) in the enterohepatic circulation of pigs by administering living bacteria capable of epimerising endogenous amidated chenodeoxycholic acid (CDCA) to UDCA. We first demonstrated that combining Bifidobacterium animalis DN-173 010, as a bile salt-hydrolysing bacterium, and Clostridium absonum ATCC 27555, as a CDCA to UDCA epimerising bacterium, led to the efficient epimerisation of glyco- and tauro-CDCA in vitro, with respective UDCA yields of 55.8 (SE 2.8) and 36.6 (SE 1.5)%. This strain combination was then administered to hypercholesterolaemic pigs over a 3-week period, as two daily preprandial doses of either viable (six experimental pigs) or heat-inactivated bacteria (six controls). The main effects of treatment were on unconjugated bile acids (P=0.035) and UDCA (P<0.0001) absorbed into the portal vein, which increased 1.6-1.7- and 3.5-7.5-fold, respectively, under administration of living compared with inactivated bacteria. In bile, UDCA did not increase significantly, but the increase in biliary lithocholic acid with time in the controls was not observed in the experimental pigs (P=0.007), and the same trend was observed in faeces. All other variables (biliary lipid equilibrium, plasma lipid levels and partition of cholesterol between the different lipoprotein classes) remained unaffected by treatment throughout the duration of the experiment. In conclusion, it is feasible to increase the bioavailability of UDCA to the intestine and the liver by administering active bacteria. This may represent an interesting new probiotic activity, provided that in future it could be expressed by a safe food micro-organism.

  12. Acidic pH increases airway surface liquid viscosity in cystic fibrosis

    PubMed Central

    Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  13. Fortification of Ogi with Whey Increases Essential Amino Acids Content of Fortified Product

    PubMed Central

    Omole, J. O.; Durosinolorun, O.

    2017-01-01

    The inability of humans to synthesize essential amino acids (EAA) necessitates the need to increase the levels of these nutrient molecules in certain foods in which they are deficient. Maize ogi is a typical food product for both infants and adults in Africa, but with poor EAA content. This study therefore sought to assess the possibility of increasing the EAA content in maize ogi by processing it with cheese whey instead of water. Maize ogi and whey-fortified ogi were prepared by the usual procedure of grain soaking, milling, and drying. Samples from both treatments were subjected to proximate composition and amino acid profile analyses using Waters 616/626 LC (HPLC) instrument. L-lysine, L-trytophan, and L-methionine contents in maize ogi remarkably increased from 0.52, 0.15, and 0.90 mg/100 gm sample, respectively, to 0.90, 240, and 1.320 mg/100 gm sample in whey-fortified ogi. There were also significant increases in other EAA contents of whey-fortified ogi relative to its counterpart (normal maize ogi). The sum increase in EAA contents (9,405 mg) correlates with the increase in protein (1 gm) per gram sample. This study demonstrates that cheese whey increases EAA content in maize ogi and suggests that whey-fortified maize ogi may be a preferred alternative to water processed maize ogi. PMID:28848803

  14. Fortification of Ogi with Whey Increases Essential Amino Acids Content of Fortified Product.

    PubMed

    Omole, J O; Ighodaro, O M; Durosinolorun, O

    2017-01-01

    The inability of humans to synthesize essential amino acids (EAA) necessitates the need to increase the levels of these nutrient molecules in certain foods in which they are deficient. Maize ogi is a typical food product for both infants and adults in Africa, but with poor EAA content. This study therefore sought to assess the possibility of increasing the EAA content in maize ogi by processing it with cheese whey instead of water. Maize ogi and whey-fortified ogi were prepared by the usual procedure of grain soaking, milling, and drying. Samples from both treatments were subjected to proximate composition and amino acid profile analyses using Waters 616/626 LC (HPLC) instrument. L-lysine, L-trytophan, and L-methionine contents in maize ogi remarkably increased from 0.52, 0.15, and 0.90 mg/100 gm sample, respectively, to 0.90, 240, and 1.320 mg/100 gm sample in whey-fortified ogi. There were also significant increases in other EAA contents of whey-fortified ogi relative to its counterpart (normal maize ogi). The sum increase in EAA contents (9,405 mg) correlates with the increase in protein (1 gm) per gram sample. This study demonstrates that cheese whey increases EAA content in maize ogi and suggests that whey-fortified maize ogi may be a preferred alternative to water processed maize ogi.

  15. Acidic pH increases airway surface liquid viscosity in cystic fibrosis.

    PubMed

    Tang, Xiao Xiao; Ostedgaard, Lynda S; Hoegger, Mark J; Moninger, Thomas O; Karp, Philip H; McMenimen, James D; Choudhury, Biswa; Varki, Ajit; Stoltz, David A; Welsh, Michael J

    2016-03-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3- concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF.

  16. Increasing erucic acid content through combination of endogenous low polyunsaturated fatty acids alleles with Ld-LPAAT + Bn-fae1 transgenes in rapeseed (Brassica napus L.).

    PubMed

    Nath, Ujjal K; Wilmer, Jeroen A; Wallington, Emma J; Becker, Heiko C; Möllers, Christian

    2009-02-01

    High erucic acid rapeseed (HEAR) oil is of interest for industrial purposes because erucic acid (22:1) and its derivatives are important renewable raw materials for the oleochemical industry. Currently available cultivars contain only about 50% erucic acid in the seed oil. A substantial increase in erucic acid content would significantly reduce processing costs and could increase market prospects of HEAR oil. It has been proposed that erucic acid content in rapeseed is limited because of insufficient fatty acid elongation, lack of insertion of erucic acid into the central sn-2 position of the triaclyglycerol backbone and due to competitive desaturation of the precursor oleic acid (18:1) to linoleic acid (18:2). The objective of the present study was to increase erucic content of HEAR winter rapeseed through over expression of the rapeseed fatty acid elongase gene (fae1) in combination with expression of the lysophosphatidic acid acyltransferase gene from Limnanthes douglasii (Ld-LPAAT), which enables insertion of erucic acid into the sn-2 glycerol position. Furthermore, mutant alleles for low contents of polyunsaturated fatty acids (18:2 + 18:3) were combined with the transgenic material. Selected transgenic lines showed up to 63% erucic acid in the seed oil in comparison to a mean of 54% erucic acid of segregating non-transgenic HEAR plants. Amongst 220 F(2) plants derived from the cross between a transgenic HEAR line and a non-transgenic HEAR line with a low content of polyunsaturated fatty acids, recombinant F(2) plants were identified with an erucic acid content of up to 72% and a polyunsaturated fatty acid content as low as 6%. Regression analysis revealed that a reduction of 10% in polyunsaturated fatty acids content led to a 6.5% increase in erucic acid content. Results from selected F(2) plants were confirmed in the next generation by analysing F(4) seeds harvested from five F(3) plants per selected F(2) plant. F(3) lines contained up to 72% erucic acid and

  17. [Comparative study of the increase in acid solubility resistance of enamel using different fluoride treatments].

    PubMed

    Rodríguez Miro, M J; Gallego Rodríguez, J; Elías Avila, L; Albuerne Dihigo, R; Alfonso Laguárdia, D

    1988-01-01

    This investigation was performed to evaluate, comparatively, the effect of topical application of Duraphat, Flulak, Fluor-Protector, Bifluorid 12, Profilac, Fluoro-gel-P and Fluocal-gel. Colorimetric technique was used for such purposes. It was found that 67.5% of 283 children treated with those different treatments increased their enamel resistance to acid dissolution, although notable differences were found in the use of these products. Average of increase ranged between 10.7 and 23.5%. Lacs and varnishes provide best results than gels with regard to acid dissolution rate of enamel. Behave of the two national products evaluated (Flulak and Profilac) was similar to the rest of lacs and varnishes, justifying their use at national level for the prevention of caries, avoiding in that way unnecessary importations.

  18. Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep.

    PubMed

    Gadhia, Monika M; Maliszewski, Anne M; O'Meara, Meghan C; Thorn, Stephanie R; Lavezzi, Jinny R; Limesand, Sean W; Hay, William W; Brown, Laura D; Rozance, Paul J

    2013-02-15

    Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10-14 days during late gestation to target a 25-50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group (P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) (P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. β-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group (P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing late-gestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased β-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the β-cell. This may be enhanced by the paracrine action of glucagon on the β-cell.

  19. Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep

    PubMed Central

    Gadhia, Monika M.; Maliszewski, Anne M.; O'Meara, Meghan C.; Thorn, Stephanie R.; Lavezzi, Jinny R.; Limesand, Sean W.; Hay, William W.; Brown, Laura D.

    2013-01-01

    Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10–14 days during late gestation to target a 25–50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group (P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) (P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. β-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group (P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing late-gestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased β-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the β-cell. This may be enhanced by the paracrine action of glucagon on the β-cell. PMID:23211516

  20. Humic substances increase survival of freshwater shrimp Caridina sp. D to acid mine drainage.

    PubMed

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2013-02-01

    Humic substances (HS) are known to decrease the toxicity of heavy metals to aquatic organisms, and it has been suggested that they can provide buffering protection in low pH conditions. Despite this, little is known about the ability for HS to increase survival to acid mine drainage (AMD). In this study, the ability of HS to increase survival of the freshwater shrimp (Caridina sp. D sensu Page et al. in Biol Lett 1:139-142, 2005) to acid mine drainage was investigated using test waters collected from the Mount Morgan open pit in Central Queensland with the addition of Aldrich humic acid (AHA). The AMD water from the Mount Morgan open pit is highly acidic (pH 2.67) as well as contaminated with heavy metals (1780 mg/L aluminum, 101 mg/L copper [Cu], 173 mg/L manganese, 51.8 mg/L zinc [Zn], and 51.8 mg/L iron). Freshwater shrimp were exposed to dilutions in the range of 0.5 % to 5 % AMD water with and without the addition of 10 or 20 mg/L AHA. In the absence of HS, all shrimp died in the 2.5 % AMD treatment. In contrast, addition of HS increased survival in the 2.5 % AMD treatment by ≤66 % as well as significantly decreased the concentration of dissolved Cu, cobalt, cadmium, and Zn. The decreased toxicity of AMD in the presence of HS is likely to be due to complexation and precipitation of heavy metals with the HS; it is also possible that HS caused changes to the physiological condition of the shrimp, thus increasing their survival. These results are valuable in contributing to an improved understanding of potential role of HS in ameliorating the toxicity of AMD environments.

  1. Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine-induced seizures.

    PubMed

    Ferhat, Lotfi; Esclapez, Monique; Represa, Alfonso; Fattoum, Abdellatif; Shirao, Tomoaki; Ben-Ari, Yezekiel

    2003-01-01

    We have previously shown that, in HEK 293 cells, overexpression of acidic calponin, an actin-binding protein, induces remodeling of actin filaments, leading to a change in cell morphology. In addition, this protein is found in dendritic spines of adult hippocampal neurons. We hypothesized that this protein plays a role in regulating actin-based filaments during dendritic spine plasticity. To assess this hypothesis, the pilocarpine model of temporal lobe epilepsy was selected because an important reorganization of the glutamatergic network, which includes an aberrant sprouting of granule cell axons, neo-synaptogenesis, and dendritic spine remodeling, is well established in the dentate gyrus. This reorganization begins after the initial period of status epilepticus after pilocarpine injection, during the silent period when animals display a normal behavior, and reaches a plateau at the chronic stage when the animals have developed spontaneous recurrent seizures. Our data show that the intensity of immunolabeling for acidic calponin was clearly increased in the inner one-third of the molecular layer of the dentate gyrus, the site of mossy fiber sprouting, and neo-synaptogenesis, at 1 and 2 weeks after pilocarpine injection (silent period) when the reorganization was taking place. In contrast, in chronic pilocarpine-treated animals, when the reorganization was established, the levels of labeling for acidic calponin in the inner molecular layer were similar to those observed in control rats. In addition, double immunostaining studies suggested that the increase in acidic calponin levels occurred within the dendritic spines. Altogether, these results are consistent with an involvement of acidic calponin in dendritic spine plasticity.

  2. Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

    PubMed Central

    Brose, Stephen A.; Golovko, Svetlana A.; Golovko, Mikhail Y.

    2016-01-01

    Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on NADH2+/NAD+ and NADPH2+/NADP+ ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased NADH2+/NAD+ and NADPH2+/NADP+ ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke. PMID:27965531

  3. Effects of small temperature increase and subchronic acid stress on juvenile rainbow trout during winter

    SciTech Connect

    D`Cruz, L.M.; Morgan, I.J.; Wood, C.M.

    1995-12-31

    Increasing water temperatures, as predicted by global warming are potentially problematic to freshwater fish, whose body temperature is set by their environment. In addition, fish living in softwater lakes face the detrimental effects of acid rain. To determine the cost of living in a warmer climate, two ninety day exposures were conducted during the winter in softwater. In the first exposure, fish were fed to satiation twice daily, while in the second exposure, fish were fed 1% of their wet body weight every four days. Monthly sampling was conducted to determine while body energy reserves: protein, lipids and carbohydrates, and changes in plasma Na and Cl concentrations. Oxygen consumption and nitrogen waste excretion rates were also measured. Fish exposed to acid and fed to satiation showed no ionoregulatory disturbances, an atypical result. Moreover, fish exposed to pH 5.2 had increased appetites, resulting in increased growth. In comparison, fish in the second exposure that were fed a limited ration and exposed to pH 5.2 had a greater mortality rate and lower plasma Na and Cl concentrations, with greater detrimental effects observed in fish exposed to +2 C above ambient. The findings suggest that NaCl present in commercial fish food may compensate for bronchial ion loss during acid exposure, as a result of a stimulation of appetite.

  4. Increasing Fatty Acid Oxidation Remodels the Hypothalamic Neurometabolome to Mitigate Stress and Inflammation

    PubMed Central

    McFadden, Joseph W.; Aja, Susan; Li, Qun; Bandaru, Veera V. R.; Kim, Eun-Kyoung; Haughey, Norman J.; Kuhajda, Francis P.; Ronnett, Gabriele V.

    2014-01-01

    Modification of hypothalamic fatty acid (FA) metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO) from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1) and fatty acid oxidation (FAOx), exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK) in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS), and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism. PMID:25541737

  5. Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

    PubMed

    van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

    2016-07-01

    Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

  6. Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea.

    PubMed

    Camilleri, Michael; Busciglio, Irene; Acosta, Andres; Shin, Andrea; Carlson, Paula; Burton, Duane; Ryks, Michael; Rhoten, Deborah; Lamsam, Jesse; Lueke, Alan; Donato, Leslie J; Zinsmeister, Alan R

    2014-10-01

    Approximately 25% of patients with irritable bowel syndrome-diarrhea (IBS-D) have increased total fecal bile acids (BA) and serum C4 (surrogate for BA synthesis). BA synthesis-related genes (KLB and FGFR4) are associated with colonic transit (CT) in IBS-D. Our aims were: (i) to compare phenotype and pathophysiology in IBS-D patients with increased or normal fecal excretion or synthesis of BA; and (ii) to explore association of variations in two candidate bile-acid synthesis genes (KLB and FGFR4) in these two subgroups of IBS-D. A total of 64 IBS-D patients underwent on one occasion: fasting serum C4 and FGF19, total fecal fat and BA excretion, CT, intestinal and colonic permeability, and candidate genotyping (rs17618244 (KLB), rs351855 (FGFR4)). Colonic sensation and tone were measured in 47 of the IBS-D patients. IBS-D subgroups were identified by fecal BA >2,337 mM per 48 h or by serum C4 >47.1 ng/ml. IBS-D patients with fecal BA >2,337 mM per 48 h (19/54) had significantly greater body mass index, fecal fat, percent chenodeoxycholic acid (CDCA) in feces, and intestinal permeability, and borderline increased CT (P=0.13). Those IBS-D patients with serum C4 >47.1 ng/ml (13/54) had increased total fecal BA excretion and borderline increased colonic permeability. Variants in genes involved in feedback regulation of BA synthesis (KLB, P=0.06 and FGFR4, P=0.09) were potentially associated with the subgroup with elevated serum C4. IBS-D with increased BA excretion or synthesis is associated with significant pathophysiological changes relative to patients with normal BA profile. BA diarrhea is identified more effectively with total fecal BA than with serum C4.

  7. Lignosulfonic acid promotes hypertrophy in 3T3-L1 cells without increasing lipid content and increases their 2-deoxyglucose uptake

    PubMed Central

    Hasegawa, Yasushi; Nakagawa, Erina; Kadota, Yukiya; Kawaminami, Satoshi

    2017-01-01

    Objective Adipose tissue plays a key role in the development of obesity and diabetes. We previously reported that lignosulfonic acid suppresses the rise in blood glucose levels through the inhibition of α-glucosidase activity and intestinal glucose absorption. The purpose of this study is to examine further biological activities of lignosulfonic acid. Methods In this study, we examined the effect of lignosulfonic acid on differentiation of 3T3-L1 cells. Results While lignosulfonic acid inhibited proliferation (mitotic clonal expansion) after induction of differentiation, lignosulfonic acid significantly increased the size of accumulated lipid droplets in the cells. Semi-quantitative reverse transcription polymerase chain reaction analysis showed that lignosulfonic acid increased the expression of the adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), leading to increased glucose transporter 4 (Glut-4) expression and 2-deoxyglucose uptake in differentiated 3T3-L1 cells. Additionally, feeding lignosulfonic acid to diabetic KK-Ay mice suppressed increase of blood glucose level. Conclusion Lignosulfonic acid may be useful as a functional anti-diabetic component of food. PMID:27383805

  8. Lignosulfonic acid promotes hypertrophy in 3T3-L1 cells without increasing lipid content and increases their 2-deoxyglucose uptake.

    PubMed

    Hasegawa, Yasushi; Nakagawa, Erina; Kadota, Yukiya; Kawaminami, Satoshi

    2017-01-01

    Adipose tissue plays a key role in the development of obesity and diabetes. We previously reported that lignosulfonic acid suppresses the rise in blood glucose levels through the inhibition of α-glucosidase activity and intestinal glucose absorption. The purpose of this study is to examine further biological activities of lignosulfonic acid. In this study, we examined the effect of lignosulfonic acid on differentiation of 3T3-L1 cells. While lignosulfonic acid inhibited proliferation (mitotic clonal expansion) after induction of differentiation, lignosulfonic acid significantly increased the size of accumulated lipid droplets in the cells. Semi-quantitative reverse transcription polymerase chain reaction analysis showed that lignosulfonic acid increased the expression of the adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), leading to increased glucose transporter 4 (Glut-4) expression and 2-deoxyglucose uptake in differentiated 3T3-L1 cells. Additionally, feeding lignosulfonic acid to diabetic KK-Ay mice suppressed increase of blood glucose level. Lignosulfonic acid may be useful as a functional anti-diabetic component of food.

  9. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    PubMed

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid.

  10. Dietary fatty acid enrichment increases egg size and quality of yellow seahorse Hippocampus kuda.

    PubMed

    Saavedra, M; Masdeu, M; Hale, P; Sibbons, C M; Holt, W V

    2014-02-01

    Seahorses populations in the wild have been declining and to restore them a better knowledge of seahorse reproduction is required. This study examines the effect of dietary quality on seahorse fecundity and egg quality. Two different diets were tested with Hippocampus kuda females: frozen mysis (control) and frozen mysis enriched with a liposome spray containing essential fatty acids. Diets were given to females (two groups of five) over a seven week period. After this period, males (fed the control diet) and females were paired and the eggs dropped by the females were collected. Fatty acid profile were analysed and eggs were counted and measured. Results showed that females fed on enriched mysis had larger eggs and that these had a higher content of total polyunsaturated fatty acids. The size of the egg was especially affected in the first spawn, where egg size for females fed the enriched diet was significantly higher than the egg size from control females. This effect was reduced in the following spawning where no significant differences were found. Egg size is an important quality descriptor as seahorse juveniles originating from smaller eggs and/or eggs of poor quality will have less chances of overcoming adverse conditions in the wild and consequently have lower survival and growth rates. This study shows that enriching frozen mysis with polyunsaturated fatty acids increases egg size and egg quality of H. kuda.

  11. Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells

    PubMed Central

    Armstrong, J L; Ruiz, M; Boddy, A V; Redfern, C P F; Pearson, A D J; Veal, G J

    2005-01-01

    Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the key mechanism underlying the favourable clinical properties of 13-cis retinoic acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism is thought to contribute to resistance, and strategies to modulate this may increase the clinical efficacy of 13cisRA. The aim of this study was to test the hypothesis that retinoids, such as acitretin, which bind preferentially to cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the RA hydroxylase CYP26, such as R116010, can increase the intracellular availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 μM) or R116010 (1 or 10 μM) in combination with either 10 μM ATRA or 13cisRA induced a selective increase in intracellular levels of ATRA, while 13cisRA levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1. The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma. PMID:15714209

  12. Dietary n-3 polyunsaturated fatty acids increase oxidative stress in rats with intracerebral hemorrhagic stroke.

    PubMed

    Park, Yongsoon; Nam, Somyoung; Yi, Hyeong-Joong; Hong, Hyun-Jong; Lee, Myoungsook

    2009-11-01

    Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.

  13. Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats.

    PubMed

    Toufektsian, Marie-Claire; Salen, Patricia; Laporte, François; Tonelli, Chiara; de Lorgeril, Michel

    2011-01-01

    Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 μL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.

  14. Mechanisms of p-methoxycinnamic acid-induced increase in insulin secretion.

    PubMed

    Adisakwattana, S; Hsu, W H; Yibchok-anun, S

    2011-10-01

    p-Methoxycinnamic acid (p-MCA) is a cinnamic acid derivative that shows various pharmacologic actions such as hepatoprotective and antihyperglycemic activities. The present study was to elucidate the mechanisms by which p-MCA increases [Ca²⁺]i and insulin secretion in INS-1 cells. p-MCA (100 μM) increased [Ca²⁺]i in INS-1 cells. The p-MCA-induced insulin secretion and rise in [Ca²⁺]i were markedly inhibited in the absence of extracellular Ca²⁺ or in the presence of an L-type Ca²⁺ channel blocker nimodipine. These results suggested that p-MCA increased Ca²⁺ influx via the L-type Ca²⁺ channels. Diazoxide, an ATP-sensitive K⁺ channel opener, did not alter p-MCA-induced insulin secretion, nor [Ca²⁺]i response. In addition, p-MCA enhanced glucose-, glibenclamide-induced insulin secretion whereas it also potentiated the increase in insulin secretion induced by arginine, and Bay K 8644, an L-type Ca²⁺ channel agonist. Taken together, our results suggest that p-MCA stimulated insulin secretion from pancreatic β-cells by increasing Ca²⁺ influx via the L-type Ca²⁺ channels, but not through the closure of ATP-sensitive K⁺ channels.

  15. Efficient increase of ɣ-aminobutyric acid (GABA) content in tomato fruits by targeted mutagenesis.

    PubMed

    Nonaka, Satoko; Arai, Chikako; Takayama, Mariko; Matsukura, Chiaki; Ezura, Hiroshi

    2017-08-01

    γ-Aminobutyric acid (GABA) is a non-proteinogenic amino acid that has hypotensive effects. Tomato (Solanum lycopersicum L.) is among the most widely cultivated and consumed vegetables in the world and contains higher levels of GABA than other major crops. Increasing these levels can further enhance the blood pressure-lowering function of tomato fruit. Glutamate decarboxylase (GAD) is a key enzyme in GABA biosynthesis; it has a C-terminal autoinhibitory domain that regulates enzymatic function, and deleting this domain increases GAD activity. The tomato genome has five GAD genes (SlGAD1-5), of which two (SlGAD2 and SlGAD3) are expressed during tomato fruit development. To increase GABA content in tomato, we deleted the autoinhibitory domain of SlGAD2 and SlGAD3 using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9 technology. Introducing a stop codon immediately before the autoinhibitory domain increased GABA accumulation by 7 to 15 fold while having variable effects on plant and fruit size and yield. This is the first study describing the application of the CRISPR/Cas9 system to increase GABA content in tomato fruits. Our findings provide a basis for the improvement of other types of crop by CRISPR/Cas9-based genetic modification.

  16. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids.

    PubMed

    Lachmandas, Ekta; van den Heuvel, Corina N A M; Damen, Michelle S M A; Cleophas, Maartje C P; Netea, Mihai G; van Crevel, Reinout

    2016-01-01

    Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.

  17. Inhibition by apomorphine of the metoclopramide-induced catalepsy and increase in striatal homovanillic acid content.

    PubMed Central

    Ahtee, L

    1975-01-01

    1 The mechanism of the cataleptic effect of metoclopramide was analyzed by using drugs which alter the activity of dopaminergic or cholinergic neurones or the content of psi-aminobutyric acid in the central nervous system of rats. 2 The cataleptic effect of metoclopramide (20 mg/kg) was antagonized by apomorphine (10 mg/kg) and by atropine (50 mg/kg). Aminoxyacete acid (AOAA, 25-50 mg/kg) potentiated the catalepsy induced by metoclopramide (5 mg/kg). 3 Metoclopramide alone did not alter the rectal temperature of rats. It did not alter the AOAA-induced hypothermia, but it partially antagonized apomorphine-induced hypothermia. 4 Metoclopramide induced a six-fold increase in striatal homovanillic acid (HVA) concentration, but it did not change the dopamine or noradrenaline content in the brain of rats. Apomorphine decreased the striatal HVA concentration in control and in metoclopramide-treated rats. Atropine and AOAA did not alter the metoclopramide-induced increase in striatal HVA concentration. 5 The results suggest that metoclopramide produces catalepsy by blocking striatal dopamine receptors. PMID:1239323

  18. D-tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration.

    PubMed

    Buemann, B; Toubro, S; Holst, J J; Rehfeld, J F; Bibby, B M; Astrup, A

    2000-08-01

    D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.

  19. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance.

    PubMed

    Yew Tan, Chong; Virtue, Samuel; Murfitt, Steven; Roberts, Lee D; Robert, Lee D; Phua, Yi Hui; Dale, Martin; Griffin, Julian L; Tinahones, Francisco; Scherer, Philipp E; Vidal-Puig, Antonio

    2015-12-17

    The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue.

  20. Twice-weekly consumption of farmed Atlantic salmon increases plasma content of phospholipid n-3 fatty acids

    USDA-ARS?s Scientific Manuscript database

    Elevated intake of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is related to risk reduction of cardiovascular and other diseases. Increased consumption of seafood such as farmed Atlantic salmon is an effective way to consume n-3 but there is a paucity of data as ...

  1. Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice

    PubMed Central

    Matsuoka, T; Adair, J E; Lih, F B; Hsi, L C; Rubino, M; Eling, T E; Tomer, K B; Yashiro, M; Hirakawa, K; Olden, K; Roberts, J D

    2010-01-01

    Background: Dietary (n-6)-polyunsaturated fatty acids influence cancer development, but the mechanisms have not been well characterised in gastric carcinoma. Methods: We used two in vivo models to investigate the effects of these common dietary components on tumour metastasis. In a model of experimental metastasis, immunocompromised mice were fed diets containing linoleic acid (LA) at 2% (LLA), 8% (HLA) or 12% (VHLA) by weight and inoculated intraperitoneally (i.p.) with human gastric carcinoma cells (OCUM-2MD3). To model spontaneous metastasis, OCUM-2MD3 tumours were grafted onto the stomach walls of mice fed with the different diets. In in vitro assays, we investigated invasion and ERK phosphorylation of OCUM-2MD3 cells in the presence or absence of LA. Finally, we tested whether a cyclooxygenase (COX) inhibitor, indomethacin, could block peritoneal metastasis in vivo. Results: Both the HLA and VHLA groups showed increased incidence of tumour nodules (LA: 53% HLA: 89% VHLA: 100% P<0.03); the VHLA group also displayed increased numbers of tumour nodules and higher total volume relative to LLA group in experimental metastasis model. Both liver invasion (78%) and metastasis to the peritoneal cavity (67%) were more frequent in VHLA group compared with the LLA group (22% and 11%, respectively; P<0.03) in spontaneous metastasis model. We also found that the invasive ability of these cells is greatly enhanced when exposed to LA in vitro. Linoleic acid also increased invasion of other scirrhous gastric carcinoma cells, OCUM-12, NUGC3 and MKN-45. Linoleic acid effect on OCUM-2MD3 cells seems to be dependent on phosphorylation of ERK. The data suggest that invasion and phosphorylation of ERK were dependent on COX. Indomethacin decreased the number of tumours and total tumour volume in both LLA and VHLA groups. Finally, COX-1, which is known to be an important enzyme in the generation of bioactive metabolites from dietary fatty acids, appears to be responsible for the

  2. Overexpression of PGC-1α Increases Peroxisomal and Mitochondrial Fatty Acid Oxidation in Human Primary Myotubes.

    PubMed

    Huang, Tai-Yu; Zheng, Donghai; Houmard, Joseph A; Brault, Jeffrey J; Hickner, Robert C; Cortright, Ronald N

    2017-01-10

    Peroxisomes are indispensable organelles for lipid metabolism in humans and their biogenesis has been assumed to be under regulation by peroxisome proliferator-activated receptors (PPARs). However, recent studies in hepatocytes suggest that the mitochondrial proliferator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) also acts as an upstream transcriptional regulator for enhancing peroxisomal abundance and associated activity. It is unknown whether the regulatory mechanism(s) for enhancing peroxisomal function is through the same node as mitochondrial biogenesis in human skeletal muscle (HSkM) and whether fatty acid oxidation (FAO) is affected. Primary myotubes from vastus lateralis biopsies from lean donors (BMI =24.0 ± 0.6 kg/m(2), N = 6) were exposed to adenovirus encoding human PGC-1α or GFP control. Peroxisomal biogenesis proteins (Peroxins) and genes (PEXs) responsible for proliferation and functions were assessed by western blotting and real-time qRT-PCR respectively. 1-(14)C palmitic acid and 1-(14)C lignoceric acid (exclusive peroxisomal specific substrate) were used to assess mitochondrial oxidation of peroxisomal derived metabolites. Following overexpression of PGC-1α, 1) Peroxisomal membrane protein 70kD (PMP70), PEX19, and mitochondrial citrate synthetase protein content were significantly elevated (P<0.05) 2) PGC-1α, PMP70, key PEXs, and peroxisomal β-oxidation mRNA expression levels were significantly upregulated (P<0.05) and 3) A concomitant increase in lignoceric acid oxidation by both peroxisomal and mitochondrial activity was observed (P<0.05). These novel findings demonstrate that, in addition to the proliferative effect on mitochondria, PGC-1α can induce peroxisomes and accompanying elevations in long-chain and very-long-chain fatty acid oxidation by a peroxisomal-mitochondrial functional cooperation as observed in HSkM cells.

  3. Increasing Soluble Phosphate Species by Treatment of Phosphate Rocks with Acidic Waste.

    PubMed

    Santos, Wedisson O; Hesterberg, Dean; Mattiello, Edson M; Vergütz, Leonardus; Barreto, Matheus S C; Silva, Ivo R; Souza Filho, Luiz F S

    2016-11-01

    The development of efficient fertilizers with a diminished environmental footprint will help meet the increasing demand for food and nutrients by a growing global population. Our objective was to evaluate whether an acidic mine waste (AMW) could be used beneficially by reacting it with sparingly soluble phosphate rocks (PRs) to produce more soluble P fertilizer materials. Three PRs from Brazil and Peru were reacted with different concentrations of AMW. Changes in mineralogy and P species were determined using a combination of X-ray diffraction and phosphorus K-edge XANES spectroscopy, in addition to extractable P concentrations. Increasing the AMW concentration typically increased extractable P. X-ray diffraction data showed transformation of apatite to other species when PRs were reacted with AMW at ≥50% (v/v) in water, with gypsum or anhydrite forming at AMW concentrations as low as 12.5%. Linear combination fitting analysis of X-ray absorption near edge structure spectra also indicated a progressive transformation of apatite to noncrystalline Fe(III)-phosphate and more soluble Ca-phosphates with increasing AMW concentration. Because this AMW is costly to dispose of, reacting it with PR to produce a higher-grade phosphate fertilizer material could decrease the environmental impacts of the AMW and diminish the consumption of pure acids in conventional P fertilizer production.

  4. Gallic acid induces HeLa cell death via increasing GSH depletion rather than ROS levels.

    PubMed

    Park, Woo Hyun

    2017-02-01

    Gallic acid (GA; 3,4,5-triphydroxyl-benzoic acid) is widely dispersed in various plants, fruits and foods and it shows various biological properties including anticancer effects. This study investigated the effects of GA on HeLa cervical cancer cells in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). GA dose-dependently inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC) at 24 or 72 h. The susceptibility of HeLa cells to GA was higher than that of HUVEC. GA induced apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). GA increased ROS levels including O2•- in HeLa cells at 24 h and it also induced GSH depletion. N-acetyl cysteine (NAC) increased the growth inhibition of GA-treated HeLa cells and enhanced the death of these cells. NAC differently influenced ROS levels in GA-treated HeLa cells and significantly increased GSH depletion in these cells. L-buthionine sulfoximine (BSO) increased MMP (∆ψm) loss, ROS levels and GSH depletion in GA-treated HeLa cells. In conclusion, GA significantly inhibited the growth of HeLa cells. GA-induced HeLa cell death was tightly related to GSH depletion rather than ROS level changes.

  5. Increased expression of fatty acid binding protein 4 in preeclamptic Placenta and its relevance to preeclampsia.

    PubMed

    Yan, Yuying; Peng, Huilian; Wang, Peng; Wang, Hanzhi; Dong, Minyue

    2016-03-01

    The aim of this investigation was to determine the expression of fatty acid binding protein 4 (FABP4) in the placenta from women with preeclampsia and normal pregnancy, and to delineate the regulatory effects on thophoblast cell by FABP4. We determined the expression of FABP4 by real-time polymerase chain reaction (PCR) for messenger ribonucleic acid (mRNA) or enzyme-linked immunesorbent assay (ELISA) and Western blotting for protein. Small interference of ribonucleic acid (siRNA) and specific FABP4 inhibitor were used to inhibit FABP4. The proliferation, migration and invasion of trophoblastic cells (Swan-71 and Jar) were evaluated with cell counting kit-8, wound-healing test and transwell analysis respectively. We found the expression of FABP4 was significantly higher in the placenta of preeclamptic women than that of women with normal pregnancy (t = 4.244, P < 0.001 for mRNA; t = 4.536, P < 0.001 for protein). FABP4 siRNA significantly reduced the proliferation of trophoblasts (P < 0.001). The specific inhibition of FABP4 inhibited the proliferation of trophoblasts in a dose-dependent manner (P < 0.001) and the inhibitory effect increased as the concentration of inhibitor increased. FABP4 siRNA and specific inhibitor significantly decreased the migration (P < 0.001) and invasion (P < 0.001) of trophoblasts. We concluded the increase in placental FABP4 expression in preeclampsia may affect the function of trophoblast, and this increase may have a role in the pathogenesis of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Reducing isozyme competition increases target fatty acid accumulation in seed triacylglycerols of transgenic Arabidopsis.

    PubMed

    van Erp, Harrie; Shockey, Jay; Zhang, Meng; Adhikari, Neil D; Browse, John

    2015-05-01

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on hydroxy fatty acids (HFAs) and conjugated polyenoic FAs (α-eleostearic acids [ESAs]) using Arabidopsis (Arabidopsis thaliana) as a model. These FAs are found naturally in seed oils of castor (Ricinus communis) and tung tree (Vernicia fordii), respectively, and used for the production of lubricants, nylon, and paints. Transgenic oils typically contain less target FA than that produced in the source species. We hypothesized that competition between endogenous and transgenic isozymes for substrates limits accumulation of unique FAs in Arabidopsis seeds. This hypothesis was tested by introducing a mutation in Arabidopsis diacylglycerol acyltransferase1 (AtDGAT1) in a line expressing castor FA hydroxylase and acyl-Coenzyme A:RcDGAT2 in its seeds. This led to a 17% increase in the proportion of HFA in seed oil. Expression of castor phospholipid:diacylglycerol acyltransferase 1A in this line increased the proportion of HFA by an additional 12%. To determine if our observations are more widely applicable, we investigated if isozyme competition influenced production of ESA. Expression of tung tree FA conjugase/desaturase in Arabidopsis produced approximately 7.5% ESA in seed lipids. Coexpression of VfDGAT2 increased ESA levels to approximately 11%. Overexpression of VfDGAT2 combined with suppression of AtDGAT1 increased ESA accumulation to 14% to 15%. Our results indicate that isozyme competition is a limiting factor in the engineering of unusual FAs in heterologous plant systems and that reduction of competition through mutation and RNA suppression may be a useful component of seed metabolic engineering strategies.

  7. Effect of increased protein intake on renal acid load and renal hemodynamic responses.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; van Baak, Marleen A

    2016-03-01

    Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function.

  8. Injection volumes of dextranomer/hyaluronic acid are increasing in the endoscopic management of vesicoureteral reflux.

    PubMed

    Sorensen, Mathew D; Koyle, Martin A; Cowan, Charles A; Zamilpa, Ismael; Shnorhavorian, Margarett; Lendvay, Thomas S

    2010-05-01

    Dextranomer/hyaluronic acid (Deflux) has been increasingly used for the treatment of vesicoureteral reflux (VUR). Experience has shown that injecting more volume of material is necessary to achieve greater success. We evaluate trends in the number of vials being used to treat VUR using a multi-institutional database and data from patients treated at our own institution. Children of age 0-19 years in the Pediatric Health Information System (PHIS) database from 2003 to 2008 were extracted with a VUR diagnosis (ICD-9 593.7x) and subureteric injection procedure code (CPT 52327). We identified children with reflux treated with endoscopic injection at Seattle Children's Hospital from 2005 to 2008. Hospital trends of the number of vials used were evaluated using multivariate linear regression. From 2003 to 2008, we identified 4,078 endoscopic injection procedures in PHIS. There was a 33% increase in the average number of vials used per patient (p < 0.0001) with more than a threefold increase in the number of patients receiving three or more vials per procedure. All institutions increased the average vials used per patient with the most pronounced increase at the highest-volume centers. These trends were also present in the 186 children treated at our own institution. Over the study period there was an increase in the number of vials of dextranomer/hyaluronic acid being used per patient to treat children with VUR. This practice may improve success rates but will increase the cost of treatment due to the inherent expense of the material.

  9. Organic amendments increase soil solution phosphate concentrations in an acid soil: A controlled environment study

    SciTech Connect

    Schefe, C.R.; Patti, A.F.; Clune, T.S.; Jackson, R.

    2008-04-15

    Soil acidification affects at least 4 million hectares of agricultural land in Victoria, Australia. Low soil pH can inhibit plant growth through increased soluble aluminum (Al) concentrations and decreased available phosphorus (P). The addition of organic amendments may increase P availability through competition for P binding sites, solubilization of poorly soluble P pools, and increased solution pH. The effect of two organic amendments (lignite and compost) on P solubility in an acid soil was determined through controlled environment (incubation) studies. Three days after the addition of lignite and compost, both treatments increased orthophosphate and total P measured in soil solution, with the compost treatments having the greatest positive effect. Increased incubation time (26 days) increased soil solution P concentrations in both untreated and amended soils, with the greatest effect seen in total P concentrations. The measured differences in solution P concentrations between the lignite- and compost-amended treatments were likely caused by differences in solution chemistry, predominantly solution pH and cation dynamics. Soil amendment with lignite or compost also increased microbial activity in the incubation systems, as measured by carbon dioxide respiration. Based on the results presented, it is proposed that the measured increase in soil solution P with amendment addition was likely caused by both chemical and biological processes, including biotic and abiotic P solubilization reactions, and the formation of soluble organic-metal complexes.

  10. Attempts to increase inosinic acid in broiler meat by using feed additives.

    PubMed

    Wang, X F; Liu, G H; Cai, H Y; Chang, W H; Ma, J S; Zheng, A J; Zhang, S

    2014-11-01

    To explore regulation of inosinic acid content in chicken meat as a result of feed additives, 576 one-day-old male Arbor Acres broilers were randomly allotted into 8 dietary treatments including control, purine nucleotide (P), betaine (B), soybean isoflavone (S), purine nucleotide + betaine (PB), purine nucleotide + soybean isoflavone (PS), betaine +soybean isoflavone (BS), and purine nucleotide + betaine + soybean isoflavone (PBS) by a 2 × 2 × 2 factorial arrangement. At d 42 of age, broilers were slaughtered, and growth performance, carcass characteristics, inosinic acid content, and activities of enzyme closely related to inosinic acid metabolism of broilers were measured. The results revealed that these feed additives did not affect ADG and ADFI of the broilers (P > 0.05). However, supplementing purine nucleotides lowered feed/gain of broilers in PS and PBS groups (P < 0.05). There was a significant interaction on feed/gain of broilers between purine nucleotides and soybean isoflavone (P < 0.05). The abdominal fat percentages in groups B, S, BS, and PBS were lower than the control group, respectively (P < 0.05). The thigh muscle percentages of groups P and B were higher than that of group PB (P < 0.05). There were certain interactions on the percentage of thigh muscle (P = 0.05) and abdominal fat (P < 0.05) between P, B, and S groups. Compared with the control group, inosinic acid content in broiler breast meat was improved by using feed additives (P < 0.05). Supplementing purine nucleotides, betaine, soybean isoflavone, and their combinations increased alkaline phosphatase activity in breast meat of broilers (P < 0.05). Purine nucleotides improved the activity of adenosine deaminase, but decreased the activity of 5'-nucleotidase. Soybean isoflavone lowered the activity of alkaline phosphatase. There were no significant interactions on activities of creatine kinase, adenosine deaminase, alkaline phosphatase, and 5'-nucleotidase between these additives (P > 0

  11. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    PubMed

    Kunkel, Steven D; Elmore, Christopher J; Bongers, Kale S; Ebert, Scott M; Fox, Daniel K; Dyle, Michael C; Bullard, Steven A; Adams, Christopher M

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  12. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    PubMed Central

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735

  13. Acetylsalicylic acid (ASA) increases the solubility of cholesterol when incorporated in lipid membranes.

    PubMed

    Alsop, Richard J; Barrett, Matthew A; Zheng, Songbo; Dies, Hannah; Rheinstädter, Maikel C

    2014-06-28

    Cholesterol has been well established as a mediator of cell membrane fluidity. By interacting with lipid tails, cholesterol causes the membrane tails to be constrained thereby reducing membrane fluidity, well known as the condensation effect. Acetylsalicylic acid (ASA), the main ingredient in aspirin, has recently been shown to increase fluidity in lipid bilayers by primarily interacting with lipid head groups. We used high-resolution X-ray diffraction to study both ASA and cholesterol coexisting in model membranes of dimyristoylphosphatidylcholine (DMPC). While a high cholesterol concentration of 40 mol% cholesterol leads to the formation of immiscible cholesterol bilayers, as was reported previously, increasing the amount of ASA in the membranes between 0 to 12.5 mol% was found to significantly increase the fluidity of the bilayers and dissolve the cholesterol plaques. We, therefore, present experimental evidence for an interaction between cholesterol and ASA on the level of the cell membrane at elevated levels of cholesterol and ASA.

  14. Short bouts of anaerobic exercise increase non-esterified fatty acids release in obesity.

    PubMed

    Salvadori, Alberto; Fanari, Paolo; Marzullo, Paolo; Codecasa, Franco; Tovaglieri, Ilaria; Cornacchia, Mauro; Brunani, Amelia; Luzi, Livio; Longhini, Erminio

    2014-02-01

    It is demonstrated that aerobic exercise plays an important role in weight loss programs for obesity by increasing 24 h metabolic rate. While aerobic exercise can result in health and fitness benefits in obese subjects, also independently of weight loss, not completely clear are the effects of bouts of hard exercise on metabolic outcomes. The aim of this study was to test the hypothesis that short-term aerobic activity with anaerobic bouts might result in a greater improvement in the management of obesity than aerobic activity alone. We studied 16 obese subjects (eight men) during a progressive cycloergometric test up to exhaustion, before and after 4 weeks of two different training schedules (6 days/week). Insulin and glycaemia, non-esterified fatty acids (NEFA) and lactic acid were sampled. Group A (eight subjects, four men) performed an aerobic cycle workout; Group B (eight subjects, four men) performed a 25 min aerobic workout followed by 5 min of anaerobic workout. All the subjects maintained their individual eating habits. The post-training test showed a decrease in AUCs NEFA in Group A (p < 0.05) and an increase in Group B (p < 0.05), together with an increase in lactic acid in Group A and a decrease in Group B (p < 0.01). β-cell function (HOMA2-B) revealed a reduction only in Group A (p < 0.05). Group B achieved a greatest reduction in body fat mass than Group A (p < 0.05). Aerobic plus anaerobic training seem to produce a greater response in lipid metabolism and not significant modifications in glucose indexes; then, in training prescription for obesity, we might suggest at starting weight loss program aerobic with short bouts of anaerobic training to reduce fat mass and subsequently a prolonged aerobic training alone to ameliorate the metabolic profile.

  15. Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.

    PubMed

    Guéant Rodriguez, R M; Spada, R; Pooya, S; Jeannesson, E; Moreno Garcia, M A; Anello, G; Bosco, P; Elia, M; Romano, A; Alberto, J M; Juillière, Y; Guéant, J L

    2013-08-10

    The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations. Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort. Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P<0.001). Subjects with homocysteine in the upper quartile (≥ 18 μmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 μmol/L), in both populations (P<0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate. This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Increased cis-to-trans urocanic acid ratio in the skin of chronic spontaneous urticaria patients.

    PubMed

    Pham, Duy Le; Lim, Kyung-Min; Joo, Kyung-Mi; Park, Hae-Sim; Leung, Donald Y M; Ye, Young-Min

    2017-05-02

    Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P < 0.05) and decreased in AD lesions (P < 0.01). The cis-to-trans-UCA ratio in SC specimens from CSU patients was significantly greater than those from AD and NC subjects. AD lesions had lower FBP and PCA contents compared to NC skin (both P < 0.001), and higher TEWL and pH compared to CSU lesions. Moreover, cis-UCA, but not trans-UCA, enhanced the IgE-mediated basophil activation, as well as IgE- and calcium-mediated degranulation of LAD-2 cells, in a dose-dependent manner. These findings suggest that increased cis-to-trans UCA ratio in the epidermis is a distinct feature of CSU, which could enhance mast cell degranulation. Modulation of cis-UCA may be a potential target for skin diseases associated with IgE-mediated mast cell degranulation.

  17. All-Trans Retinoic Acid Increases Aquaporin 3 Expression in Human Vaginal Epithelial Cells.

    PubMed

    Lee, Hyun-Suk; Kim, Sun-Ouck; Ahn, Kyuyoun; Park, Kwangsung

    2016-12-01

    Water channel aquaporin 3 (AQP3) is an aquaglyceroporin that transports small neutral solutes and water. All-trans retinoic acid (ATRA), a member of the retinoid drug class, acts as a regulator in several biological processes. To investigate the effect of ATRA on the expression of AQP3 in human vaginal epithelial cells. Human vaginal mucosal epithelial cells (CRL2616) were treated with ATRA 0, 0.01, 0.1, and 1 μmol/L for 24 hours to examine the dose-dependent effects of ATRA and with ATRA 1 μmol/L for 0, 3, 6, 12, and 24 hours. The expression of AQP3 and retinoic acid receptor (RAR) was determined by western blot analysis and reverse transcription polymerase chain reaction. AQP3 was detected in the cell membrane of human vaginal epithelial cells. ATRA increased the protein expression and mRNA levels of AQP3 in a dose-dependent manner (P < .05). ATRA also increased the protein expression of RARα (P < .05). Treatment of CRL2616 cells with an RAR antagonist (Ro 41-5253) significantly decreased AQP3 protein expression (P < .05). ATRA mediated by RARα increased AQP3 gene and protein expression in human vaginal mucosal epithelial cells. These results imply that AQP3 regulated by ATRA could play an important role in the mechanism of vaginal lubrication. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Biochar enhances Aspergillus niger rock phosphate solubilization by increasing organic acid production and alleviating fluoride toxicity.

    PubMed

    Mendes, Gilberto de Oliveira; Zafra, David Lopez; Vassilev, Nikolay Bojkov; Silva, Ivo Ribeiro; Ribeiro, José Ivo; Costa, Maurício Dutra

    2014-05-01

    During fungal rock phosphate (RP) solubilization, a significant quantity of fluoride (F(-)) is released together with phosphorus (P), strongly inhibiting the process. In the present study, the effect of two F(-) adsorbents [activated alumina (Al2O3) and biochar] on RP solubilization by Aspergillus niger was examined. Al2O3 adsorbed part of the F(-) released but also adsorbed soluble P, which makes it inappropriate for microbial RP solubilization systems. In contrast, biochar adsorbed only F(-) while enhancing phosphate solubilization 3-fold, leading to the accumulation of up to 160 mg of P per liter. By comparing the values of F(-) measured in solution at the end of incubation and those from a predictive model, it was estimated that up to 19 mg of F(-) per liter can be removed from solution by biochar when added at 3 g liter(-1) to the culture medium. Thus, biochar acted as an F(-) sink during RP solubilization and led to an F(-) concentration in solution that was less inhibitory to the process. In the presence of biochar, A. niger produced larger amounts of citric, gluconic, and oxalic acids, whether RP was present or not. Our results show that biochar enhances RP solubilization through two interrelated processes: partial removal of the released F(-) and increased organic acid production. Given the importance of organic acids for P solubilization and that most of the RPs contain high concentrations of F(-), the proposed solubilization system offers an important technological improvement for the microbial production of soluble P fertilizers from RP.

  19. The most primitive metazoan animals, the placozoans, show high sensitivity to increasing ocean temperatures and acidities.

    PubMed

    Schleicherová, Dáša; Dulias, Katharina; Osigus, Hans-Jűrgen; Paknia, Omid; Hadrys, Heike; Schierwater, Bernd

    2017-02-01

    The increase in atmospheric carbon dioxide (CO2) leads to rising temperatures and acidification in the oceans, which directly or indirectly affects all marine organisms, from bacteria to animals. We here ask whether the simplest-and possibly also the oldest-metazoan animals, the placozoans, are particularly sensitive to ocean warming and acidification. Placozoans are found in all warm and temperate oceans and are soft-bodied, microscopic invertebrates lacking any calcified structures, organs, or symmetry. We here show that placozoans respond highly sensitive to temperature and acidity stress. The data reveal differential responses in different placozoan lineages and encourage efforts to develop placozoans as a potential biomarker system.

  20. Increased production of free fatty acids in Aspergillus oryzae by disruption of a predicted acyl-CoA synthetase gene.

    PubMed

    Tamano, Koichi; Bruno, Kenneth S; Koike, Hideaki; Ishii, Tomoko; Miura, Ai; Umemura, Myco; Culley, David E; Baker, Scott E; Machida, Masayuki

    2015-04-01

    Fatty acids are attractive molecules as source materials for the production of biodiesel fuel. Previously, we attained a 2.4-fold increase in fatty acid production by increasing the expression of fatty acid synthesis-related genes in Aspergillus oryzae. In this study, we achieved an additional increase in the production of fatty acids by disrupting a predicted acyl-CoA synthetase gene in A. oryzae. The A. oryzae genome is predicted to encode six acyl-CoA synthetase genes and disruption of AO090011000642, one of the six genes, resulted in a 9.2-fold higher accumulation (corresponding to an increased production of 0.23 mmol/g dry cell weight) of intracellular fatty acid in comparison to the wild-type strain. Furthermore, by introducing a niaD marker from Aspergillus nidulans to the disruptant, as well as changing the concentration of nitrogen in the culture medium from 10 to 350 mM, fatty acid productivity reached 0.54 mmol/g dry cell weight. Analysis of the relative composition of the major intracellular free fatty acids caused by disruption of AO090011000642 in comparison to the wild-type strain showed an increase in stearic acid (7 to 26 %), decrease in linoleic acid (50 to 27 %), and no significant changes in palmitic or oleic acid (each around 20-25 %).

  1. The effect of transient increases in kynurenic acid and quinolinic acid levels early in life on behavior in adulthood: Implications for schizophrenia.

    PubMed

    Iaccarino, Hannah F; Suckow, Raymond F; Xie, Shan; Bucci, David J

    2013-11-01

    Kynurenic acid is a tryptophan metabolite that is synthesized and released in the brain by astrocytes and acts as an antagonist of nicotinic acetylcholine receptors and N-methyl-d-aspartate glutamate receptors, both of which are critically involved in cognition as well as neural plasticity and brain development. The concentration of kynurenic acid is increased in the brains of persons with schizophrenia and this increase has been implicated in the cognitive and social impairments associated with the disease. In addition, growing evidence suggests that the increase in kynurenic acid may begin early in life. For example, exposure to influenza A virus during development results in a transient increase in kynurenic acid concentration that could disrupt normal brain development and lead to cognitive deficits later in life. Changes in kynurenic acid may thus provide a link between developmental exposure to viruses and the increased risk of subsequently developing schizophrenia. To test this, we mimicked the effects of influenza A exposure by treating rats with kynurenine, the precursor of kynurenic acid, on postnatal days 7-10. We observed a transient increase in both kynurenic acid and quinolinic acid during treatment. When rats were subsequently behaviorally tested as adults, those previously treated with kynurenine exhibited decreased social behavior and locomotor activity. In contrast, attentional function and fear conditioning were not affected. Together with other recent findings, these data have several implications for understanding how viral-induced changes in tryptophan metabolism during development may contribute to schizophrenia-related symptoms later in life.

  2. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.

    PubMed

    Vuille-dit-Bille, Raphael N; Camargo, Simone M; Emmenegger, Luca; Sasse, Tom; Kummer, Eva; Jando, Julia; Hamie, Qeumars M; Meier, Chantal F; Hunziker, Schirin; Forras-Kaufmann, Zsofia; Kuyumcu, Sena; Fox, Mark; Schwizer, Werner; Fried, Michael; Lindenmeyer, Maja; Götze, Oliver; Verrey, François

    2015-04-01

    Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

  3. Saturated fatty acid intake can influence increase in plasminogen activator inhibitor-1 in obese adolescents.

    PubMed

    Masquio, D C L; de Piano, A; Campos, R M S; Sanches, P L; Corgosinho, F C; Carnier, J; Oyama, L M; do Nascimento, C M P O; de Mello, M T; Tufik, S; Dâmaso, A R

    2014-04-01

    The aim of this study was to verify if saturated fatty acid intake adjusted by tertiles can influence metabolic, inflammation, and plasminogen activator inhibitor-1 (PAI-1) in obese adolescents. Body mass, height, body mass index, waist circumference, blood pressure, and body composition of 108 obese adolescents were obtained. Fasting glucose, insulin, PAI-1, and CRP were determined. Insulin resistance was assessed by Homeostasis Model Assessment (HOMA-IR) and insulin sensitivity by Quantitative Insulin Sensitivity Check Index (QUICKI). Dietetic intake was estimated by a 3-day dietary record, and volunteers were divided according to consumption of saturated fatty acids: tertile 1 [Low Saturated Fatty Acid Intake (Low-SFA): ≤12.14 g], tertile 2 [Moderate Saturated Fatty Intake (Moderate SFA intake): 12.15-20.48 g], and tertile 3 [High Saturated Fatty Acid Intake (High-SFA Intake); >20.48 g]. Statistical analysis was performed using STATISTICA 7.0 software and the significance level was set at p<0.05. The most important finding in the present study is that Moderate and High-SFA intakes presented significantly higher values of PAI-1 than Low-SFA Intake. PAI-1 was positively associated with saturated fatty intake, waist circumference, mean blood pressure, and HOMA-IR. SFA intake was predictor of PAI-1 independent of body fat, HOMA-IR and total-cholesterol. In addition, PAI-1 was an independent predictor of blood pressure. HOMA-IR and QUICKI presented significantly higher and lower, respectively, in High-SFA compared to Moderate-SFA intake. High-SFA influenced cardiovascular disease risks, since it increased PAI-1 and insulin resistance, and decreased insulin sensibility, leading to vicious cycle among food ingestion, pro-thrombotic state, and cardiovascular risks in obese adolescents. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome.

    PubMed

    Sheedy, John R; Wettenhall, Richard E H; Scanlon, Denis; Gooley, Paul R; Lewis, Donald P; McGregor, Neil; Stapleton, David I; Butt, Henry L; DE Meirleir, Kenny L

    2009-01-01

    Patients with chronic fatigue syndrome (CFS) are affected by symptoms of cognitive dysfunction and neurological impairment, the cause of which has yet to be elucidated. However, these symptoms are strikingly similar to those of patients presented with D-lactic acidosis. A significant increase of Gram positive facultative anaerobic faecal microorganisms in 108 CFS patients as compared to 177 control subjects (p<0.01) is presented in this report. The viable count of D-lactic acid producing Enterococcus and Streptococcus spp. in the faecal samples from the CFS group (3.5 x 10(7) cfu/L and 9.8 x 10(7) cfu/L respectively) were significantly higher than those for the control group (5.0 x 10(6) cfu/L and 8.9 x 10(4) cfu/L respectively). Analysis of exometabolic profiles of Enterococcus faecalis and Streptococcus sanguinis, representatives of Enterococcus and Streptococcus spp. respectively, by NMR and HPLC showed that these organisms produced significantly more lactic acid (p<0.01) from (13)C-labeled glucose, than the Gram negative Escherichia coli. Further, both E. faecalis and S. sanguinis secrete more D-lactic acid than E. coli. This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptom expressions in a subgroup of patients with CFS. Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications.

  5. Phosphatidic acid increases intracellular free Ca2+ and cardiac contractile force.

    PubMed

    Xu, Y J; Panagia, V; Shao, Q; Wang, X; Dhalla, N S

    1996-08-01

    Although phosphatidic acid (PA) is mainly formed due to the hydrolysis of phosphatidylcholine by myocardial phospholipase D, its functional significance in the heart is not fully understood. The present study was designed to determine the effects of PA on intracellular free Ca2+ level ([Ca2+]i) in freshly isolated adult rat cardiomyocytes by using fura 2-acextoxmethylester and free fura 2 technique. Addition of PA at concentrations of 1-200 microM produced a concentration-dependent increase in [Ca2+]i from the basal level of 117 +/- 8 nM; maximal increase in [Ca2+]i was 233 +/- 50 nM, whereas median effective concentration (EC50) for PA was 45 +/- 1.2 microM. This increase in [Ca2+]i was abolished by the removal of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and was partially attenuated by Ca2+ channel blockers, verapamil or diltiazem. Preincubation of cardiomyocytes with cyclopiazonic acid and thapsigargin or with ryanodine [to deplete sarcoplasmic reticulum (SR) Ca2+] attenuated the PA-induced increase in [Ca2+]i by 66, 37, and 43%, respectively. Furthermore, the response of [Ca2+]i to PA was blunted by 2-nitro-4 carboxyphenylcarbonate, an inhibitor of phospholipase C, but was unaffected by staurosporine, a protein kinase C inhibitor. PA was also observed to induce Ca2+ efflux from the myocytes. In addition, an injection of PA (0.34 microgram/100 g body wt i.v.) in rats produced a significant increase of the left ventricular developed pressure as well as the maximum rates of cardiac contraction and relaxation within 5 min. These data suggest that the PA-induced increase in [Ca2+]i in cardiomyocytes is a consequence of both Ca2+ influx from the extracellular source and Ca2+ release from the intracellular SR stores. Furthermore, these in vitro data suggest the possibility that PA may regulate [Ca2+]i and contractile parameters in the heart.

  6. Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats.

    PubMed

    Zhao, Wei-Man; Jiang, Shu-Wen; Chen, Yang; Zhong, Ze-Yu; Wang, Zhong-Jian; Zhang, Mian; Li, Ying; Xu, Ping; Liu, Li; Liu, Xiao-Dong

    2015-07-01

    The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  7. Improvement of daptomycin production via increased resistance to decanoic acid in Streptomyces roseosporus.

    PubMed

    Lee, Sung-Kwon; Kim, Hong Rip; Jin, Ying-Yu; Yang, Seung Hwan; Suh, Joo-Won

    2016-10-01

    Daptomycin, a cyclic anionic lipopeptide compound produced by Streptomyces roseosporus, is used to treat skin infections caused by multi-drug resistant gram-positive pathogens. The biosynthesis of daptomycin is initiated by the condensation of decanoic acid (DA, a 10-carbon unit fatty acid) and the N-terminal l-tryptophan. So, the addition of DA to the fermentation medium is essential for increasing daptomycin production. However, increasing of DA concentration in the fermentation medium was not possible due to the high toxicity of DA. The previous studies reported that the cell growth of S. roseosporus was halted from 1 mM DA. In order to improve daptomycin production with increasing DA concentration in the medium, the DA-resistant S. roseosporus was developed via a sequential-adaptation method. The DA-resistant strain (DAR) showed complete resistance to 1 mM DA, and the daptomycin production was increased 1.4-fold (40.5 ± 0.7 mg/L) compared with the wild-type (28.5 ± 0.8 mg/L) at 1 mM DA. Additionally, the initial step of the daptomycin biosynthesis was enhanced by the overexpression of dptE and dptF in DAR. The dptEF overexpression DAR showed 3.9-fold (156.3 ± 8.2 mg/L) increase in the daptomycin production compared with DAR (40.1 ± 2.6 mg/L) at 1 mM DA.

  8. Banding of urea increased ammonia volatilization in a dry acidic soil.

    PubMed

    Rochette, Philippe; Macdonald, J Douglas; Angers, Denis A; Chantigny, Martin H; Gasser, Marc-Olivier; Bertrand, Normand

    2009-01-01

    Volatilization of ammonia following application of urea contributes to smog formation and degradation of natural ecosystems. The objective of this study was to evaluate the impact of (i) incorporation and banding of urea and (ii) surface broadcast of slow-release urea types on NH(3) volatilization in a dry acidic soil. Volatilization was measured using wind tunnels for 25 d after standard urea (140 kg N ha(-1)) was broadcast, broadcast and incorporated (0-5 cm), or incorporated in shallow bands (3-5 cm) to a conventionally tilled silty loam soil. Urea supplemented with a urease inhibitor or coated with a polymer was also broadcast at the soil surface. Little N diffused out of the polymer-coated granules and ammonia losses were low (4% of applied N). Use of a urease inhibitor also resulted in a low NH(3) loss (5% of applied N) while maintaining soil mineral N at levels similar to plots where untreated urea was broadcast. The rate of hydrolysis of urea broadcast at the soil surface was slowed by the lack of moisture and NH(3) loss (9% applied N) was the lowest of all treatments with standard urea. Incorporation of broadcast urea increased emissions (16% applied N) by increasing urea hydrolysis relative to surface application. Furthermore, incorporation in band also increased emissions (27% applied N) due to a localized increase in soil pH from 6.0 to 8.7. We conclude that incorporating urea in bands in a dry acidic soil can increase NH(3) volatilization compared to broadcast application followed by incorporation.

  9. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    SciTech Connect

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. )

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  10. Acidic pH increases the avidity of FcγR for immune complexes

    PubMed Central

    López, D H; Trevani, A S; Salamone, G; Andonegui, G; Raiden, S; Giordano, M; Geffner, J R

    1999-01-01

    The interaction of immunoglobulin G (IgG) antibodies with FcγR constitutes a critical mechanism through which IgG antibody effector functions are mediated. In the current work we have examined whether human neutrophil FcγR exhibit pH dependence in their association with IgG. Binding assays were performed in culture medium adjusted to different pH values. It was found that the binding of either heat‐aggregated human IgG (AIgG), soluble immune complexes (sIC) or IgG‐coated erythrocytes (IgG‐E) was markedly higher at pH 6·5 than at pH 7·3. This effect was not observed when saturation of FcγR was achieved, suggesting that acidic pH increases the avidity of FcγR for IC without modifying the total binding capacity. Similar results were observed for the binding of AIgG to either monocytes, natural killer (NK) or K562 cells, suggesting that acidic pH increases the avidity of both, FcγRII and FcγRIII. Additional experiments were performed to analyse whether the binding of IgG to FcγRI also showed pH dependence. To this aim, we employed interferon‐γ‐treated human neutrophils and mouse inflammatory macrophages, previously incubated with blocking antibodies directed to FcγRII and FcγRIII. Acidic pH did not enhance the binding of AIgG nor monomeric IgG under these experimental conditions. Further studies are required to determine whether the enhancement of FcγR avidity for IC could be attributed to titration of histidine(s) residues on the Fc fragment of IgG. PMID:10583607

  11. Effect of increased methionine level on performance and apparent ileal digestibility of amino acids in ducks.

    PubMed

    Jamroz, D; Wiliczkiewicz, A; Lemme, A; Orda, J; Skorupińska, J; Wertelecki, T

    2009-10-01

    The experiment was conducted with 960 one-day-old ducklings fed mixtures (I control - 0.28% methionine) additionally supplemented with DL-methionine (DL-Met) at amounts: 0.03% (group II), 0.07% (III), 0.12% (IV) and 0.18% (V). The performance, carcass quality and apparent ileal digestibility of amino acids as the criterions of methionine (Met) effectivity were considered. The analysis of growth and development of ducks as an effect of diversified DL-Met supplements indicate that increased content of this amino acid in the diets has not affected clearly the performance parameters. The body weight of 21-day-old ducklings was significantly affected only by the level of 0.12% of added Met in comparison to control group. On day 42, the differences among groups were negligible; only the addition of 0.12% DL-Met has increased the body weight by 2.4% when compared with control (p > 0.05). Feed conversion estimated for a period of 1-42 days has not been influenced by Met supplementation. The indistinct, however, visible tendency of better ileal amino acids' apparent digestibility (for Asp.a.,Thr, Ser, Glu, Lys) was noted in the groups fed supplemented diets. Application of 0.07% and 0.18% of DL-met, has significantly (p < 0.05) improved the coefficient of cysteine (Cys) apparent ileal digestibility; however, the improvement of Met apparent ileal digestibility has been achieved by the addition of 0.18% Met. The mortality of ducklings in the experiment was very low and varied between 3.15% (II) and 0.0% (groups I and III). In general, application of 0.12% of DL-Met to mixture containing 0.28% Met had positive effect on the productive output of birds and also improved the apparent ileal digestibility of Cys and Met.

  12. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    PubMed Central

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors. PMID:24971025

  13. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork.

    PubMed

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors.

  14. Increased sodium and fluctuations in minerals in acid limes expressing witches' broom symptoms.

    PubMed

    Al-Ghaithi, Aisha G; Hanif, Muhammad Asif; Al-Busaidi, Walid M; Al-Sadi, Abdullah M

    2016-01-01

    Witches' broom disease of lime (WBDL), caused by 'Candidatus Phytoplasma aurantifolia', is a very serious disease of acid limes. The disease destroyed more than one million lime trees in the Middle East. WBDL results in the production of small, clustered leaves in some branches of lime trees. Branches develop symptoms with time and become unproductive, until the whole tree collapses within 4-8 years of first symptom appearance. This study was conducted to investigate differences in minerals between symptomatic and asymptomatic leaves of infected lime trees. The study included one set of leaves from uninfected trees and two sets of infected leaves: symptomatic leaves and asymptomatic leaves obtained from randomly selected acid lime trees. Nested polymerase chain reaction detected phytoplasma in the symptomatic and asymptomatic leaves from the six infected trees, but not from the uninfected trees. Phylogenetic analysis showed that all phytoplasmas belong to the 16S rRNA group II-B. Mineral analysis revealed that the level of Na significantly increased by four times in the symptomatic leaves compared to the non-symptomatic leaves and to the uninfected leaves. In addition, symptom development resulted in a significant increase in the levels of P and K by 1.6 and 1.5 times, respectively, and a significant decrease in the levels of Ca and B by 1.2 and 1.8 times, respectively. There was no significant effect of WBDL on the levels of N, Cu, Zn, and Fe. The development of witches' broom disease symptoms was found to be associated with changes in some minerals. The study discusses factors and consequences of changes in the mineral content of acid limes infected by phytoplasma.

  15. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

    PubMed

    Herbel, B K; McGuire, M K; McGuire, M A; Shultz, T D

    1998-02-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

  16. Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells

    PubMed Central

    Heino, Terhi J; Alm, Jessica J; Halkosaari, Heikki J; Välimäki, Ville-Valtteri

    2016-01-01

    Background and purpose Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (μCT), and histology. Results Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID:27196705

  17. Lactoferrin interacts with bile acids and increases fecal cholesterol excretion in rats.

    PubMed

    Nakamura, Kanae; Morishita, Satoru; Ono, Tomoji; Murakoshi, Michiaki; Sugiyama, Keikichi; Kato, Hisanori; Ikeda, Ikuo; Nishino, Hoyoku

    2017-02-01

    Lactoferrin (LF) is a multifunctional cationic protein (pI 8.2-8.9) in mammalian milk. We previously reported that enteric-LF prevented hypercholesterolemia and atherosclerosis in a diet-induced atherosclerosis model using Microminipig, although the underlying mechanisms remain unclear. Because LF is assumed to electrostatically interact with bile acids to inhibit intestinal cholesterol absorption, LF could promote cholesterol excretion. In this study, we assessed the interaction between LF and taurocholate in vitro, and the effect of LF on cholesterol excretion in rats. The binding rate of taurocholate to LF was significantly higher than that to transferrin (pI 5.2-6.3). When rats were administered a high-cholesterol diet (HCD) containing 5% LF, LF was detected using ELISA in the upper small intestine from 7.5 to 60 min after the administration. Rats were fed one of the following diets: control, HCD, or HCD + 5% LF for 21 days. Fecal neutral steroids and hepatic cholesterol levels in the HCD group were significantly higher than those in the control group. The addition of LF to a HCD significantly increased fecal neutral steroids levels (22% increase, p < 0.05) and reduced hepatic cholesterol levels (17% decrease, p < 0.05). These parameters were inversely correlated (R = -0.63, p < 0.05). These results suggest that LF promotes cholesterol excretion via interactions with bile acids.

  18. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

    PubMed

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-06-15

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. ©2014 American Association for Cancer Research.

  19. Phosphatidic acid osmotically destabilizes lysosomes through increased permeability to K+ and H+.

    PubMed

    Yi, Y-P; Wang, X; Zhang, G; Fu, T-S; Zhang, G-J

    2006-06-01

    Lysosomal destabilization is a critical event not only for the organelle but also for living cells. However, what factors can affect lysosomal stability is not fully studied. In this work, the effects of phosphatidic acid (PA) on the lysosomal integrity were investigated. Through the measurements of lysosomal beta-hexosaminidase free activity, intralysosomal pH, leakage of lysosomal protons and lysosomal latency loss in hypotonic sucrose medium, we established that PA could increase the lysosomal permeability to K+ and H+, and enhance the lysosomal osmotic sensitivity. Treatment of lysosomes with PA promoted entry of K+ into the organelle via K+/H+ exchange, which could produce osmotic stresses and osmotically destabilize the lysosomes. In addition, PA-induced increase in the lysosomal osmotic sensitivity caused the lysosomes to become more liable to destabilization in osmotic shocks. The results suggest that PA may play a role in the lysosomal destabilization.

  20. Hyaluronic acid is increased in the skin and urine in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Imai, T.; Yamauchi, M.; Nagao, K.

    1996-01-01

    We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

  1. Hyaluronic acid is increased in the skin and urine in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Imai, T.; Yamauchi, M.; Nagao, K.

    1996-01-01

    We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

  2. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

    PubMed Central

    Herms, Albert; Bosch, Marta; Reddy, Babu J.N.; Schieber, Nicole L.; Fajardo, Alba; Rupérez, Celia; Fernández-Vidal, Andrea; Ferguson, Charles; Rentero, Carles; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Gross, Steven P.; Pol, Albert

    2015-01-01

    Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

  3. IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism

    PubMed Central

    Grassian, Alexandra R.; Parker, Seth J.; Davidson, Shawn M.; Divakarun, Ajit S.; Green, Courtney R.; Zhang, Xiamei; Slocum, Kelly L.; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D.; Straub, Christopher; Growney, Joseph D.; Vander Heiden, Matthew G.; Murphy, Anne N.; Pagliarini, Raymond; Metallo, Christian M.

    2016-01-01

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. PMID:24755473

  4. Capric acid and hydroxypropylmethylcellulose increase the immunogenicity of nasally administered peptide vaccines.

    PubMed

    Nordone, Sushila K; Peacock, James W; Kirwan, Shaun M; Staats, Herman F

    2006-06-01

    Immunization by the nasal route is an established method for the induction of mucosal and systemic humoral and cell-mediated antigen-specific responses. However, the effectiveness of nasal immunization is often hampered by the need for increased doses of antigen. Bioadhesives and absorption enhancers were investigated for their ability to enhance immune responses in mice after nasal immunization with model HIV-1 peptide and protein immunogens. Two additives, hydroxypropylmethylcellulose (HPMC) and capric acid, consistently enhanced antigen-specific serum IgG endpoint titers under conditions in which antigen dose was limiting. Nasal immunization of mice with 20 microg of an HIV-1 peptide immunogen plus cholera toxin (CT) as adjuvant induced serum antipeptide IgG titers of 1:9.5log2 after four immunizations while the addition of CA or HPMC to the vaccine formulation increased serum antipeptide IgG titers to 1:15.4log2 and 1:17.6log2, respectively. When 5 microg recombinant HIV-1 gp41 was used as the immunogen, the addition of CA or HPMC to the vaccine formulation increased serum anti-gp41 IgG titers to 1:11.6log2 and 1:8.8log2, respectively, compared to 1:5.2log2 after three nasal immunizations with 5 microg gp41 + CT alone. Thus, HPMC and capric acid may be useful additives that increase the immunogenicity of nasally administered vaccines and permit less antigen to be used with each immunization.

  5. Increase of ascorbic acid content and nutritional quality in spinach leaves during physiological acclimation to low temperature.

    PubMed

    Proietti, Simona; Moscatello, Stefano; Famiani, Franco; Battistelli, Alberto

    2009-08-01

    The effect of acclimation to 10 degrees C on the leaf content of ascorbic and oxalic acids, was investigated in spinach (Spinacia oleracea L.). At 10 degrees C the content of ascorbic acid in leaves increased and after 7 days it was about 41% higher than in plants remaining under a 25 degrees C/20 degrees C day/night temperature regime. In contrast, the content of oxalate, remained unchanged. Transfer to 10 degrees C increased the ascorbic but not the oxalic acid content of the leaf intercellular washing fluid (IWF). Oxalate oxidase (OXO EC 1.2.3.4) activity was not detected in extracts of leaf blades. Therefore, oxalic acid degradation via OXO was not involved in the control of its content. Our results show that low temperature acclimation increases nutritional quality of spinach leaves via a physiological rise of ascorbic acid that does not feed-forward on the content of oxalic acid.

  6. Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts

    PubMed Central

    Sitarz, Kamil S.; Elliott, Hannah R.; Karaman, Betül S.; Relton, Caroline; Chinnery, Patrick F.; Horvath, Rita

    2014-01-01

    Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. Although it is usually well tolerated, a severe hepatotoxic reaction has been repeatedly reported after VPA administration. A profound toxic reaction on administration of VPA has been observed in several patients carrying POLG mutations, and heterozygous genetic variation in POLG has been strongly associated with VPA-induced liver toxicity. Here we studied the effect of VPA in fibroblasts of five patients carrying pathogenic mutations in the POLG gene. VPA administration caused a significant increase in the expression of POLG and several regulators of mitochondrial biogenesis. It was further supported by elevated mtDNA copy numbers. The effect of VPA on mitochondrial biogenesis was observed in both control and patient cell lines, but the capacity of mutant POLG to increase the expression of mitochondrial genes and to increase mtDNA copy numbers was less effective. No evidence of substantive differences in DNA methylation across the genome was observed between POLG mutated patients and controls. Given the marked perturbation of gene expression observed in the cell lines studied, we conclude that altered DNA methylation is unlikely to make a major contribution to POLG-mediated VPA toxicity. Our data provide experimental evidence that VPA triggers increased mitochondrial biogenesis by altering the expression of several mitochondrial genes; however, the capacity of POLG-deficient liver cells to address the increased metabolic rate caused by VPA administration is significantly impaired. PMID:24725338

  7. Reducing isozyme competition increases target fatty acid accumulation in seed triacylglycerols of transgenic Arabidopsis

    USDA-ARS?s Scientific Manuscript database

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on the engineering of industrial FAs, specifically hydroxy fatty acids (HFA) and conjugated polyenoic fatty acids (a-eleostearic acid, ESA), using Arabidopsis (Arabidopsis thaliana) as a m...

  8. Adaptation of in vivo amino acid kinetics facilitates increased amino acid availability for fetal growth in adolescent and adult pregnancies alike

    USDA-ARS?s Scientific Manuscript database

    During pregnancy, adult women with a normal BMI synthesize extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and ...

  9. Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema sylvestre leaves.

    PubMed

    Nakamura, Y; Tsumura, Y; Tonogai, Y; Shibata, T

    1999-06-01

    Gymnemic acids are the saponins with a triterpenoid structure contained in Gymnema sylvestre leaves and have the hypoglycemic effects. In spite of the cholesterol-binding properties of saponins, the effect of gymnemic acids on cholesterol metabolism has not been elucidated to date. We investigated the effects of gymnemic acids on fecal steroid excretion in rats. Three kinds of extracts from Gymnema sylvestre leaves, extract (GSE), acid precipitate (GSA) and column fractionate (GSF), of which the gymnemagenin (an aglycone of gymnemic acids) concentrations are 58.87, 161.6, and 363.3 mg/g respectively, were used for the experiments. These were administered to rats orally at the dose of 0.05-1.0 g/kg for 22 d. Rats were given free access to water and nonpurified diet without cholesterol, and the differences in fecal excretion of steroids and gymnemic acids were investigated. Although there were no significant effects of GSE, GSA and GSF decreased body weight gain and food intakes in a dose-dependent manner (P < 0.01). GSF (1.0 g/kg) significantly increased fecal excretion of neutral steroids and bile acids in a dose-dependent manner (P < 0.05), especially those of cholesterol and cholic acid (CA)-derived bile acids. The increases in fecal steroid excretion of cholesterol, total neutral steroids, total bile acids and CA-related bile acids were acute and significantly correlated with fecal gymnemagenin levels (r2 = 0.2316-0.9861, P < 0. 05). These results demonstrated for the first time that a high dose of gymnemic acids increases fecal cholesterol and CA-derived bile acid excretion. Further studies are needed to clarify the effect of gymnemic acids on cholesterol metabolism.

  10. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels.

    PubMed

    Burke, Katie T; Horn, Paul S; Tso, Patrick; Heubi, James E; Woollett, Laura A

    2009-07-01

    Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly ( approximately 3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7alpha-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.

  11. Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat

    PubMed Central

    Wooton-Kee, Clavia Ruth; Cohen, David E.; Vore, Mary

    2008-01-01

    Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool. PMID:18292185

  12. Dicarboxylic acids with limited numbers of hydrocarbons stabilize cell membrane and increase osmotic resistance in rat erythrocytes.

    PubMed

    Mineo, Hitoshi; Amita, Nozomi; Kawawake, Megumi; Higuchi, Ayaka

    2013-11-01

    We examined the effect of dicarboxylic acids having 0 to 6 hydrocarbons and their corresponding monocarboxylic or tricarboxylic acids in changing the osmotic fragility (OF) in rat red blood cells (RBCs). Malonic, succinic, glutaric and adipic acids, which are dicarboxylic acids with 1, 2, 3 and 4 straight hydrocarbons located between two carboxylic groups, decreased the OF in a concentration-dependent manner. Other long-chain dicarboxylic acids did not change the OF in rat RBCs. The benzoic acid derivatives, isophthalic and terephthalic acids, but not phthalic acid, decreased the OF in a concentration-dependent manner. Benzene-1,2,3-tricarboxylic acid, but not benzene-1,3,5-tricarboxylic acid, also decreased the OF in rat RBCs. On the other hand, monocarboxylic acids possessing 2 to 7 straight hydrocarbons and benzoic acid increased the OF in rat RBCs. In short-chain dicarboxylic acids, a limited number of hydrocarbons between the two carboxylic groups are thought to form a V- or U-shaped structure and interact with phospholipids in the RBC membrane. In benzene dicarboxylic and tricarboxylic acids, a part of benzene nucleus between the two carboxylic groups is thought to enter the plasma membrane and act on acyl-chain in phospholipids in the RBC membrane. For dicarboxylic and tricarboxylic acids, limited numbers of hydrocarbons in molecules are speculated to enter the RBC membrane with the hydrophilic carboxylic groups remaining outside, stabilizing the structure of the cell membrane and resulting in an increase in osmotic resistance in rat RBCs. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Dehydroepiandrosterone prevents linoleic acid-induced endothelial cell senescence by increasing autophagy.

    PubMed

    Lee, Min Jung; Kim, Eun Hee; Lee, Sang Ah; Kang, Yu Mi; Jung, Chang Hee; Yoon, Hae Kyeong; Seol, So Mi; Lee, Yoo La; Lee, Woo Je; Park, Joong-Yeol

    2015-09-01

    Autophagy has emerged as a potentially important factor in the pathogenesis of atherosclerosis. Dehydroepiandrosterone (DHEA) is an adrenal steroid of great recent interest due to its anti-aging and anti-atherogenic effects; however, little is known about its role in autophagy and endothelial senescence. The aim of this study was to investigate whether DHEA prevents linoleic acid (LA)-induced endothelial senescence by enhancing autophagy. After pre-treatement with or without DHEA prior to LA treatment in human aortic endothelial cells (HAECs), the level of senescence was compared by senescence-associated acidic β-galactosidase (SA-β-Gal) staining and hyperphosphorylated pRB (ppRB) protein level. Autophagy was detected by LC3 conversion and measuring the level of p62/SQSTM1 (sequestosome 1), a protein degraded by autophagy. The fusion of autophagosome and lysosome was confirmed by fluorescence microscopy. Pre-treatment with DHEA inhibited LA-induced endothelial senescence. DHEA increased the conversion of LC3-I to LC3-II and decreased the level of p62 in a time- and dose-dependent manner. Although both DHEA and LA treatment increased the conversion of LC3-I to LC3-II, treatment of LA increased p62 and decreased fusion of autophagosome and lysosome, which reflected decreased autophagic flux. However, pre-treatment with DHEA restored autophagic flux inhibited by LA. When we evaluated signaling pathways, we found that JNK activation involved in LC3 conversion induced by DHEA. DHEA prevents LA-induced endothelial senescence by restoring autophagy and autophagic flux through JNK activation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Increased Numbers of Nonattached Osteoclasts After Long-Term Zoledronic Acid Therapy in Mice

    PubMed Central

    Kuroshima, Shinichiro; Go, Virginia-Arlene A.

    2012-01-01

    Osteoclasts are key players in the maintenance of bone, which is an endocrine target and organ. Bisphosphonates, used for the management of metastatic bone diseases and osteoporosis, suppress osteoclasts. However, the impact of continuously suppressed osteoclasts is unknown. In this study, mice received zoledronic acid (ZA) for 13 months, nearly half the lifespan of mice, and the effects of continual osteoclast suppression on the bone environment and oral wound healing were determined. ZA therapy suppressed osteoclasts, resulting in significantly more bone mass compared with control. Despite continuous and intense suppression of bone loss in mice receiving ZA, serum calcium levels were maintained in the normal range. No differences were noted in serum tartrate-resistant acid phosphatase (TRAP) 5b levels between ZA-treated and control mice. Histomorphometric analyses of bones revealed that ZA therapy significantly decreased osteoclasts on the bone surface but, instead, substantially increased TRAP+ mononuclear cells and osteoclasts that were not on the bone surface. When oral trauma was induced, such TRAP+ mononuclear and nonattached osteoclasts increased considerably with increased inflammatory cell infiltration in the wounds. As a result, oral wound healing was hindered at the connective tissue level. Healing of the epithelium was unaffected. These findings indicate that the continual suppression of osteoclasts does not affect serum calcium levels and that long-term ZA therapy stimulates nonattached osteoclast and TRAP+ mononuclear cell formation that are expanded rapidly in response to oral trauma. Caution should be exercised when using the serum TRAcP5b to estimate the efficacy of antiresorptive therapy. PMID:22109892

  15. Salivary total sialic acid levels increase in breast cancer patients: a preliminary study.

    PubMed

    Oztürk, Leyla Koç; Emekli-Alturfan, Ebru; Kaşikci, Emel; Demir, Gokhan; Yarat, Aysen

    2011-09-01

    Breast cancer is the most common cancer in women living in the Western world, even though it occurs worldwide. Cancer and cancer therapy induce multiple oral complications including dental and periodontal disease. Saliva is a complex and dynamic biologic fluid, which reflects both oral and systemic changes. While saliva is easily accessible body fluid, there has been little effort to study its value in cancer diagnosis. Sialic acids (SA), the end moieties of the carbohydrate chains, are biologically important and essential for functions of glycoconjugates that are reported to be altered in both blood and saliva of various cancer patients. Increased sialylation has been shown to be a characteristic feature in cancer tissue and blood in breast cancer patients. However, there is no data about salivary SA in breast cancer. The aim of this study was to evaluate salivary total sialic acid (TSA) levels in breast cancer patients who were under chemotheraphy. The study included 15 breast cancer patients in different stages and 10 healthy individuals as age-matched controls. Unstimulated whole saliva was collected. Salivary total protein and SA levels were determined. Flow rate was calculated from salivary volume by the time of secretion. Salivary SA was significantly higher and total protein was lower in breast cancer patients compared to controls. It is concluded that sialylation may be increased in saliva of patients with breast cancer as the same way for cancer tissue and for blood . Increased salivary SA may therefore be useful as a non-invasive predictive marker for breast cancer patients and for the prevention and management of oral complications of cancer and cancer therapy to improve oral function and quality-of-life. The effects of different types of chemotherapies and different stages of the disease on salivary SA levels and salivary sialo-glycomic are worthy of being further investigated in breast cancer patients.

  16. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    SciTech Connect

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  17. Soil Drench Treatment with ß-Aminobutyric Acid Increases Drought Tolerance of Potato

    PubMed Central

    Sós-Hegedűs, Anita; Juhász, Zsófia; Poór, Péter; Kondrák, Mihály; Antal, Ferenc; Tari, Irma; Mauch-Mani, Brigitte; Bánfalvi, Zsófia

    2014-01-01

    The non-protein amino acid β-aminobutyric acid (BABA) is known to be a priming agent for a more efficient activation of cellular defence responses and a potent inducer of resistance against biotic and abiotic stresses in plants. Nevertheless, most of the studies on priming have been carried out in Arabidopsis. In potato, the effect of BABA was demonstrated only on biotic stress tolerance. We investigated the effect of BABA on the drought tolerance of potato and found that soil drenched with BABA at a final concentration of 0.3 mM improves the drought tolerance of potato. Water loss from the leaves of the primed plants is attenuated and the yield is increased compared to the unprimed drought-stressed plants. The metabolite composition of the tubers of the BABA-treated plants is less affected by drought than the tuber composition of the non-treated plants. Nitric oxide and ROS (reactive oxygen species) production is increased in the BABA-treated roots but not in the leaves. In the leaves of the BABA-treated plants, the expression of the drought-inducible gene StDS2 is delayed, but the expression of ETR1, encoding an ethylene receptor, is maintained for a longer period under the drought conditions than in the leaves of the non-treated, drought-stressed control plants. This result suggests that the ethylene-inducible gene expression remains suppressed in primed plants leading to a longer leaf life and increased tuber yield compared to the non-treated, drought-stressed plants. The priming effect of BABA in potato, however, is transient and reverts to an unprimed state within a few weeks. PMID:25489951

  18. Biochar Enhances Aspergillus niger Rock Phosphate Solubilization by Increasing Organic Acid Production and Alleviating Fluoride Toxicity

    PubMed Central

    Mendes, Gilberto de Oliveira; Zafra, David Lopez; Vassilev, Nikolay Bojkov; Silva, Ivo Ribeiro; Ribeiro, José Ivo

    2014-01-01

    During fungal rock phosphate (RP) solubilization, a significant quantity of fluoride (F−) is released together with phosphorus (P), strongly inhibiting the process. In the present study, the effect of two F− adsorbents [activated alumina (Al2O3) and biochar] on RP solubilization by Aspergillus niger was examined. Al2O3 adsorbed part of the F− released but also adsorbed soluble P, which makes it inappropriate for microbial RP solubilization systems. In contrast, biochar adsorbed only F− while enhancing phosphate solubilization 3-fold, leading to the accumulation of up to 160 mg of P per liter. By comparing the values of F− measured in solution at the end of incubation and those from a predictive model, it was estimated that up to 19 mg of F− per liter can be removed from solution by biochar when added at 3 g liter−1 to the culture medium. Thus, biochar acted as an F− sink during RP solubilization and led to an F− concentration in solution that was less inhibitory to the process. In the presence of biochar, A. niger produced larger amounts of citric, gluconic, and oxalic acids, whether RP was present or not. Our results show that biochar enhances RP solubilization through two interrelated processes: partial removal of the released F− and increased organic acid production. Given the importance of organic acids for P solubilization and that most of the RPs contain high concentrations of F−, the proposed solubilization system offers an important technological improvement for the microbial production of soluble P fertilizers from RP. PMID:24610849

  19. Low ascorbic acid and increased oxidative stress in gulo−/− mice during development

    PubMed Central

    Harrison, Fiona E.; Meredith, M. Elizabeth; Dawes, Sean M.; Saskowski, Jeanette L.; May, James M.

    2010-01-01

    Vitamin C (ascorbic acid, AA) depletion during pre-natal and post-natal development can lead to oxidative stress in the developing brains and other organs. Such damage may lead to irreversible effects on later brain function. We studied the relationship between AA deficiency and oxidative stress during development in gulonolactone oxidase (gulo) knockout mice that are unable to synthesize their own ascorbic acid. Heterozygous gulo(+/−) mice can synthesize AA and typically have similar tissue levels to wild-type mice. Gulo(+/−) dams were mated with gulo(+/−) males to provide offspring of each possible genotype. Overall, embryonic day 20 (E20) and post-natal day 1 (P1) pups were protected against oxidative stress by sufficient AA transfer during pregnancy. On post-natal day 10 (P10) AA levels were dramatically lower in liver and cerebellum in gulo (−/−) mice and malondialdehyde (MDA) levels were significantly increased. In post-natal day 18 pups (P18) AA levels decreased further in gulo(−/−) mice and oxidative stress was observed in the accompanying elevations in MDA in liver, and F2-isoprostanes in cortex. Further, total glutathione levels were higher in gulo(−/−) mice in cortex, cerebellum and liver, indicating that a compensatory antioxidant system was activated. These data show a direct relationship between AA level and oxidative stress in the gulo(−/−) mice. They reinforce the critical role of ascorbic acid in preventing oxidative stress in the developing brain in animals that, like humans, cannot synthesize their own AA. PMID:20599829

  20. Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan12

    PubMed Central

    Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Obando, Alina Soto; Hoxha, Sany; Ja, William W

    2015-01-01

    Background: Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. Objectives: We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. Methods: We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. Results: An acidic diet increased Drosophila gustatory responses (40–230%) and food intake (5–50%) and extended survival (10–160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5–20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Conclusions: Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and

  1. Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

    PubMed

    Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

    2015-12-01

    Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

  2. Increased BDNF expression in fetal brain in the valproic acid model of autism.

    PubMed

    Almeida, Luis E F; Roby, Clinton D; Krueger, Bruce K

    2014-03-01

    Human fetal exposure to valproic acid (VPA), a widely-used anti-epileptic and mood-stabilizing drug, leads to an increased incidence of behavioral and intellectual impairments including autism; VPA administration to pregnant rats and mice at gestational days 12.5 (E12.5) or E13.5 leads to autistic-like symptoms in the offspring and is widely used as an animal model for autism. We report here that this VPA administration protocol transiently increased both BDNF mRNA and BDNF protein levels 5-6-fold in the fetal mouse brain. VPA exposure in utero induced smaller increases in the expression of mRNA encoding the other neurotrophins, NT3 (2.5-fold) and NT4 (2-fold). Expression of the neurotrophin receptors, trkA, trkB and trkC were minimally affected, while levels of the low-affinity neurotrophin receptor, p75(NTR), doubled. Of the nine 5'-untranslated exons of the mouse BDNF gene, only expression of exons I, IV and VI was stimulated by VPA in utero. In light of the well-established role of BDNF in regulating neurogenesis and the laminar fate of postmitotic neurons in the developing cortex, an aberrant increase in BDNF expression in the fetal brain may contribute to VPA-induced cognitive disorders by altering brain development. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Liopo, Anton; Su, Richard; Tsyboulski, Dmitri A.; Oraevsky, Alexander A.

    2016-08-01

    Enhanced delivery of optical clearing agents (OCA) through skin may improve sensitivity of optical and optoacoustic (OA) methods of imaging, sensing, and monitoring. This report describes a two-step method for enhancement of light penetration through skin. Here, we demonstrate that topical application of hyaluronic acid (HA) improves skin penetration of hydrophilic and lipophilic OCA and thus enhances their performance. We examined the OC effect of 100% polyethylene and polypropylene glycols (PPGs) and their mixture after pretreatment by HA, and demonstrated significant increase in efficiency of light penetration through skin. Increased light transmission resulted in a significant increase of OA image contrast in vitro. Topical pretreatment of skin for about 30 min with 0.5% HA in aqueous solution offers effective delivery of low molecular weight OCA such as a mixture of PPG-425 and polyethylene glycol (PEG)-400. The developed approach of pretreatment by HA prior to application of clearing agents (PEG and PPG) resulted in a ˜47-fold increase in transmission of red and near-infrared light and significantly enhanced contrast of OA images.

  4. Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype.

    PubMed

    Hénique, Carole; Mansouri, Abdelhak; Vavrova, Eliska; Lenoir, Véronique; Ferry, Arnaud; Esnous, Catherine; Ramond, Elodie; Girard, Jean; Bouillaud, Frédéric; Prip-Buus, Carina; Cohen, Isabelle

    2015-06-01

    Adult skeletal muscle is a dynamic, remarkably plastic tissue, which allows myofibers to switch from fast/glycolytic to slow/oxidative types and to increase mitochondrial fatty acid oxidation (mFAO) capacity and vascularization in response to exercise training. mFAO is the main muscle energy source during endurance exercise, with carnitine palmitoyltransferase 1 (CPT1) being the key regulatory enzyme. Whether increasing muscle mFAO affects skeletal muscle physiology in adulthood actually remains unknown. To investigate this, we used in vivo electrotransfer technology to express in mouse tibialis anterior (TA), a fast/glycolytic muscle, a mutated CPT1 form (CPT1mt) that is active but insensitive to malonyl-CoA, its physiologic inhibitor. In young (2-mo-old) adult mice, muscle CPT1mt expression enhanced mFAO (+40%), but also increased the percentage of oxidative fibers (+28%), glycogen content, and capillary-to-fiber density (+45%). This CPT1mt-induced muscle remodeling, which mimicked exercise-induced oxidative phenotype, led to a greater resistance to muscle fatigue. In the context of aging, characterized by sarcopenia and reduced oxidative capacity, CPT1mt expression in TAs from aged (20-mo-old) mice partially reversed aging-associated sarcopenia and fiber-type transition, and increased muscle capillarity. These findings provide evidence that mFAO regulates muscle phenotype and may be a potential target to combat age-related decline in muscle function.

  5. Gibberellic acid, a plant growth regulator, increases mast cell recruitment and alters Substance P levels.

    PubMed

    Erin, Nuray; Afacan, Berna; Ersoy, Yasemin; Ercan, Feriha; Balci, Mustafa Kemal

    2008-12-05

    Gibberellic acid (GA3), a plant growth regulator, is used commonly in agriculture. Its potential hazardous effects on human health, however, were relatively unexplored. Several studies demonstrated that in animals chronic GA3 consumption increased tumor formation and oxidative stress. Mast cells and Substance P (SP) play an important role in inflammation. Because chronic inflammation triggers serious conditions, including tumor formation, we examined changes in mast cell recruitment and activation as well as SP levels in skin and urinary bladder. Wistar Albino rats were treated with either a single GA3 dose or multiple GA3 doses for 30 days. Sub-chronic exposure to GA3 markedly increased mast cell recruitment and activation in both tissues. Treatment with 2mg/kg GA3 dose for 30 days decreased SP levels in skin and bladder. SP levels returned to control values in bladder and further increased in skin following 30-day treatment with the 20mg/kg GA3 dose. There was marked urothelial loss and inflammatory cell infiltration in bladder of 30-day GA3 treated groups. In skin, single GA3 doses also decreased SP levels and enhanced mast cell activation and recruitment. Since both SP and mast cell activation elicit inflammatory responses, these results demonstrate that exposure to plant growth regulators may increase inflammatory skin and bladder disease and that use of GA3 should be clearly monitored.

  6. Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

    PubMed Central

    Bagley, Heidi N.; Wang, Yan; Campbell, Michael S.; Yu, Xing; Lane, Robert H.; Joss-Moore, Lisa A.

    2013-01-01

    Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPARγ agonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPARγ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR. PMID:23533720

  7. Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

    PubMed

    Lee, Bonggi; Kwon, Misung; Choi, Jae Sue; Jeong, Hyoung Oh; Chung, Hae Young; Kim, Hyeung-Rak

    2015-12-01

    Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes.

  8. Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa

    PubMed Central

    Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

    2017-01-01

    The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors. PMID:28398349

  9. Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa.

    PubMed

    Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

    2017-08-01

    The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors.

  10. Rehabilitating acid soils for increasing crop productivity through low-cost liming material.

    PubMed

    Bhat, Javid Ahmad; Kundu, Manik Chandra; Hazra, Gora Chand; Santra, Gour Hari; Mandal, Biswapati

    2010-09-15

    Productivity of red and lateritic soils is low because of their acidity and deficiencies in few essential nutrients viz., nitrogen, phosphorus, calcium, zinc, boron, molybdenum etc. We compared the effectiveness of basic slag, a low-cost liming material, with that of calcite as an ameliorant for these soils using mustard followed by rice as test crops. Experiments were conducted with three levels of each of basic slag and calcite along with a control on farmers' fields at 14 different locations. Influence of farmyard manure (FYM) and poultry manure (PM) on the effectiveness of the slag was also tested. On an average, basic slag performed better than calcite in increasing yields of both mustard and rice and left over higher amounts of available Ca, Si and Zn in residual soils. The slag also improved N, P, K and Ca nutrition of mustard and Si and Zn nutrition of rice with a favorable benefit:cost (B:C) ratio over the calcite (4.82 vs. 1.44). Effectiveness of the basic slag improved when it was applied in combination with FYM or PM (B:C, 5.83 and 6.27). Basic slag can, therefore, be advocated for use in the acidic red and lateritic soils for economically improving their productivity.

  11. The type and concentration of milk increase the in vitro bioaccessibility of coffee chlorogenic acids.

    PubMed

    Tagliazucchi, Davide; Helal, Ahmed; Verzelloni, Elena; Conte, Angela

    2012-11-07

    Coffee with different types and concentrations of milk was digested with pepsin (2 h) and pancreatin (2 h) to simulate gastropancreatic digestion. Chlorogenic acids (CGAs) were determined by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry in ultrafiltrate (cutoff 3 kDa) to evaluate their bioaccessibility. After digestion, bioaccessible CGAs decreased from 80.2 to 53.0 and 69.5 μmol/200 mL in coffee without milk and coffee-whole milk, respectively. When whole, semiskimmed, skimmed, or diluted milk were present, the increase in bioaccessibility was dependent on fat content (r = 0.99, p < 0.001). No relationship was observed between bioaccessibility and proteins, carbohydrates, and calcium content. The addition of milk to coffee caused an immediate decrease in the bioaccessibility due to CGAs binding to proteins. After digestion, 86-94% of bound CGAs remained in the high molecular weight fraction. Casein bound 5-caffeoylquinic acid with high affinity (K(D) of 37.9 ± 2.3 μmol/L; n = 0.88 ± 0.06).

  12. GSF2 deletion increases lactic acid production by alleviating glucose repression in Saccharomyces cerevisiae

    PubMed Central

    Baek, Seung-Ho; Kwon, Eunice Y.; Kim, Seon-Young; Hahn, Ji-Sook

    2016-01-01

    Improving lactic acid (LA) tolerance is important for cost-effective microbial production of LA under acidic fermentation conditions. Previously, we generated LA-tolerant D-LA-producing S. cerevisiae strain JHY5310 by laboratory adaptive evolution of JHY5210. In this study, we performed whole genome sequencing of JHY5310, identifying four loss-of-function mutations in GSF2, SYN8, STM1, and SIF2 genes, which are responsible for the LA tolerance of JHY5310. Among the mutations, a nonsense mutation in GSF2 was identified as the major contributor to the improved LA tolerance and LA production in JHY5310. Deletion of GSF2 in the parental strain JHY5210 significantly improved glucose uptake and D-LA production levels, while derepressing glucose-repressed genes including genes involved in the respiratory pathway. Therefore, more efficient generation of ATP and NAD+ via respiration might rescue the growth defects of the LA-producing strain, where ATP depletion through extensive export of lactate and proton is one of major reasons for the impaired growth. Accordingly, alleviation of glucose repression by deleting MIG1 or HXK2 in JHY5210 also improved D-LA production. GSF2 deletion could be applied to various bioprocesses where increasing biomass yield or respiratory flux is desirable. PMID:27708428

  13. Placement in an acidic environment increase the solubility of white mineral trioxide aggregate

    PubMed Central

    Yavari, Hamid Reza; Borna, Zahra; Rahimi, Saeed; Shahi, Shahriar; Valizadeh, Hadi; Ghojazadeh, Morteza

    2013-01-01

    Aims: The aim of the present study was to evaluate solubility of white mineral trioxide aggregate (WMTA) in an acidic environment. Materials and Methods: Twenty-four metal rings were prepared, filled with WMTA and randomly divided into two groups. The samples in groups 1 and 2 were set in synthetic tissue fluid with pH values of 7.4 and 4.4, respectively and then were transferred to beakers containing synthetic tissue fluid with pH values of 7.7 and 4.4. Solubility of WMTA samples were calculated at the 9 experimental intervals. Data was analyzed with two-factor ANOVA and Bonferroni test (P < 0.03). Results: The total solubility of WMTA in groups 1 and 2 were −9.1796 ± 1.9158% and −1.1192 ± 2.6236%, (P = 0.028) with weight changes of 9.1574 ± 2.1432% and 7.3276 ± 1.5823%, respectively (P = 0.002). Statistical analysis revealed significant differences between the two groups. Conclusions: It was concluded that solubility of WMTA increases in acidic environments and additional therapeutic precautions should be taken to decrease inflammation in endodontic treatment. PMID:23833462

  14. Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids.

    PubMed Central

    Garlick, P J; Grant, I

    1988-01-01

    Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin. PMID:3052439

  15. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  16. Acetic acid increases the phage-encoded enterotoxin A expression in Staphylococcus aureus

    PubMed Central

    2010-01-01

    Background The effects of acetic acid, a common food preservative, on the bacteriophage-encoded enterotoxin A (SEA) expression and production in Staphylococcus aureus was investigated in pH-controlled batch cultures carried out at pH 7.0, 6.5, 6.0, 5.5, 5.0, and 4.5. Also, genomic analysis of S. aureus strains carrying sea was performed to map differences within the gene and in the temperate phage carrying sea. Results The sea expression profile was similar from pH 7.0 to 5.5, with the relative expression peaking in the transition between exponential and stationary growth phase and falling during stationary phase. The levels of sea mRNA were below the detection limit at pH 5.0 and 4.5, confirmed by very low SEA levels at these pH values. The level of relative sea expression at pH 6.0 and 5.5 were nine and four times higher, respectively, in the transitional phase than in the exponential growth phase, compared to pH 7.0 and pH 6.5, where only a slight increase in relative expression in the transitional phase was observed. Furthermore, the increase in sea expression levels at pH 6.0 and 5.5 were observed to be linked to increased intracellular sea gene copy numbers and extracellular sea-containing phage copy numbers. The extracellular SEA levels increased over time, with highest levels produced at pH 6.0 in the four growth phases investigated. Using mitomycin C, it was verified that SEA was at least partially produced as a consequence of prophage induction of the sea-phage in the three S. aureus strains tested. Finally, genetic analysis of six S. aureus strains carrying the sea gene showed specific sea phage-groups and two versions of the sea gene that may explain the different sea expression and production levels observed in this study. Conclusions Our findings suggest that the increased sea expression in S. aureus caused by acetic acid induced the sea-encoding prophage, linking SEA production to the lifecycle of the phage. PMID:20487538

  17. Use of Methacrylic Acid-Containing Hydrogels to Increase Protein Transport Across the Intestinal Epithelium

    NASA Astrophysics Data System (ADS)

    Blanchette, James; Lopez, Jennifer; Park, Kinam; Peppas, Nicholas

    2002-03-01

    Oral protein delivery requires protection from the harsh environment of the stomach, release in the small intestine and passage from the intestinal lumen into the circulation. Hydrogels that swell in response to the pH change when passing from the stomach to the small intestine can accomplish the first two points. The ability to enhance the permeability of intestinal epithelial cells is currently under investigation. Methacrylic acid-containing hydrogels have shown the ability to bind calcium ions that decreases the concentration of free extracellular calcium for these epithelial cells. This change triggers a number of intracellular events including rearrangement of the cytoskeleton leading to increased permeability. Studies done on Caco-2 cells (human colon adenocarcinoma) measuring changes in transepithelial resistance are used to assess the effect of the polymer-cell interactions on the integrity of intestinal epithelial cell monolayers.

  18. Evidence that nitric acid increases relative humidity in low-temperature cirrus clouds.

    PubMed

    Gao, R S; Popp, P J; Fahey, D W; Marcy, T P; Herman, R L; Weinstock, E M; Baumgardner, D G; Garrett, T J; Rosenlof, K H; Thompson, T L; Bui, P T; Ridley, B A; Wofsy, S C; Toon, O B; Tolbert, M A; Kärcher, B; Peter, Th; Hudson, P K; Weinheimer, A J; Heymsfield, A J

    2004-01-23

    In situ measurements of the relative humidity with respect to ice (RHi) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RHi values show a sharp increase to average values of over 130% in both cloud types. These enhanced RHi values are attributed to the presence of a new class of HNO3-containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

  19. Azetidine-2-carboxylic acid resistant mutants of Arabidopsis thaliana with increased salt tolerance

    SciTech Connect

    Lehle, F.R.; Murphy, M.A.; Khan, R.A. )

    1989-04-01

    Nineteen mutant Arabidopsis families resistant to the proline analog azetidine-2-carboxylic acid (ACA) were characterized in terms of NaCl tolerance and proline content. Mutants were selected from about 64,000 progeny of about 16,000 self-pollinated Columbia parents which had been mutated with ethyl methane sulfonate during seed imbibition. Selections were performed during seed germination on aseptic agar medium containing 0.2 to 0.25 mM ACA. Nineteen mutant families, 12 clearly independent, retained resistance to ACA in the M{sub 4} generation. Based on germination on 150 mM NaCl, 13 of the mutant families were more tolerant than the wild type. Two mutants of intermediate resistance to ACA were markedly more salt tolerant than the others. Four mutant families appeared to overproduce proline. Of these, only 3 showed slight increases in salt tolerance.

  20. Evidence That Nitric Acid Increases Relative Humidity in Low-Temperature Cirrus Clouds

    NASA Technical Reports Server (NTRS)

    Gao, R. S.; Popp, P. J.; Fahey, D. W.; Marcy, T. P.; Herman, R. L.; Weinstock, E. M.; Baumgardner, D. G.; Garrett, T. J.; Rosenlof, K. H.; Thompson, T. L.

    2004-01-01

    In situ measurements of the relative humidity with respect to ice (RH(sub(i)) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RH(sub i) values show a sharp increase to average values of over 130% in both cloud types. These enhanced RH(sub i) values are attributed to the presence of a new class of NHO3- containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

  1. Evidence That Nitric Acid Increases Relative Humidity in Low-Temperature Cirrus Clouds

    NASA Technical Reports Server (NTRS)

    Gao, R. S.; Popp, P. J.; Fahey, D. W.; Marcy, T. P.; Herman, R. L.; Weinstock, E. M.; Baumgardner, D. G.; Garrett, T. J.; Rosenlof, K. H.; Thompson, T. L.

    2004-01-01

    In situ measurements of the relative humidity with respect to ice (RH(sub(i)) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RH(sub i) values show a sharp increase to average values of over 130% in both cloud types. These enhanced RH(sub i) values are attributed to the presence of a new class of NHO3- containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

  2. Effects of increasing acidity on metal(loid) bioprecipitation in groundwater: column studies

    SciTech Connect

    Alexander C. Davis; Bradley M. Patterson; Michelle E. Grassi; Blair S. Robertson; Henning Prommer; Allan J. McKinley

    2007-10-15

    Large-scale column experiments were carried out over a period of 545 days to assess the effect of increasing acidity on bacterial denitrification, sulfate reduction, and metal(loid) bioprecipitation in groundwater affected by acid mine drainage. At a groundwater pH of 5.5, denitrification and Cu{sup 2+} removal, probably via malachite (Cu{sub 2}(OH){sub 2}CO{sub 3}) precipitation, were observed in the ethanol-amended column. Sulfate reduction, sulfide production, and Zn{sup 2+} removal were also observed, with Zn{sup 2+} removal observed in the zone of sulfate reduction, indicating likely precipitation as sphalerite (ZnS). Se{sup 6+} removal was also observed in the sulfate reducing zone, probably as direct bioreduction to elemental selenium via ethanol/acetate oxidation or sulfide oxidation precipitating elemental sulfur. A step decrease in groundwater pH from 5.5 to 4.25 resulted in increased denitrification and sulfate reduction half-lives, migration of both these redox zones along the ethanol-amended column, and the formation of an elevated Cu{sup 2+} plume. Additionally, an elevated Zn{sup 2+} plume formed in the previous sulfate reducing zone of the ethanol-amended column, suggesting dissolution of precipitated sphalerite as a result of the reduction in groundwater pH. As Cu{sup 2+} passed through the zone of sphalerite dissolution, SEM imaging and EDS detection suggested that Cu{sup 2+} removal had occurred via chalcocite (Cu{sub 2}S) or covellite (CuS) precipitation. 23 refs., 8 figs.

  3. In vitro availability of zinc from infant foods with increasing phytic acid contents.

    PubMed

    Bosscher, D; Lu, Z; Janssens, G; Van Caillie-Bertrand, M; Robberecht, H; De Rycke, H; De Wilde, R; Deelstra, H

    2001-08-01

    An in vitro method was used to determine the availability of Zn from infant foods containing increasing amounts of phytate, and to quantify the effect of the phytate:Zn molar ratio on the availability. During the in vitro assay, digestive conditions of infants, younger and older than 4 months of age, were carefully simulated since the solubility of phytate-Zn complexes during digestion is pH dependent. Availability was measured with a continuous flow dialysis in vitro procedure with previous intralumen digestive stage. Zn concentrations were determined with flame atomic absorption spectrometry. Phytic acid content was measured with HPLC. Adding phytate to infant formula lowered Zn availability to 2.84 (sd 0.17) % when the phytate:Zn molar ratio increased to 2.2 as compared with cows' milk-based formula (6.65 (sd 0.55) %). Availability from vegetables (23.83 (sd 2.17) %) significantly decreased at a ratio > 7.9 (15.12 (sd 1.63) %). Zn availability from soyabean-based formula (2.26 (sd 0.36) %) was lower compared with cows' milk-based formula (6.65 (sd 0.55) %). Availability between soyabean- and cows' milk-based formula was similar when a phytate:Zn ratio of 2.2 (2.84 (sd 0.17) %) was obtained in the cows' milk formula. The negative effect of phytic acid on Zn availability was dependent on the type of the food and the phytate content, and should be considered when using soyabean-based formulas during early infancy.

  4. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice

    PubMed Central

    Strong, Randy; Miller, Richard A.; Astle, Clinton M.; Floyd, Robert A.; Flurkey, Kevin; Hensley, Kenneth L.; Javors, Martin A.; Leeuwenburgh, Christiaan; Nelson, James F.; Ongini, Ennio; Nadon, Nancy L.; Warner, Huber R.; Harrison, David E.

    2009-01-01

    The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas Health Science Center, San Antonio, UT). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-α-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA (p = 0.12) nor aspirin (p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  5. (-)-Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women.

    PubMed

    Lim, Kiwon; Ryu, Sungpil; Nho, Ho-Sung; Choi, Sung-Keun; Kwon, Taedong; Suh, Heajung; So, Jaemoo; Tomita, Kyoko; Okuhara, Yasuhide; Shigematsu, Norihiro

    2003-06-01

    (-)-Hydroxycitric acid (HCA) is a competitive inhibitor of the enzyme ATPcitrate-lyase, which inhibits lipogenesis in the body. Moreover, HCA increases endurance exercise performance in trained mice and athletes. However, had not been investigated in untrained animals and humans. Therefore, we investigated the effects of short-term HCA ingestion on endurance exercise performance and fat metabolism in untrained women. In two experiments designed as a double-blind crossover test, six subjects ingested 250 mg of HCA or placebo (same amount of dextrin) via capsule for 5 d and then participated in cycle ergometer exercise. They cycled at 40% VO2max for 1 h and then the exercise intensity was increased to 60% VO2max until exhaustion on day 5 of each experiment. HCA tended to decrease the respiratory exchange ratio (RER) and carbohydrate oxidation during 1 h of exercise. In addition, exercise time to exhaustion was significantly enhanced (p<0.05). These results suggest that HCA increases fat metabolism, which may be associated with a decrease in glycogen utilization during the same intensity exercise and enhanced exercise performance.

  6. Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression.

    PubMed

    Lee, Jeong-Min; Jang, Young-Saeng; Jin, Bo-Ra; Kim, Sun-Jin; Kim, Hyeon-Jin; Kwon, Bo-Eun; Ko, Hyun-Jeong; Yoon, Sung-Il; Lee, Geun-Shik; Kim, Woan-Sub; Seo, Goo-Young; Kim, Pyeung-Hyeun

    2016-11-01

    Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, TβRIII) and activation of canonical TGF-β signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α (GLα) transcription and GLα promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TβRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and α4β7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9(+)IgA(+) plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.

  7. Increased urinary lysophosphatidic acid in mouse with subtotal nephrectomy: potential involvement in chronic kidney disease.

    PubMed

    Mirzoyan, Koryun; Baïotto, Anna; Dupuy, Aude; Marsal, Dimitri; Denis, Colette; Vinel, Claire; Sicard, Pierre; Bertrand-Michel, Justine; Bascands, Jean-Loup; Schanstra, Joost P; Klein, Julie; Saulnier-Blache, Jean-Sébastien

    2016-12-01

    Increased incidence of chronic kidney disease (CKD) with consecutive progression to end-stage renal disease represents a significant burden to healthcare systems. Renal tubulointerstitial fibrosis (TIF) is a classical hallmark of CKD and is well correlated with the loss of renal function. The bioactive lysophospholipid lysophosphatidic acid (LPA), acting through specific G-protein-coupled receptors, was previously shown to be involved in TIF development in a mouse model of unilateral ureteral obstruction. Here, we study the role of LPA in a mouse subjected to subtotal nephrectomy (SNx), a more chronic and progressive model of CKD. Five months after surgical nephron reduction, SNx mice showed massive albuminuria, extensive TIF, and glomerular hypertrophy when compared to sham-operated animals. Urinary and plasma levels of LPA were analyzed using liquid chromatography tandem mass spectrometry. LPA was significantly increased in SNx urine, not in plasma, and was significantly correlated with albuminuria and TIF. Moreover, SNx mice showed significant downregulation in the renal expression of lipid phosphate phosphohydrolases (LPP1, 2, and 3) that might be involved in reduced LPA bioavailability through dephosphorylation. We concluded that SNx increases urinary LPA through a mechanism that could involve co-excretion of plasma LPA with albumin associated with a reduction of its catabolism in the kidney. Because of the previously demonstrated profibrotic activity of LPA, the association of urinary LPA with TIF suggests the potential involvement of LPA in the development of advanced CKD in the SNx mouse model. Targeting LPA metabolism might represent an interesting approach in CKD treatment.

  8. Drought-Induced Increases in Abscisic Acid Levels in the Root Apex of Sunflower 1

    PubMed Central

    Robertson, J. Mason; Pharis, Richard P.; Huang, Yan Y.; Reid, David M.; Yeung, Edward C.

    1985-01-01

    Abscisic acid (ABA) levels in 3-mm apical root segments of slowly droughted sunflower plants (Helianthus annuus L. cv Russian Giant) were analyzed as the methyl ester by selected ion monitoring gas chromatography-mass spectrometry using characteristic ions. An internal standard, hexadeuterated ABA (d6ABA) was used for quantitative analysis. Sunflower seedlings, grown in aeroponic chambers, were slowly droughted over a 7-day period. Drought stress increased ABA levels in the root tips at 24, 72, and 168 hour sample times. Control plants had 57 to 106 nanograms per gram ABA dry weight in the root tips (leaf water potential, −0.35 to −0.42 megapascals). The greatest increase in ABA, about 20-fold, was found after 72 hours of drought (leaf water potential, −1.34 to −1.47 megapascals). Levels of ABA also increased (about 7− to 54-fold) in 3-mm apical root segments which were excised and then allowed to dessicate for 1 hour at room temperature. PMID:16664535

  9. Suberoylanilide hydroxamic acid (SAHA) at subtoxic concentrations increases the adhesivity of human leukemic cells to fibronectin.

    PubMed

    Kuzelová, Katerina; Pluskalová, Michaela; Brodská, Barbora; Otevrelová, Petra; Elknerová, Klára; Grebenová, Dana; Hrkal, Zbynek

    2010-01-01

    Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) which is being introduced into clinic for the treatment of hematological diseases. We studied the effect of this compound on six human hematopoietic cell lines (JURL-MK1, K562, CML-T1, Karpas-299, HL-60, and ML-2) as well as on normal human lymphocytes and on leukemic primary cells. SAHA induced dose-dependent and cell type-dependent cell death which displayed apoptotic features (caspase-3 activation and apoptotic DNA fragmentation) in most cell types including the normal lymphocytes. At subtoxic concentrations (0.5-1 microM), SAHA increased the cell adhesivity to fibronectin (FN) in all leukemia/lymphoma-derived cell lines but not in normal lymphocytes. This increase was accompanied by an enhanced expression of integrin beta1 and paxillin, an essential constituent of focal adhesion complexes, both at the protein and mRNA level. On the other hand, the inhibition of ROCK protein, an important regulator of cytoskeleton structure, had no consistent effect on SAHA-induced increase in the cell adhesivity. The promotion of cell adhesivity to FN seems to be specific for SAHA as we observed no such effects with other HDAC inhibitors (trichostatin A and sodium butyrate).

  10. Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Production Significantly Increases during Tricarboxylic Acid Cycle Stress

    PubMed Central

    Vuong, Cuong; Kidder, Joshua B.; Jacobson, Erik R.; Otto, Michael; Proctor, Richard A.; Somerville, Greg A.

    2005-01-01

    Staphylococcal polysaccharide intercellular adhesin (PIA) is important for the development of a mature biofilm. PIA production is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same environmental conditions are known to repress tricarboxylic acid (TCA) cycle activity, leading us to hypothesize that altering TCA cycle activity would affect PIA production. Culturing Staphylococcus epidermidis with a low concentration of the TCA cycle inhibitor fluorocitrate dramatically increased PIA production without impairing glucose catabolism, the growth rate, or the growth yields. These data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, or the redox status of the cell. These changes in the metabolic status of the bacteria result in the attenuation or augmentation of PIA production. PMID:15838022

  11. A synthetic five amino acid propeptide increases dopamine neuron differentiation and neurochemical function

    PubMed Central

    Littrell, OM; Fuqua, JL; Richardson, AD; Turchan-Cholewo, J.; Hascup, ER; Huettl, P; Pomerleau, F; Bradley, LH; Gash, DM; Gerhardt, GA

    2012-01-01

    A major consequence of Parkinson’s disease (PD) involves the loss of dopaminergic neurons in the substantia nigra (SN) and a subsequent loss of dopamine (DA) in the striatum. We have shown that glial cell line-derived neurotrophic factor (GDNF) shows robust restorative and protective effects for DA neurons in rats, non-human primates and possibly in humans. Despite GDNF’s therapeutic potential, its clinical value has been questioned due to its limited diffusion to target areas from its large size and chemical structure. Several comparatively smaller peptides are thought to be generated from the prosequence. A five amino-acid peptide, dopamine neuron stimulating peptide-5 (DNSP-5), has been proposed to demonstrate biological activity relevant to neurodegenerative disease. We tested the in vitro effects of DNSP-5 in primary dopaminergic neurons dissected from the ventral mesencephalon of E14 Sprague Dawley rat fetuses. Cells were treated with several doses (0.03, 0.1, 1.0, 10.0 ng/mL) of GDNF, DNSP-5, or an equivalent volume of citrate buffer (vehicle). Morphological features of tyrosine hydroxylase positive neurons were quantified for each dose. DNSP-5 significantly increased (p<0.001) all differentiation parameters compared to citrate vehicle (at one or more dose). For in vivo studies, a unilateral DNSP-5 treatment (30 µg) was administered directly to the SN. Microdialysis in the ipsilateral striatum was performed 28 days after treatment to determine extracellular levels of DA and its primary metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). A single treatment significantly increased (~66%) extracellular DA levels compared to vehicle, while DA metabolites were unchanged. Finally, the protective effects of DNSP-5 against staurosporine-induced cytotoxicity were investigated in a neuronal cell line showing substantial protection by DNSP-5. Altogether, these studies strongly indicate biological activity of DNSP-5 and suggest that DNSP-5 has

  12. Increased fatty acid unsaturation and production of arachidonic acid by homologous over-expression of the mitochondrial malic enzyme in Mortierella alpina.

    PubMed

    Hao, Guangfei; Chen, Haiqin; Du, Kai; Huang, Xiaoyun; Song, Yuanda; Gu, Zhennan; Wang, Lei; Zhang, Hao; Chen, Wei; Chen, Yong Q

    2014-09-01

    Malic enzyme (ME) catalyses the oxidative decarboxylation of L-malate to pyruvate and provides NADPH for intracellular metabolism, such as fatty acid synthesis. Here, the mitochondrial ME (mME) gene from Mortierella alpina was homologously over-expressed. Compared with controls, fungal arachidonic acid (ARA; 20:4 n-6) content increased by 60 % without affecting the total fatty acid content. Our results suggest that enhancing mME activity may be an effective mean to increase industrial production of ARA in M. alpina.

  13. Growth hormone increases somatostatin release and messenger ribonucleic acid levels in the rat hypothalamus.

    PubMed

    Aguila, M C; McCann, S M

    1993-09-24

    Growth hormone (GH) suppresses its own secretion by stimulating somatostatin (SRIF) release. Thus, the possible regulation of GH-releasing factor (GRF) and SRIF release and SRIF messenger ribonucleic acid (mRNA) by GH was studied in the hypothalamus of male rats in vitro. The median eminences (ME's) were incubated in buffer containing 10(-7)-10(-11) M GH for 30 min. SRIF and GRF released into the medium were quantitated by RIA. The release of SRIF from ME fragments was significantly increased (P < 0.001) by 10(-9) M GH; however, 10(-9) M GH also inhibited (P < 0.01) GRF release from the ME. To determine the effect of GH on SRIF mRNA levels, periventricular nucleus (PeN) explants were cultured during 6 h in medium with 10(-7)-10(-11) M GH. Levels of SRIF mRNA (determined by an S1 nuclease protection assay) were significantly elevated in the presence of 10(-10)-10(-7) M GH. Likewise, 10(-9) M GH significantly stimulated SRIF release from PeN explants at 30 min and at 6 h. Surprisingly, 10(-9) M GH also significantly increased GRF release from the PeN explants at these times as well. This GRF was not responsible for the increased SRIF release or SRIF mRNA induced by GH since GRF antibody did not modify the GH-induced increases in SRIF release and mRNA levels. These results demonstrate a negative short-loop feedback of GH mediated at the ME by suppression of GRF and stimulation of SRIF release, whereas in the PeN GH increased both SRIF release and SRIF mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Plasma circulating nucleic acids levels increase according to the morbidity of Plasmodium vivax malaria.

    PubMed

    Franklin, Bernardo S; Vitorino, Barbara L F; Coelho, Helena C; Menezes-Neto, Armando; Santos, Marina L S; Campos, Fernanda M F; Brito, Cristiana F; Fontes, Cor J; Lacerda, Marcus V; Carvalho, Luzia H

    2011-01-01

    Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity.

  15. Plasma Circulating Nucleic Acids Levels Increase According to the Morbidity of Plasmodium vivax Malaria

    PubMed Central

    Franklin, Bernardo S.; Vitorino, Barbara L. F.; Coelho, Helena C.; Menezes-Neto, Armando; Santos, Marina L. S.; Campos, Fernanda M. F.; Brito, Cristiana F.; Fontes, Cor J.; Lacerda, Marcus V.; Carvalho, Luzia H.

    2011-01-01

    Background Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. Methods and Findings CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Conclusions Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity. PMID:21611202

  16. Increased production of γ-lactones from hydroxy fatty acids by whole Waltomyces lipofer cells induced with oleic acid.

    PubMed

    An, Jung-Ung; Oh, Deok-Kun

    2013-09-01

    Among several fatty acids tested, oleic acid was selected as the most efficient inducer for the production of 4-hydroxydodecanoic acid, a metabolite of β-oxidation, by Waltomyces lipofer. Cells were induced by incubation for 12 h in a medium containing 10 g l(-1) yeast extract, 10 g l(-1) peptone, 5 g l(-1) oleic acid, 1 g l(-1) glucose, and 0.05 % (w/v) Tween 80. The optimal reaction conditions for the production of γ-lactones by induced cells were pH 6.5, 35 °C, 200 rpm, 0.71 M Tris, 60 g l(-1) hydroxy fatty acid, and 20 g l(-1) cells. Non-induced cells produced 38 g l(-1) γ-dodecalactone from 60 g l(-1) 10-hydroxystearic acid after 30 h, with a conversion yield of 63 % (w/w) and a productivity of 1.3 g l(-1) h(-1) under the optimized conditions, whereas induced cells produced 51 g l(-1) γ-dodecalactone from 60 g l(-1) 10-hydroxystearic acid after 30 h, with a conversion yield of 85 % (w/w) and a productivity of 1.7 g l(-1) h(-1). The conversion yield and productivity of induced cells were 22 % and 1.3-fold higher, respectively, than those of non-induced cells. Induced cells also produced 28 g l(-1) γ-decalactone and 12 g l(-1) γ-butyrolactone from 60 g l(-1) 12-hydroxystearic acid and 60 g l(-1) 10-hydroxydecanoic acid, respectively, after 30 h. The concentration, conversion yield, and productivity of γ-dodecalactone and γ-decalactone are the highest reported thus far. This is the first study on the biotechnological production of γ-butyrolactone.

  17. Valproic acid increases conservative homologous recombination frequency and reactive oxygen species formation: a potential mechanism for valproic acid-induced neural tube defects.

    PubMed

    Defoort, Ericka N; Kim, Perry M; Winn, Louise M

    2006-04-01

    Valproic acid, a commonly used antiepileptic agent, is associated with a 1 to 2% incidence of neural tube defects when taken during pregnancy; however, the molecular mechanism by which this occurs has not been elucidated. Previous research suggests that valproic acid exposure leads to an increase in reactive oxygen species (ROS). DNA damage due to ROS can result in DNA double-strand breaks, which can be repaired through homologous recombination (HR), a process that is not error-free and can result in detrimental genetic changes. Because the developing embryo requires tight regulation of gene expression to develop properly, we propose that the loss or dysfunction of genes involved in embryonic development through aberrant HR may ultimately cause neural tube defects. To determine whether valproic acid induces HR, Chinese hamster ovary 3-6 cells, containing a neomycin direct repeat recombination substrate, were exposed to valproic acid for 4 or 24 h. A significant increase in HR after exposure to valproic acid (5 and 10 mM) for 24 h was observed, which seems to occur through a conservative HR mechanism. We also demonstrated that exposure to valproic acid (5 and 10 mM) significantly increased intracellular ROS levels, which were attenuated by preincubation with polyethylene glycol-conjugated (PEG)-catalase. A significant change in the ratio of 8-hydroxy-2'-deoxyguanosine/2'-de-oxyguanosine, a measure of DNA oxidation, was not observed after valproic acid exposure; however, preincubation with PEG-catalase significantly blocked the increase in HR. These data demonstrate that valproic acid increases HR frequency and provides a possible mechanism for valproic acid-induced neural tube defects.

  18. A thraustochytrid diacylglycerol acyltransferase 2 with broad substrate specificity strongly increases oleic acid content in engineered Arabidopsis thaliana seeds

    PubMed Central

    Zhang, Chunyu; Iskandarov, Umidjon; Cahoon, Edgar B.

    2013-01-01

    Diacylglycerol acyltransferase (DGAT) catalyses the last step in acyl-CoA-dependent triacylglycerol (TAG) biosynthesis and is an important determinant of cellular oil content and quality. In this study, a gene, designated TaDGAT2, encoding a type 2 DGAT (DGAT2)-related enzyme was identified from the oleaginous marine protist Thraustochytrium aureum. The deduced TaDGAT2 sequence contains a ~460 amino acid domain most closely related to DGAT2s from Dictyostelium sp. (45–50% identity). Recombinant TaDGAT2 restored TAG biosynthesis to the Saccharomyces cerevisiae H1246 TAG-deficient mutant, and microsomes from the complemented mutant displayed DGAT activity with C16 and C18 saturated and unsaturated fatty acyl-CoA and diacylglycerol substrates. To examine its biotechnological potential, TaDGAT2 was expressed under control of a strong seed-specific promoter in wild-type Arabidopsis thaliana and the high linoleic acid fad3fae1 mutant. In both backgrounds, little change was detected in seed oil content, but a striking increase in oleic acid content of seeds was observed. This increase was greatest in fad3fae1 seeds, where relative amounts of oleic acid increased nearly 2-fold to >50% of total fatty acids. In addition, >2-fold increase in oleic acid levels was detected in the triacylglycerol sn-2 position and in the major seed phospholipid phosphatidylcholine. These results suggest that increased seed oleic acid content mediated by TaDGAT2 is influenced in part by the fatty acid composition of host cells and occurs not by enhancing oleic acid content at the TAG sn-3 position directly but by increasing total oleic acid levels in seeds, presumably by limiting flux through phosphatidylcholine-based desaturation reactions. PMID:23814277

  19. A thraustochytrid diacylglycerol acyltransferase 2 with broad substrate specificity strongly increases oleic acid content in engineered Arabidopsis thaliana seeds.

    PubMed

    Zhang, Chunyu; Iskandarov, Umidjon; Klotz, Elliott T; Stevens, Robyn L; Cahoon, Rebecca E; Nazarenus, Tara J; Pereira, Suzette L; Cahoon, Edgar B

    2013-08-01

    Diacylglycerol acyltransferase (DGAT) catalyses the last step in acyl-CoA-dependent triacylglycerol (TAG) biosynthesis and is an important determinant of cellular oil content and quality. In this study, a gene, designated TaDGAT2, encoding a type 2 DGAT (DGAT2)-related enzyme was identified from the oleaginous marine protist Thraustochytrium aureum. The deduced TaDGAT2 sequence contains a ~460 amino acid domain most closely related to DGAT2s from Dictyostelium sp. (45-50% identity). Recombinant TaDGAT2 restored TAG biosynthesis to the Saccharomyces cerevisiae H1246 TAG-deficient mutant, and microsomes from the complemented mutant displayed DGAT activity with C16 and C18 saturated and unsaturated fatty acyl-CoA and diacylglycerol substrates. To examine its biotechnological potential, TaDGAT2 was expressed under control of a strong seed-specific promoter in wild-type Arabidopsis thaliana and the high linoleic acid fad3fae1 mutant. In both backgrounds, little change was detected in seed oil content, but a striking increase in oleic acid content of seeds was observed. This increase was greatest in fad3fae1 seeds, where relative amounts of oleic acid increased nearly 2-fold to >50% of total fatty acids. In addition, >2-fold increase in oleic acid levels was detected in the triacylglycerol sn-2 position and in the major seed phospholipid phosphatidylcholine. These results suggest that increased seed oleic acid content mediated by TaDGAT2 is influenced in part by the fatty acid composition of host cells and occurs not by enhancing oleic acid content at the TAG sn-3 position directly but by increasing total oleic acid levels in seeds, presumably by limiting flux through phosphatidylcholine-based desaturation reactions.

  20. Dietary supplementation of conjugated linoleic acid in horses increases plasma conjugated linoleic acid and decreases plasma arachidonic acid but does not alter body fat.

    PubMed

    Headley, S; Coverdale, J A; Jenkins, T C; Klein, C M; Sharp, J L; Vernon, K L

    2012-12-01

    Studies using dietary supplementation of eicosapentaenoic and docosahexaenoic fatty acids (FA) in horses report inconsistent anti-inflammatory results but consistently report an increase in plasma arachidonic acid (C20:4), the major substrate of cyclooxygenase (COX) II inflammatory pathway. Conjugated linoleic acid has shown anti-inflammatory effects in laboratory and food animal species, but effects of CLA supplementation in horses have not been reported. Our objective was to determine the effects of CLA supplementation on plasma CLA and C20:4 and body fat in healthy horses at maintenance. In a crossover study, 12 mature mares were blocked by breed, age, and BCS and separated into 2 treatment groups (n = 6/group). Groups were fed CLA and corn oil (CO; isocaloric control) for two 6-wk feeding periods, separated by a 4-wk period during which treatment was withheld. Corn oil or CLA supplement (55% mixed CLA isomers) was incorporated into diets at 0.01% BW/d. Mares were fed individually and restricted to dry lots to control forage intake. Rump fat thickness (RFT), BW, and BCS were measured before (d 0) and after (d 42) each feeding period. Blood was collected on d 0, 14, 28, and 42 of each 6-wk period for GLC analysis of plasma CLA isomers (cis-9, trans-11; trans-10, cis-12; and trans-9, trans-11) and C20:4. An ANOVA was conducted to compare the response of RFT, BW, and BCS of CLA-treated and control mares. A mixed methods analysis with repeated measures was used to detect differences in plasma FA concentrations. There were no differences in BW, RFT, or BCS between treatment groups. All CLA isomers present in the CLA supplement were greater in plasma of horses fed CLA compared with controls (P < 0.01). Additionally, plasma concentrations of C20:4 were decreased in horses fed CLA (P < 0.05). This decline in C20:4 may impact the COX II pathway and warrants further investigation. These results suggest that in an equine model, dietary CLA increases circulating

  1. Method for construction of bacterial strains with increased succinic acid production

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia; Chatterjee, Ranjini

    2000-01-01

    A fermentation process for producing succinic acid is provided comprising selecting a bacterial strain that does not produce succinic acid in high yield, disrupting the normal regulation of sugar metabolism of said bacterial strain, and combining the mutant bacterial strain and selected sugar in anaerobic conditions to facilitate production of succinic acid. Also provided is a method for changing low yield succinic acid producing bacteria to high yield succinic acid producing bacteria comprising selecting a bacterial strain having a phosphotransferase system and altering the phosphotransferase system so as to allow the bacterial strain to simultaneously metabolize different sugars.

  2. Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

    PubMed

    Kondo, Atsuo; Morota, Nobuhito; Date, Hiroaki; Yoshifuji, Kazuhisa; Morishima, Toshibumi; Miyazato, Minoru; Shirane, Reizo; Sakai, Hideki; Pooh, Kyong Hon; Watanabe, Tomoyuki

    2015-07-14

    The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan.

  3. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins

    PubMed Central

    Hannukainen, Jarna C; Nuutila, Pirjo; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher V˙O2,max (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)−1 min−1, P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  4. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus.

    PubMed

    Bandara, Suren B; Eubig, Paul A; Sadowski, Renee N; Schantz, Susan L

    2016-02-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus

    PubMed Central

    Bandara, Suren B.; Eubig, Paul A.; Sadowski, Renee N.; Schantz, Susan L.

    2016-01-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID:26543103

  6. Increased adhesion between neutral lipid bilayers: interbilayer bridges formed by tannic acid.

    PubMed Central

    Simon, S A; Disalvo, E A; Gawrisch, K; Borovyagin, V; Toone, E; Schiffman, S S; Needham, D; McIntosh, T J

    1994-01-01

    Tannic acid (TA) is a naturally occurring polyphenolic compound that aggregates membranes and neutral phosolipid vesicles and precipitates many proteins. This study analyzes TA binding to lipid membranes and the ensuing aggregation. The optical density of dispersions of phosphatidylcholine (PC) vesicles increased upon the addition of TA and electron micrographs showed that TA caused the vesicles to aggregate and form stacks of tightly packed disks. Solution calorimetry showed that TA bound to PC bilayers with a molar binding enthalpy of -8.3 kcal/mol and zeta potential measurements revealed that TA imparted a small negative charge to PC vesicles. Monolayer studies showed that TA bound to PC with a dissociation constant of 1.5 microM and reduced the dipole potential by up to 250 mV. Both the increase in optical density and decrease in dipole potential produced by TA could be reversed by the addition of polyvinylpyrrolidone, a compound that chelates TA by providing H-bond acceptor groups. NMR, micropipette aspiration, and x-ray diffraction experiments showed that TA incorporated into liquid crystalline PC membranes, increasing the area per lipid molecule and decreasing the bilayer thickness by 2 to 4%. 2H-NMR quadrupole splitting measurements also showed that TA associated with a PC molecule for times much less than 10(-4) s. In gel phase bilayers, TA caused the hydrocarbon chains from apposing monolayers to fully interdigitate. X-ray diffraction measurements of both gel and liquid crystalline dispersions showed that TA, at a critical concentration of about 1 mM, reduced the fluid spacing between adjacent bilayers by 8-10 A. These data place severe constraints on how TA can pack between adjacent bilayers and cause vesicles to adhere. We conclude that TA promotes vesicle aggregation by reducing the fluid spacing between bilayers by the formation of transient interbilayer bridges by inserting its digallic acid residues into the interfacial regions of adjacent bilayers

  7. Dietary Conjugated Linoleic Acid (CLA) increases milk yield without losing body weight in lactating sows.

    PubMed

    Lee, Sung-Hoon; Joo, Young-Kuk; Lee, Jin-Woo; Ha, Young-Joo; Yeo, Joon-Mo; Kim, Wan-Young

    2014-01-01

    This study was conducted to evaluate the effects of dietary conjugated linoleic acid (CLA) on the performance of lactating sows and piglets as well as the immunity of piglets suckling from sows fed CLA. Eighteen multiparous Duroc sows with an average body weight (BW) of 232.0 ± 6.38 kg were randomly selected and assigned to two dietary treatments (n = 9 for each treatment), control (no CLA addition) and 1% CLA supplementation. For the control diet, CLA was replaced with soybean oil. Experimental diets were fed to sows during a 28-day lactation period. Litter size for each sow was standardized to nine piglets by cross-fostering within 24 hours after birth. Sow milk and blood samples were taken from sows and piglets after 21 and 27 days of lactation, respectively. Loss of BW was significantly (p < 0.05) higher in sows fed control diet compared to sows fed CLA diet. Piglet weights at weaning and weight gain during suckling were significantly (p < 0.05) higher in sows fed CLA compared to sows fed control diet. Serum non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. IgG concentrations of the groups supplemented with CLA increased by 49% in sow serum (p < 0.0001), 23% in milk (p < 0.05), and 35% in piglet serum (p < 0.05) compared with the control group. Sows fed CLA showed an increase of 10% in milk yield compared with sows fed soybean oil (p < 0.05), even though there was no difference in daily feed intake between the treatments. Milk fat content was significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. Solid-not-fat yield was significantly (p < 0.05) higher in sows supplemented with CLA than in sows fed control diet and also protein-to-fat ratio in milk was significantly (p < 0.05) higher in sows fed CLA compared with the control group. The results show that CLA supplementation to sows increased milk yield without losing BW during

  8. A geographic cline in leaf salicylic acid with increasing elevation in Arabidopsis thaliana

    PubMed Central

    Zhang, Nana; Tonsor, Stephen J; Traw, M Brian

    2015-01-01

    Salicylic acid (SA) occupies a key role as a hormone central to both plant resistance to bacterial pathogens and tolerance of abiotic stresses. Plants at high elevation experience colder temperatures and elevated UV levels. While it has been predicted that SA concentrations will be higher in plants from high elevation populations, few studies have addressed this question. Here, we asked how concentrations of SA vary in natural populations of Arabidopsis thaliana collected across an elevational gradient on the Iberian Peninsula. In a series of common garden experiments, we found that constitutive SA concentrations were highest in genotypes from the low elevation populations. This result was in the opposite direction from our prediction and is an exception to the general finding that phenolic compounds increase with increasing elevation. These data suggest that high constitutive SA is not associated with resistance to cold temperatures in these plants. Furthermore, we also found that leaf constitutive camalexin concentrations, an important defense against some bacterial and fungal enemies, were highest in the low elevation populations, suggesting that pathogen pressures may be important. Further examination of this elevational cline will likely provide additional insights into the interplay between phenolic compounds and biotic and abiotic stress. PMID:25875692

  9. Goat milk fat naturally enriched with conjugated linoleic acid increased lipoproteins and reduced triacylglycerol in rats.

    PubMed

    Rodrigues, Raphaela; Soares, Juliana; Garcia, Hugo; Nascimento, Claudenice; Medeiros, Maria; Bomfim, Marco; Medeiros, Maria Carmo; Queiroga, Rita

    2014-03-24

    Goat milk is source of different lipids, including conjugated linoleic acid (CLA). CLA reduces body fat and protect against cardiovascular diseases. In the present study fat from goat milk naturally enriched with CLA was used. Male Wistar rats were divided into three groups that received during a 10 week diet with different lipid sources: soybean oil (CON), coconut oil (CO) and goat milk fat naturally enriched with CLA (GM-CLA). We evaluated the effects of a GM-CLA on biochemistry parameters--high density lipoprotein (HDL), triacylglycerol (TAG), TAG/HDL ratio, total cholesterol and glucose, body weight and histopathological aspects of the intestine and liver. GM-CLA increased body weight from the second to the fifth week of the experiment compared to CON. Feed intake differed between the CON group and GM-CLA early in the first to third week of the experiments and later between the ninth and tenth week. The CLA-diet group showed increased levels of HDL, reduced levels of TAG and TAG/HDL ratio and no effect on LDL, but enhanced total cholesterol. Serum glucose of the GM-CLA group showed no difference from the control group. Thus, a GM-CLA diet promoted growth in young rats and acted as protector of cardiovascular function, but further studies are still needed to clarify these effects.

  10. Is increased arachidonic acid release a cause or a consequence of replicative senescence?

    PubMed

    Lorenzini, A; Hrelia, S; Bordoni, A; Biagi, P; Frisoni, L; Marinucci, T; Cristofalo, V J

    2001-01-01

    Arachidonic acid (AA) has been related to both stimulation and inhibition of cellular proliferation. During replicative senescence of human fibroblasts, increased levels of AA have been thought to play a causal role in the limited proliferative capacity of the cells. To clarify the role of AA in the proliferation of normal fibroblasts and in cellular senescence, we examined uptake from and release of AA into the culture media and its effects on DNA synthesis. Our results indicate that some aspects of AA metabolism in normal human fibroblasts aged in culture are significantly different in comparison to early passage cells. Particularly, AA release following different mitogenic stimulation is higher in senescent than in young cells. Notwithstanding this significant difference, AA, at the concentration used, has no inhibitory effect on fibroblast DNA synthesis. Moreover AA and prostaglandins are responsible for the proliferative block in neither senescent cells nor mediate ceramide inhibition of DNA synthesis. So our results suggest that the increasing AA release is not causal, but rather the result of in vitro aging.

  11. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation[S

    PubMed Central

    Bot, Martine; de Jager, Saskia C. A.; MacAleese, Luke; Lagraauw, H. Maxime; van Berkel, Theo J. C.; Quax, Paul H. A.; Kuiper, Johan; Heeren, Ron M. A.; Biessen, Erik A. L.; Bot, Ilze

    2013-01-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. PMID:23396975

  12. Retinoic acid increases zif268 early gene expression in rat preosteoblastic cells.

    PubMed Central

    Suva, L J; Ernst, M; Rodan, G A

    1991-01-01

    In this study we demonstrate that retinoic acid (RA) increases the expression of transcription factor zif268 mRNA in primary cultures of fetal rat calvarial cells and in simian virus 40-immortalized clonal rat calvarial preosteoblastic cells (RCT-1), which differentiate in response to RA, but not in the more differentiated RCT-3 and ROS 17/2.8 cells. The increased expression of zif268 mRNA is rapid (maximal within 1 h), transient (returns to basal levels by 3 h), detectable at RA doses of 10(-12)M, and independent of protein synthesis. The relative stimulation of zif268 mRNA by RA was much larger than that of other early genes, including c-fos, c-jun, and junB. The rate of transcription of RA-stimulated RCT-1 cells, estimated by nuclear run-on assays, was elevated, suggesting that RA regulation of zif268 gene transcription was at least in part transcriptional. Moreover, RA stimulated the transcriptional activity of a Zif268CAT (chloramphenicol acetyltransferase) plasmid containing 632 bp of zif268 5' regulatory sequences in RCT-1 cells but not in the more differentiated RCT-3 cells. These in vitro data support the in vivo observations which localize zif268 and RA receptor-gamma transcripts to bone and cartilage during development, suggesting that both RA and zif268 may play a role in osteoblast differentiation. Images PMID:1708092

  13. Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid

    PubMed Central

    Iyengar, Sloka S.; LaFrancois, John J.; Friedman, Daniel; Drew, Liam J.; Denny, Christine A.; Burghardt, Nesha S.; Wu, Melody V.; Hsieh, Jenny; Hen, René; Scharfman, Helen E.

    2016-01-01

    Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA. PMID:25476494

  14. Increased presence of monounsaturated fatty acids in the stratum corneum of human skin equivalents.

    PubMed

    Thakoersing, Varsha S; van Smeden, Jeroen; Mulder, Aat A; Vreeken, Rob J; El Ghalbzouri, Abdoelwaheb; Bouwstra, Joke A

    2013-01-01

    Previous results showed that our in-house human skin equivalents (HSEs) differ in their stratum corneum (SC) lipid organization compared with human SC. To elucidate the cause of the altered SC lipid organization in the HSEs, a recently developed liquid chromatography/mass spectrometry method was used to study the free fatty acid (FFA) and ceramide composition in detail. In addition, the SC lipid composition of the HSEs and human skin was examined quantitatively with high-performance thin-layer chromatography. Our results reveal that all our HSEs have an increased presence of monounsaturated FFAs compared with human SC. Moreover, the HSEs display the presence of ceramide species with a monounsaturated acyl chain, which are not detected in human SC. All HSEs also exhibit an altered expression of stearoyl-CoA desaturase, the enzyme that converts saturated FFAs to monounsaturated FFAs. Furthermore, the HSEs show the presence of 12 ceramide subclasses, similar to native human SC. However, the HSEs have increased levels of ceramides EOS and EOH and ceramide species with short total carbon chains and a reduced FFA level compared with human SC. The presence of unsaturated lipid chains in HSE offers new opportunities to mimic the lipid properties of human SC more closely.

  15. Extreme soil acidity from biodegradable trap and skeet targets increases severity of pollution at shooting ranges.

    PubMed

    McTee, Michael R; Mummey, Daniel L; Ramsey, Philip W; Hinman, Nancy W

    2016-01-01

    Lead pollution at shooting ranges overshadows the potential for contamination issues from trap and skeet targets. We studied the environmental influence of targets sold as biodegradable by determining the components of the targets and sampling soils at a former sporting clay range. Targets comprised approximately 53% CaCO3, 41% S(0), and 6% modifiers, and on a molar basis, there was 2.3 times more S(0) than CaCO3. We observed a positive correlation between target cover and SO4(2-) (ρ=0.82, P<0.001), which indicated the oxidation of S(0) to H2SO4. Sulfate was negatively correlated with pH (ρ=-0.93, P<0.001) because insufficient CaCO3 existed in the targets to neutralize all the acid produced from S(0) oxidation. Plant cover decreased with decreasing soil pH (ρ=0.62, P=0.006). For sites that had pH values below 3, 24tons of lime per 1000tons of soil would be required to raise soil pH to 6.5. Lime-facilitated pH increases would be transitory because S(0) would continue to oxidize to H2SO4 until the S(0) is depleted. This study demonstrates that biodegradable trap and skeet targets can acidify soil, which has implications for increasing the mobility of Pb from shotgun pellets.

  16. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

    PubMed

    Bot, Martine; de Jager, Saskia C A; MacAleese, Luke; Lagraauw, H Maxime; van Berkel, Theo J C; Quax, Paul H A; Kuiper, Johan; Heeren, Ron M A; Biessen, Erik A L; Bot, Ilze

    2013-05-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

  17. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity

    PubMed Central

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M.; Park, Jin-Byung

    2016-01-01

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass. PMID:27681369

  18. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

    PubMed

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  19. Antagonizing Retinoic Acid Receptors Increases Myeloid Cell Production by Cultured Human Hematopoietic Stem Cells.

    PubMed

    Brown, Geoffrey; Marchwicka, Aleksandra; Cunningham, Alan; Toellner, Kai-Michael; Marcinkowska, Ewa

    2017-02-01

    Activities of the retinoic acid receptor (RAR)α and RARγ are important to hematopoiesis. Here, we have investigated the effects of receptor selective agonists and antagonists on the primitive human hematopoietic cell lines KG1 and NB-4 and purified normal human hematopoietic stem cells (HSCs). Agonizing RARα (by AGN195183) was effective in driving neutrophil differentiation of NB-4 cells and this agonist synergized with a low amount (10 nM) of 1α,25-dihydroxyvitamin D3 to drive monocyte differentiation of NB-4 and KG1 cells. Treatment of cultures of human HSCs (supplemented with stem cell factor ± interleukin 3) with an antagonist of all RARs (AGN194310) or of RARα (AGN196996) prolonged the lifespan of cultures, up to 55 days, and increased the production of neutrophils and monocytes. Slowing down of cell differentiation was not observed, and instead, hematopoietic stem and progenitor cells had expanded in number. Antagonism of RARγ (by AGN205728) did not affect cultures of HSCs. Studies of CV-1 and LNCaP cells transfected with RAR expression vectors and a reporter vector revealed that RARγ and RARβ are activated by sub-nM all-trans retinoic acid (EC50-0.3 nM): ~50-fold more is required for activation of RARα (EC50-16 nM). These findings further support the notion that the balance of expression and activity of RARα and RARγ are important to hematopoietic stem and progenitor cell expansion and differentiation.

  20. An Arabidopsis purple acid phosphatase with phytase activity increases foliar ascorbate.

    PubMed

    Zhang, Wenyan; Gruszewski, Hope A; Chevone, Boris I; Nessler, Craig L

    2008-02-01

    Ascorbate (AsA) is the most abundant antioxidant in plant cells and a cofactor for a large number of key enzymes. However, the mechanism of how AsA levels are regulated in plant cells remains unknown. The Arabidopsis (Arabidopsis thaliana) activation-tagged mutant AT23040 showed a pleiotropic phenotype, including ozone resistance, rapid growth, and leaves containing higher AsA than wild-type plants. The phenotype was caused by activation of a purple acid phosphatase (PAP) gene, AtPAP15, which contains a dinuclear metal center in the active site. AtPAP15 was universally expressed in all tested organs in wild-type plants. Overexpression of AtPAP15 with the 35S cauliflower mosaic virus promoter produced mutants with up to 2-fold increased foliar AsA, 20% to 30% decrease in foliar phytate, enhanced salt tolerance, and decreased abscisic acid sensitivity. Two independent SALK T-DNA insertion mutants in AtPAP15 had 30% less foliar AsA and 15% to 20% more phytate than wild-type plants and decreased tolerance to abiotic stresses. Enzyme activity of partially purified AtPAP15 from plant crude extract and recombinant AtPAP15 expressed in bacteria and yeast was highest when phytate was used as substrate, indicating that AtPAP15 is a phytase. Recombinant AtPAP15 also showed enzyme activity on the substrate myoinositol-1-phosphate, indicating that the AtPAP15 is a phytase that hydrolyzes myoinositol hexakisphosphate to yield myoinositol and free phosphate. Myoinositol is a known precursor for AsA biosynthesis in plants. Thus, AtPAP15 may modulate AsA levels by controlling the input of myoinositol into this branch of AsA biosynthesis in Arabidopsis.

  1. High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells.

    PubMed

    Pellis, Linette; Dommels, Yvonne; Venema, Dini; Polanen, Ab van; Lips, Esther; Baykus, Hakan; Kok, Frans; Kampman, Ellen; Keijer, Jaap

    2008-04-01

    Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate-methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.

  2. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  3. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  4. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

    PubMed Central

    Ulleryd, Marcus A.; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov

    2016-01-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics, S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus. Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival. PMID:26857576

  5. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis.

    PubMed

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E

    2016-04-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.

  6. Primary Action of Indole-3-acetic Acid in Crown Gall Tumors: Increase of Solute Uptake.

    PubMed

    Rausch, T; Kahl, G; Hilgenberg, W

    1984-06-01

    Exogenously added indole-3-acetic acid at a concentration of 100 micromolars stimulates d-glucose uptake (or 3-O-methyl-d-glucose uptake) by 25% in crown gall tumors induced on potato tuber tissue by Agrobacterium tumefaciens strain C 58. The titration of the endogenous IAA with the auxin antagonist 2-naphthaleneacetic acid at 100 micromolars reduces d-glucose uptake by about 80%. The apparent inhibition constant K(i) is 21 micromolars. Other auxin antagonists like 1-naphthoxyacetic acid and 2-(p-chlorophenoxy)-2-methylpropionic acid show similar effects. The uptake of the amino acids leucine, methionine, tryptophan, lysine, and aspartic acid is also inhibited by 2-naphthaleneacetic acid to similar degrees. The auxins 1-naphthaleneacetic acid and 2-naphthoxyacetic acid at concentrations between 10 and 100 micromolars inhibit solute uptake only slightly (inhibition less than 20%). The impact of the results on the postulated role of indole-3-acetic acid as a modifier of the electrochemical proton gradient across the plasmalemma in crown gall tumor tissue is discussed.

  7. The influence of thermal processing on the fatty acid profile of pork and lamb meat fed diet with increased levels of unsaturated fatty acids.

    PubMed

    Janiszewski, Piotr; Grześkowiak, Eugenia; Lisiak, Dariusz; Borys, Bronisław; Borzuta, Karol; Pospiech, Edward; Poławska, Ewa

    2016-01-01

    The research was carried out on 32 crossbred pigs of Polish Large White × Danish Landrace with Duroc and 80 rams, crossbreds of the Prolific-Dairy Koludzka Sheep with the Ile de France, a meat sheep. The fodder for the animals was enriched with the unsaturated fatty acids originated mainly from linseed and rapeseed oils. The fatty acid profile was determined in cooked longissimus lumborum, roasted triceps brachii and raw ripened rump from pigs as well as in grilled lambs' legs and their corresponding raw materials. Roasting caused the most pronounced increase of the saturated fatty acids and decrease in the polyunsaturated fatty acids of heated pork muscles. The smallest changes were observed in grilled lamb legs. The heating processes applied in this study, in most cases, did not cause essential changes in the indices of pro-health properties of fatty acid, therefore meat in the majority fulfil the latest recommendations of EFSA and FAO/WHO according to human health.

  8. Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism.

    PubMed

    Edalatmanesh, Mohammad Amin; Nikfarjam, Haniyeh; Vafaee, Farzaneh; Moghadas, Marzieh

    2013-08-14

    Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and the range of interests and activities. However, neuronal processing studies have suggested that hyper-perception, hyper-attention, and enhanced memory, which may lie at the heart of most autistic symptoms. Pregnant Wistar rats were administered by either Valproic Acid (VPA, 500mg/kg) or Phosphate Buffer Saline (PBS) during fetal neural tube development on embryonic day 12.5. All offspring were subjected to various tests. The present study examined social interaction, repetitive behaviors, nociception and tactile threshold, anxiety as well as spatial memory. Histological analyses of cells in five regions of the hippocampus were done to determine neuronal density in both groups. A single intra-peritoneal injection of VPA to pregnant rats produced severe autistic-like symptoms in the offspring. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions, enhanced stereotyped, repetitive behaviors, increased nociception threshold and anxiety at postnatal day (PND) 30 and PND 60. The Morris water maze learning paradigm revealed enhanced spatial memory at PND 60. Furthermore, histological analysis showed that the neuronal density in five separate regions of hippocampus (CA1, CA2, CA3, Dentate gyrus and Subiculum) were increased at PND 67. This work suggests that early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological and neuroanatomical hypotheses. This study provides further evidence to support the notion that spatial memory and hippocampal cell density are increased in this animal model of autism. Published by Elsevier B.V.

  9. Life at acidic pH imposes an increased energetic cost for a eukaryotic acidophile.

    PubMed

    Messerli, Mark A; Amaral-Zettler, Linda A; Zettler, Erik; Jung, Sung-Kwon; Smith, Peter J S; Sogin, Mitchell L

    2005-07-01

    Organisms growing in acidic environments, pH<3, would be expected to possess fundamentally different molecular structures and physiological controls in comparison with similar species restricted to neutral pH. We begin to investigate this premise by determining the magnitude of the transmembrane electrochemical H+ gradient in an acidophilic Chlamydomonas sp. (ATCC PRA-125) isolated from the Rio Tinto, a heavy metal laden, acidic river (pH 1.7-2.5). This acidophile grows most rapidly at pH 2 but is capable of growth over a wide pH range (1.5-7.0), while Chlamydomonas reinhardtii is restricted to growth at pH>or=3 with optimal growth between pH 5.5 and 8.5. With the fluorescent H+ indicator, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), we show that the acidophilic Chlamydomonas maintains an average cytosolic pH of 6.6 in culture medium at both pH 2 and pH 7 while Chlamydomonas reinhardtii maintains an average cytosolic pH of 7.1 in pH 7 culture medium. The transmembrane electric potential difference of Chlamydomonas sp., measured using intracellular electrodes at both pH 2 and 7, is close to 0 mV, a rare value for plants, animals and protists. The 40,000-fold difference in [H+] could be the result of either active or passive mechanisms. Evidence for active maintenance was detected by monitoring the rate of ATP consumption. At the peak, cells consume about 7% more ATP per second in medium at pH 2 than at pH 7. This increased rate of consumption is sufficient to account for removal of H+ entering the cytosol across a membrane with relatively high permeability to H+ (7x10(-8) cm s-1). Our results indicate that the small increase in the rate of ATP consumption can account for maintenance of the transmembrane H+ gradient without the imposition of cell surface H+ barriers.

  10. Increased Expression of Fatty-Acid and Calcium Metabolism Genes in Failing Human Heart

    PubMed Central

    Rodríguez-Penas, Diego; Feijóo-Bandín, Sandra; Noguera-Moreno, Teresa; Calaza, Manuel; Álvarez-Barredo, María; Mosquera-Leal, Ana; Parrington, John; Brugada, Josep; Portolés, Manuel; Rivera, Miguel; González-Juanatey, José Ramón; Lago, Francisca

    2012-01-01

    Background Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca2+)-handling in the human heart. Methods RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6). Results Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca2+-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca2+-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM. Conclusion DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca2+-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca2+-handling genes

  11. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

    PubMed

    Mika, Adriana; Stepnowski, Piotr; Chmielewski, Michal; Malgorzewicz, Sylwia; Kaska, Lukasz; Proczko, Monika; Ratnicki-Sklucki, Krzysztof; Sledzinski, Maciej; Sledzinski, Tomasz

    2016-07-01

    We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI.

  12. Acetylsalicylic acid and ascorbic acid combination improves cognition; via antioxidant effect or increased expression of NMDARs and nAChRs?

    PubMed

    Kara, Yusuf; Doguc, Duygu Kumbul; Kulac, Esin; Gultekin, Fatih

    2014-05-01

    Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expressions of NR2A, NR2B, nAChRα7, α4 and β2. Forty male rats (16-18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin+ascorbic acid-treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin+ascorbic acid group (p < 0.05). While 8-hydroxy-2-deoxyguanosine and malondialdehyde levels were significantly decreased, NR2B and nAChRα7 expressions were significantly increased in the aspirin+ascorbic acid group as compared to the control group (p < 0.05). Subchronic treatment with aspirin+ascorbic acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process.

  13. Fifteen weeks of dietary n-3 polyunsaturated fatty acid deprivation increases turnover of n-6 docosapentaenoic acid in rat-brain phospholipids

    PubMed Central

    Igarashi, Miki; Kim, Hyung-Wook; Gao, Fei; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.

    2012-01-01

    Docosapentaenoic acid (DPAn-6, 22:5n-6) is an n-6 polyunsaturated fatty acid (PUFA) whose brain concentration can be increased in rodents by dietary n-3 PUFA deficiency, which may contribute to their behavioral dysfunction. We used our in vivo intravenous infusion method to see if brain DPAn-6 turnover and metabolism also were altered with deprivation. We studied male rats that had been fed for 15 weeks post-weaning an n-3 PUFA adequate diet containing 4.6% alpha-linolenic acid (α-LNA, 18:3n-3) or a deficient diet (0.2% α-LNA), each lacking docosahexaenoic acid (22:6n-3) and arachidonic acid (AA, 20:4n-6). [1-14C]DPAn-6 was infused intravenously for 5 min in unanesthetized rats, after which the brain underwent high-energy microwaving, and then was analyzed. The n-3 PUFA deficient compared with adequate diet increased DPAn-6 and decreased DHA concentrations in plasma and brain, while minimally changing brain AA concentration. Incorporation rates of unesterified DPAn-6 from plasma into individual brain phospholipids were increased 5.2–7.7 fold, while turnover rates were increased 2.1–4.7 fold. The observations suggest that increased metabolism and brain concentrations of DPAn-6 and its metabolites, together with a reduced brain DHA concentration, contribute to behavioral and functional abnormalities reported with dietary n-3 PUFA deprivation in rodents. PMID:22142872

  14. Humic substances of varying types increase survivorship of the freshwater shrimp Caridina sp. D to acid mine drainage.

    PubMed

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2014-07-01

    Differences relating to the ability of various types of humic substances (HS) to influence toxicity of pollutants have been reported in the literature, but there still remains a gap in understanding whether various HS will have the same influence on the toxicity of acid mine drainage (AMD). This study investigated differences in the ability of Aldrich humic acid (AHA), Suwannee River humic acid and Suwannee River fulvic acid to decrease toxicity of AMD to the freshwater shrimp (Caridina sp. D). Toxicity tests were conducted over 96 h and used Mount Morgan open pit water as source of AMD and Dee River water as control/diluents. Concentrations of 0-4 % AMD at 0 mg/L HS, 10 mg/L AHA, 10 mg/L Suwannee River humic acid and 10 mg/L Suwannee River fulvic acid were used. Significantly higher survival of shrimp was recorded in the HS treatments compared with the treatment containing no HS. No significant differences were found among HS type. HS considerably increased LC50 values irrespective of type, from 1.29 (0 mg/L HS) to 2.12 % (AHA); 2.19 (Suwannee River humic acid) and 2.22 % (Suwannee River fulvic acid). These results support previous work that HS decrease the toxicity of AMD to freshwater organisms, but with the novel finding that this ability occurs irrespective of HS type. These results increase the stock of knowledge regarding HS and may contribute to a possible remediation option for AMD environments.

  15. Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5.

    PubMed

    Brossaud, Julie; Roumes, Hélène; Helbling, Jean-Christophe; Moisan, Marie-Pierre; Pallet, Véronique; Ferreira, Guillaume; Biyong, Essi-Fanny; Redonnet, Anabelle; Corcuff, Jean-Benoît

    2017-07-01

    Glucocorticoid receptor (GR) function is modulated by phosphorylation. As retinoic acid (RA) can activate some cytoplasmic kinases able to phosphorylate GR, we investigated whether RA could modulate GR phosphorylation in neuronal cells in a context of long-term glucocorticoid exposure. A 4-day treatment of dexamethasone (Dex) plus RA, showed that RA potentiated the (Dex)-induced phosphorylation on GR Serine 220 (pSer220GR) in the nucleus of a hippocampal HT22 cell line. This treatment increased the cytoplasmic ratio of p35/p25 proteins, which are major CDK5 cofactors. Roscovitine, a pharmacological CDK5 inhibitor, or a siRNA against CDK5 prevented RA potentiation of GR phosphorylation. Furthermore, roscovitine counter-acted the effect of RA on GR sensitive target proteins such as BDNF or tissue-transglutaminase. These data help understanding the interaction between RA- and glucocorticoid-signalling pathways, both of which have strong influences on the adult brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Metabolic rates associated with membrane fatty acids in mice selected for increased maximal metabolic rate

    PubMed Central

    Wone, Bernard W. M.; Donovan, Edward R.; Cushman, John C.; Hayes, Jack P.

    2014-01-01

    Aerobic metabolism of vertebrates is linked to membrane fatty acid (FA) composition. Although the membrane pacemaker hypothesis posits that desaturation of FAs accounts for variation in resting or basal metabolic rate (BMR), little is known about the FA profiles that underpin variation in maximal metabolic rate (MMR). We examined membrane FA composition of liver and skeletal muscle in mice after seven generations of selection for increased MMR. In both liver and skeletal muscle, unsaturation index did not differ between control and high-MMR mice. We also examined membrane FA composition at the individual-level of variation. In liver, 18:0, 20:3 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In gastrocnemius muscle, 18:2 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In addition, muscle 16:1 n-7, 18:1 n-9, and 22:5 n-3 FAs were significant predictors of BMR, whereas no liver FAs were significant predictors of BMR. Our findings indicate that (i) individual variation in MMR and BMR appear to be linked to membrane FA composition in the skeletal muscle and liver, and (ii) FAs that differ between selected and control lines are involved in pathways that can affect MMR or BMR. PMID:23422919

  17. Increased osteoblast functions on nanophase titania dispersed in poly-lactic-co-glycolic acid composites

    NASA Astrophysics Data System (ADS)

    Liu, Huinan; Slamovich, Elliott B.; Webster, Thomas J.

    2005-07-01

    The design of nanophase titania/poly-lactic-co-glycolic acid (PLGA) composites offers an exciting approach to combine the advantages of a degradable polymer with nano-size ceramic grains to optimize physical and biological properties for bone regeneration. Importantly, nanophase titania mimics the size scale of constituent components of bone since it is a nanostructured composite composed of nanometre dimensioned hydroxyapatite well dispersed in a mostly collagen matrix. For these reasons, the objective of the present in vitro study was to investigate osteoblast (bone-forming cell) adhesion and long-term functions on nanophase titania/PLGA composites. Since nanophase titania tended to significantly agglomerate when added to polymers, different sonication output powers were applied in this study to improve titania dispersion. Results demonstrated that the dispersion of titania in PLGA was enhanced by increasing the intensity of sonication and that greater osteoblast adhesion correlated with improved nanophase titania dispersion in PLGA. Moreover, results correlated better osteoblast long-term functions, such as alkaline phosphatase activity and calcium-containing mineral deposition, on nanophase titania/PLGA composites compared to plain PLGA. In fact, the greatest collagen production by osteoblasts occurred when cultured on nanophase titania sonicated in PLGA at the highest powers. In this manner, the present study demonstrates that PLGA composites with well dispersed nanophase titania can enhance osteoblast functions necessary for improved bone tissue engineering applications.

  18. Increased Secondary/Primary Bile Acid Ratio in Chronic Heart Failure.

    PubMed

    Mayerhofer, Cristiane C K; Ueland, Thor; Broch, Kaspar; Vincent, Royce P; Cross, Gemma F; Dahl, Christen P; Aukrust, Pål; Gullestad, Lars; Hov, Johannes R; Trøseid, Marius

    2017-09-01

    Bile acids (BAs) are now recognized as signaling molecules and emerging evidence suggests that BAs affect cardiovascular function. The gut microbiota has recently been linked to the severity of heart failure (HF), and microbial metabolism has a major impact on BA homeostasis. We aimed to investigate the pattern of BAs, and particularly microbiota-transformed (secondary) BAs, in patients with chronic HF. This was a prospective, observational, single-center study including 142 patients with chronic HF and 20 age- and sex-matched healthy control subjects. We measured plasma levels of primary, secondary, and total BAs, and explored their associations with clinical characteristics and survival. Plasma levels of primary BAs were lower (P < .01) and the ratios of secondary to primary BAs higher (P < .001) in patients with HF compared with control subjects. Approximately 40% of patients in the upper tertile of the ratio of secondary to primary BAs died during 5.6 years of follow-up (unadjusted Cox regression: hazard ratio 1.93, 95% confidence interval 1.01-3.68, compared with the lower tertiles). However, this association was attenuated and no longer significant in multivariate analyses. Levels of primary BAs were reduced and specific secondary BAs increased in patients with chronic HF. This pattern was associated with reduced overall survival in univariate analysis, but not in multivariate analyses. Future studies should assess the regulation and potential role of BA metabolism in HF. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Increase the elongation at break of poly (lactic acid) composites for use in food packaging films

    NASA Astrophysics Data System (ADS)

    El-Hadi, Ahmed M.

    2017-05-01

    Poly (3-hydroxy butyrate) (PHB), cellulose nano crystal (CNC) and a plasticizer (TBC) are mixed together with PLLA with the aim to increase the elongation at break for use in the food packing sector. Spherical (CNC) and fibril nano crystal (CNF) were prepared by hydrolysis of microcrystalline cellulose (MCC) in distilled water, and then stirred using a magnetic stirrer for 15 days and ultrasonic treatment without using any acids as green method. The morphology, thermal, and mechanical properties were studied using POM, DSC, WAXD, SEM and tensile testing, respectively. DSC demonstrated that the addition of PHB, CNC and TBC to PLLA matrix lead to reduce Tg, TCC and Tm than pure PLLA. FT-IR verified that the carbonyl group C=O appeared broad and some peaks in the PLLA composites 5, 6 and 7 shifted from 3.98 × 108 to 4.07 × 108 Hz, at 3.54 × 108 to 3.44 × 108 Hz, at 3.19 × 108 to 3.13 × 108 Hz. Mechanical testing shows that pure PLLA is brittle, and the elongation at break of PLLA composites reaches up to 205%, making it suitable to use in food packaging.

  20. α-lipoic acid reduces hypertension and increases baroreflex sensitivity in renovascular hypertensive rats.

    PubMed

    Queiroz, Thyago M; Guimarães, Drielle D; Mendes-Junior, Leônidas G; Braga, Valdir A

    2012-11-09

    Renovascular hypertension has robust effects on control of blood pressure, including an impairment in baroreflex mechanisms, which involves oxidative stress. Although α-lipoic acid (LA) has been described as a potent antioxidant, its effect on renovascular hypertension and baroreflex sensitivity (BRS) has not been investigated. In the present study we analyzed the effects caused by chronic treatment with LA on blood pressure, heart rate and baroreflex sensitivity (sympathetic and parasympathetic components) in renovascular hypertensive rats. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for four weeks to develop hypertension. Four weeks post-surgery, rats were treated with LA (60 mg/kg) or saline for 14 days orally. On the 15th day mean arterial pressure (MAP) and heart rate (HR) were recorded. In addition, baroreflex sensitivity test using phenylephrine (8 µg/kg, i.v.) and sodium nitroprusside (25 µg/kg, i.v.) was performed. Chronic treatment with LA decreased blood pressure in hypertensive animals; however, no significant changes in baseline HR were observed. Regarding baroreflex, LA treatment increased the sensitivity of both the sympathetic and parasympathetic components. All parameters studied were not affected by treatment with LA in normotensive animals. Our data suggest that chronic treatment with LA promotes antihypertensive effect and improves baroreflex sensitivity in rats with renovascular hypertension.

  1. Increase the elongation at break of poly (lactic acid) composites for use in food packaging films

    PubMed Central

    El-hadi, Ahmed M.

    2017-01-01

    Poly (3-hydroxy butyrate) (PHB), cellulose nano crystal (CNC) and a plasticizer (TBC) are mixed together with PLLA with the aim to increase the elongation at break for use in the food packing sector. Spherical (CNC) and fibril nano crystal (CNF) were prepared by hydrolysis of microcrystalline cellulose (MCC) in distilled water, and then stirred using a magnetic stirrer for 15 days and ultrasonic treatment without using any acids as green method. The morphology, thermal, and mechanical properties were studied using POM, DSC, WAXD, SEM and tensile testing, respectively. DSC demonstrated that the addition of PHB, CNC and TBC to PLLA matrix lead to reduce Tg, TCC and Tm than pure PLLA. FT-IR verified that the carbonyl group C=O appeared broad and some peaks in the PLLA composites 5, 6 and 7 shifted from 3.98 × 108 to 4.07 × 108 Hz, at 3.54 × 108 to 3.44 × 108 Hz, at 3.19 × 108 to 3.13 × 108 Hz. Mechanical testing shows that pure PLLA is brittle, and the elongation at break of PLLA composites reaches up to 205%, making it suitable to use in food packaging. PMID:28466854

  2. Increase the elongation at break of poly (lactic acid) composites for use in food packaging films.

    PubMed

    El-Hadi, Ahmed M

    2017-05-03

    Poly (3-hydroxy butyrate) (PHB), cellulose nano crystal (CNC) and a plasticizer (TBC) are mixed together with PLLA with the aim to increase the elongation at break for use in the food packing sector. Spherical (CNC) and fibril nano crystal (CNF) were prepared by hydrolysis of microcrystalline cellulose (MCC) in distilled water, and then stirred using a magnetic stirrer for 15 days and ultrasonic treatment without using any acids as green method. The morphology, thermal, and mechanical properties were studied using POM, DSC, WAXD, SEM and tensile testing, respectively. DSC demonstrated that the addition of PHB, CNC and TBC to PLLA matrix lead to reduce Tg, TCC and Tm than pure PLLA. FT-IR verified that the carbonyl group C=O appeared broad and some peaks in the PLLA composites 5, 6 and 7 shifted from 3.98 × 10(8) to 4.07 × 10(8) Hz, at 3.54 × 10(8) to 3.44 × 10(8) Hz, at 3.19 × 10(8) to 3.13 × 10(8) Hz. Mechanical testing shows that pure PLLA is brittle, and the elongation at break of PLLA composites reaches up to 205%, making it suitable to use in food packaging.

  3. CPT1{alpha} over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

    SciTech Connect

    Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion; Gahl, Anja; Scheeder, Martin R.L.; Cardoso, M. Cristina; Leonhardt, Heinrich; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika . E-mail: monika.leonhardt@inw.agrl.ethz.ch

    2005-12-16

    To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1{alpha} (CPT1{alpha}). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1{alpha} transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1{alpha} over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1{alpha} over-expressing cells in a concentration-dependent manner. Both, PA and CPT1{alpha} over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1{alpha}, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo.

  4. Eicosapentaenoic acid increases cytochrome P-450 2J2 gene expression and epoxyeicosatrienoic acid production via peroxisome proliferator-activated receptor γ in endothelial cells.

    PubMed

    Wang, Dahai; Hirase, Tetsuaki; Nitto, Takeaki; Soma, Masaaki; Node, Koichi

    2009-12-01

    ω-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on cardiovascular diseases. Cytochrome P-450 (CYP) 2J2 that is expressed in endothelial cells metabolizes arachidonic acids to biologically active epoxyeicosatrienoic acids (EETs) that possess anti-inflammatory and anti-thrombotic effects. We studied the effects of EPA and DHA on the expression of CYP 2J2 mRNA by reverse transcription-polymerase chain reaction in cultured human umbilical vein endothelial cells and found that EPA, but not DHA, increased the expression of CYP 2J2 mRNA in a dose-dependent and a time-dependent manner. EPA-induced CYP 2J2 expression was significantly inhibited by pretreatment with a peroxisome proliferator-activated receptor (PPAR) γ antagonist, GW9662. EPA, but not DHA, caused a significant increase in cellular levels of 11,12-dihydroxyeicosatrienoic acid that is a stable metabolite of 11,12-EET, which was blocked by pretreatment with GW9662. These data demonstrate that EPA increases CYP 2J2 mRNA expression and 11,12-EET production via PPARγ in endothelial cells and indicate a novel protective role of EPA and PPARγ against vascular inflammation.

  5. Heat exposure increases circulating fatty acids but not lipid oxidation at rest and during exercise.

    PubMed

    O'Hearn, Katharine; Tingelstad, Hans Christian; Blondin, Denis; Tang, Vera; Filion, Lionel G; Haman, François

    2016-01-01

    Alterations in lipid oxidation during exercise have been well studied, but limited data exists on the effects of passive heat exposure and exercise in the heat on changes in lipid oxidation. This study was designed to examine: (1) the effects of heat exposure on lipid metabolism during passive heating and subsequent exercise in the heat by focusing on changes in whole-body lipid oxidation and plasma lipid concentrations, and (2) the effects of extended passive pre-heating on exercise performance in the heat. Male participants (n=8) were passively heated for 120 min at 42 °C, then exercised on a treadmill in the same temperature at 50% V̇O2 max for 30 min (HEAT). This same procedure was followed on a separate occasion at 23 °C (CON). Results showed that lipid oxidation rates were not different between HEAT and CON during passive heating or exercise. However, non-esterified fatty acid (NEFA) concentrations were significantly higher following passive heating (618 µM, 95% CI: 479-757) compared to CON (391 µM, 95% CI: 270-511). The same trend was observed following exercise (2036 µM, 95% CI: 1604-2469 for HEAT and 1351 µM, 95% CI: 1002-1699). Triacylglycerol, phospholipid and cholesterol levels were not different between HEAT and CON at any point. Four of 8 participants could not complete 30 min of exercise in HEAT, resulting in a 14% decline in total external work. Rate of perceived exertion over the final 5 min of exercise was higher in HEAT (9.5) than CON (5). We conclude that: (1) heat exposure results in increased circulating NEFA at rest and during exercise without changes in whole-body lipid utilization, and (2) passive pre-heating reduces work capacity during exercise in the heat and increases the perceived intensity of a given workload. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Exercise and a High Fat Diet Synergistically Increase the Pantothenic Acid Requirement in Rats.

    PubMed

    Takahashi, Kei; Fukuwatari, Tsutomu; Shibata, Katsumi

    2015-01-01

    It is thought that both exercise and dietary composition increase the utilization of, and thus the requirement for, certain water-soluble vitamins. However, there have been no studies evaluating the combined impacts of exercise and dietary composition on vitamin utilization. In this experiment, rats were fed a pantothenic acid (PaA)-restricted (0.004 g PaA-Ca/kg diet) diet containing 5% (ordinary amount of dietary fat) or 20% fat (high fat), and were forced to swim until exhaustion every other day for 22 d. PaA status was assessed by urinary excretion, which reflects body stores of water-soluble vitamins. The urinary excretion of PaA in rats fed a 5% fat diet was not affected by swimming (5% fat + non-swimming vs. 5% fat + swim; p>0.05). Excretion of PaA was decreased by the high-fat diet (5% fat + non-swim vs. 20% fat + non-swim; p<0.05) and synergistically decreased by exercise (20% fat + non-swim vs. 20% fat + swim; p<0.05). There was a significant interaction between exercise and a high-fat diet. Plasma PaA concentrations showed changes similar to those seen for urinary excretion. The experiment was then repeated using rats fed a PaA-sufficient (0.016 g PaA-Ca/kg diet) diet, and PaA excretion was again synergistically decreased by the combination of exercise and a high-fat diet (p<0.05). These results suggest that the combination of exercise and a high-fat diet synergistically increases the requirement for PaA.

  7. Valproic Acid Increases Expression of Neuronal Stem/Progenitor Cell in Spinal Cord Injury

    PubMed Central

    Bang, Woo-Seok; Cho, Dae-Chul; Kim, Hye-Jeong; Sung, Joo-Kyung

    2013-01-01

    Objective This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model. Methods Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively. Results Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group. Conclusion Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI. PMID:24044073

  8. Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler.

    PubMed

    You, Hi-Jin; Namgoong, Sik; Rhee, Sung-Mi; Han, Seung-Kyu

    2016-03-01

    A new injectable tissue-engineered soft tissue consisting of a mixture of hyaluronic acid (HA) filler and cultured human fibroblasts have been developed by the authors. To establish this method as a standard treatment, a further study was required to determine whether the injected fibroblasts could stay at the injected place or move to other sites. In addition, effective strategies were needed to increase viability of the injected fibroblasts. The purpose of this study was to track the injected fibroblasts and to determine the effect of adding prostaglandin E1 (PGE1) or vitamin C on the viability of fibroblasts.Human fibroblasts labeled with fluorescence dye were suspended in HA filler and injected into 4 sites on the back of nude mice. The injected bioimplants consisted of one of the 4 followings: HA filler without cells (HA group), fibroblasts suspended in HA filler (HA + FB group), PGE1-supplemented fibroblasts in HA filler (HA + FB + PGE1 group), and vitamin C-supplemented fibroblasts in HA filler (HA + FB + VC group). At 4 weeks after injection, locations and intensities of the fluorescence signals were evaluated using a live imaging system.The fluorescence signals of the fibroblast-containing groups were visible only at the injected sites without dispersing to other sites. The HA +FB + PGE1 group showed a significantly higher fluorescence signal than the HA + FB and the HA + FB +VC groups (P < 0.05, each). There was no statistical difference between the HA + FB and HA + FB +VC groups (P = 0.69).The results of the current study collectively suggest that injected fibroblasts suspended in HA filler stay at the injected place without moving to other sites. In addition, PGE1 treatment may increase the remaining rhodamine B isothiocynanate dye at the injected site of the human dermal fibroblasts.

  9. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition.

    PubMed

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-04-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development.

  10. Increased uric acid levels in bipolar disorder subjects during different phases of illness.

    PubMed

    Albert, Umberto; De Cori, David; Aguglia, Andrea; Barbaro, Francesca; Bogetto, Filippo; Maina, Giuseppe

    2015-03-01

    Recent evidence indicates the possible involvement of adenosine and the purinergic system in the pathophysiology of bipolar disorder (BD). The aim of this study is to compare serum uric acid (UA) levels in a large group of BD patients (in mania, depression and euthymia) vs. a control group of patients with different psychiatric disorders. 150 BD (SCID-I; DSM-IV) patients were compared to 150 age- and gender-matched subjects with MDD, OCD, or Schizophrenia. Mean serum UA values were compared with the ANOVA, with Bonferroni's post-hoc tests. Mean serum UA levels (5.06 ± 1.45 vs. 4.17 ± 1.05 mg/dL) and rates of hyperuricaemia (30.7% vs. 6.7%) were significantly higher in the bipolar than in the control group. No differences were detected between bipolars in different phases of illness, with all three groups (manic, depressive and euthymic bipolars) showing significantly higher UA levels as compared to controls. No correlations were found between UA levels and YMRS or HAM-D scores. Mean UA levels were also higher in bipolars never exposed to mood stabilizers vs. controls (5.08 ± 1.43 vs. 4.17 ± 1.05 mg/dL), with no differences compared to other bipolars. Our study suffers from the lack of a healthy comparison group; moreover, longitudinal data are missing. Our study provides further evidence of a purinergic dysfunction associated with BD, in all phases of the illness. It is possible that increased UA levels are a trait marker of higher vulnerability to bipolar disorder, and are even more increased during mania (mostly in the first manic episode of drug-naïve patients). Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Sustained low abscisic acid levels increase seedling vigor under cold stress in rice (Oryza sativa L.).

    PubMed

    Mega, Ryosuke; Meguro-Maoka, Ayano; Endo, Akira; Shimosaka, Etsuo; Murayama, Seiji; Nambara, Eiji; Seo, Mitsunori; Kanno, Yuri; Abrams, Suzanne R; Sato, Yutaka

    2015-09-09

    Stress-induced abscisic acid (ABA) is mainly catabolized by ABA 8'-hydroxylase (ABA8ox), which also strictly regulates endogenous ABA levels. Although three members of the ABA8ox gene family are conserved in rice, it is not clear which stressors induce expression of these genes. Here, we found that OsABA8ox1 was induced by cold stress within 24 h and that OsABA8ox2 and OsABA8ox3 were not. In contrast, OsABA8ox2 and OsABA8ox3 were ABA-inducible, but OsABA8ox1 was not. OsABA8ox1, OsABA8ox2, and OsABA8ox3 restored germination of a cyp707a1/a2/a3 triple mutant of Arabidopsis to rates comparable to those of the wild type, indicating that OsABA8ox1, OsABA8ox2, and OsABA8ox3 function as ABA-catabolic genes in vivo. Transgenic rice lines overexpressing OsABA8ox1 showed decreased levels of ABA and increased seedling vigor at 15 °C. These results indicate that sustained low levels of ABA lead to increased seedling vigor during cold stress. On the other hand, excessively low endogenous ABA levels caused reduced drought and cold tolerance, although some of the transgenic rice lines expressing OsABA8ox1 at moderate levels did not show these harmful effects. Adequate regulation of endogenous ABA levels is thought to be crucial for maintaining seedling vigor under cold stress and for cold and drought tolerance in rice.

  12. Refractory GERD: increased body mass index is associated with persisting acid exposure but not hypersensitive esophagus or functional heartburn.

    PubMed

    Viazis, Nikos; Karamanolis, George P; Anastasiou, Jiannis; Keyoglou, Anastasia; Vlachogiannakos, Jiannis; Ladas, Spiros D; Karamanolis, Dimitrios G

    2013-12-01

    To compare the incidence of persistent abnormal acid exposure, hypersensitive esophagus (HE), and functional heartburn (FH) in obese/overweight and normal-weight patients referred for impedance-pH monitoring, because of persisting gastroesophageal reflux disease (GERD) symptoms despite therapy with proton pump inhibitors (PPIs). ΜETHODS: Patients with normal endoscopy and typical GERD symptoms, despite PPI therapy twice daily, underwent 24-h impedance-pH monitoring while on therapy. Distal esophageal acid exposure (% time pH<4) was measured and reflux episodes were classified into acid or nonacid. A positive symptom index was defined when at least 50% of symptom events were preceded by reflux episodes. Patients were categorized as those with persistent abnormal acid exposure, those with HE, and those with FH. The incidence of persistent abnormal acid exposure, HE, and FH between overweight/obese patients (BMI≥25 kg/m) and normal-weight patients (BMI<25 kg/m) was subsequently evaluated. A total of 246 patients (women: 158, men: 88, increased BMI: 151, normal BMI: 95, mean age 55, range 18-75 years) were included. Persistent abnormal acid exposure was found in 39 patients (increased BMI: 31, normal BMI: 8), HE in 77 patients (increased BMI: 43, normal BMI: 34), and FH in 118 patients (increased BMI: 69, normal BMI: 49). When comparing BMI among all three groups, patients with increased BMI were more likely to have acid reflux than HE or FH (P=0.03). In patients with GERD symptoms refractory to double-dose PPI therapy, those with increased BMI are more likely to have persistent abnormal acid exposure than HE or FH.

  13. Climate change and increased zinc concentrations in a Rocky Mountain acid rock drainage stream

    NASA Astrophysics Data System (ADS)

    Crouch, C. M.; Todd, A. S.; McKnight, D. M.

    2009-12-01

    The Snake River Watershed in Colorado is impacted by acid rock drainage (ARD) originating from both natural sources and sources associated with the historic mining in the watershed. Downstream of mines, the high metal ion concentrations, low pH, and metal oxide deposition cause contamination which disrupts ecosystem functions, impairs biological diversity, and contaminates surface and groundwater drinking supplies. One obvious measure of the severity of this contamination is that the self-sustaining trout populations in the watershed are quite sparse. While elevated concentrations of numerous trace metals are present, dissolved zinc is used as an indicator of trout habitat water quality because the fish are so impacted by its presence. Water quality was monitored along the Snake River from 1980 to 1990 and since then less frequent sampling was conducted as part of research studies and efforts to designate portions of the watershed for mitigation. Metals concentrations during the seasonal low flows of September and October have been observed to increase significantly over that time. In particular, at a site in the headwaters well above the historic mining impacts, zinc concentrations, which were measured between 0.3 and 0.4 mg/L through the 1980s, have now exceeded 1.2 mg/L in the past several years. This four-fold increase in zinc concentrations is associated with an increase in sulfate concentrations, which indicates that these water quality changes are driven primarily by accelerated natural weathering of pyrite in the watershed. The observed increase in natural ARD - possibly the result of climate change - may have implications for mitigation. Currently, these trends are being evaluated by reanalyzing the archived samples to delineate the spatial and temporal changes in contamination. Processes which may be driving the accelerated natural weathering include the earlier occurrence of peak snowmelt due to climate change which causes lower stream flows and drier

  14. Increased production of apolipoprotein B and its lipoproteins by oleic acid in Caco-2 cells.

    PubMed

    Dashti, N; Smith, E A; Alaupovic, P

    1990-01-01

    The production of lipids, apolipoproteins (apo), and lipoproteins induced by oleic acid has been examined in Caco-2 cells. The rates of accumulation in the control medium of 15-day-old Caco-2 cells of triglycerides, unesterified cholesterol, and cholesteryl esters were 102 +/- 8, 73 +/- 5, and 11 +/- 1 ng/mg cell protein/h, respectively; the accumulation rates for apolipoproteins A-I, B, C-III, and E were 111 +/- 9, 53 +/- 4, 13 +/- 1, and 63 +/- 4 ng/mg cell protein/h, respectively. Whereas apolipoproteins A-IV and C-II were detected by immunoblotting, apoA-II was absent in most culture media. In contrast to an early production of apolipoproteins A-I and E occurring 2 days after plating, the apoB expression appeared to be differentiation-dependent and was not measurable in the medium until the sixth day post-confluency. In the control medium, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipid-poor very high density lipoproteins (VHDL) accounted for 12%, 46%, 18%, and 24% of the total lipid and apolipoprotein contents, respectively. The triglyceride-rich VLDL contained mainly apoE (75%) and apoB (23%), while the protein moiety of LDL was composed of apoB (59%), apoE (20%), apoA-I (15%), and apoC-III (6%). The cholesterol-rich HDL contained mainly apoA-I (69%) and apoE (27%). In the control medium, major portions of apolipoproteins B and C-III (93-97%) were present in LDL, whereas the main parts of apoA-I (92%) and apoE (76%) were associated with HDL and VHDL. Oleate increased the production of triglycerides 10-fold, cholesteryl esters 7-fold, and apoB 2- to 4-fold. There was also a moderate increase (39%) in the production of apoC-III but no significant changes in those of apolipoproteins A-I and E. These increases were reflected mainly in a 55-fold elevation in the concentration of VLDL, and a 2-fold increase in the level of LDL; there were no significant changes in HDL and VHDL. VLDL contained the

  15. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities.

    PubMed

    Kohli, Rohit; Kirby, Michelle; Setchell, Kenneth D R; Jha, Pinky; Klustaitis, Kori; Woollett, Laura A; Pfluger, Paul T; Balistreri, William F; Tso, Patrick; Jandacek, Ronald J; Woods, Stephen C; Heubi, James E; Tschoep, Matthias H; D'Alessio, David A; Shroyer, Noah F; Seeley, Randy J

    2010-09-01

    Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective "jejunization" of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery.

  16. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities

    PubMed Central

    Kirby, Michelle; Setchell, Kenneth D. R.; Jha, Pinky; Klustaitis, Kori; Woollett, Laura A.; Pfluger, Paul T.; Balistreri, William F.; Tso, Patrick; Jandacek, Ronald J.; Woods, Stephen C.; Heubi, James E.; Tschoep, Matthias H.; D'Alessio, David A.; Shroyer, Noah F.; Seeley, Randy J.

    2010-01-01

    Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective “jejunization” of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery. PMID

  17. Acid-adaptation does not increase the resistance of Listeria monocytogenes to irradiation in a seafood salad.

    PubMed

    Foley, D M; Trimboli, S L; Lamb, J; Gogley, J; Thompson, J; Caporaso, F; Calicchia, M; Prakash, A

    2005-03-15

    Stress adaptation of microbial cells enables the cells to survive better when they are subsequently exposed to other types of stresses. In the food industry, pathogens are commonly stressed during food processing and this is a concern where pathogens such as Listeria monocytogenes are involved. Research was conducted to determine if acid adaptation of L. monocytogenes provides resistance to ionizing irradiation. Three different strains of L. monocytogenes were acid-adapted using three different acids (acetic, citric, lactic) in Tryptic Soy Broth, at a pH 5.5 for 1 h, 4 h, or continuous acid exposure. The acid-adapted L. monocytogenes were then exposed to a low level of gamma irradiation (0.59-0.72 kGy) along with a non-acid adapted L. monocytogenes control. In a test tube study, the 1-h acetic acid-adapted L. monocytogenes strains showed the greatest difference from the control, a reduced kill of 1.1 log CFU/g but this difference was not significant by ANOVA (p=0.054). The reduction achieved after 4 h and continuous acid exposure also did not significantly differ from the control. To determine whether acid adaptation affected radiation resistance within a food product, a refrigerated storage shelf-life study was completed. Acetic acid was used to acid adapt a three-strain cocktail of L. monocytogenes for a period of 1 h. The organisms were then inoculated into a seafood salad (pH 5.15) and subsequently exposed to low dose gamma irradiation (0.7 to 4.5 kGy). L. monocytogenes was reduced or eliminated by irradiation regardless of acid adaptation; no increased resistance was observed.

  18. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-09-23

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  19. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    PubMed Central

    Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  20. Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release.

    PubMed

    Miralles, F; Marsal, J; Peres, J; Solsona, C

    1996-04-01

    The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05-0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca(2+) concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflammatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1 - 1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K+ current and Ca(2+)-activated K(+) current in a concentration-dependent manner. Niflumic acid (0.1 - 1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na(+) current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K+ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca(2+) with each impulse.

  1. Elaidate, an 18-carbon trans-monoenoic fatty acid, but not physiological fatty acids increases intracellular Zn(2+) in human macrophages.

    PubMed

    Zacherl, Janelle R; Tourkova, Irina; St Croix, Claudette M; Robinson, Lisa J; Peck Palmer, Octavia M; Mihalik, Stephanie J; Blair, Harry C

    2015-04-01

    Artificial trans fatty acids promote atherosclerosis by blocking macrophage clearance of cell debris. Classical fatty-acid response mechanisms include TLR4-NF-κB activation, and Erk1/2 phosphorylation, but these may not indicate long-term mechanisms. Indeed, nuclear NF-κB was increased by 60 min treatment by 30 μM of the 18 carbon trans unsaturated fatty acid elaidic acid (elaidate), the physiological cis-unsaturated fatty acid oleic acid (oleate), and the 18 or 16 carbon saturated fatty acids stearic and palmitic acid (stearate or palmitate). However, except for stearate, effects on related pathways were minimal at 44 h. To determine longer term effects of trans fatty acids, we compared mRNA expression profiles of (trans) elaidate to (cis) oleate, 30 μM, at 44 h in human macrophages. We found that elaidate changed Zn(2+) -homeostasis gene mRNAs markedly. This might be important because Zn(2+) is a major regulator of macrophage activity. Messenger RNAs of seven Zn(2+) -binding metallothioneins decreased 2-4-fold; the zinc importer SLC39A10 increased twofold, in elaidate relative to oleate-treated cells. Results were followed by quantitative PCR comparing cis, trans, and saturated fatty acid effects on Zn(2+) -homeostasis gene mRNAs. This confirmed that elaidate uniquely decreased metallothionein expression and increased SLC39A10 at 44 h. Further, intracellular Zn(2+) was measured using N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl) amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenoxy]-ethoxy]-4-methoxyphenyl]glycine, acetoxymethyl ester (FluoZin-3-AM). This showed that, at 44 h, only cells treated with elaidate had increased Zn(2+) . The durable effect of elaidate on Zn(2+) activation is a novel and specific effect of trans fatty acids on peripheral macrophage metabolism. © 2014 Wiley Periodicals, Inc.

  2. Increase in the ozone decay time in acidic ozone water and its effects on sterilization of biological warfare agents.

    PubMed

    Uhm, Han S; Hong, Yi F; Lee, Han Y; Park, Yun H

    2009-09-15

    The sterilization properties of ozone in acidic water are investigated in this study. Acidification of water increases the ozone decay time by several times compared to the decay time in neutral water, thereby enhancing the sterilization strength of ozone in acidic water. A simple analytical model involving the viable microbial counts after contact with acidic ozone water was derived, and a sterilization experiment was conducted on bacterial cells using the acidic ozone water. The acidic ozone water was found to kill very effectively endospores of Bacillus atrophaeus ATCC 9372, thereby demonstrating the potential for disinfection of a large surface area in a very short time and for reinstating the contaminated environment as free from toxic biological agents.

  3. Glycyrrhetinic acid might increase the nephrotoxicity of bakuchiol by inhibiting cytochrome P450 isoenzymes

    PubMed Central

    Zhao, Zijing; Yuan, Mei

    2016-01-01

    Background Licorice, a popular traditional Chinese medicine (TCM), is widely used to moderate the effects (detoxification) of other herbs in TCM and often combined with Fructus Psoraleae. However, the classical TCM book states that Fructus Psoraleae is incompatible with licorice; the mechanism underlying this incompatibility has not been identified. Glycyrrhetinic acid (GA), the active metabolite of licorice, may increase the toxicity of bakuchiol (BAK), the main chemical ingredient in Psoralea corylifolia, by inhibiting its detoxification enzymes CYP450s. Methods The effect of concomitant GA administration on BAK-induced nephrotoxicity was investigated, and the metabolic interaction between BAK and GA was further studied in vitro and in vivo. The cytotoxicity was assessed using an MTT assay in a co-culture model of HK-2 cell and human liver microsomes (HLMs). The effect of GA on the metabolism of BAK, and on the activities of CYP isoforms were investigated in HLMs. The toxicokinetics and tissue exposure of BAK as well as the renal and hepatic functional markers were measured after the administration of a single oral dose in rats. Results In vitro studies showed that the metabolic detoxification of BAK was significantly reduced by GA, and BAK was toxic to HK-2 cells, as indicated by 25∼40% decreases in viability when combined with GA. Further investigation revealed that GA significantly inhibited the metabolism of BAK in HLMs in a dose-dependent manner. GA strongly inhibits CYP3A4 and weakly inhibits CYP2C9 and CYP1A2; these CYP isoforms are involved in the metabolism of BAK. In vivo experiment found that a single oral dose of BAK combined with GA or in the presence of 1-aminobenzotriazole (ABT), altered the toxicokinetics of BAK in rats, increased the internal exposure, suppressed the elimination of BAK prototype, and therefore may have enhanced the renal toxicity. Conclusion The present study demonstrated that GA inhibits CYP isoforms and subsequently may

  4. Amelioration of acidic soil increases the toxicity of the weak base carbendazim to the earthworm Eisenia fetida.

    PubMed

    Liu, Kailin; Wang, Shaoyun; Luo, Kun; Liu, Xiangying; Yu, Yunlong

    2013-12-01

    Ameliorating acidic soils is a common practice and may affect the bioavailability of an ionizable organic pollutant to organisms. The toxicity of the weak base carbendazim to the earthworm (Eisenia fetida) was studied in an acidic soil (pH-H₂O, 4.6) and in the ameliorated soil (pH-H₂O, 7.5). The results indicated that the median lethal concentration of carbendazim for E. fetida decreased from 21.8 mg/kg in acidic soil to 7.35 mg/kg in the ameliorated soil. To understand why the amelioration increased carbendazim toxicity to the earthworm, the authors measured the carbendazim concentrations in the soil porewater. The authors found increased carbendazim concentrations in porewater, resulting in increased toxicity of carbendazim to earthworms. The increased pore concentrations result from decreased adsorption because of the effects of pH and calcium ions.

  5. Lability of High Molecular Weight Dissolved Organic Matter Polysaccharides Increases with Mild Acid or Base Treatment.

    NASA Astrophysics Data System (ADS)

    Pedler Sherwood, B.; Sosa, O.; Nelson, C. E.; Repeta, D.; DeLong, E.

    2016-02-01

    Approximately 662 Pg of dissolved organic carbon (DOC) has accumulated in the global ocean, yet the biological and chemical constraints on DOC turnover remain poorly understood. High molecular weight dissolved organic matter (HMWDOM) is largely comprised of semi-labile polysaccharides. These polysaccharides resist degradation even in the presence of nutrient amendments, suggesting unknown factors of polysaccharide composition affect microbial degradation. In a series of microcosm incubations conducted at station ALOHA in the North Pacific Subtropical Gyre, we tested the affect of mild base (KOH-DOM) and acid (HCl-DOM) treatments on polysaccharide lability. KOH-DOM, HCl-DOM, and untreated HMWDOM was added to seawater from the deep chlorophyll maximum and 200m. Microcosms amended with KOH-DOM and HCl-DOM yielded higher bacterial abundance and greater carbon drawdown relative to untreated HMWDOM and unamended controls. Microcosms amended with KOH-DOM and HCl-DOM also showed significant production of fluorescent DOM (fDOM), whereas untreated HMWDOM and unamended controls showed a net decrease in fDOM as measured by parallel factor analysis of DOM excitation-emission spectra. Metagenomic analyses revealed that microcosms amended with untreated HMWDOM and controls became dominated by Alteromonas genera ( 60% total sequence reads). In contrast, KOH-DOM and HCl-DOM amended microcosms yielded greater bacterial diversity; Alteromonas genera comprised 25% of sequence reads, with differences primarily accounted for by proportional increases in vibrio, roseobacter, rugeria and marinomonas clades. Transcriptomic analyses identified differential gene expression during growth on each DOM fraction. This study provides new insight into specific chemical moieties that may limit the bacterial degradation rate of semi-labile HMWDOM in the ocean.

  6. Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro.

    PubMed

    Frajese, Giovanni Vanni; Benvenuto, Monica; Fantini, Massimo; Ambrosin, Elena; Sacchetti, Pamela; Masuelli, Laura; Giganti, Maria Gabriella; Modesti, Andrea; Bei, Roberto

    2016-06-01

    Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

  7. Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

    PubMed Central

    FRAJESE, GIOVANNI VANNI; BENVENUTO, MONICA; FANTINI, MASSIMO; AMBROSIN, ELENA; SACCHETTI, PAMELA; MASUELLI, LAURA; GIGANTI, MARIA GABRIELLA; MODESTI, ANDREA; BEI, ROBERTO

    2016-01-01

    Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro. PMID:27313770

  8. Improvement of pea biomass and seed productivity by simultaneous increase of phloem and embryo loading with amino acids.

    PubMed

    Zhang, Lizhi; Garneau, Matthew G; Majumdar, Rajtilak; Grant, Jan; Tegeder, Mechthild

    2015-01-01

    The development of sink organs such as fruits and seeds strongly depends on the amount of nitrogen that is moved within the phloem from photosynthetic-active source leaves to the reproductive sinks. In many plant species nitrogen is transported as amino acids. In pea (Pisum sativum L.), source to sink partitioning of amino acids requires at least two active transport events mediated by plasma membrane-localized proteins, and these are: (i) amino acid phloem loading; and (ii) import of amino acids into the seed cotyledons via epidermal transfer cells. As each of these transport steps might potentially be limiting to efficient nitrogen delivery to the pea embryo, we manipulated both simultaneously. Additional copies of the pea amino acid permease PsAAP1 were introduced into the pea genome and expression of the transporter was targeted to the sieve element-companion cell complexes of the leaf phloem and to the epidermis of the seed cotyledons. The transgenic pea plants showed increased phloem loading and embryo loading of amino acids resulting in improved long distance transport of nitrogen, sink development and seed protein accumulation. Analyses of root and leaf tissues further revealed that genetic manipulation positively affected root nitrogen uptake, as well as primary source and sink metabolism. Overall, the results suggest that amino acid phloem loading exerts regulatory control over pea biomass production and seed yield, and that import of amino acids into the cotyledons limits seed protein levels. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  9. CYP2J2 Overexpression Ameliorates Hyperlipidemia via Increased Fatty Acid Oxidation Mediated by the AMPK Pathway

    PubMed Central

    Zhang, Shasha; Chen, Guangzhi; Li, Ning; Dai, Meiyan; Chen, Chen; Wang, Peihua; Tang, Huiru; Hoopes, Samantha L.; Zeldin, Darryl C.; Wang, Dao Wen; Xu, Xizhen

    2015-01-01

    Objective The study aims to investigate the effect of Cytochrome P450 2J2 (CYP2J2) overexpression on hyperlipidemia in mice and further to explore their effect on fatty acid oxidation in vivo and in vitro. Methods The effects and mechanisms of endothelial-specific CYP2J2 transgene (Tie2-CYP2J2-Tr) on lipid and fatty acids metabolism were investigated in high fat diet (HFD)-treated mice. HepG2, LO2 cells and HUVECs were exposed to 0.4 mM free fatty acid (FFA) for 24h and used as a model to investigate the roles of CYP2J2 overexpression and epoxyeicosatrienoic acids (EETs) on fatty acid β oxidation in vitro. Results Tie2-CYP2J2-Tr mice had significantly lower plasma and liver triglycerides, lower liver cholesterol and fatty acids, and the reduction in HFD-induced lipid accumulation. CYP2J2 overexpression resulted in activation of the hepatic and endothelial AMPKα, increased ACC phosphorylation, increased expression of CPT-1 and PPARα, which were all reduced by HFD treatment. In FFA-treated HepG2, LO2 and HUVECs, both CYP2J2 overexpression and EETs significantly decreased lipid accumulation and increased fatty acid oxidation via activating the AMPK and PPARα pathway. Conclusions Endothelial specific CYP2J2 overexpression alleviates HFD–induced hyperlipidemia in vivo. CYP2J2 ameliorates FFA-induced dyslipidemia via increased fatty acid oxidation mediated by the AMPK and PPARα pathway. PMID:26053032

  10. Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria

    PubMed Central

    Benton, Carley R; Holloway, Graham P; Campbell, S E; Yoshida, Yuko; Tandon, Narendra N; Glatz, Jan F C; Luiken, Joost J J F P; Spriet, Lawrence L; Bonen, Arend

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) alter the expression of genes involved in regulating lipid metabolism. Rosiglitazone, a PPARγ agonist, induces tissue-specific effects on lipid metabolism; however, its mode of action in skeletal muscle remains unclear. Since fatty acid translocase (FAT/CD36) was recently identified as a possible regulator of skeletal muscle fatty acid transport and mitochondrial fatty acid oxidation, we examined in this tissue the effects of rosiglitazone infusion (7 days, 1 mg day−1) on FAT/CD36 mRNA and protein, its plasmalemmal content and fatty acid transport. In addition, in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria we examined rates of fatty acid oxidation, FAT/CD36 and carnitine palmitoyltransferase I (CPTI) protein, and CPTI and β-hydroxyacyl CoA dehydrogenase (β-HAD) activities. Rosiglitazone did not alter FAT/CD36 mRNA or protein expression, FAT/CD36 plasmalemmal content, or the rate of fatty acid transport into muscle (P > 0.05). In contrast, rosiglitazone increased the rates of fatty acid oxidation in both SS (+21%) and IMF mitochondria (+36%). This was accompanied by concomitant increases in FAT/CD36 in subsarcolemmal (SS) (+43%) and intermyofibrillar (IMF) mitochondria (+46%), while SS and IMF CPTI protein content, and CPTI submaximal and maximal activities (P > 0.05) were not altered. Similarly, citrate synthase (CS) and β-HAD activities were also not altered by rosiglitazone in SS and IMF mitochondria (P > 0.05). These studies provide another example whereby changes in mitochondrial fatty oxidation are associated with concomitant changes in mitochondrial FAT/CD36 independent of any changes in CPTI. Moreover, these studies identify for the first time a mechanism by which rosiglitazone stimulates fatty acid oxidation in skeletal muscle, namely the chronic, subcellular relocation of FAT/CD36 to mitochondria. PMID:18238811

  11. Fish oil at low dietary levels enhances physiological activity of sesamin to increase hepatic fatty acid oxidation in rats.

    PubMed

    Ide, Takashi

    2012-11-01

    We previously demonstrated that a diet containing fish oil at a level of 80 g/kg strongly stimulated the physiological activity of a sesame sesamin preparation containing sesamin and episesamin at equal amounts to increase hepatic fatty acid oxidation. This study was conducted to clarify whether fish oil at lower dietary levels enhances the physiological activity of sesamin to increase hepatic fatty acid oxidation. Rats were fed experimental diets supplemented with 0 or 2 g sesamin/kg, and containing 0, 15 or 30 g fish oil/kg for 15 days. Among rats fed sesamin-free diets, diets containing 15 and 30 g fish oil/kg slightly increased the activity of enzymes involved in hepatic fatty acid oxidation. Sesamin increased these values irrespective of the presence or absence of fish oil in diets; however, the extent of the increase of many parameters was much greater in rats given fish oil-containing diets than in those fed a fish oil-free diet. Diets simultaneously containing sesamin and fish oil increased the gene expression of various peroxisomal fatty acid oxidation enzymes in a synergistic manner; but they were ineffective in causing a synergistic increase in mRNA levels of mitochondrial fatty acid oxidation enzymes. The extent of the synergistic increase in the activity of hepatic fatty acid oxidation enzymes and mRNA levels of the peroxisomal enzymes was indistinguishable between diets containing 15 and 30 g fish oil/kg and appeared comparable to that observed previously with a diet containing 80 g fish oil/kg.

  12. Preadaptation to Cold Stress in Salmonella enterica Serovar Typhimurium Increases Survival during Subsequent Acid Stress Exposure

    PubMed Central

    Shah, Jigna; Desai, Prerak T.; Chen, Dong; Stevens, John R.

    2013-01-01

    Salmonella is an important cause of bacterial food-borne gastroenteritis. Salmonella encounters multiple abiotic stresses during pathogen elimination methods used in food processing, and these stresses may influence its subsequent survivability within the host or in the environment. Upon ingestion, Salmonella is exposed to gastrointestinal acidity, a first line of the host innate defense system. This study tested the hypothesis that abiotic stresses encountered during food processing alter the metabolic mechanisms in Salmonella that enable survival and persistence during subsequent exposure to the host gastrointestinal acidic environment. Out of the four different abiotic stresses tested, viz., cold, peroxide, osmotic, and acid, preadaptation of the log-phase culture to cold stress (5°C for 5 h) significantly enhanced survival during subsequent acid stress (pH 4.0 for 90 min). The gene expression profile of Salmonella preadapted to cold stress revealed induction of multiple genes associated with amino acid metabolism, oxidative stress, and DNA repair, while only a few of the genes in the above-mentioned stress response and repair pathways were induced upon exposure to acid stress alone. Preadaptation to cold stress decreased the NAD+/NADH ratio and hydroxyl (OH·) radical formation compared with those achieved with the exposure to acid stress alone, indicating alteration of aerobic respiration and the oxidative state of the bacteria. The results from this study suggest that preadaptation to cold stress rescues Salmonella from the deleterious effect of subsequent acid stress exposure by induction of genes involved in stress response and repair pathways, by modification of aerobic respiration, and by redox modulation. PMID:24056458

  13. Valproic Acid Increases CD133 Positive Cells that Show Low Sensitivity to Cytostatics in Neuroblastoma

    PubMed Central

    Khalil, Mohamed Ashraf; Hraběta, Jan; Groh, Tomáš; Procházka, Pavel; Doktorová, Helena; Eckschlager, Tomáš

    2016-01-01

    Valproic acid (VPA) is a well-known antiepileptic drug that exhibits antitumor activities through its action as a histone deacetylase inhibitor. CD133 is considered to be a cancer stem cell marker in several tumors including neuroblastoma. CD133 transcription is strictly regulated by epigenetic modifications. We evaluated the epigenetic effects of treatment with 1mM VPA and its influence on the expression of CD133 in four human neuroblastoma cell lines. Chemoresistance and cell cycle of CD133+ and CD133− populations were examined by flow cytometry. We performed bisulfite conversion followed by methylation-sensitive high resolution melting analysis to assess the methylation status of CD133 promoters P1 and P3. Our results revealed that VPA induced CD133 expression that was associated with increased acetylation of histones H3 and H4. On treatment with VPA and cytostatics, CD133+ cells were mainly detected in the S and G2/M phases of the cell cycle and they showed less activated caspase-3 compared to CD133− cells. UKF-NB-3 neuroblastoma cells which express CD133 displayed higher colony and neurosphere formation capacities when treated with VPA, unlike IMR-32 which lacks for CD133 protein. Induction of CD133 in UKF-NB-3 was associated with increased expression of phosphorylated Akt and pluripotency transcription factors Nanog, Oct-4 and Sox2. VPA did not induce CD133 expression in cell lines with methylated P1 and P3 promoters, where the CD133 protein was not detected. Applying the demethylating agent 5-aza-2’-deoxycytidine to the cell lines with methylated promoters resulted in CD133 re-expression that was associated with a drop in P1 and P3 methylation level. In conclusion, CD133 expression in neuroblastoma can be regulated by histone acetylation and/or methylation of its CpG promoters. VPA can induce CD133+ cells which display high proliferation potential and low sensitivity to cytostatics in neuroblastoma. These results give new insight into the possible

  14. Ursolic Acid Increases Glucose Uptake through the PI3K Signaling Pathway in Adipocytes

    PubMed Central

    He, Yonghan; Li, Wen; Li, Ying; Zhang, Shuocheng; Wang, Yanwen; Sun, Changhao

    2014-01-01

    Background Ursolic acid (UA), a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels. Objective The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes. Methods and Results The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively). 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI) 3-kinase (PI3K) inhibitor wortmannin (1 µM), but not by SB203580 (10 µM), the inhibitor of mitogen-activated protein kinase (MAPK), or compound C (2.5 µM), the inhibitor of AMP-activated kinase (AMPK) inhibitor. Furthmore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK) and phosphoinositide-dependent serine/threoninekinase (AKT) were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC) and the expression of glucose transporter 4 (GLUT4) were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied. Conclusions Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect. PMID:25329874

  15. Fibers from fruit by-products enhance probiotic viability and fatty acid profile and increase CLA content in yoghurts.

    PubMed

    do Espírito Santo, Ana Paula; Cartolano, Nathalie S; Silva, Thaiane F; Soares, Fabiana A S M; Gioielli, Luiz A; Perego, Patrizia; Converti, Attilio; Oliveira, Maricê N

    2012-03-15

    This study evaluated the effect of the supplementation of total dietary fiber from apple, banana or passion fruit processing by-products on the post-acidification, total titratable acidity, bacteria counts and fatty acid profiles in skim milk yoghurts co-fermented by four different probiotics strains: Lactobacillus acidophilus L10 and Bifidobacterium animalis subsp. lactis BL04, HN019 and B94. Apple and banana fibers increased the probiotic viability during shelf-life. All the fibers were able to increase the short chain and polyunsaturated fatty acid contents of yoghurts compared to their respective controls. A synergistic effect between the type of fiber and the probiotic strain on the conjugated linoleic acid content was observed, and the amount of α-linolenic acid was increased by banana fiber. The results of this study demonstrate, for the first time, that fruit fibers can improve the fatty acid profile of probiotic yoghurts and point out the suitability of using fibers from fruit processing the by-products to develop new high value-added fermented dairy products.

  16. Neutral detergent fiber increases endogenous ileal losses but has no effect on ileal digestibility of amino acids in growing pigs.

    PubMed

    Mariscal-Landín, Gerardo; Reis de Souza, Tércia Cesária; Bayardo Uribe, Alejandro

    2017-02-01

    Two experiments were conducted to determine the effect of neutral detergent fiber (NDF) on endogenous amino acids and protein ileal losses; and also apparent ileal digestibility (AID), and standardized ileal digestibility (SID) of amino acids and crude protein. Sixteen barrows were fed four protein-free diets containing graded NDF levels in Experiment 1. NDF was a mixture of sugarcane bagasse and corn leaves (SBCL). Twenty-four barrows were fed diets with soybean protein concentrate (SPC) or casein as protein sources and SBCL or corncobs (CC) as NDF sources in Experiment 2. In Experiment 1, a linear increase (P < 0.05) in endogenous amino acid and protein ileal losses was observed with increased NDF levels, except for arginine, histidine, methionine and proline. In Experiment 2, protein (P < 0.001) and NDF (P < 0.01) sources significantly affected AID of dry matter, which was higher in casein diets (71.7%) and CC diets (70.7%). Protein and NDF sources significantly affected (P < 0.05) SID of crude protein, which was higher in casein diets (92.8%) and CC diets (92.7%). NDF source had no effect (P > 0.05) on SID of amino acids. Overall, this study showed that NDF increased endogenous amino acid and protein ileal losses, but did not affect ileal digestibility of amino acids. © 2016 Japanese Society of Animal Science.

  17. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid.

    PubMed

    Heseker, Helmut B; Mason, Joel B; Selhub, Jacob; Rosenberg, Irwin H; Jacques, Paul F

    2009-07-01

    Some countries have introduced mandatory folic acid fortification, whereas others support periconceptional supplementation of women in childbearing age. Several European countries are considering whether to adopt a fortification policy. Projections of the possible beneficial effects of increased folic acid intake assume that the measure will result in a considerable reduction in neural-tube defects (NTD) in the target population. Therefore, the objective of the present study is to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of NTD. Countries with mandatory fortification achieved a significant increase in folate intake and a significant decline in the prevalence of NTD. This was also true for supplementation trials. However, the prevalence of NTD at birth declined to approximately five cases at birth per 10 000 births and seven to eight cases at birth or abortion per 10 000 births. This decline was independent of the amount of folic acid administered and apparently reveals a 'floor effect' for folic acid-preventable NTD. This clearly shows that not all cases of NTD are preventable by increasing the folate intake. The relative decline depends on the initial NTD rate. Countries with NTD prevalence close to the observed floor may have much smaller reductions in NTD rates with folic acid fortification. Additionally, potential adverse effects of fortification on other vulnerable population groups have to be seriously considered. Policy decisions concerning national mandatory fortification programmes must take into account realistically projected benefits as well as the evidence of risks to all vulnerable groups.

  18. Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice[S

    PubMed Central

    Shen, Wan; Chuang, Chia-Chi; Martinez, Kristina; Reid, Tanya; Brown, J. Mark; Xi, Lin; Hixson, Lindsay; Hopkins, Robin; Starnes, Joseph; McIntosh, Michael

    2013-01-01

    The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA. PMID:23401602

  19. β-Lactamase inhibitor, clavulanic acid, attenuates ethanol intake and increases glial glutamate transporters expression in alcohol preferring rats.

    PubMed

    Hakami, Alqassem Y; Sari, Youssef

    2017-09-14

    Studies from our laboratory showed that upregulation of glutamate transporter 1 (GLT-1) and cystine-glutamate exchanger (xCT) expression with ceftriaxone, β-lactam antibiotic, in the brain was associated with attenuation of ethanol consumption. In this study, we tested clavulanic acid, which is another β-lactam compound with negligible antimicrobial activity, on ethanol consumption and expression of GLT-1, xCT and glutamate aspartate transporter (GLAST) in male alcohol-preferring (P) rats. Clavulanic acid has the central β-lactam pharmacophore that is critical for the upregulation of GLT-1 and xCT expression. We found that clavulanic acid, at 5mg/kg (i.p.) dose, significantly attenuated ethanol consumption and ethanol preference in P rats as compared to vehicle-treated group. This effect was associated with a significant increase in water intake in clavulanic acid treated group. Importantly, we found that clavulanic acid increased the expression of GLT-1 and xCT in nucleus accumbens. However, there was no effect of clavulanic acid on GLAST expression in the nucleus accumbens. Clavulanic acid treatment did not upregulate the expression of GLT-1, xCT and GLAST in prefrontal cortex. These findings revealed that clavulanic acid at 20-40 fold lower dose than ceftriaxone can attenuate ethanol consumption, in part through upregulation of GLT-1 and xCT expression in the nucleus accumbens. Thus, we suggest that clavulanic acid might be used as an alternative option to ceftriaxone to attenuate ethanol drinking behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. PPARgamma agonist induced cardiac enlargement is associated with reduced fatty acid and increased glucose utilization in myocardium of Wistar rats.

    PubMed

    Edgley, Amanda J; Thalén, Pia G; Dahllöf, Björn; Lanne, Boel; Ljung, Bengt; Oakes, Nicholas D

    2006-05-24

    In toxicological studies, high doses of peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists cause cardiac enlargement. To investigate whether this could be explained by a large shift from free fatty acid to glucose utilization by the heart, Wistar rats were treated for 2-3 weeks with a potent, selective PPARgamma agonist (X334, 3 micromol/kg/d), or vehicle. X334 treatment increased body-weight gain and ventricular mass. Treatment lowered plasma triglycerides by 61%, free fatty acid levels by 72%, insulin levels by 45%, and reduced total plasma protein concentration by 7% (indicating plasma volume expansion) compared to vehicle animals. Fasting plasma glucose levels were unaltered. To assess cardiac free fatty acid and glucose utilization in vivo we used simultaneous infusions of non-beta-oxidizable free fatty acid analogue, [9,10-(3)H](R)-2-bromopalmitate and [U-(14)C]2-deoxy-d-glucose tracers, which yield indices of local free fatty acid and glucose utilization. In anesthetized, 7 h fasted animals, left ventricular glucose utilization was increased to 182% while free fatty acid utilization was reduced by 28% (P<0.05) compared to vehicle. In separate studies we attempted to prevent the X334-induced hypolipidemia. Various dietary fat supplements were unsuccessful. By contrast, restricting the time during which the treated animals had access to food (promoting endogenous lipolysis), restored plasma free fatty acid from 27% to 72% of vehicle control levels and prevented the cardiac enlargement. Body-weight gain in these treated-food restricted rats was not different from vehicle controls. In conclusion, the cardiac enlargement caused by intense PPARgamma activation in normal animals is associated with marked changes in free fatty acid/glucose utilization and the enlargement can be prevented by restoring free fatty acid availability.

  1. Uric Acid Excretion Predicts Increased Blood Pressure Among American Adolescents of African Descent.

    PubMed

    Mrug, Sylvie; Mrug, Michal; Morris, Anjana Madan; Reynolds, Nina; Patel, Anita; Hill, Danielle C; Feig, Daniel I

    2017-04-01

    Hyperuricemia predicts the incidence of hypertension in adults and its treatment has blood pressure (BP)-lowering effects in adolescents. To date, no studies have examined the predictive usage of hyperuricemia or urinary uric acid excretion on BP changes in adolescents. Mechanistic models suggest that uric acid impairs both endothelial function and vascular compliance, which would potentially exacerbate a myriad of hypertensive mechanisms, yet little is known about interaction of uric acid and other hypertension risk factors. The primary study was aimed at the effects of stress on BP in adolescents. A community sample of 84 low-income, urban adolescents (50% male, 95% African American, mean age = 13.36 ± 1 years) was recruited from public schools. Youth completed a 12-hour (overnight) urine collection at home and their BP was measured during rest and in response to acute psychosocial stress. Seventy-six of the adolescents participated in a follow-up visit at 1.5 years when their resting BP was reassessed. In this substudy, we assessed the relationship of renal urate excretion and BP reactivity. After adjusting for resting BP levels at baseline and other covariates, higher levels of uric acid excretion predicted greater BP reactivity to acute psychosocial stress and higher resting BP at 18 months. Urinary excretion of uric acid can serve as an alternative, noninvasive measure of serum uric acid levels that are predictive of BP changes. As hyperuricemia-associated hypertension is treatable, urban adolescents may benefit from routine screening for hyperuricemia or high uric acid excretion. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  2. Azadirachta indica extract-artesunic acid combination produces an increased cure rate of Plasmodium berghei-infected mice.

    PubMed

    Anagu, Onyeka Linda; Attama, Anthony Amaechi; Okore, Vincent Chima; Gugu, Harrison Thaddeus; Ngene, Augustine Arinze; Esimone, Charles Okechukwu

    2014-07-01

    Available artemisinin-combination therapies (ACTs) are expensive. Various traditional herbal remedies for malaria involve plants, proven scientifically to have antiplasmodial effects, e.g., Azadirachta indica A. Juss. (Meliaceae). Combination of an artemisinin-based compound and a medicinal herb extract will provide an indigenous alternative/herb-based ACT. The in vivo schizontocidal activity of the crude aqueous extract of 100, 500, and 1000 mg/kg of A. indica fresh leaves (NCE) and 6, 15, and 20 mg/kg of artesunic acid were determined, alone and in combination, while keeping the dose of artesunic acid constant at 15 mg/kg, using the Peter's 4-day suppressive test and Swiss albino mice. The ED50 was calculated from the dose-response relationships. Percentage survival and cure were also determined. The average yield of two extractions of NCE was 8.33 ± 1.67%. Combination of 1000 mg/kg of NCE and 15 mg/kg of artesunic acid, produced a significant reduction of parasitemia (96.87%), compared to 20 mg/kg of artesunic acid alone (68.14%). The combination had an ED50 of 0.58 mg/kg while that of artesunic acid alone was 8.814 mg/kg. The combinations of NCE with artesunic acid produced a cure, although the artesunic acid did not produce a cure in 30 d. NCE increased the activity of artesunic acid in terms of reduction in parasitemia, and increased survival time and cure rate. The combination of an artemisinin and aqueous extract of neem leaf is possible, providing a potentiated reduction of parasitemia, and increased cure rate.

  3. Pre-harvest application of oxalic acid increases quality and resistance to Penicillium expansum in kiwifruit during postharvest storage.

    PubMed

    Zhu, Yuyan; Yu, Jie; Brecht, Jeffrey K; Jiang, Tianjia; Zheng, Xiaolin

    2016-01-01

    Kiwifruit (Actinidia deliciosa cv. Bruno) fruits were sprayed with 5mM oxalic acid (OA) at 130, 137, and 144 days after full blossom, and then harvested at commercial maturity [soluble solid content (SSC) around 10.0%] and stored at room temperature (20 ± 1 °C). Pre-harvest application of OA led to fruit with higher ascorbic acid content at harvest, slowed the decreases in fruit firmness and ascorbic acid content and increase in SSC during storage, and also decreased the natural disease incidence, lesion diameter, and patulin accumulation in fruit inoculated with Penicillium expansum, indicating that the OA treatment increased quality and induced disease resistance in kiwifruit. It was suggested that the increase in activities of defense-related enzymes and in levels of substances related to disease resistance might collectively contribute to resistance in kiwifruit against fungi such as P. expansum in storage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Aspartic acid aminotransferase activity is increased in actively spiking compared with non-spiking human epileptic cortex.

    PubMed Central

    Kish, S J; Dixon, L M; Sherwin, A L

    1988-01-01

    Increased concentration of the excitatory neurotransmitter aspartic acid in actively spiking human epileptic cerebral cortex was recently described. In order to further characterise changes in the aspartergic system in epileptic brain, the behaviour of aspartic acid aminotransferase (AAT), a key enzyme involved in aspartic acid metabolism has now been examined. Electrocorticography performed during surgery was employed to identify cortical epileptic spike foci in 16 patients undergoing temporal lobectomy for intractable seizures. Patients with spontaneously spiking lateral temporal cortex (n = 8) were compared with a non-spiking control group (n = 8) of patients in whom the epileptic lesions were confined to the hippocampus sparing the temporal convexity. Mean activity of AAT in spiking cortex was significantly elevated by 16-18%, with aspartic acid concentration increased by 28%. Possible explanations for the enhanced AAT activity include increased proliferation of cortical AAT-containing astrocytes at the spiking focus and/or a generalised increase in neuronal or extraneuronal metabolism consequent to the ongoing epileptic discharge. It is suggested that the data provide additional support for a disturbance of central excitatory aspartic acid mechanisms in human epileptic brain. PMID:2898010

  5. The content of free amino acids in the stratum corneum is increased in senile xerosis.

    PubMed

    Takahashi, Masae; Tezuka, Tadashi

    2004-03-01

    Xerosis is one of the characteristics of aged skin. Xerosis may be caused by a decrease in the stratum corneum free amino acids which are natural moisturizing factors derived from filaggrin. In aged skin, filaggrin is immunohistochemically decreased compared with the levels in young skin. However, the differences in stratum corneum amino acids between aged and young skin have not been analyzed quantitatively. Therefore, in this study we determined the stratum corneum amino acids per 1000 stratum corneum cells in aged and young skin by high-performance liquid chromatography. The amount of filaggrin mRNA in the epidermis was also compared between aged and young skin using RT-PCR. The total amount of amino acids in the stratum corneum was larger in aged senile xerosis skin than in young skin. Only a few amino acids were found in the stratum corneum of ichthyosis vulgaris patients (control skin). The expression of filaggrin mRNA in aged skin was, however, similar to that in young skin. These findings suggest that the immunohistochemical decrease in filaggrin in aged skin may be caused by promotion of filaggrin proteolysis in the upper layers of the stratum spinulosum.

  6. Changes in plasma amino acid concentrations with increasing age in patients with propionic acidemia.

    PubMed

    Scholl-Bürgi, Sabine; Sass, Jörn Oliver; Heinz-Erian, Peter; Amann, Edda; Haberlandt, Edda; Albrecht, Ursula; Ertl, Claudia; Sigl, Sara Baumgartner; Lagler, Florian; Rostasy, Kevin; Karall, Daniela

    2010-05-01

    The objective of the study is to analyze plasma amino acid concentrations in propionic acidemia (PA) for the purpose of elucidating possible correlations between propionyl-CoA carboxylase deficiency and distinct amino acid behavior. Plasma concentrations of 19 amino acids were measured in 240 random samples from 11 patients (6 families) with enzymatically and/or genetically proven propionic acidemia (sampling period, January 2001-December 2007). They were compared with reference values from the literature and correlated with age using the Pearson correlation coefficient test. Decreased plasma concentrations were observed for glutamine, histidine, threonine, valine, isoleucine, leucine, phenylalanine and arginine. Levels of glycine, alanine and aspartate were elevated, while values of serine, asparagine, ornithine and glutamate were normal. For lysine, proline and methionine a clear association was not possible. Significant correlations with age were observed for 13 amino acids (positive correlation: asparagine, glutamine, proline, alanine, histidine, threonine, methionine, arginine; negative correlation: leucine, phenylalanine, ornithine, glutamate and aspartate). This study gives new insight over long-term changes in plasma amino acid concentrations and may provide options for future therapies (e.g., substitution of anaplerotic substances) in PA patients.

  7. Cassava interspecific hybrids with increased protein content and improved amino acid profiles.

    PubMed

    Gomes, P T C; Nassar, N M A

    2013-04-12

    Cassava (Manihot esculenta) is a principal food for large populations of poor people in the tropics and subtropics. Its edible roots are poor in protein and lack several essential amino acids. Interspecific hybrids may acquire high protein characteristics from wild species. We analyzed 19 hybrids of M. esculenta with its wild relative, M. oligantha, for crude protein, amino acid profile, and total cyanide. Some hybrids produced roots with high protein content of up to 5.7%, while the common cultivar that we examined had just 2.3% crude protein. The essential amino acids alanine, phenylalanine, and valine were detected in the hybrids. The sulfur-containing amino acids cysteine and methionine were found at relatively high concentrations in the roots of 4 hybrids. The proportion of lysine in one hybrid was 20 times higher than in the common cultivar. The levels of total cyanide ranged from 19.73 to 172.56 mg/kg and most of the roots analyzed were classified as "non-toxic" and "low toxic". Furthermore, 2 progenies showed reasonable levels of cyanide, but higher protein content and amino acid profile more advantageous than the common cassava.

  8. Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis.

    PubMed

    Vara-Messler, Marianela; Pasqualini, Maria E; Comba, Andrea; Silva, Renata; Buccellati, Carola; Trenti, Annalisa; Trevisi, Lucia; Eynard, Aldo R; Sala, Angelo; Bolego, Chiara; Valentich, Mirta A

    2017-03-01

    The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma. BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma. After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERβ in tumor lysates. These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.

  9. Treatment of flaxseed to reduce biohydrogenation of a-linolenic acid by ruminal microbes in sheep and cattle and increase n-3 fatty acid concentrations in red meat

    USDA-ARS?s Scientific Manuscript database

    Our study determined if flaxseed treated with a formaldehyde-free process increased n-3 fatty acid (FA) levels in ruminant muscle. Twenty-four lambs (initial BW 43.8 ± 4.4 kg) were randomly divided into 4 groups for a 90-d trial. One treatment group (FLX) was fed 136 g/d of non-treated ground flaxse...

  10. Compared with stearic acid, palmitic acid increased the yield of milk fat and improved feed efficiency across production level of cows.

    PubMed

    Rico, J E; Allen, M S; Lock, A L

    2014-02-01

    The effects of dietary palmitic and stearic acids on feed intake, yields of milk and milk components, and feed efficiency of dairy cows were evaluated in an experiment with a crossover arrangement of treatments with a covariate period. Cows with a wide range of milk production (38 to 65 kg/d) were used to determine if response to fat supplementation varied according to production level. Thirty-two Holstein cows (143 ± 61 d in milk) were assigned randomly to a treatment sequence within level of milk production. Treatments were diets supplemented (2% of diet dry matter) with palmitic acid (PA; 97.9% C16:0) or stearic acid (SA; 97.4% C18:0). Treatment periods were 21 d and cows were fed a nonfat supplemented diet for 14 d immediately before the first treatment period. The final 4d of each period were used for sample and data collection. Milk production measured during the covariate period (preliminary milk yield) was used as the covariate. No interactions were detected between treatment and preliminary milk yield for the production response variables measured. Compared with SA, the PA treatment increased milk fat concentration (3.66 vs. 3.55%) and yield (1.68 vs. 1.59 kg/d), and 3.5% fat-corrected milk yield (47.5 vs. 45.6 kg/d). Treatment did not affect dry matter intake, milk yield, milk protein yield, body weight, or body condition score. Milk protein concentration was lower for PA compared with SA treatment (3.24 vs. 3.29%). The PA treatment increased feed efficiency (3.5% fat-corrected milk yield/dry matter intake) compared with SA (1.48 vs. 1.40). The increase in milk fat yield by PA was entirely accounted for by a 24% increase in 16-carbon fatty acid output into milk. Yields of de novo (3.2%) and preformed fatty acids (2.9%) were only slightly decreased by PA relative to SA. The PA treatment increased plasma concentration of nonesterified fatty acids (96.3 vs. 88.2 μEq/L) and glucose (56.6 vs. 55.7 mg/dL) compared with SA, but insulin and

  11. [Evaluation of the possibilities to increase the content of conjugated linoleic acid (CLA) in meat and meat product].

    PubMed

    Piotrowska, Anna; Swiader, Katarzyna; Waszkiewicz-Robak, Bozena; Swiderski, Franciszek

    2012-01-01

    The paper characterizes pro-health properties of conjugated linoleic acid (CLA) and assesses the possibility of increasing their content in pork and pork meat products. Studies conducted on animals indicate antitumor, antiatherosclerotic and antiinflammatory effect ofCLA, also find impact on reducing body fat and increasing muscle growth. However, the number of observations concerning human populations is insufficient to fully evaluate the relationship between CLA intake and reducing the risk of lifestyle diseases. Therefore, it is necessary to conduct further research. Literature data indicate that the use in pigs feed suplementation with CLA preparations, can increase the content of these compounds in the meat and also show, that isomer cis-9, trans-11 is accumulated at significantly higher level. However, these changes were accompanied by increased the share of saturated fatty acids at the expense of monounsaturated which is unfavorable for human health. A better way to increase the CLA content in pork meat appears to be the addition of CLA preparation during the production process, because it does not affect the level of saturated fats. Pork and pork meat products enriched in CLA are characterized by low susceptibility to oxidation, which may result from the coupling of double bonds, antioxidantive properties of conjugated linoleic acid and the increased content of saturated fatty acids. The issue of beneficial effects on human health of pork and pork products with a higher content of CLA, requires further studies conducted on humans. Only then these products can be classified as a functional foods.

  12. Role of a single amino acid substitution of VP3 H142D for increased acid resistance of foot-and-mouth disease virus serotype A.

    PubMed

    Biswal, Jitendra K; Das, Biswajit; Sharma, Gaurav K; Khulape, Sagar A; Pattnaik, Bramhadev

    2016-04-01

    Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their dissociation into pentamers at pH value below 6.5. After the uptake of FMDV by receptor-mediated endocytosis, the acid-dependent dissociation process is required for the release of FMDV genome inside endosomes. Nevertheless, dissociation of FMDV particles in mildly acidic conditions renders the inactivated FMD vaccine less effective. To improve the acid stability of inactivated FMD vaccine during the manufacturing process, a serotype A IND 40/2000 (in-use vaccine strain) mutant with increased resistance to acid inactivation was generated through reverse genetics approach. Based upon the earlier reports, the crucial amino acid residue, H142 of VP3 capsid protein was substituted separately to various amino acid residues Arg (R), Phe (F), Ala (A), and Asp (D) on the full-genome length cDNA clone. While the H142 → R or H142 → F or H142 → A substitutions resulted in non-infectious FMDV, H142 → D mutation on VP3 protein (H3142D) resulted in the generation of mutant virus with enhanced resistance to acid-induced inactivation. In addition, H3142D substitution did not alter the replication ability and antigenicity of mutant as compared to the parental virus. However, the virus competition experiments revealed that the H3142D substitution conferred a loss of fitness for the mutant virus. Results from this study demonstrate that the H3142D substitution is the molecular determinant of acid-resistant phenotype in FMDV serotype A.

  13. Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic Vascularity, and Islet Size in Growth-Restricted Fetal Sheep.

    PubMed

    Brown, Laura D; Davis, Melissa; Wai, Sandra; Wesolowski, Stephanie R; Hay, William W; Limesand, Sean W; Rozance, Paul J

    2016-10-01

    Placental insufficiency is associated with reduced supply of amino acids to the fetus and leads to intrauterine growth restriction (IUGR). IUGR fetuses are characterized by lower glucose-stimulated insulin secretion, smaller pancreatic islets with less β-cells, and impaired pancreatic vascularity. To test whether supplemental amino acids infused into the IUGR fetus could improve these complications of IUGR we used acute (hours) and chronic (11 d) direct fetal amino acid infusions into a sheep model of placental insufficiency and IUGR near the end of gestation. IUGR fetuses had attenuated acute amino acid-stimulated insulin secretion compared with control fetuses. These results were confirmed in isolated IUGR pancreatic islets. After the chronic fetal amino acid infusion, fetal glucose-stimulated insulin secretion and islet size were restored to control values. These changes were associated with normalization of fetal pancreatic vascularity and higher fetal pancreatic vascular endothelial growth factor A protein concentrations. These results demonstrate that decreased fetal amino acid supply contributes to the pathogenesis of pancreatic islet defects in IUGR. Moreover, the results show that pancreatic islets in IUGR fetuses retain their ability to respond to increased amino acids near the end of gestation after chronic fetal growth restriction.

  14. Omega-3 fatty acids prevent the ketamine-induced increase in acetylcholinesterase activity in an animal model of schizophrenia.

    PubMed

    Zugno, Alexandra I; Chipindo, Helder; Canever, Lara; Budni, Josiane; Alves de Castro, Adalberto; Bittencourt de Oliveira, Mariana; Heylmann, Alexandra Stephanie; Gomes Wessler, Patrícia; da Rosa Silveira, Flávia; Damázio, Louyse S; Mastella, Gustavo Antunes; Kist, Luiza W; Bogo, Maurício R; Quevedo, João; Gama, Clarissa S

    2015-01-15

    Schizophrenia is a debilitating neurodevelopmental disorder that is associated with dysfunction in the cholinergic system. Early prevention is a target of treatment to improve long-term outcomes. Therefore, we evaluated the preventive effects of omega-3 fatty acids on AChE activity in the prefrontal cortex, hippocampus and striatum in an animal model of schizophrenia. Young Wistar rats (30 days old) were initially treated with omega-3 fatty acids or vehicle alone. Animals received ketamine to induce an animal model of schizophrenia or saline plus omega-3 fatty acids or vehicle alone for 7 consecutive days beginning on day 15. A total of 22 days elapsed between the treatment and intervention. Animals were sacrificed, and brain structures were dissected to evaluate AChE activity and gene expression. Our results demonstrate that ketamine increased AChE activity in these three structures, and omega-3 fatty acids plus ketamine showed lower values for the studied parameters, which indicate a partial preventive mechanism of omega-3 fatty acid supplementation. We observed no effect on AChE expression. Together, these results indicate that omega-3 fatty acid supplementation effectively reduced AChE activity in an animal model of schizophrenia in all studied structures. In conclusion, the present study provides evidence that ketamine and omega-3 fatty acids affect the cholinergic system, and this effect may be associated with the physiopathology of schizophrenia. Further studies are required to investigate the mechanisms that are associated with this effect. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Camelina meal increases egg n-3 fatty acid content without altering quality or production in laying hens.

    PubMed

    Kakani, Radhika; Fowler, Justin; Haq, Akram-Ul; Murphy, Eric J; Rosenberger, Thad A; Berhow, Mark; Bailey, Christopher A

    2012-05-01

    Camelina sativa is an oilseed plant rich in n-3 and n-6 fatty acids and extruding the seeds results in high protein meal (*40%) containing high levels of n-3 fatty acids. In this study, we examined the effects of feeding extruded defatted camelina meal to commercial laying hens, measuring egg production, quality, and fatty acid composition. Lohmann White Leghorn hens (29 weeks old) were randomly allocated to three dietary treatment groups (n = 25 per group) and data was collected over a 12 week production period. All the treatment groups were fed a corn soy based experimental diet containing 0% (control), 5, or 10% extruded camelina meal. We found no significant differences in percent hen-day egg production and feed consumed per dozen eggs. Egg shell strength was significantly higher in both camelina groups compared to the controls. Egg total n-3 fatty acid content increased 1.9- and 2.7-fold in 5 and 10% camelina groups respectively relative to the control. A similar increase in DHA content also occurred. Further camelina meal did not alter glucosinolate levels and no detectable glucosinolates or metabolic product isothiocyanates were found in the eggs from either the 5 or 10% camelina groups. These results indicate that camelina meal is a viable dietary source of n-3 fatty acids for poultry and its dietary inclusion results in eggs enriched with n-3 fatty acids.

  16. Patatin-related phospholipase pPLAIIIδ increases seed oil content with long-chain fatty acids in Arabidopsis.

    PubMed

    Li, Maoyin; Bahn, Sung Chul; Fan, Chuchuan; Li, Jia; Phan, Tien; Ortiz, Michael; Roth, Mary R; Welti, Ruth; Jaworski, Jan; Wang, Xuemin

    2013-05-01

    The release of fatty acids from membrane lipids has been implicated in various metabolic and physiological processes, but in many cases, the enzymes involved and their functions in plants remain unclear. Patatin-related phospholipase As (pPLAs) constitute a major family of acyl-hydrolyzing enzymes in plants. Here, we show that pPLAIIIδ promotes the production of triacylglycerols with 20- and 22-carbon fatty acids in Arabidopsis (Arabidopsis thaliana). Of the four pPLAIIIs (α, β, γ, δ), only pPLAIIIδ gene knockout results in a decrease in seed oil content, and pPLAIIIδ is most highly expressed in developing embryos. The overexpression of pPLAIIIδ increases the content of triacylglycerol and 20- and 22-carbon fatty acids in seeds with a corresponding decrease in 18-carbon fatty acids. Several genes in the glycerolipid biosynthetic pathways are up-regulated in pPLAIIIδ-overexpressing siliques. pPLAIIIδ hydrolyzes phosphatidylcholine and also acyl-coenzyme A to release fatty acids. pPLAIIIδ-overexpressing plants have a lower level, whereas pPLAIIIδ knockout plants have a higher level, of acyl-coenzyme A than the wild type. Whereas seed yield decreases in transgenic plants that ubiquitously overexpress pPLAIIIδ, seed-specific overexpression of pPLAIIIδ increases seed oil content without any detrimental effect on overall seed yield. These results indicate that pPLAIIIδ-mediated phospholipid turnover plays a role in fatty acid remodeling and glycerolipid production.

  17. Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women.

    PubMed

    Green, Timothy J; Liu, Yazheng; Dadgar, Samira; Li, Wangyang; Böhni, Ruth; Kitts, David D

    2013-06-01

    Mandatory folic acid fortification of grains such as wheat flour has been introduced in several countries to reduce the incidence of neural tube defects. There are concerns, however, that folic acid could mask the hematologic signs of vitamin B-12 deficiency and lead to other adverse health outcomes in the population. Calcium L-5-methyltetrahydrofolic acid (L-5-MTHF), a synthetic form of reduced folate, should not mask vitamin B-12 deficiency and may be safer than folic acid. Unfortunately, L-5-MTHF is not stable in most food matrices such as bread. Microencapsulation of L-5-MTHF with sodium ascorbate and a modified starch is effective at preventing loss of the vitamin during baking and storage. Our aim was to assess the efficacy of wheat rolls fortified with microencapsulated L-5-MTHF or equimolar folic acid compared with wheat rolls containing no added folate (placebo) at increasing blood folate concentrations during 16 wk. Healthy men and women aged 18-45 y (n = 45) were randomly assigned to consume wheat rolls that contained L-5-MTHF (452 μg/d), the molar equivalent of folic acid (400 μg/d), or placebo. At 16 wk, the mean (95% CI) erythrocyte folate was 0.48 (0.27, 0.71) and 0.37 (0.17, 0.57) μmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P = 0.001) groups, respectively, than in the placebo group. Likewise, the mean plasma folate was 23 (12, 34) and 23 (12, 34) nmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P < 0.001) groups, respectively, than in the placebo group. There were no significant differences in blood folate concentrations between the L-5-MTHF and folic acid wheat roll groups. Both microencapsulated L-5-MTHF and folic acid-fortified wheat rolls increased blood folate concentrations compared with placebo.

  18. n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats.

    PubMed

    Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu

    2015-02-01

    We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline.

  19. Excess Linoleic Acid Increases Collagen I/III Ratio and “Stiffens” the Heart Muscle Following High Fat Diets*

    PubMed Central

    Beam, Julianne; Botta, Amy; Ye, Jiayu; Soliman, Hesham; Matier, Brieanne J.; Forrest, Mary; MacLeod, Kathleen M.; Ghosh, Sanjoy

    2015-01-01

    Controversy exists on the benefits versus harms of n-6 polyunsaturated fatty acids (n-6 PUFA). Although n-6 PUFA demonstrates anti-atherosclerotic properties, survival following cardiac remodeling may be compromised. We hypothesized that n-6 PUFA like linoleic acid (LA) or other downstream PUFAs like γ-linolenic acid or arachidonic acid alter the transforming growth factor-β (TGFβ)-collagen axis in the heart. Excess dietary LA increased the collagen I/III ratio in the mouse myocardium, leading to cardiac “stiffening” characterized by impaired transmitral flow indicative of early diastolic dysfunction within 5 weeks. In vitro, LA under TGFβ1 stimulation increased collagen I and lysyl oxidase (LOX), the enzyme that cross-links soluble collagen resulting in deposited collagen. Overexpression of fatty acid desaturase 2 (fads2), which metabolizes LA to downstream PUFAs, reduced collagen deposits, LOX maturation, and activity with LA, whereas overexpressing fads1, unrelated to LA desaturation, did not. Furthermore, fads2 knockdown by RNAi elevated LOX activity and collagen deposits in fibroblasts with LA but not oleic acid, implying a buildup of LA for aggravating such pro-fibrotic effects. As direct incubation with γ-linolenic acid or arachidonic acid also attenuated collagen deposits and LOX activity, we concluded that LA itself, independent of other downstream PUFAs, promotes the pro-fibrotic effects of n-6 PUFA. Overall, these results attempt to reconcile opposing views of n-6 PUFA on the cardiovascular system and present evidence supporting a cardiac muscle-specific effect of n-6 PUFAs. Therefore, aggravation of the collagen I/III ratio and cardiac stiffening by excess n-6 PUFA represent a novel pathway of cardiac lipotoxicity caused by high n-6 PUFA diets. PMID:26240151

  20. Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge

    PubMed Central

    Long, Nathan M.; Rule, Daniel C.; Tuersunjiang, Nuermaimaiti; Nathanielsz, Peter W.; Ford, Stephen P.

    2015-01-01

    Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an ad libitum feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term. All ewes were fed to requirements during lactation. After weaning, F1 male offspring were fed only to maintenance requirements until adulthood (control = 7, obese = 6), when they were fed ad libitum for 12 weeks with intake monitored. At the end of the feeding challenge offspring were given an intravenous glucose tolerance test (IVGTT), necropsied, and adipose tissue collected. During the feeding trial F1obese males consumed more (P < 0.01), gained more weight (P < 0.01) and became heavier (P < 0.05) than F1control males. During IVGTT, Obese F1 offspring were hyperglycemic and hypoinsulinemic (P < 0.01) compared to F1 control F1. At necropsy perirenal and omental adipose depots weights were 47% and 58% greater respectively and subcutaneous fat thickness 41% greater in F1obese vs F1control males (P < 0.05). Adipocyte diameters were greater (P ≤ 0.04) in perirenal, omental and subcutaneous adipose depots in F1obese males (11, 8 and 7% increase vs. control, respectively). When adipose tissue was incubated for 2 hrs with C-14 labeled acetate, subcutaneous, perirenal, and omental adipose tissue of F1 obese males exhibited greater incorporation (290, 83, and 90% increase vs. control, respectively P < 0.05) of acetate into lipids. Expression of fatty acid transporting, binding, and syntheses mRNA and protein was increased (P < 0.05) compared to F1 control offspring. Maternal obesity increased appetite and adiposity associated with increased adipocyte diameters and increased fatty acid synthesis in over-nourished adult male offspring. PMID:25875659

  1. Combined incubation of cadmium, docosahexaenoic and eicosapentaenoic acid results in increased uptake of cadmium and elevated docosapentaenoic acid content in hepatocytes in vitro.

    PubMed

    Linhartova, Pavla; Sampels, Sabine

    2015-12-01

    Human hepatocellular cells Hep G2 were used to mimic and investigate the effect of the intake of cadmium (Cd(2+)) contaminated fish on cytotoxicity, fatty acid (FA) and phospholipid class composition. Cells were incubated with a combination of Cd(2+) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) fish specific FA. We measured a significant increased proportion of EPA and DHA in the treated cells compared to the control line confirming the uptake. While doses of 25 μM DHA showed to be toxic to the cells, repeated short term incubations (2 h) at lower doses resulted in an increased uptake of DHA. The resarzurin assay, evaluating cell viability, showed a significant decrease in cell viability between Cd(2+) incubation time and, further, the pre-incubation with BSA-FA complex resulted in significantly increased cell viability. On the metabolic level, increased concentrations of EPA and DHA resulted in an increased proportion of docosapentaenoic acid (DPA) which indicated an increased metabolism. Also 24-h combined incubations of 5 μM Cd(2+) and EPA and DHA showed a significant increase DPA in the total lipid fraction of the cells. In addition, incubation with 5 μM Cd(2+) for 24 h also decreased the total cardiolipin (CL) fraction from the identified phospholipids. We confirmed that the applied FA were taken up by the cells. A combination of EPA, DHA and Cd(2+) influenced lysosomal integrity, cell viability and lipid metabolism in the cells. The most important finding is that DHA and EPA reduced the detrimental effect of Cd(2+) on cell viability. The exact effects and kinetics behind our observations still need further evaluation.

  2. Adaptation and transcriptome analysis of Aureobasidium pullulans in corncob hydrolysate for increased inhibitor tolerance to malic acid production.

    PubMed

    Zou, Xiang; Wang, Yongkang; Tu, Guangwei; Zan, Zhanquan; Wu, Xiaoyan

    2015-01-01

    Malic acid is a dicarboxylic acid widely used in the food industry, and is also a potential C4 platform chemical. Corncob is a low-cost renewable feedstock from agricultural industry. However, side-reaction products (furfural, 5-hydroxymethylfurfural (HMF), formic acid, and acetic acid) that severely hinder fermentation are formed during corncob pretreatment. The process for producing malic acid from a hydrolysate of corncob was investigated with a polymalic acid (PMA)-producing Aureobasidium pullulans strain. Under the optimal hydrolysate sugar concentration 110 g/L, A. pullulans was further adapted in an aerobic fibrous bed bioreactor (AFBB) by gradually increasing the sugar concentration of hydrolysate. After nine batches of fermentation, the production and productivity of malic acid reached 38.6 g/L and 0.4 g/L h, respectively, which was higher than that in the first batch (27.6 g/L and 0.29 g/L h, respectively). The adapted strain could grow under the stress of 0.5 g/L furfural, 3 g/L HMF, 2g/L acetic acid, and 0.5 g/L formic acid, whereas the wild type did not. Transcriptome analysis revealed that the differentially expressed genes were related to carbohydrate transport and metabolism, lipid transport and metabolism, signal transduction mechanism, redox metabolism, and energy production and conversion under 0.5 g/L furfural and 3 g/L HMF stress conditions. In total, 42 genes in the adapted strain were upregulated by 15-fold or more, and qRT-PCR also confirmed that the expression levels of key genes (i.e. SIR, GSS, CYS, and GSR) involved in sulfur assimilation pathway were upregulated by over 10-fold in adapted strain for cellular protection against oxidative stress.

  3. Adaptation and Transcriptome Analysis of Aureobasidium pullulans in Corncob Hydrolysate for Increased Inhibitor Tolerance to Malic Acid Production

    PubMed Central

    Zou, Xiang; Wang, Yongkang; Tu, Guangwei; Zan, Zhanquan; Wu, Xiaoyan

    2015-01-01

    Malic acid is a dicarboxylic acid widely used in the food industry, and is also a potential C4 platform chemical. Corncob is a low-cost renewable feedstock from agricultural industry. However, side-reaction products (furfural, 5-hydroxymethylfurfural (HMF), formic acid, and acetic acid) that severely hinder fermentation are formed during corncob pretreatment. The process for producing malic acid from a hydrolysate of corncob was investigated with a polymalic acid (PMA)-producing Aureobasidium pullulans strain. Under the optimal hydrolysate sugar concentration 110 g/L, A. pullulans was further adapted in an aerobic fibrous bed bioreactor (AFBB) by gradually increasing the sugar concentration of hydrolysate. After nine batches of fermentation, the production and productivity of malic acid reached 38.6 g/L and 0.4 g/L h, respectively, which was higher than that in the first batch (27.6 g/L and 0.29 g/L h, respectively). The adapted strain could grow under the stress of 0.5 g/L furfural, 3 g/L HMF, 2g/L acetic acid, and 0.5 g/L formic acid, whereas the wild type did not. Transcriptome analysis revealed that the differentially expressed genes were related to carbohydrate transport and metabolism, lipid transport and metabolism, signal transduction mechanism, redox metabolism, and energy production and conversion under 0.5 g/L furfural and 3 g/L HMF stress conditions. In total, 42 genes in the adapted strain were upregulated by 15-fold or more, and qRT-PCR also confirmed that the expression levels of key genes (i.e. SIR, GSS, CYS, and GSR) involved in sulfur assimilation pathway were upregulated by over 10-fold in adapted strain for cellular protection against oxidative stress. PMID:25793624

  4. Reducing dietary intake of linoleic acid of mouse dams during lactation increases offspring brain n-3 LCPUFA content.

    PubMed

    Schipper, L; Oosting, A; Scheurink, A J W; van Dijk, G; van der Beek, E M

    2016-07-01

    Omega (n-)3 and n-6 long chain polyunsaturated fatty acids (LCPUFA) accumulation in the infant brain after birth is strongly driven by dietary supply of n-3 and n-6 LCPUFAs and their C18 precursors through breast milk or infant formula. n-3 LCPUFA accretion is associated with positive effects on neurodevelopmental outcome whereas high n-6 LCPUFA accumulation is considered disadvantageous. Maternal diet is crucial for breast milk fatty acid composition. Unfortunately, global increases in linoleic acid (C18:2n-6; LA) intake have dramatically increased n-6 LCPUFA and reduced n-3 LCPUFA availability for breastfed infants. We investigated the effects of reducing maternal dietary LA, or increasing n-3 LCPUFA, during lactation on milk and offspring brain fatty acids in mice. Offspring brain n-3 LCPUFA was higher following both interventions, although effects were mediated by different mechanisms. Because of competitive interactions between n-3 and n-6 fatty acids, lowering maternal LA intake may support neurodevelopment in breastfed infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Increased amoxicillin-clavulanic acid resistance in Escherichia coli blood isolates, Spain.

    PubMed

    Oteo, Jesús; Campos, José; Lázaro, Edurne; Cuevas, Oscar; García-Cobos, Silvia; Pérez-Vázquez, María; de Abajo, F J

    2008-08-01

    To determine the evolution and trends of amoxicillin-clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006.

  6. Pros and cons of increasing folic acid and vitamin B12 intake by fortification

    USDA-ARS?s Scientific Manuscript database

    There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects (NTDs). The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes brie...

  7. Increased Amoxicillin–Clavulanic Acid Resistance in Escherichia coli Blood Isolates, Spain

    PubMed Central

    Oteo, Jesús; Lázaro, Edurne; Cuevas, Óscar; García-Cobos, Silvia; Pérez-Vázquez, María; de Abajo, F. J.

    2008-01-01

    To determine the evolution and trends of amoxicillin–clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006. PMID:18680650

  8. Increased urinary excretion of beta-aminoisobutyric acid in a Danish family.

    PubMed

    Sjølin, K E

    1988-08-01

    During collection of a control material for determination of urinary excretion of beta-aminoisobutyric acid (beta-AIB), female high excretors were found in four generations in a Danish family. The heredity seemed to be sex related and dominant, unlike previous communications about genetically conditioned high excretors of beta-AIB.

  9. Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury.

    PubMed

    Holzer, P; Livingston, E H; Guth, P H

    1991-08-01

    Disruption of the gastric mucosal barrier is quickly followed by an increase in gastric mucosal blood flow, which is thought to be a defensive reaction to prevent further injury. This study examined how this increase in blood flow is brought about. When the stomach of urethane-anesthetized rats was perfused with 0.15N HCl, disruption of the gastric mucosal barrier with 15% ethanol increased the disappearance of acid from the gastric lumen and enhanced gastric mucosal blood flow. This increase in blood flow was blocked by local arterial infusion of tetrodotoxin (60 ng/min) to the stomach and by chemical ablation of capsaicin-sensitive sensory neurons. Inhibition of the blood flow increase was associated with exaggeration of gross and histological injury to the mucosa. IV injection of atropine (0.2 mg/kg) or pyrilamine (2 mg/kg) did not affect blood flow increase in response to barrier disruption, whereas morphine injection (2 mg/kg) inhibited it. The current findings show that the increase in gastric mucosal blood flow that follows disruption of the gastric mucosal barrier in the presence of acid is mediated by sensory neurons that seem to monitor acid back-diffusion and in turn signal for a protective increase in blood flow.

  10. Effects of step-wise increases in dietary carbohydrate on circulating saturated Fatty acids and palmitoleic Acid in adults with metabolic syndrome.

    PubMed

    Volk, Brittanie M; Kunces, Laura J; Freidenreich, Daniel J; Kupchak, Brian R; Saenz, Catherine; Artistizabal, Juan C; Fernandez, Maria Luz; Bruno, Richard S; Maresh, Carl M; Kraemer, William J; Phinney, Stephen D; Volek, Jeff S

    2014-01-01

    Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.

  11. Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome

    PubMed Central

    Volk, Brittanie M.; Kunces, Laura J.; Freidenreich, Daniel J.; Kupchak, Brian R.; Saenz, Catherine; Artistizabal, Juan C.; Fernandez, Maria Luz; Bruno, Richard S.; Maresh, Carl M.; Kraemer, William J.; Phinney, Stephen D.; Volek, Jeff S.

    2014-01-01

    Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes. PMID:25415333

  12. Dietary fish oil increases fat absorption and fecal bile acid content without altering bile acid synthesis in 20-d-old weanling rats following massive ileocecal resection.

    PubMed

    Yang, Qing; Lan, Tian; Chen, Yuegang; Dawson, Paul A

    2012-07-01

    Dietary fish oil (FO) was reported to lower fecal fat excretion in a weanling rat model of short bowel syndrome (SBS) after ileocecal resection (ICR), and to induce changes in secretion and synthesis of bile acid (BA) in adults. We hypothesized that dietary FO, as compared with corn oil (CO), increases intestinal fat absorption in weanling SBS rats in part due to increased hepatic BA synthesis and luminal BA concentrations. After undergoing ICR, 20-d-old rats were fed ad lib for 7 d with a CO or FO diet containing 5% sucrose polybehenate (SPB), a marker for dietary fat absorption. Fecal fatty acid, fecal and intestine luminal BA, liver mRNA expressions of cholesterol 7α-hydroxylase (Cyp7α1) and sterol-12α-hydroxylase (Cyp8β1), and serum 7α-hydroxy-4-cholesten-3-1 (7αC4) levels were determined. As compared with CO-ICR rats, FO-ICR rats had higher intestinal absorption of total fat and most individual fatty acids. Although the BA content per gram of dry stool was increased in FO-ICR rats, there were no differences between groups for the BA content in remnant jejunum, liver mRNA expression of BA biosynthetic enzymes, Cyp7α1 and Cyp8β1, or serum 7αC4, a marker for BA synthesis. Dietary FO increases dietary fat absorption without increasing hepatic BA synthesis in weanling SBS rats.

  13. Increased dietary sodium chloride concentrations reduce endogenous amino acid flow and influence the physiological response to the ingestion of phytic acid by broiler chickens.

    PubMed

    Cowieson, A J; Bedford, M R; Ravindran, V; Selle, P H

    2011-10-01

    A total of 240 Ross 308 broilers were used to investigate the effect of sodium (1·5 or 2·5 g/kg), phytate-P (0 or 3·2 g/kg), and phytase (0 or 1000 FTU/kg; 2x2x2 factorial) on endogenous amino acid flow using the enzyme-hydrolysed casein method. The ingestion of phytate increased endogenous amino acid flow (∼30%) compared with the phytate-free control diets. Phytase reduced endogenous amino acid flow only when fed in concert with phytate, resulting in a significant phytate x phytase interaction. Increasing dietary sodium concentration from 1·5 to 2·5 g/kg reduced endogenous amino acid flow by around 10%. This reduction of endogenous flow was particularly evident in diets which contained phytate, resulting in a significant sodium x phytate interaction for several amino acids, including Thr and Ser. Further, high sodium concentrations muted the effect of phytase resulting in a significant sodium x phytase interaction for some amino acids. The concentration of Asp, Thr, Ser and some other amino acids was increased in the endogenous protein in response to the ingestion of phytate. Both sodium and phytase essentially restored the composition of endogenous protein to that of the phytate-free control. Further, as both sodium and phytase had similar effects there were significant interactions between sodium and phytase for most amino acids, such that one was only effective in the absence of the other. These data confirm previous reports that phytate is a nutritional aggressor, causing quantitative and qualitative changes in endogenous protein flow. However, this is the first report which has shown that dietary sodium concentrations play a role in the severity of this antinutritional effect and consequently may blunt the efficacy of exogenous phytase. The mechanism is obscure, though it has been previously demonstrated that sodium can disrupt phytate:protein complexes, thus mitigating one of the mechanisms by which phytate exerts its antinutritional effect.

  14. Fatty acid amide hydrolase (FAAH) regulates hypercapnia/ischemia-induced increases in n-acylethanolamines in mouse brain.

    PubMed

    Lin, Lin; Metherel, Adam H; Jones, Peter J; Bazinet, Richard P

    2017-09-01

    N-acylethanolamines (NAEs) are endogenous lipid ligands for several receptors including cannabinoid receptors and peroxisome proliferator-activated receptor-alpha (PPAR-α), which regulate numerous physiological functions. Fatty acid amide hydrolase (FAAH) is largely responsible for the degradation of NAEs. However, at high concentrations of ethanolamines and unesterified fatty acids, FAAH can also catalyze the reverse reaction, producing NAEs. Several brain insults such as ischemia and hypoxia increase brain unesterified fatty acids. Because FAAH can catalyze the synthesis of NAE, we aimed to test whether FAAH was necessary for CO2 -induced hypercapnia/ischemia increases in NAE. To test this, we examined levels of NAEs, 1- and 2-arachidonoylglycerols as well as their corresponding fatty acid precursors in wild-type and mice lacking FAAH (FAAH-KO) with three Kill methods: (i) head-focused, high-energy microwave irradiation (microwave), (ii) 5 min CO2 followed by microwave irradiation (CO2 + microwave), and (iii) 5 min CO2 only (CO2 ). Both CO2 -induced groups increased, to a similar extent, brain levels of unesterified oleic, arachidonic, and docosahexaenoic acid and 1- and 2-arachidonoylglycerols compared to the microwave group in both wild-type and FAAH-KO mice. Oleoylethanolamide (OEA), arachidonoylethanolamide (AEA), and docosahexaenoylethanolamide (DHEA) levels were about 8-, 7-, and 2.5-fold higher, respectively, in the FAAH-KO mice compared with the wild-type mice. Interestingly, the concentrations of OEA, AEA, and DHEA increased 2.5- to 4-fold in response to both CO2 -induced groups in wild-type mice, but DHEA increased only in the CO2 group in FAAH-KO mice. Our study demonstrates that FAAH is necessary for CO2 - induced increases in OEA and AEA but not DHEA. Targeting brain FAAH could impair the production of NAEs in response to brain injuries. © 2017 International Society for Neurochemistry.

  15. Overexpression of a phosphatidic acid phosphatase type 2 leads to an increase in triacylglycerol production in oleaginous Rhodococcus strains.

    PubMed

    Hernández, Martín A; Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo; Alvarez, Héctor M

    2015-03-01

    Oleaginous Rhodococcus strains are able to accumulate large amounts of triacylglycerol (TAG). Phosphatidic acid phosphatase (PAP) enzyme catalyzes the dephosphorylation of phosphatidic acid (PA) to yield diacylglycerol (DAG), a key precursor for TAG biosynthesis. Studies to establish its role in lipid metabolism have been mainly focused in eukaryotes but not in bacteria. In this work, we identified and characterized a putative PAP type 2 (PAP2) encoded by the ro00075 gene in Rhodococcus jostii RHA1. Heterologous expression of ro00075 in Escherichia coli resulted in a fourfold increase in PAP activity and twofold in DAG content. The conditional deletion of ro00075 in RHA1 led to a decrease in the content of DAG and TAG, whereas its overexpression in both RHA1 and Rhodococcus opacus PD630 promoted an increase up to 10 to 15 % by cellular dry weight in TAG content. On the other hand, expression of ro00075 in the non-oleaginous strain Rhodococcus fascians F7 promoted an increase in total fatty acid content up to 7 % at the expense of free fatty acid (FFA), DAG, and TAG fractions. Moreover, co-expression of ro00075/atf2 genes resulted in a fourfold increase in total fatty acid content by a further increase of the FFA and TAG fractions. The results of this study suggest that ro00075 encodes for a PAP2 enzyme actively involved in TAG biosynthesis. Overexpression of this gene, as single one or with an atf gene, provides an alternative approach to increase the biosynthesis and accumulation of bacterial oils as a potential source of raw material for biofuel production.

  16. Specific changes in mitochondrial lipidome alter mitochondrial proteome and increase the geroprotective efficiency of lithocholic acid in chronologically aging yeast

    PubMed Central

    Leonov, Anna; Arlia-Ciommo, Anthony; Bourque, Simon D.; Koupaki, Olivia; Kyryakov, Pavlo; Dakik, Pam鼳la; McAuley, M鼳lissa; Medkour, Younes; Mohammad, Karamat; Maulo, Tamara Di; Titorenko, Vladimir I.

    2017-01-01

    We have previously found that exogenously added lithocholic acid delays yeast chronological aging. We demonstrated that lithocholic acid enters the yeast cell, is sorted to mitochondria, resides in both mitochondrial membranes, changes the relative concentrations of different membrane phospholipids, triggers changes in the concentrations of many mitochondrial proteins, and alters some key aspects of mitochondrial functionality. We hypothesized that the lithocholic acid-driven changes in mitochondrial lipidome may have a causal role in the remodeling of mitochondrial proteome, which may in turn alter the functional state of mitochondria to create a mitochondrial pattern that delays yeast chronological aging. Here, we test this hypothesis by investigating how the ups1?, ups2? and psd1? mutations that eliminate enzymes involved in mitochondrial phospholipid metabolism influence the mitochondrial lipidome. We also assessed how these mutations affect the mitochondrial proteome, influence mitochondrial functionality and impinge on the efficiency of aging delay by lithocholic acid. Our findings provide evidence that 1) lithocholic acid initially creates a distinct pro-longevity pattern of mitochondrial lipidome by proportionally decreasing phosphatidylethanolamine and cardiolipin concentrations to maintain equimolar concentrations of these phospholipids, and by increasing phosphatidic acid concentration; 2) this pattern of mitochondrial lipidome allows to establish a specific, aging-delaying pattern of mitochondrial proteome; and 3) this pattern of mitochondrial proteome plays an essential role in creating a distinctive, geroprotective pattern of mitochondrial functionality. PMID:28410198

  17. Effect of penicillin on the increase in membrane conductance induced by γ-aminobutyric acid at the crab neuromuscular junction

    PubMed Central

    Earl, Janet; Large, W. A.

    1973-01-01

    The effects of penicillin and picrotoxin on the increase in membrane conductance produced by γ-aminobutyric acid (GABA) at the hermit crab neuromuscular junction were investigated. Penicillin failed to block the effects of GABA, while picrotoxin proved to be a potent antagonist. PMID:4733733

  18. Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence

    USDA-ARS?s Scientific Manuscript database

    Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence. In the January issue of this journal, Johnston (1) includes our group’s recent analysis of data from the 1999-2002 National Health and Nutrition Examination...

  19. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    PubMed Central

    2012-01-01

    Correction to Rao J S, Kim H W, Kellom M, Greenstein D, Chen M, Kraft A D, Harry G J, Rapoport S I, Basselin M. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. Journal of Neuroinflammation 8:101.

  20. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

    SciTech Connect

    Korsten, M.A.; Rosman, A.S.; Fishbein, S.; Shlein, R.D.; Goldberg, H.E.; Biener, A. )

    1991-06-01

    OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency.

  1. Studies on the increase in serum concentrations of urea cycle amino acids among subjects exposed to cadmium

    SciTech Connect

    Nishino, H.; Shiroishi, K. ); Kagamimori, S.; Naruse, Y. ); Watanabe, M. )

    1988-05-01

    Itai-itai disease (I disease) is a combination of renal tubular damage and osteomalacia accompanied by osteoporosis among subjects exposed to cadmium (Cd). When the renal tubular damage progresses, the excretion of amino acids, especially, threonine, hydroxyproline, proline, citrulline, ornithine, arginine, etc. increase in urine. It was reported that the increase in urinary excretion of citrulline, arginine and ornithine may be associated with an inhibition of urea synthesis in the urea cycle. The authors have found that serum citrulline, arginine and ornithine also increased in I disease patients. In order to investigate the mechanism of the increase in these serum amino acids, comparative studies were performed using both healthy subjects and patients with renal disease as control groups.

  2. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

    PubMed

    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.

  3. Long-term ritonavir exposure increases fatty acid and glycerol recycling in 3T3-L1 adipocytes as compensatory mechanisms for increased triacylglycerol hydrolysis.

    PubMed

    Adler-Wailes, Diane C; Guiney, Evan L; Wolins, Nathan E; Yanovski, Jack A

    2010-05-01

    Lipodystrophy with high nonesterified fatty acid (FA) efflux is reported in humans receiving highly active antiretroviral therapy (HAART) to treat HIV infection. Ritonavir, a common component of HAART, alters adipocyte FA efflux, but the mechanism for this effect is not established. To investigate ritonavir-induced changes in FA flux and recycling through acylglycerols, we exposed differentiated murine 3T3-L1 adipocytes to ritonavir for 14 d. FA efflux, uptake, and incorporation into acylglycerols were measured. To identify a mediator of FA efflux, we measured adipocyte triacylglycerol lipase (ATGL) transcript and protein. To determine whether ritonavir-treated adipocytes increased glycerol backbone synthesis for FA reesterification, we measured labeled glycerol and pyruvate incorporation into triacylglycerol (TAG). Ritonavir-treated cells had increased FA efflux, uptake, and incorporation into TAG (all P < 0.01). Ritonavir increased FA efflux without consistently increasing glycerol release or changing TAG mass, suggesting increased partial TAG hydrolysis. Ritonavir-treated adipocytes expressed significantly more ATGL mRNA (P < 0.05) and protein (P < 0.05). Ritonavir increased glycerol (P < 0.01) but not pyruvate (P = 0.41), utilization for TAG backbone synthesis. Consistent with this substrate utilization, glycerol kinase transcript (required for glycerol incorporation into TAG backbone) was up-regulated (P < 0.01), whereas phosphoenolpyruvate carboxykinase transcript (required for pyruvate utilization) was down-regulated (P < 0.001). In 3T3-L1 adipocytes, long-term ritonavir exposure perturbs FA metabolism by increasing ATGL-mediated partial TAG hydrolysis, thu