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Sample records for 4-phenyl butyric acid

  1. The Future of Butyric Acid in Industry

    PubMed Central

    Dwidar, Mohammed; Park, Jae-Yeon; Mitchell, Robert J.; Sang, Byoung-In

    2012-01-01

    In this paper, the different applications of butyric acid and its current and future production status are highlighted, with a particular emphasis on the biofuels industry. As such, this paper discusses different issues regarding butyric acid fermentations and provides suggestions for future improvements and their approaches. PMID:22593687

  2. Spectroscopic studies on 9H-carbazole-9-(4-phenyl) boronic acid pinacol ester by DFT method

    NASA Astrophysics Data System (ADS)

    Sas, E. B.; Kurt, M.; Can, M.; Horzum, N.; Atac, A.

    2016-08-01

    9H-Carbazole-9-(4-phenyl) boronic acid pinacol ester (9-CPBAPE) molecule was investigated by FT-IR, Raman, UV-vis, 1H and 13C NMR spectra. FT-IR, FT-Raman and dispersive Raman spectra were recorded in the solid phase. 1H, 13C NMR and UV-vis spectra were recorded in dimethyl sulfoxide (DMSO) solution. The results of theoretical calculations for the spectra of the title molecule were compared with the experimental spectra. The highest occupied molecular orbital (HOMO) the lowest unoccupied molecular orbital (LUMO) and molecular electrostatic potential (MEP) analyses were performed. The theoretical calculations for the molecular structure and spectroscopic studies were performed with DFT (B3LYP) and 6-311G (d,p) basis set calculations using the Gaussian 09 program. The total (TDOS), partial (PDOS) density of state and overlap population density of state (OPDOS) diagrams analyses were performed using GaussSum 2.2 program.

  3. Catalytic upgrading of butyric acid towards fine chemicals and biofuels

    PubMed Central

    Sjöblom, Magnus; Matsakas, Leonidas; Christakopoulos, Paul; Rova, Ulrika

    2016-01-01

    Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl-butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the production of green fuels and chemicals. PMID:26994015

  4. Biogas Production on Demand Regulated by Butyric Acid Addition

    NASA Astrophysics Data System (ADS)

    Kasper, K.; Schiffels, J.; Krafft, S.; Kuperjans, I.; Elbers, G.; Selmer, T.

    2016-03-01

    Investigating effects of volatile fatty acids on the biogas process it was observed that butyric acid can be used for transient stimulation of the methane production in biogas plants operating with low energy substrates like cattle manure. Upon addition of butyrate the methane output of the reactors doubled within 24 h and reached almost 3-times higher methane yields within 3-4 days. Butyrate was quantitatively eliminated and the reactors returned to the original productivity state within 3 days when application of butyrate was stopped. The opportunity to use butyrate feeding for increased biogas production on demand is discussed.

  5. Anti-inflammatory effects of 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester, potential inhibitors of neuropeptide bioactivation.

    PubMed

    Bauer, John D; Sunman, Jeffrey A; Foster, Michael S; Thompson, Jeremy R; Ogonowski, Alison A; Cutler, Stephen J; May, Sheldon W; Pollock, Stanley H

    2007-03-01

    Substance P (SP) and calcitonin gene-related peptide (CGRP) are well established mediators of inflammation. Therefore, inhibition of the biosynthesis of these neuropeptides is an attractive potential strategy for pharmacological intervention against a number of inflammatory diseases. The final step in the biosynthesis of SP and CGRP is the conversion of their glycine-extended precursors to the active amidated peptide, and this process is catalyzed by sequential action of the enzymes peptidylglycine alpha-monooxygenase (PAM) and peptidylamidoglycolate lyase. We have demonstrated previously that 4-phenyl-3-butenoic acid (PBA) is a PAM inhibitor, and we have also shown that in vivo inhibition of serum PAM by PBA correlates with this compound's ability to inhibit carrageenan-induced edema in the rat. Here we demonstrate the ability of PBA to inhibit all three phases of adjuvant-induced polyarthritis (AIP) in rats; this represents the first time that an amidation inhibitor has been shown to be active in a model of chronic inflammation. We recently introduced 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid (AOPHA) as one of a new series of mechanism-based amidation inhibitors. We now report for the first time that AOPHA and its methyl ester (AOPHA-Me) are active inhibitors of serum PAM in vivo, and we show that AOPHA-Me correspondingly inhibits carrageenan-induced edema in rats in a dose-dependent manner. Neither PBA nor AOPHA-Me exhibits significant cyclooxygenase (COX) inhibition in vitro; thus, the anti-inflammatory activities of PBA and AOPHA-Me are apparently not a consequence of COX inhibition. We discuss possible pharmacological mechanisms that may account for the activities of these new anti-inflammatory compounds.

  6. Redetermined structure of 4,4'-bi-pyridine-1,4-phenyl-enedi-acetic acid (1/1) co-crystal.

    PubMed

    Paul, Rima; Bora, Sanchay Jyoti

    2015-10-01

    The asymmetric unit of the title 1:1 co-crystal, C10H8N2·C10H10O4, consists of one half-mol-ecule each of 4,4'-bi-pyridine and 1,4-phenyl-enedi-acetic acid: the complete mol-ecules are generated by crystallographic inversion centres. The dihedral angle between the -CO2H group and the benzene ring in the diacid is 73.02 (7)°. In the crystal, the components are linked by O-H⋯N hydrogen bonds, generating [1-2-1] chains of alternating amine and carb-oxy-lic acid mol-ecules. The chains are cross-linked by C-H⋯O inter-actions. This structure was previously incorrectly described as a (C10H10N2)(2+)·(C10H8O4)(2-) mol-ecular salt [Jia et al. (2009 ▸). Acta Cryst. E65, o2490-o2490]. PMID:26594486

  7. Protective effects of valproic acid on the nigrostriatal dopamine system in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

    PubMed

    Kidd, S K; Schneider, J S

    2011-10-27

    The use of animal models (including the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP] mouse model) to mimic dopaminergic (DAergic) cell loss and striatal dopamine (DA) depletion, as seen in Parkinson's disease (PD), has implicated a multitude of factors that might be associated with DAergic cell death in PD including excitotoxicity, inflammation, and oxidative stress. All of these factors have been shown to be reduced by administration of histone deacetylase (HDAC) inhibitors (HDACis) resulting in some degree of neuroprotection in various models of neurodegenerative disease including in Huntington's disease and amyotrophic lateral sclerosis. However, there is limited information of effects of HDACis in PD models. We have previously shown HDACis to be partially protective against 1-methyl-4-phenylpyridinium (MPP(+))-mediated cell loss in vitro. The present study was conducted to extend these findings to an in vivo PD model. The HDACi valproic acid (VPA) was co-administered with MPTP for 5 days to male FVBn mice and continued for an additional 2 weeks, throughout the period of active neurodegeneration associated with MPTP-mediated DAergic cell loss. VPA was able to partially prevent striatal dopamine depletion and almost completely protect against substantia nigra DAergic cell loss. These results suggest that VPA may be a potential disease-modifying therapy for PD. PMID:21846494

  8. Fragrance material review on 2-methyl-4-phenyl-2-butyl acetate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 2-methyl-4-phenyl-2-butyl acetate when used as a fragrance ingredient is presented. 2-Methyl-4-phenyl-2-butyl acetate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-4-phenyl-2-butyl acetate were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, skin sensitization, and elicitation data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

  9. 4-(2-Methyl-4-chlorophenoxy) butyric acid (MCPB)

    Integrated Risk Information System (IRIS)

    4 - ( 2 - Methyl - 4 - chlorophenoxy ) butyric acid ( MCPB ) ; CASRN 94 - 81 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Hea

  10. Butyric acid fermentation of sodium hydroxide pretreated rice straw with undefined mixed culture.

    PubMed

    Ai, Binling; Li, Jianzheng; Chi, Xue; Meng, Jia; Liu, Chong; Shi, En

    2014-05-01

    This study describes an alternative mixed culture fermentation technology to anaerobically convert lignocellulosic biomass into butyric acid, a valuable product with wide application, without supplementary cellulolytic enzymes. Rice straw was soaked in 1% NaOH solution to increase digestibility. Among the tested pretreatment conditions, soaking rice straw at 50°C for 72 h removed ~66% of the lignin, but retained ~84% of the cellulose and ~71% of the hemicellulose. By using an undefined cellulose-degrading butyrate-producing microbial community as butyric acid producer in batch fermentation, about 6 g/l of butyric acid was produced from the pretreated rice straw, which accounted for ~76% of the total volatile fatty acids. In the repeated-batch operation, the butyric acid production declined batch by batch, which was most possibly caused by the shift of microbial community structure monitored by denaturing gradient gel electrophoresis. In this study, batch operation was observed to be more suitable for butyric acid production.

  11. Butyric acid production from softwood hydrolysate by acetate-consuming Clostridium sp. S1 with high butyric acid yield and selectivity.

    PubMed

    Kim, Minsun; Kim, Ki-Yeon; Lee, Kyung Min; Youn, Sung Hun; Lee, Sun-Mi; Woo, Han Min; Oh, Min-Kyu; Um, Youngsoon

    2016-10-01

    The aim of this work was to study the butyric acid production from softwood hydrolysate by acetate-consuming Clostridium sp. S1. Results showed that Clostridium sp. S1 produced butyric acid by simultaneously utilizing glucose and mannose in softwood hydrolysate and, more remarkably, it consumed acetic acid in hydrolysate. Clostridium sp. S1 utilized each of glucose, mannose, and xylose as well as mixed sugars simultaneously with partially repressed xylose utilization. When softwood (Japanese larch) hydrolysate containing glucose and mannose as the main sugars was used, Clostridium sp. S1 produced 21.17g/L butyric acid with the yield of 0.47g/g sugar and the selectivity of 1 (g butyric acid/g total acids) owing to the consumption of acetic acid in hydrolysate. The results demonstrate potential of Clostridium sp. S1 to produce butyric acid selectively and effectively from hydrolysate not only by utilizing mixed sugars simultaneously but also by converting acetic acid to butyric acid. PMID:27474955

  12. Effect of butyric acid on the performance and carcass yield of broiler chickens.

    PubMed

    Leeson, S; Namkung, H; Antongiovanni, M; Lee, E H

    2005-09-01

    Short-chain fatty acids such as butyrate are considered potential alternatives to antibiotic growth promoters. The efficacy of butyric acid on performance and carcass characteristics of broiler chickens was tested in two studies. The effect of dietary butyrate on the ability to withstand coccidial oocyte challenge also was investigated. In experiment 1, male broiler chickens were fed diets supplemented with 0 or 11 ppm virginiamycin or 0.2 or 0.4% butyric acid (as mono-, di-, and triglyceride). In experiment 2, broilers were fed bacitracin methylene disalicylate or 0.1 or 0.2% butyric acid. In another trial, birds vaccinated against coccidiosis were challenged with oocytes at 21 d and examined 6 d later. In experiment 1, diet treatments had no effect on body weight gain. Feed intake of the birds fed 0.4% butyric acid was decreased (P < 0.01) compared with birds fed the nonmedicated diet during the starter period, whereas birds fed 0.2% butyric acid had similar feed intake to the control birds. In experiment 2, diet treatments did not affect the performance of broiler chicks while carcass weight and breast meat yield increased (P < 0.01) in birds fed 0.2% butyric acid. With oocyte challenge, birds that had received butyric acid before challenge showed higher growth rate following the challenge compared with birds that received nonmedicated feed. Bacitracin decreased (P < 0.05%) duodenal villi crypt depth, whereas villus length was similar in birds fed butyric acid or the nonmedicated control diet. These results show that 0.2% butyric acid can help to maintain the performance and carcass quality of broilers, especially in vaccinated birds challenged with coccidiosis. PMID:16206563

  13. Butyric acid from anaerobic fermentation of lignocellulosic biomass hydrolysates by Clostridium sp. strain RPT-4213

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel Clostridium sp. strain RPT-4213 was found producing butyrate under strict anaerobic conditions. This strain produced 9.47 g L-1 butyric acid from MRS media (0.48 g/g glucose). RPT-4213 was also used to ferment dilute acid pretreated hydrolysates including wheat straw (WSH), corn fiber (CFH...

  14. Butyric acid esterification kinetics over Amberlyst solid acid catalysts: the effect of alcohol carbon chain length.

    PubMed

    Pappu, Venkata K S; Kanyi, Victor; Santhanakrishnan, Arati; Lira, Carl T; Miller, Dennis J

    2013-02-01

    The liquid phase esterification of butyric acid with a series of linear and branched alcohols is examined. Four strong cation exchange resins, Amberlyst™ 15, Amberlyst™ 36, Amberlyst™ BD 20, and Amberlyst™ 70, were used along with para-toluenesulfonic acid as a homogeneous catalyst. The effect of increasing alcohol carbon chain length and branching on esterification rate at 60°C is presented. For all catalysts, the decrease in turnover frequency (TOF) with increasing carbon chain length of the alcohol is described in terms of steric hindrance, alcohol polarity, and hydroxyl group concentration. The kinetics of butyric acid esterification with 2-ethylhexanol using Amberlyst™ 70 catalyst is described with an activity-based, pseudo-homogeneous kinetic model that includes autocatalysis by butyric acid.

  15. Effects of ptb knockout on butyric acid fermentation by Clostridium tyrobutyricum.

    PubMed

    Zhang, Yali; Yu, Mingrui; Yang, Shang-Tian

    2012-01-01

    Clostridium tyrobutyricum ATCC 25755 is an anaerobic, rod-shaped, gram-positive bacterium that produces butyrate, acetate, hydrogen, and carbon dioxide from various saccharides, including glucose and xylose. Phosphotransbutyrylase (PTB) is a key enzyme in the butyric acid synthesis pathway. In this work, effects of ptb knockout by homologous recombination on metabolic flux and product distribution were investigated. When compared with the wild type, the activities of PTB and butyrate kinase in ptb knockout mutant decreased 76 and 42%, respectively; meanwhile, phosphotransacetylase and acetate kinase increased 7 and 29%, respectively. However, ptb knockout did not significantly reduce butyric acid production from glucose or xylose in batch fermentations. Instead, it increased acetic acid and hydrogen production 33.3-53.8% and ≈ 11%, respectively. Thus, the ptb knockout did increase the carbon flux toward acetate synthesis, resulting in a significant decrease (28-35% reduction) in the butyrate/acetate ratio in ptb mutant fermentations. In addition, the mutant displayed a higher specific growth rate (0.20 h(-1) vs. 0.15 h(-1) on glucose and 0.14 h(-1) vs. 0.10 h(-1) on xylose) and tolerance to butyric acid. Consequently, batch fermentation with the mutant gave higher fermentation rate and productivities (26-48% increase for butyrate, 81-100% increase for acetate, and 38-46% increase for hydrogen). This mutant thus can be used more efficiently than the parental strain in fermentations to produce butyrate, acetate, and hydrogen from glucose and xylose.

  16. Butyric acid from anaerobic fermentation of lignocellulosic biomass hydrolysates by Clostridium tyrobutyricum strain RPT-4213

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly isolated Clostridium sp. strain RPT-4213 was found to produce butyrate under anaerobic conditions. Fermentations using Lactobacilli MRS Broth produced 9.47 g L-1 butyric acid from glucose (0.48 g/g glucose). However, the strain was not capable of utilizing five carbon sugars. To assess the a...

  17. Lipopolysaccharide Stimulates Butyric Acid-Induced Apoptosis in Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Kurita-Ochiai, Tomoko; Fukushima, Kazuo; Ochiai, Kuniyasu

    1999-01-01

    We previously reported that butyric acid, an extracellular metabolite from periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. In this study, we examined the ability of butyric acid to induce apoptosis in peripheral blood mononuclear cells (PBMC) and the effect of bacterial lipopolysaccharide (LPS) on this apoptosis. Butyric acid significantly inhibited the anti-CD3 monoclonal antibody- and concanavalin A-induced proliferative responses in a dose-dependent fashion. This inhibition of PBMC growth by butyric acid depended on apoptosis in vitro. It was characterized by internucleosomal DNA digestion and revealed by gel electrophoresis followed by a colorimetric DNA fragmentation assay to occur in a concentration-dependent fashion. Butyric acid-induced PBMC apoptosis was accompanied by caspase-3 protease activity but not by caspase-1 protease activity. LPS potentiated butyric acid-induced PBMC apoptosis in a dose-dependent manner. Flow-cytometric analysis revealed that LPS increased the proportion of sub-G1 cells and the number of late-stage apoptotic cells induced by butyric acid. Annexin V binding experiments with fractionated subpopulations of PBMC in flow cytometory revealed that LPS accelerated the butyric acid-induced CD3+-T-cell apoptosis followed by similar levels of both CD4+- and CD8+-T-cell apoptosis. The addition of LPS to PBMC cultures did not cause DNA fragmentation, suggesting that LPS was unable to induce PBMC apoptosis directly. These data suggest that LPS, in combination with butyric acid, potentiates CD3+ PBMC T-cell apoptosis and plays a role in the apoptotic depletion of CD4+ and CD8+ cells. PMID:9864191

  18. Gamma amino butyric acid accumulation in medicinal plants without stress

    PubMed Central

    Anju, P.; Moothedath, Ismail; Rema Shree, Azhimala Bhaskaranpillai

    2014-01-01

    Introduction: Gamma amino butyric acid (GABA) is an important ubiquitous four carbon nonprotein amino acid with an amino group attached to gamma carbon instead of beta carbon. It exists in different organisms including bacteria, plants, and animals and plays a crucial role in humans by regulating neuronal excitability throughout the nervous system. It is directly responsible for the regulation of muscle tone and also effective in lowering stress, blood pressure, and hypertension. Aim and Objective: The aim of the study was to develop the fingerprint profile of selected medicinally and economically important plants having central nervous system (CNS) activity and to determine the quantity of GABA in the selected plants grown under natural conditions without any added stress. Materials and Methods: The high-performance thin layer chromatography analysis was performed on precoated silica gel plate 60F–254 plate (20 cm × 10 cm) in the form of bands with width 8 mm using Hamilton syringe (100 μl) using n-butanol, acetic acid, and water in the proportion 5:2:2 as mobile phase in a CAMAG chamber which was previously saturated for 30 min. CAMAG TLC scanner 3 was used for the densitometric scanning at 550 nm. Specific marker compounds were used for the quantification. Results and Conclusion: Among the screened medicinal plants, Zingiber officinale and Solanum torvum were found to have GABA. The percentage of GABA present in Z. officinale and S. torvum were found to be 0.0114% and 0.0119%, respectively. The present work confirmed that among the selected CNS active medicinal plants, only two plants contain GABA. We found a negative correlation with plant having CNS activity and accumulation of GABA. The GABA shunt is a conserved pathway in eukaryotes and prokaryotes but, although the role of GABA as a neurotransmitter in mammals is clearly established, its role in plants is still vague. PMID:25861139

  19. Anticarcinogenic actions of tributyrin, a butyric acid prodrug.

    PubMed

    Heidor, Renato; Ortega, Juliana Festa; de Conti, Aline; Ong, Thomas Prates; Moreno, Fernando Salvador

    2012-12-01

    Bioactive food compounds (BFCs) exhibit potential anticarcinogenic effects that deserve to be explored. Butyric acid (BA) is considered a promising BFC and has been used in clinical trials; however, its short half-life considerably restricts its therapeutic application. Tributyrin (TB), a BA prodrug present in milk fat and honey, has more favorable pharmacokinetic properties than BA, and its oral administration is also better tolerated. In vitro and in vivo studies have shown that TB acts on multiple anticancer cellular and molecular targets without affecting non-cancerous cells. Among the TB mechanisms of action, the induction of apoptosis and cell differentiation and the modulation of epigenetic mechanisms are notable. Due to its anticarcinogenic potential, strategies as lipid emulsions, nanoparticles, or structured lipids containing TB are currently being developed to improve its organoleptic characteristics and bioavailability. In addition, TB has minimal toxicity, making it an excellent candidate for combination therapy with other agents for the control of cancer. Despite the lack of data available in the literature, TB is a promising molecule for anticancer strategies. Therefore, additional preclinical and clinical studies should be performed using TB to elucidate its molecular targets and anticarcinogenic potential.

  20. Butyric acid-based feed additives help protect broiler chickens from Salmonella Enteritidis infection.

    PubMed

    Fernández-Rubio, C; Ordóñez, C; Abad-González, J; Garcia-Gallego, A; Honrubia, M Pilar; Mallo, J Jose; Balaña-Fouce, R

    2009-05-01

    Sodium butyrate is a sodium salt of a volatile short-chain fatty acid (butyric acid) used to prevent Salmonella Enteritidis infection in birds. Three groups of fifty 1-d-old broilers each were fed the following diets: T0 = standard broiler diet (control); T1 = standard broiler diet supplemented with 0.92 g/kg of an additive with free sodium butyrate (Gustor XXI B92); and T2 = standard broiler diet supplemented with 0.92 g/kg of an additive with sodium butyrate partially protected with vegetable fats (Gustor XXI BP70). Twenty percent of the birds were orally infected with Salmonella Enteritidis at d 5 posthatching and fecal Salmonella shedding was assessed at d 6, 9, 13, 20, 27, 34, and 41 of the trial. At d 42, all birds were slaughtered and 20 of them dissected: crop, cecum, liver, and spleen were sampled for bacteriological analyses. Both butyrate-based additives showed a significant reduction (P < 0.05) of Salmonella Enteritidis infection in birds from d 27 onward. However, the partially protected butyrate additive was more effective at the late phase of infection. Partially protected butyrate treatment successfully decreased infection not only in the crop and cecum but also in the liver. There were no differences in the spleen. These results suggest that sodium butyrate partially protected with vegetable fats offers a unique balance of free and protected active substances effective all along the gastrointestinal tract because it is slowly released during digestion.

  1. Stimulation of butyrate production by gluconic acid in batch culture of pig cecal digesta and identification of butyrate-producing bacteria.

    PubMed

    Tsukahara, Takamitsu; Koyama, Hironari; Okada, Masaaki; Ushida, Kazunari

    2002-08-01

    Gluconic acid reaches the large intestine to stimulate lactic acid bacteria. However, the fermentation pattern of gluconic acid has yet to be elucidated. Accordingly, we examined the fermentation properties induced by gluconic acid in the pig cecal digesta in vitro. We also tested sorbitol and glucose, substrates for which the fermentation rate and patterns are known. The gluconic acid-utilizing bacteria were further isolated from pig cecal digesta and identified to examine the effect of gluconic acid on hind gut fermentation. Gluconic acid was fermented more slowly than were the other two substrates. Gluconic acid stimulated butyrate production; the butyrate molar percentage reached 26%, which is considered a high butyrate production. The majority of gluconic acid fermenters were identified as lactic acid bacteria, such as Lactobacillus reuteri and L. mucosae, and acid-utilizing bacteria, such as Megasphaera elsdenii and Mitsuokella multiacida. The gluconic acid fermented by lactic acid bacteria, and the lactate and acetate that were produced were used to form butyrate by acid-utilizing bacteria, such as M. elsdenii. Gluconic acid may be useful as a prebiotic to stimulate butyrate production in the large intestine.

  2. Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

    PubMed Central

    Malago, Joshua J.; Sangu, Catherine L.

    2015-01-01

    Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis (UC). However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at exploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid (AA)-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate (SB) intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of AA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of AA-induced UC and its potency surpasses that of intrarectal or oral butyrate. PMID:25743124

  3. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation.

    PubMed

    Zeng, Huawei; Claycombe, Kate J; Reindl, Katie M

    2015-10-01

    Consumption of a high-fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk, while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer-preventive effects. To distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen), we examined the effects of physiologically relevant doses of butyrate (0.5-2 mmol/l) and DCA (0.05-0.3 mmol/l) on colon cell proliferation. We hypothesize that butyrate and DCA each modulates the cell cycle and apoptosis via common and distinct cellular signaling targets. In this study, we demonstrated that both butyrate and DCA inhibited cell proliferation by up to 89% and 92% and increased cell apoptosis rate by up to 3.1- and 4.5-fold, respectively. Cell cycle analyses revealed that butyrate led to an increase in G1 and G2 fractions with a concomitant drop in the S-phase fraction, but DCA induced an increase in only G1 fraction with a concomitant drop in the S-phase fraction when compared with the untreated cells. The examination of early cellular signaling revealed that DCA but not butyrate increased intracellular reactive oxygen species, genomic DNA breakage, the activation of ERK1/2, caspase-3 and PARP. In contrast, DCA decreased activated Rb protein level, and butyrate but not DCA increased p21 expression. Collectively, although both butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases tumor suppressor activation in cell cycle and apoptosis pathways.

  4. 40 CFR 180.318 - 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...)butanoic acid, and its metabolite MCPA, (4-chloro-2-methylphenoxy)acetic acid, in or on the following food... acid; tolerance for residues. 180.318 Section 180.318 Protection of Environment ENVIRONMENTAL... FOOD Specific Tolerances § 180.318 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for...

  5. 40 CFR 180.318 - 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...)butanoic acid, and its metabolite MCPA, (4-chloro-2-methylphenoxy)acetic acid, in or on the following food... acid; tolerance for residues. 180.318 Section 180.318 Protection of Environment ENVIRONMENTAL... FOOD Specific Tolerances § 180.318 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for...

  6. 40 CFR 180.318 - 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...)butanoic acid, and its metabolite MCPA, (4-chloro-2-methylphenoxy)acetic acid, in or on the following food... acid; tolerance for residues. 180.318 Section 180.318 Protection of Environment ENVIRONMENTAL... FOOD Specific Tolerances § 180.318 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for...

  7. Comparison of Butyric acid concentrations in ordinary and probiotic yogurt samples in Iran

    PubMed Central

    Vaseji, N; Mojgani, N; Amirinia, C; Iranmanesh, M

    2012-01-01

    Background and objectives Butyric acid has many applications in chemical, food and pharmaceutical industries. Applications of butyric acid are as an additive to food, flavorings, varnishes, perfumes, pharmaceuticals and disinfectants. Butyric acid concentrations have positive impact on the quality control of milk, yogurt and other probiotic dairy products. The present investigation was undertaken to determine and compare the concentrations of butyric acid (C4) in the ordinary and probiotic yogurt samples by GC method. Materials and Methods Probiotic yogurt samples were prepared under laboratory scale conditions using two different commercial starters ABY1 and 211, while ordinary yogurt samples lacked the probiotic starter cultures. All samples were analyzed in duplicate, for C4 concentrations by gas chromatography after day 1, 2, 10 and 20 of production, during storage at 4°C. The results were analyzed using ANOVA and Duncan test. Results The level of the mentioned fatty acid in ABY1 yogurt sample was significantly higher (0.2%) than in 211 samples (0.17%). These values were significantly lower in ordinary yogurt samples and only 0.07% was recorded in these samples on first day of storage which decreased gradually during storage. The level of reduction in the yogurt samples tested during different time intervals was not similar in all the examined samples, and some showed enhanced reduction than other samples. Conclusions Compared to ordinary yogurt samples, probiotic yogurt samples used in study showed higher levels of butyric acid with increased shelf life. PMID:22973475

  8. Butyric acid fermentation from pretreated and hydrolysed wheat straw by an adapted Clostridium tyrobutyricum strain

    PubMed Central

    Baroi, G N; Baumann, I; Westermann, P; Gavala, H N

    2015-01-01

    Butyric acid is a valuable building-block for the production of chemicals and materials and nowadays it is produced exclusively from petroleum. The aim of this study was to develop a suitable and robust strain of Clostridium tyrobutyricum that produces butyric acid at a high yield and selectivity from lignocellulosic biomasses. Pretreated (by wet explosion) and enzymatically hydrolysed wheat straw (PHWS), rich in C6 and C5 sugars (71.6 and 55.4 g l−1 of glucose and xylose respectively), was used as substrate. After one year of serial selections, an adapted strain of C. tyrobutyricum was developed. The adapted strain was able to grow in 80% (v v−1) PHWS without addition of yeast extract compared with an initial tolerance to less than 10% PHWS and was able to ferment both glucose and xylose. It is noticeable that the adapted C. tyrobutyricum strain was characterized by a high yield and selectivity to butyric acid. Specifically, the butyric acid yield at 60–80% PHWS lie between 0.37 and 0.46 g g−1 of sugar, while the selectivity for butyric acid was as high as 0.9–1.0 g g−1 of acid. Moreover, the strain exhibited a robust response in regards to growth and product profile at pH 6 and 7. PMID:26230610

  9. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of DCA and...

  10. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of D...

  11. Isolation of acetic, propionic and butyric acid-forming bacteria from biogas plants.

    PubMed

    Cibis, Katharina Gabriela; Gneipel, Armin; König, Helmut

    2016-02-20

    In this study, acetic, propionic and butyric acid-forming bacteria were isolated from thermophilic and mesophilic biogas plants (BGP) located in Germany. The fermenters were fed with maize silage and cattle or swine manure. Furthermore, pressurized laboratory fermenters digesting maize silage were sampled. Enrichment cultures for the isolation of acid-forming bacteria were grown in minimal medium supplemented with one of the following carbon sources: Na(+)-dl-lactate, succinate, ethanol, glycerol, glucose or a mixture of amino acids. These substrates could be converted by the isolates to acetic, propionic or butyric acid. In total, 49 isolates were obtained, which belonged to the phyla Firmicutes, Tenericutes or Thermotogae. According to 16S rRNA gene sequences, most isolates were related to Clostridium sporosphaeroides, Defluviitoga tunisiensis and Dendrosporobacter quercicolus. Acetic, propionic or butyric acid were produced in cultures of isolates affiliated to Bacillus thermoamylovorans, Clostridium aminovalericum, Clostridium cochlearium/Clostridium tetani, C. sporosphaeroides, D. quercicolus, Proteiniborus ethanoligenes, Selenomonas bovis and Tepidanaerobacter sp. Isolates related to Thermoanaerobacterium thermosaccharolyticum produced acetic, butyric and lactic acid, and isolates related to D. tunisiensis formed acetic acid. Specific primer sets targeting 16S rRNA gene sequences were designed and used for real-time quantitative PCR (qPCR). The isolates were physiologically characterized and their role in BGP discussed.

  12. Production of Butyric Acid and Butanol from Biomass

    SciTech Connect

    David E. Ramey; Shang-Tian Yang

    2005-08-25

    Environmental Energy Inc has shown that BUTANOL REPLACES GASOLINE - 100 pct and has no pollution problems, and further proved it is possible to produce 2.5 gallons of butanol per bushel corn at a production cost of less than $1.00 per gallon. There are 25 pct more Btu-s available and an additional 17 pct more from hydrogen given off, from the same corn when making butanol instead of ethanol that is 42 pct more Btu-s more energy out than it takes to make - that is the plow to tire equation is positive for butanol. Butanol is far safer to handle than gasoline or ethanol. Butanol when substituted for gasoline gives better gas mileage and does not pollute as attested to in 10 states. Butanol should now receive the same recognition as a fuel alcohol in U.S. legislation as ethanol. There are many benefits to this technology in that Butanol replaces gasoline gallon for gallon as demonstrated in a 10,000 miles trip across the United States July-August 2005. No modifications at all were made to a 1992 Buick Park Avenue; essentially your family car can go down the road on Butanol today with no modifications, Butanol replaces gasoline. It is that simple. Since Butanol replaces gasoline more Butanol needs to be made. There are many small farms across America which can grow energy crops and they can easily apply this technology. There is also an abundance of plant biomass present as low-value agricultural commodities or processing wastes requiring proper disposal to avoid pollution problems. One example is in the corn refinery industry with 10 million metric tons of corn byproducts that pose significant environmental problems. Whey lactose presents another waste management problem, 123,000 metric tons US, which can now be turned into automobile fuel. The fibrous bed bioreactor - FBB - with cells immobilized in the fibrous matrix packed in the reactor has been successfully used for several organic acid fermentations, including butyric and propionic acids with greatly increased

  13. Butyric acid fermentation in a fibrous bed bioreactor with immobilized Clostridium tyrobutyricum from cane molasses.

    PubMed

    Jiang, Ling; Wang, Jufang; Liang, Shizhong; Wang, Xiaoning; Cen, Peilin; Xu, Zhinan

    2009-07-01

    Butyrate fermentation by immobilized Clostridium tyrobutyricum was successfully carried out in a fibrous bed bioreactor using cane molasses. Batch fermentations were conducted to investigate the influence of pH on the metabolism of the strain, and the results showed that the fermentation gave a highest butyrate production of 26.2 g l(-1) with yield of 0.47 g g(-1) and reactor productivity up to 4.13 g l(-1)h(-1) at pH 6.0. When repeated-batch fermentation was carried out, long-term operation with high butyrate yield, volumetric productivity was achieved. Several cane molasses pretreatment techniques were investigated, and it was found that sulfuric acid treatment gave better results regarding butyrate concentration (34.6+/-0.8 g l(-1)), yield (0.58+/-0.01 g g(-1)), and sugar utilization (90.8+/-0.9%). Also, fed-batch fermentation from cane molasses pretreated with sulfuric acid was performed to further increase the concentration of butyrate up to 55.2 g l(-1).

  14. Production of γ-Amino Butyric Acid in Tea Leaves wit Treatment of Lactic Acid Bacteria

    NASA Astrophysics Data System (ADS)

    Watanabe, Yuko; Hayakawa, Kiyoshi; Ueno, Hiroshi

    Lactic acid bacteria was searched for producing termented tea that contained a lot of γ-amino butyric acid(GABA). Also examined were the growth condition, GABA production and changes in catechin contents in the tea leaves. Lactobacillus brevis L12 was found to be suitable for the production of fermented tea since it gave as much GABA as gabaron tea when tea leaves being suspended with water at 10% and incubated for 4 days at 25°C. The amount of GABA produced was more than calculated based upon the content of glutamic acid in tea leaves. It is probable to assume that glutamate derived from glutamine and theanine is converted into GABA.

  15. Eicosanoid modulation by the short-chain fatty acid n-butyrate in human monocytes.

    PubMed

    Kovarik, Johannes J; Hölzl, Markus A; Hofer, Johannes; Waidhofer-Söllner, Petra; Sobanov, Yury; Koeffel, René; Saemann, Marcus D; Mechtcheriakova, Diana; Zlabinger, Gerhard J

    2013-07-01

    n-Butyrate deriving from bacterial fermentation in the mammalian intestine is a key determinant in gastrointestinal homeostasis. We examined the effects of this short-chain fatty acid and Toll-like receptor 2 (TLR) and TLR4 engagement on inflammatory/immunity-associated genes, cyclo-oxygenases (COXs), prostaglandins (PGs) and leukotrienes (LTs) in human monocytes. Before RNA isolation, freshly isolated human monocytes were co-incubated for different time-points with 1 mm n-butyrate alone or in combination with bacterial stimuli. Based on a knowledge-driven approach, a signature of 180 immunity/inflammation-associated genes was picked and real-time PCR analysis was performed. Pathway analysis was carried out using a web-based database analysing program. Based on these gene expression studies the findings were evaluated at the protein/mediator level by Western blot analysis, FACS and ELISA. Following co-incubation with n-butyrate and lipopolysaccharide, key enzymes of the eicosanoid pathway, like PTGS2 (COX-2), TXS, ALOX5, LTA4H and LTC4S, were significantly up-regulated compared with stimulation with lipopolysaccharide alone. Furthermore, release of the lipid mediators PGE(2), 15d-PGJ(2), LTB(4) and thromboxane B(2) was increased by n-butyrate. Regarding signalling, n-butyrate had no additional effect on mitogen-activated protein kinase and interfered differently with early and late phases of nuclear factor-κB signalling. Our results suggest that among many other mediators of eicosanoid signalling n-butyrate massively induces PGE(2) production by increasing the expression of PTGS2 (COX-2) in monocytes following TLR4 and TLR2 activation and induces secretion of LTB(4) and thromboxane B(2). This underscores the role of n-butyrate as a crucial mediator of gut-specific immunity.

  16. 4-(2,4-Dichlorophenoxy)butyric acid (2,4-DB)

    Integrated Risk Information System (IRIS)

    4 - ( 2,4 - Dichlorophenoxy ) butyric acid ( 2,4 - DB ) ; CASRN 94 - 82 - 6 Health assessment information on a chemical substance is included in IRIS only after a comprehensive review of chronic toxicity data by U.S . EPA health scientists from several Program Offices and the Office of Research and

  17. Draft Genome Sequence of the Butyric Acid Producer Clostridium tyrobutyricum Strain CIP I-776 (IFP923)

    PubMed Central

    Clément, Benjamin; Lopes Ferreira, Nicolas

    2016-01-01

    Here, we report the draft genome sequence of Clostridium tyrobutyricum CIP I-776 (IFP923), an efficient producer of butyric acid. The genome consists of a single chromosome of 3.19 Mb and provides useful data concerning the metabolic capacities of the strain. PMID:26941139

  18. Exploring the Genome of a Butyric Acid Producer, Clostridium butyricum INCQS635.

    PubMed

    Bruce, Thiago; Leite, Fernanda Gomes; Tschoeke, Diogo Antonio; Miranda, Milene; Pereira, Nei; Valle, Rogério; Thompson, Cristiane C; Thompson, Fabiano L

    2014-11-20

    The draft genome sequence of Clostridium butyricum INCQS635 was obtained by means of ion sequencing. The genome provides further insight into the genetic repertoire involved with metabolic pathways related to the fermentation of different compounds and organic solvents synthesis (i.e., butyric acid) with biofuel applications.

  19. Exploring the Genome of a Butyric Acid Producer, Clostridium butyricum INCQS635

    PubMed Central

    Leite, Fernanda Gomes; Tschoeke, Diogo Antonio; Miranda, Milene; Pereira, Nei; Valle, Rogério; Thompson, Cristiane C.

    2014-01-01

    The draft genome sequence of Clostridium butyricum INCQS635 was obtained by means of ion sequencing. The genome provides further insight into the genetic repertoire involved with metabolic pathways related to the fermentation of different compounds and organic solvents synthesis (i.e., butyric acid) with biofuel applications. PMID:25414496

  20. Radiation induces acid tolerance of Clostridium tyrobutyricum and enhances bioproduction of butyric acid through a metabolic switch

    PubMed Central

    2014-01-01

    Background Butyric acid as a renewable resource has become an increasingly attractive alternative to petroleum-based fuels. Clostridium tyrobutyricum ATCC 25755T is well documented as a fermentation strain for the production of acids. However, it has been reported that butyrate inhibits its growth, and the accumulation of acetate also inhibits biomass synthesis, making production of butyric acid from conventional fermentation processes economically challenging. The present study aimed to identify whether irradiation of C. tyrobutyricum cells makes them more tolerant to butyric acid inhibition and increases the production of butyrate compared with wild type. Results In this work, the fermentation kinetics of C. tyrobutyricum cultures after being classically adapted for growth at 3.6, 7.2 and 10.8 g·L-1 equivalents were studied. The results showed that, regardless of the irradiation used, there was a gradual inhibition of cell growth at butyric acid concentrations above 10.8 g·L-1, with no growth observed at butyric acid concentrations above 3.6 g·L-1 for the wild-type strain during the first 54 h of fermentation. The sodium dodecyl sulfate polyacrylamide gel electrophoresis also showed significantly different expression levels of proteins with molecular mass around the wild-type and irradiated strains. The results showed that the proportion of proteins with molecular weights of 85 and 106 kDa was much higher for the irradiated strains. The specific growth rate decreased by 50% (from 0.42 to 0.21 h-1) and the final concentration of butyrate increased by 68% (from 22.7 to 33.4 g·L-1) for the strain irradiated at 114 AMeV and 40 Gy compared with the wild-type strains. Conclusions This study demonstrates that butyric acid production from glucose can be significantly improved and enhanced by using 12C6+ heavy ion-irradiated C. tyrobutyricum. The approach is economical, making it competitive compared with similar fermentation processes. It may prove useful as

  1. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC.

    PubMed

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R; Lambers, Tim T; van Tol, Eric A; de Jonge, Wouter J

    2016-06-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production. PMID:27151945

  2. Uptake and metabolism of the short-chain fatty acid butyrate, a critical review of the literature.

    PubMed

    Astbury, Stuart M; Corfe, Bernard M

    2012-07-01

    Butyrate is a short-chain fatty acid (SCFA) formed by bacterial fermentation of fibre in the colon, and serves as an energy source for colonocytes. The action of butyrate as a histone deacetylase inhibitor (HDACi) has led to a number of clinical trials testing its effectiveness as a potential treatment for cancer. The biology of butyrate transport is therefore relevant to both its physiological and pharmacological benefits. This review of the literature was carried out to assess the evidence for both the uptake and metabolism of butyrate, in an attempt to determine possible mechanism (s) by which butyrate can act as an HDACi. It is noted that although uptake and metabolism are well characterised, there are still significant gaps in the knowledgebase around the intracellular handing of butyrate, where assumptions or dated evidence are relied upon.

  3. Induction of cellular deoxyribonucleic acid synthesis in butyrate-treated cells by simian virus 40 deoxyribonucleic acid

    SciTech Connect

    Kawasaki, S.; Diamond, L.; Baserga, R.

    1981-11-01

    Sodium butyrate (3mM) inhibited the entry into the S phase of quiescent 3T3 cells stimulated by serum, but had no effect on the accumulation of cellular ribonucleic acid. Simian virus 40 infection or manual microinjection of cloned fragments from the simian virus 40 A gene caused quiescent 3T3 cells to enter the S phase even in the presence of butyrate. NGI cells, a line of 3T3 cells transformed by simian virus 40, grew vigorously in 3 mM butyrate. Homokaryons were formed between G/sub 1/ and S-phase 3T3 cells. Butyrate inhibited the induction of deoxyribonucleic acid synthesis that usually occurs in G/sub 1/ nuclei when G/sub 1/ cells are fused with S-phase cells. However, when G/sub 1/ 3T3 cells were fused with exponentially growing NGI cells, the 3T3 nuclei were induced to enter deoxyribonucleic acid synthesis. In tsAF8 cells, a ribonucleic acid polymerase II mutant that stops in the G/sub 1/ phase of the cell cycle, no temporal sequence was demonstrated between the butyrate block and the temperature-sensitive block. These results confirm previous reports that certain virally coded proteins can induce cell deoxyribonucleic acid synthesis in the absence of cellular functions that are required by serum-stimulated cells. The author's interpretation of these data is that butyrate inhibited cell growth by inhibiting the expression of genes required for the G/sub o/ ..-->.. G/sub 1/ ..-->.. S transition and that the product of the simian virus 40 A gene overrode this inhibition by providing all of the necessary functions for the entry into the S phase.

  4. Cortical and subcortical gamma amino acid butyric acid deficits in anxiety and stress disorders: Clinical implications

    PubMed Central

    Goddard, Andrew W

    2016-01-01

    Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid (GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis. PMID:27014597

  5. Proboscis Conditioning Experiments with Honeybees, Apis Mellifera Caucasica, with Butyric Acid and DEET Mixture as Conditioned and Unconditioned Stimuli

    PubMed Central

    Abramson, Charles I.; Giray, Tugrul; Mixson, T. Andrew; Nolf, Sondra L.; Wells, Harrington; Kence, Aykut; Kence, Meral

    2010-01-01

    Three experiments are described investigating whether olfactory repellents DEET and butyric acid can support the classical conditioning of proboscis extension in the honeybee, Apis mellifera caucasica (Hymenoptera: Apidae). In the first experiment DEET and butyric acid readily led to standard acquisition and extinction effects, which are comparable to the use of cinnamon as a conditioned stimulus. These results demonstrate that the odor of DEET or butyric acid is not intrinsically repellent to honey bees. In a second experiment, with DEET and butyric acid mixed with sucrose as an unconditioned stimulus, proboscis conditioning was not established. After several trials, few animals responded to the unconditioned stimulus. These results demonstrate that these chemicals are gustatory repellents when in direct contact. In the last experiment a conditioned suppression paradigm was used. Exposing animals to butyric acid or DEET when the proboscis was extended by direct sucrose stimulation or by learning revealed that retraction of the proboscis was similar to another novel odor, lavender, and in all cases greatest when the animal was not permitted to feed. These results again demonstrate that DEET or butyric acid are not olfactory repellents, and in addition, conditioned suppression is influenced by feeding state of the bee. PMID:20879917

  6. Proboscis conditioning experiments with honeybees, Apis mellifera caucasica, with butyric acid and DEET mixture as conditioned and unconditioned stimuli.

    PubMed

    Abramson, Charles I; Giray, Tugrul; Mixson, T Andrew; Nolf, Sondra L; Wells, Harrington; Kence, Aykut; Kence, Meral

    2010-01-01

    Three experiments are described investigating whether olfactory repellents DEET and butyric acid can support the classical conditioning of proboscis extension in the honeybee, Apis mellifera caucasica (Hymenoptera: Apidae). In the first experiment DEET and butyric acid readily led to standard acquisition and extinction effects, which are comparable to the use of cinnamon as a conditioned stimulus. These results demonstrate that the odor of DEET or butyric acid is not intrinsically repellent to honey bees. In a second experiment, with DEET and butyric acid mixed with sucrose as an unconditioned stimulus, proboscis conditioning was not established. After several trials, few animals responded to the unconditioned stimulus. These results demonstrate that these chemicals are gustatory repellents when in direct contact. In the last experiment a conditioned suppression paradigm was used. Exposing animals to butyric acid or DEET when the proboscis was extended by direct sucrose stimulation or by learning revealed that retraction of the proboscis was similar to another novel odor, lavender, and in all cases greatest when the animal was not permitted to feed. These results again demonstrate that DEET or butyric acid are not olfactory repellents, and in addition, conditioned suppression is influenced by feeding state of the bee.

  7. Direct hydrogenation of biomass-derived butyric acid to n-butanol over a ruthenium-tin bimetallic catalyst.

    PubMed

    Lee, Jong-Min; Upare, Pravin P; Chang, Jong-San; Hwang, Young Kyu; Lee, Jeong Ho; Hwang, Dong Won; Hong, Do-Young; Lee, Seung Hwan; Jeong, Myung-Geun; Kim, Young Dok; Kwon, Young-Uk

    2014-11-01

    Catalytic hydrogenation of organic carboxylic acids and their esters, for example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of ethyl acetate is a promising possibility for future biorefinery concepts. A hybrid conversion process based on selective hydrogenation of butyric acid combined with fermentation of glucose has been developed for producing biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly superior performance in the vapor-phase hydrogenation of biomass-derived butyric acid to n-butanol (>98% yield) for 3500 h without deactivation. PMID:25123894

  8. Direct hydrogenation of biomass-derived butyric acid to n-butanol over a ruthenium-tin bimetallic catalyst.

    PubMed

    Lee, Jong-Min; Upare, Pravin P; Chang, Jong-San; Hwang, Young Kyu; Lee, Jeong Ho; Hwang, Dong Won; Hong, Do-Young; Lee, Seung Hwan; Jeong, Myung-Geun; Kim, Young Dok; Kwon, Young-Uk

    2014-11-01

    Catalytic hydrogenation of organic carboxylic acids and their esters, for example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of ethyl acetate is a promising possibility for future biorefinery concepts. A hybrid conversion process based on selective hydrogenation of butyric acid combined with fermentation of glucose has been developed for producing biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly superior performance in the vapor-phase hydrogenation of biomass-derived butyric acid to n-butanol (>98% yield) for 3500 h without deactivation.

  9. Antioxidant properties of selected 4-phenyl hydroxycoumarins: Integrated in vitro and computational studies.

    PubMed

    Veselinović, Jovana B; Veselinović, Aleksandar M; Vitnik, Željko J; Vitnik, Vesna D; Nikolić, Goran M

    2014-05-01

    A study on the structure-activity relationship of three hydroxy 4-phenyl coumarins, carried out by employing a series of different chemical cell-free tests is presented. Different assays involving one redox reaction with the oxidant (DPPH, ABTS, FRAP and CUPRAC) were employed. Further, the measurement of inhibition of oxidative degradation, such as lipid peroxidation, was used to define compound antioxidant activity. Our results confirm the good antioxidant activity of the 7,8-dihydroxy-4-phenyl coumarin and moderate antioxidant activity of 5,7-dihydroxy-4-phenyl coumarin. In this work, quantum chemical calculations based on density functional theory have been employed at B3LYP/6-311++G(d,p) level of theory to study the influence of number and position of hydroxyl groups in coumarin molecules on antioxidant activity. Calculated values for HOMO and LUMO energies, energy gap, stabilization energies and spin density distribution confirmed experimental results and were used for SAR definition. For determination of reaction mechanism in gas phase and selected solvents bond dissociation enthalpy, adiabatic ionization potential, proton dissociation enthalpy, proton affinity, electron transfer enthalpy and gas phase acidity have been calculated. Hydrogen Atom Transfer mechanism in vacuum and Single-Electron Transfer followed by the Proton Transfer mechanism in other studied systems are most probable free radical scavenging pathways. On the basis of these findings, these hydroxy 4-phenyl coumarins may be considered as potential therapeutic candidates for pathological conditions characterized by free radical overproduction.

  10. Antioxidant properties of selected 4-phenyl hydroxycoumarins: Integrated in vitro and computational studies.

    PubMed

    Veselinović, Jovana B; Veselinović, Aleksandar M; Vitnik, Željko J; Vitnik, Vesna D; Nikolić, Goran M

    2014-05-01

    A study on the structure-activity relationship of three hydroxy 4-phenyl coumarins, carried out by employing a series of different chemical cell-free tests is presented. Different assays involving one redox reaction with the oxidant (DPPH, ABTS, FRAP and CUPRAC) were employed. Further, the measurement of inhibition of oxidative degradation, such as lipid peroxidation, was used to define compound antioxidant activity. Our results confirm the good antioxidant activity of the 7,8-dihydroxy-4-phenyl coumarin and moderate antioxidant activity of 5,7-dihydroxy-4-phenyl coumarin. In this work, quantum chemical calculations based on density functional theory have been employed at B3LYP/6-311++G(d,p) level of theory to study the influence of number and position of hydroxyl groups in coumarin molecules on antioxidant activity. Calculated values for HOMO and LUMO energies, energy gap, stabilization energies and spin density distribution confirmed experimental results and were used for SAR definition. For determination of reaction mechanism in gas phase and selected solvents bond dissociation enthalpy, adiabatic ionization potential, proton dissociation enthalpy, proton affinity, electron transfer enthalpy and gas phase acidity have been calculated. Hydrogen Atom Transfer mechanism in vacuum and Single-Electron Transfer followed by the Proton Transfer mechanism in other studied systems are most probable free radical scavenging pathways. On the basis of these findings, these hydroxy 4-phenyl coumarins may be considered as potential therapeutic candidates for pathological conditions characterized by free radical overproduction. PMID:24602768

  11. Sterically controlled azomethine ylide cycloaddition polymerization of phenyl-C61-butyric acid methyl ester.

    PubMed

    Stephen, Meera; Ramanitra, Hasina H; Santos Silva, Hugo; Dowland, Simon; Bégué, Didier; Genevičius, Kristijonas; Arlauskas, Kęstutis; Juška, Gytis; Morse, Graham E; Distler, Andreas; Hiorns, Roger C

    2016-05-01

    Phenyl-C61-butyric acid methyl ester (PCBM) is polymerized simply using a one-pot reaction to yield soluble, high molecular weight polymers. The sterically controlled azomethine ylide cycloaddition polymerization (SACAP) is demonstrated to be highly adaptable and yields polymers with probable Mn≈ 24 600 g mol(-1) and Mw≈ 73 800 g mol(-1). Products are metal-free and of possible benefit to organic and hybrid photovoltaics and electronics as they form thin films from solution and have raised LUMOs. The promising electronic properties of this new polymer are discussed. PMID:27066898

  12. Improved In Vitro Antileukemic Activity of All-Trans Retinoic Acid Loaded in Cholesteryl Butyrate Solid Lipid Nanoparticles.

    PubMed

    Silva, Elton Luiz; Lima, Flávia Alves; Carneiro, Guilherme; Ramos Jonas Periera; Gomes, Dawidson Assis; de Souza-Fagundes, Elaine Maria; Ferreira, Lucas Antônio Miranda

    2016-02-01

    All-trans retinoic acid, a hydrophobic drug, has become one of the most successful examples of differentiation agents used for treatment of acute promyelocytic leukemia. On the other hand, histone deacetylase inhibitors, such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid. Solid lipid nanoparticles represent a promising alternative for administration of hydrophobic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of all-trans retinoic acid-loaded solid lipid nanoparticles for leukemia treatment. The influence of in situ formation of an ion pairing between all-trans retinoic acid and lipophilic amines on the characteristics of the particles (size, zeta potential, encapsulation efficiency) was evaluated. Cholesteryl butyrate, a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for HL-60, Jurkat, and THP-1 cell lines. The encapsulation efficiency of all-trans retinoic acid in cholesteryl butyrate-solid lipid nanoparticles was significantly increased by the presence of the amine. Inhibition of cell viability by all-trans retinoic acid-loaded solid lipid nanoparticles was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for all-trans retinoic acid-loaded cholesteryl butyrate-solid lipid nanoparticles, with a clear increase in subdiploid DNA content. The ion pair formation in SLN containing cholesteryl butyrate can be explored as a simple and inexpensive strategy to improve the efficacy and bioavail-ability of ATRA in the treatment of the cancer and metabolic diseases in which this retinoid plays an important role. PMID:27433579

  13. [A new butyric acid-producing bacteroides species: B. splanchnicus n. sp. (author's transl)].

    PubMed

    Werner, H; Rintelen, G; Kunstek-Santos, H

    1975-01-01

    Three butyric acid-producing saccharolytic Bacteroides cultures (1651/6, BM 158, and IPP 3751) were described by WERNER and REICHERTZ in 1971 (Zbl.Bakt.Hyg., I. Abt. Orig. A 217,206-216). Since then, 6 strains closely resembling 1651/6 were isolated from stool specimens and surgically removed appendices. In the present communication, strains 1651/6, S2/34, S3/38, S4/28, S6/6, A5/2 are described as members of a new species, Bacteroides splanchnicus n.sp. The strains were morphologically very similar (Gram negative non-sporing non-motile rods, 1-2.5 mu in length and 0.7 mu in width) and fermented glucose, fructose, galactose, mannose, lactose, and arabinose (pH values of 4.6-5.4, moderate gas formation). Negative reactions (pH values of 5.8-7.2) were observed with 20 other carbohydrates. The strains were positive in the glutamic acid decarboxylase test and formed indole and H2S. In peptone-yeast extract broth and peptone-yeast extract-glucose broth acetic, propionic, isobutyric, butyric, and isovaleric acids were produced. Washed cells of strains 1651/6 and S4/28 incubated anaerobically in sterile solutions of single amino acids produced butyrate from lysine only. Abundant butyric acid was also produced from glucose. The in vitro activity of 15 antibiotics on 5 strains was studied by broth dilution tests. Uniformly, the strains showed resistance to aminoglycosides and polymyxins (MIC values, 60-500 mug/ml) and susceptibility to tetracyclines, lincomycin, clindamycin, rifampicin, and erythromycin (MIC values, 0.05-0.5 mug/ml). Chloramphenicol, penicillins, and cephalosporins showed bacteriostatic activity at concentrations of 5-40 mug/ml. The serological behaviour of 5 strains was studied in cross-agglutination and gel-diffusion experiments. Cross-reactivity was pronounced in gel-diffusion tests using rabbit antisera and autoclaved extracts and extracts prepared by repeated deep-freezing and thawing of whole cell suspensions as antigens. However, antisera against the

  14. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    PubMed

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes. PMID:26167409

  15. Effects of dietary humic and butyric acid on growth performance and response to lipopolysaccharide in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Humic acid (MFG) and fat protected butyric acid (BA) has been shown to modulate energy metabolism and inflammation. Therefore, the objectives of this study were to determine the effects of MFG and BA, alone and in combination, on growth performance and response to lipopolysaccharide (LPS) induced in...

  16. [Simultaneous determination of clevidipine butyrate and its metabolite clevidipine acid in dog blood by liquid chromatography-tandem mass spectrometry].

    PubMed

    Wei, Hui-hui; Gu, Yuan; Liu, Yan-ping; Wei, Guang-li; Chen, Yong; Liu, Chang-xiao; Si, Duan-yun

    2015-10-01

    A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18 column (150 mm x 4.6 mm, 5 µm) with a gradient mobile phase consisting of methanol and 5 mmol · L(-1) ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z 454.1 [M-H]- --> m/z 234.1 for clevidipine butyrate, m/z 354.0 [M-H]- --> m/z 208.0 for clevidipine acid and m/z 256.1 [M-H]- --> m/z 227.1 for elofesalamide (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The linear calibration curves for clevidipine butyrate and clevidipine acid were obtained in the concentration ranges of 0.5-100 ng · mL and 1-200 ng · mL(-1), separately. The lower limit of quantification of clevidipine butyrate and clevidipine acid were 0.5 ng · mL(-1) and 1 ng · mL(-1). The intra and inter-assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stability testing indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of 5 mg · h(-1) for 0.5 h.

  17. Reaction of dichlorocarbene with 4-phenyl-1,3-dioxane

    SciTech Connect

    Safiev, O.G.; Nazarov, D.V.; Zorin, V.V.; Rakhmankulov, D.L.

    1988-02-20

    The authors have established for the first time that the reaction of 4-phenyl-1,3-dioxane with the dichlorocarbene generated from chloroform by the action of a 50% aqueous solution of sodium hydroxide in the presence of triethylbenzylammonium chloride as phase-transfer catalysis leads to the formation of 4-phenyl-4-dichloromethyl-1,3-dioxane with a yield of 70% on the transformed reagent with 35% conversion with respect to the substrate. The product was isolated by column liquid chromatography. It was identified by means of the PMR and /sup 13/C NMR spectra and by the data from elemental analysis.

  18. Poly-3-hydroxy butyric acid interaction with the transgenic flax fibers: FT-IR and Raman spectra of the composite extracted from a GM flax

    NASA Astrophysics Data System (ADS)

    Wróbel-Kwiatkowska, Magdalena; Żuk, Magdalena; Szopa, Jan; Dymińska, Lucyna; Mączka, Mirosław; Hanuza, Jerzy

    2009-07-01

    The FT-IR and FT-Raman studies have been performed on commercial 3-hydroxy-butyric acid, commercial poly-3-hydroxy butyric acid as well as poly-3-hydroxy butyric acid (PHB) produced by bacteria. The data were compared to those obtained for poly-3-hydroxy butyric acid extracted from natural and genetically modified flax. Genetically modified flax was generated by expression of three bacterial genes coding for synthesis of poly-3-hydroxy butyric acid. Thus transgenic flaxes were enhanced with different amount of the PHB. The discussion of polymer structure and vibrational properties has been done in order to get insight into differences among these materials. The interaction between the cellulose of flax fibers and embedded poly-3-hydroxybutyric acid has been also discussed. The spectroscopic data provide evidences for structural changes in cellulose and in PHB when synthesized in fibers. Based on this data it is suggesting that cellulose and PHB interact by hydrogen and ester bonds.

  19. Molecular Pharmacology and Ligand Docking Studies Reveal a Single Amino Acid Difference between Mouse and Human Serotonin 5-HT2A Receptors That Impacts Behavioral Translation of Novel 4-Phenyl-2-dimethylaminotetralin Ligands

    PubMed Central

    Cordova-Sintjago, Tania; Liu, Yue; Kim, Myong S.; Morgan, Drake; Booth, Raymond G.

    2013-01-01

    During translational studies to develop 4-phenyl-2-dimethylaminotetralin (PAT) compounds for neuropsychiatric disorders, the (2R,4S)-trans-(+)- and (2S,4R)-trans-(−)-enantiomers of the analog 6-hydroxy-7-chloro-PAT (6-OH-7-Cl-PAT) demonstrated unusual pharmacology at serotonin (5-HT) 5-HT2 G protein–coupled receptors (GPCRs). The enantiomers had similar affinities (Ki) at human (h) 5-HT2A receptors (∼70 nM). In an in vivo mouse model of 5-HT2A receptor activation [(±)-(2,5)-dimethoxy-4-iodoamphetamine (DOI)–elicited head twitch], however, (−)-6-OH-7-Cl-PAT was about 5-fold more potent than the (+)-enantiomer at attenuating the DOI-elicited response. It was discovered that (+)-6-OH-7-Cl-PAT (only) had ∼40-fold-lower affinity at mouse (m) compared with h5-HT2A receptors. Molecular modeling and computational ligand docking studies indicated that the 6-OH moiety of (+)- but not (−)-6-OH-7-Cl-PAT could form a hydrogen bond with serine residue 5.46 of the h5-HT2A receptor. The m5-HT2A as well as m5-HT2B, h5-HT2B, m5-HT2C, and h5-HT2C receptors have alanine at position 5.46, obviating this interaction; (+)-6-OH-7-Cl-PAT also showed ∼50-fold lower affinity than (−)-6-OH-7-Cl-PAT at m5-HT2C and h5-HT2C receptors. Mutagenesis studies confirmed that 5-HT2A S5.46 is critical for (+)- but not (−)-6-OH-7-Cl-PAT binding, as well as function. The (+)-6-OH-7-Cl-PAT enantiomer showed partial agonist effects at h5-HT2A wild-type (WT) and m5-HT2A A5.46S point-mutated receptors but did not activate m5-HT2A WT and h5-HT2A S5.46A point-mutated receptors, or h5-HT2B, h5-HT2C, and m5-HT2C receptors; (−)-6-OH-7-Cl-PAT did not activate any of the 5-HT2 receptors. Experiments also included the (2R,4S)-trans-(+)- and (2S,4R)-trans-(−)-enantiomers of 6-methoxy-7-chloro-PAT to validate hydrogen bonding interactions proposed for the corresponding 6-OH analogs. Results indicate that PAT ligand three-dimensional structure impacts target receptor binding and translational

  20. Lipase in biphasic alginate beads as a biocatalyst for esterification of butyric acid and butanol in aqueous media.

    PubMed

    Ng, Choong Hey; Yang, Kun-Lin

    2016-01-01

    Esterification of organic acids and alcohols in aqueous media is very inefficient due to thermodynamic constraints. However, fermentation processes used to produce organic acids and alcohols are often conducted in aqueous media. To produce esters in aqueous media, biphasic alginate beads with immobilized lipase are developed for in situ esterification of butanol and butyric acid. The biphasic beads contain a solid matrix of calcium alginate and hexadecane together with 5 mg/mL of lipase as the biocatalyst. Hexadecane in the biphasic beads serves as an organic phase to facilitate the esterification reaction. Under optimized conditions, the beads are able to catalyze the production of 0.16 mmol of butyl butyrate from 0.5 mmol of butyric acid and 1.5 mmol of butanol. In contrast, when monophasic beads (without hexadecane) are used, only trace amount of butyl butyrate is produced. One main application of biphasic beads is in simultaneous fermentation and esterification (SFE) because the organic phase inside the beads is very stable and does not leach out into the culture medium. SFE is successfully conducted with an esterification yield of 6.32% using biphasic beads containing iso-octane even though the solvent is proven toxic to the butanol-producing Clostridium spp. PMID:26672465

  1. 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. PMID:26854723

  2. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.

    PubMed

    Lin, Hua V; Frassetto, Andrea; Kowalik, Edward J; Nawrocki, Andrea R; Lu, Mofei M; Kosinski, Jennifer R; Hubert, James A; Szeto, Daphne; Yao, Xiaorui; Forrest, Gail; Marsh, Donald J

    2012-01-01

    Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are metabolites formed by gut microbiota from complex dietary carbohydrates. Butyrate and acetate were reported to protect against diet-induced obesity without causing hypophagia, while propionate was shown to reduce food intake. However, the underlying mechanisms for these effects are unclear. It was suggested that SCFAs may regulate gut hormones via their endogenous receptors Free fatty acid receptors 2 (FFAR2) and 3 (FFAR3), but direct evidence is lacking. We examined the effects of SCFA administration in mice, and show that butyrate, propionate, and acetate all protected against diet-induced obesity and insulin resistance. Butyrate and propionate, but not acetate, induce gut hormones and reduce food intake. As FFAR3 is the common receptor activated by butyrate and propionate, we examined these effects in FFAR3-deficient mice. The effects of butyrate and propionate on body weight and food intake are independent of FFAR3. In addition, FFAR3 plays a minor role in butyrate stimulation of Glucagon-like peptide-1, and is not required for butyrate- and propionate-dependent induction of Glucose-dependent insulinotropic peptide. Finally, FFAR3-deficient mice show normal body weight and glucose homeostasis. Stimulation of gut hormones and food intake inhibition by butyrate and propionate may represent a novel mechanism by which gut microbiota regulates host metabolism. These effects are largely intact in FFAR3-deficient mice, indicating additional mediators are required for these beneficial effects.

  3. Resistance to butyrate impairs bile acid-induced apoptosis in human colon adenocarcinoma cells via up-regulation of Bcl-2 and inactivation of Bax.

    PubMed

    Barrasa, Juan I; Santiago-Gómez, Angélica; Olmo, Nieves; Lizarbe, María Antonia; Turnay, Javier

    2012-12-01

    A critical risk factor in colorectal carcinogenesis and tumor therapy is the resistance to the apoptotic effects of different compounds from the intestinal lumen, among them butyrate (main regulator of colonic epithelium homeostasis). Insensitivity to butyrate-induced apoptosis yields resistance to other agents, as bile acids or chemotherapy drugs, allowing the selective growth of malignant cell subpopulations. Here we analyze bile acid-induced apoptosis in a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.BR2) to determine the mechanisms that underlay the resistance to these agents in comparison with their parental butyrate-sensitive BCS-TC2 cells. This study demonstrates that DCA and CDCA still induce apoptosis in butyrate-resistant cells through increased ROS production by activation of membrane-associated enzymes and subsequent triggering of the intrinsic mitochondrial apoptotic pathway. Although this mechanism is similar to that described in butyrate-sensitive cells, cell viability is significantly higher in resistant cells. Moreover, butyrate-resistant cells show higher Bcl-2 levels that confer resistance to bile acid-induced apoptosis sequestering Bax and avoiding Bax-dependent pore formation in the mitochondria. We have confirmed that this resistance is reverted using the Bcl-2 inhibitor ABT-263, thus demonstrating that the lower sensitivity of butyrate-resistant cells to the apoptotic effects of bile acids is mainly due to increased Bcl-2 levels.

  4. Comparative Analysis of Dibutyric cAMP and Butyric Acid on the Differentiation of Human Eosinophilic Leukemia EoL-1 Cells

    PubMed Central

    2015-01-01

    Purification of enough numbers of circulating eosinophils is difficult because eosinophils account for less than 5% peripheral blood leukocytes. Human eosinophilic leukemia EoL-1 cells have been considered an in vitro source of eosinophils as they can differentiate into mature eosinophil-like cells when incubated with dibutyryl cAMP (dbcAMP) or butyric acid. In this study, the viability and phenotypic maturation of EoL-1 cells stimulated by either dbcAMP or butyric acid were comparatively analyzed. After treatment with 100 µM dbcAMP or 0.5 µM butyric acid, EoL-1 cells showed morphological signs of differentiation, although the number of nonviable EoL-1 cells was significantly increased following butyric acid treatment. Stimulation of EoL-1 cells with 0.5 µM butyric acid more effectively induced the expression of mature eosinophil markers than stimulation with dbcAMP. These results suggest that treatment of EoL-1 cells with 0.5 µM butyric acid for limited duration could be an effective strategy for inducing their differentiation. Considering that expression of CCR3 was not sufficient in EoL-1 cells stimulated with 0.5 µM butyric acid, treatment of the chemically stimulated EoL-1 cells with cytokines, which primarily support eosinophil maturation, would help to obtain differentiated EoL-1 cells with greater functional maturity. PMID:26770185

  5. Comparative Analysis of Dibutyric cAMP and Butyric Acid on the Differentiation of Human Eosinophilic Leukemia EoL-1 Cells.

    PubMed

    Jung, YunJae

    2015-12-01

    Purification of enough numbers of circulating eosinophils is difficult because eosinophils account for less than 5% peripheral blood leukocytes. Human eosinophilic leukemia EoL-1 cells have been considered an in vitro source of eosinophils as they can differentiate into mature eosinophil-like cells when incubated with dibutyryl cAMP (dbcAMP) or butyric acid. In this study, the viability and phenotypic maturation of EoL-1 cells stimulated by either dbcAMP or butyric acid were comparatively analyzed. After treatment with 100 µM dbcAMP or 0.5 µM butyric acid, EoL-1 cells showed morphological signs of differentiation, although the number of nonviable EoL-1 cells was significantly increased following butyric acid treatment. Stimulation of EoL-1 cells with 0.5 µM butyric acid more effectively induced the expression of mature eosinophil markers than stimulation with dbcAMP. These results suggest that treatment of EoL-1 cells with 0.5 µM butyric acid for limited duration could be an effective strategy for inducing their differentiation. Considering that expression of CCR3 was not sufficient in EoL-1 cells stimulated with 0.5 µM butyric acid, treatment of the chemically stimulated EoL-1 cells with cytokines, which primarily support eosinophil maturation, would help to obtain differentiated EoL-1 cells with greater functional maturity.

  6. Performance evaluation of biofilters and biotrickling filters in odor control of n-butyric acid.

    PubMed

    Ding, Ying; Han, Zhiying; Wu, Weixiang; Shi, Dezhi; Chen, Yingxu; Li, Wenhong

    2011-01-01

    With the rapid development of swine production in China, odor pollution associated with piggery facilities has become an increasing environmental concern. N-butyric acid (n-BA) is one of the key odor compounds selected to represent volatile fatty acids (VFAs) found in piggery facilities. In this study, two biofilters (BFs) packed with compost (BFC) or sludge (BFS) and two biotrickling filters (BTFs) packed with pall rings (BTFP) or multidimensional hollow balls (BTFM), respectively, were compared with regard to their performances in the removal of n-BA. The non-biological removal capacities of packing material of the bioreactors on a per unit volume basis were BFS>BFC>BTFM>BTFP. Maximum biological removal capacities per unit volume of packing material of the bioreactors all exceeded 9.1 kg/m(3)·d and in the order of BFC>BTFM>BFS>BTFP. Kinetic analysis as well as overall evaluation by radar graphs showed that the BTFs achieved superior removal rates to the BFs in the order of BTFM>BTFP>BFC>BFS. The biotrickling filter packed with multidimensional hollow balls could be an effective technology for VFAs removal. Results from this research provide economical and effective alternatives for odor control in piggery facilities.

  7. Fragrance material review on 2-methyl-4-phenyl-2-butanol.

    PubMed

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 2-methyl-4-phenyl-2-butanol when used as a fragrance ingredient is presented. 2-methyl-4-phenyl-2-butanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-4-phenyl-2-butanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, and skin sensitization data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. assessment of aryl alkyl alcohols when used as fragrance ingredients.

  8. Fragrance material review on 4-phenyl-3-buten-2-ol.

    PubMed

    Scognamiglio, J; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 4-phenyl-3-buten-2-ol when used as a fragrance ingredient is presented. 4-Phenyl-3-buten-2-ol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 4-phenyl-3-buten-2-ol were evaluated then summarized and includes physical properties, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.

  9. Effects of propionate and methylmalonate on conversions of acetate, butyrate, and D(-)-3-hydroxybutyrate to fatty acids and carbon dioxide by mammary tissue slices of goats

    SciTech Connect

    Emmanuel, B.; Kennelly, J.J.

    1985-03-01

    Incorporations of (1-carbon-14) acetate, (1-carbon-14) propionate, n-(1-carbon-14) butyrate, and D(-)-3-hydroxy(3-carbon-14) butyrate into individual milk fatty acids and their conversion to carbon dioxide were studied in vitro with caprine mammary tissue slices in the presence and absence of propionate and methylmalonate. Neither propionate nor methylmalonate affected incorporation of these substances into fatty acids. In a decreasing order butyrate, acetate, propionate, and D(-)-3-hydroxybutyrate were converted to carbon dioxide. Acetate had the highest incorporation rate into fatty acids followed by D(-)-3-hydroxybutyrate, butyrate, and propionate. Labeled propionate was incorporated mainly into odd-numbered fatty acids. Results do not support the theory that either propionate or its metabolite, methylmalonate, inhibit de novo synthesis of fatty acids in the mammary gland in relation to the etiology of low milk fat syndrome.

  10. Subclinical ketosis on dairy cows in transition period in farms with contrasting butyric acid contents in silages.

    PubMed

    Vicente, Fernando; Rodríguez, María Luisa; Martínez-Fernández, Adela; Soldado, Ana; Argamentería, Alejandro; Peláez, Mario; de la Roza-Delgado, Begoña

    2014-01-01

    This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake).

  11. Subclinical Ketosis on Dairy Cows in Transition Period in Farms with Contrasting Butyric Acid Contents in Silages

    PubMed Central

    Rodríguez, María Luisa; Martínez-Fernández, Adela; Soldado, Ana; Argamentería, Alejandro; Peláez, Mario; de la Roza-Delgado, Begoña

    2014-01-01

    This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2 = 0.56; P < 0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake). PMID:25525616

  12. Electron Affinity of Phenyl-C61-Butyric Acid Methyl Ester (PCBM)

    SciTech Connect

    Larson, Bryon W.; Whitaker, James B.; Wang, Xue B.; Popov, Alexey A.; Rumbles, Garry; Kopidakis, Nikos; Strauss, Steven H.; Boltalina, Olga V.

    2013-07-25

    The gas-phase electron affinity (EA) of phenyl-C61-butyric acid methyl ester (PCBM), one of the best-performing electron acceptors in organic photovoltaic devices, is measured by lowtemperature photoelectron spectroscopy for the first time. The obtained value of 2.63(1) eV is only ca. 0.05 eV lower than that of C60 (2.68(1) eV), compared to a 0.09 V difference in their E1/2 values measured in this work by cyclic voltammetry. Literature E(LUMO) values for PCBM that are typically estimated from cyclic voltammetry, and commonly used as a quantitative measure of acceptor properties, are dispersed over a wide range between -4.3 and -3.62 eV; the reasons for such a huge discrepancy are analyzed here, and the protocol for reliable and consistent estimations of relative fullerene-based acceptor strength in solution is proposed.

  13. Folic acid and sodium butyrate prevent tumorigenesis in a mouse model of colorectal cancer.

    PubMed

    Lu, Rong; Wang, Xia; Sun, Dan-Feng; Tian, Xiao-Qing; Zhao, Shu-Liang; Chen, Ying-Xuan; Fang, Jing-Yuan

    2008-11-01

    Colorectal cancer is a leading cause of morbidity and mortality worldwide, and its incidence has been increasing in recent years. The role of epigenetic modifications, including DNA methylation and histone modifications, has only recently been investigated. In this study, the effects of epigenetic agents such as folic acid (FA) and sodium butyrate (NaBu) on the development of colorectal cancer induced by 1,2-dimethylhydrazine (DMH) using ICR mice was examined. Of the mice treated in a chemopreventive manner with epigenetic agents, FA and NaBu, 15-50% developed colorectal cancer at 24 weeks compared with a 95% incidence of colorectal cancer in DMH-treated control mice. Folate deficiency can alter cytosine methylation in DNA leading to inappropriate activation of the proto-oncogene c-myc. We detected lower levels of p21(WAF1) gene expression in colorectal cancer samples, as well as significantly lower levels of acetylated histone H3, compared with samples from corresponding normal colorectal mucosa. In contrast, administration of NaBu increased levels of p21(WAF1) mRNA and p21(WAF1) protein, and was associated with an accumulation of histone acetylation. In summary, our results show that FA and NaBu reduce the incidence of colorectal cancer induced by DMH-induced in ICR mice, and therefore we hypothesize that targeting epigenetic targets should be further investigated for the prevention of colorectal cancer in humans.

  14. Evaluation of the in vitro genetic toxicity of 4-(2, 4-dichlorophenoxy)butyric acid.

    PubMed

    Charles, J M; Cifone, M A; Lawlor, T; Murli, H; Young, R R; Leeming, N M

    2000-12-20

    The herbicide 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB) is principally used in the USA on peanuts, soybeans and alfalfa. In Europe, it is used on undersown spring barley and grassland (with clover). The genetic toxicity in vitro of the dimethylamine salt of 2,4-DB was examined by employing a range of end points including gene mutation in bacteria (Ames test) and mammalian cell cultures (CHO/HGPRT assay), cytogenetic abnormalities in mammalian cells (CHO/chromosomal aberration assay), and induction of DNA damage and repair in rat hepatocytes. There were no indications of genotoxic potential for 2,4-DB in the first three of these assays. One of the two criteria for a positive response in the UDS assay was exceeded but the increases did not exceed the second criteria for a positive response. The test material was therefore evaluated as weakly active in this assay. The weight of the evidence clearly indicates that 2, 4-DB is not genotoxic to mammals and are consistent with the reported lack of carcinogenic potential for 2,4-DB in both mice and rats.

  15. Chemically induced Parkinson's disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion

    SciTech Connect

    Chacon, J.N.; Chedekel, M.R.; Land, E.J.; Truscott, T.G.

    1987-04-29

    Various unstable intermediate oxidation states have been postulated in the metabolic activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl pyridinium ion. We now report the first direct observation of these free radical intermediates by pulse radiolysis and flash photolysis. Studies are described of various reactions of such species, in particular with dopamine whose autoxidation to dopamine quinone is reported to be potentiated by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine.

  16. Colon cancer cell apoptosis is induced by combined exposure to the n-3 fatty acid docosahexaenoic acid and butyrate through promoter methylation.

    PubMed

    Cho, Youngmi; Turner, Nancy D; Davidson, Laurie A; Chapkin, Robert S; Carroll, Raymond J; Lupton, Joanne R

    2014-03-01

    DNA methylation and histone acetylation contribute to the transcriptional regulation of genes involved in apoptosis. We have demonstrated that docosahexaenoic acid (DHA, 22:6 n-3) and butyrate enhance colonocyte apoptosis. To determine if DHA and/or butyrate elevate apoptosis through epigenetic mechanisms thereby restoring the transcription of apoptosis-related genes, we examined global methylation; gene-specific promoter methylation of 24 apoptosis-related genes; transcription levels of Cideb, Dapk1, and Tnfrsf25; and global histone acetylation in the HCT-116 colon cancer cell line. Cells were treated with combinations of (50 µM) DHA or linoleic acid (18:2 n-6), (5 mM) butyrate or an inhibitor of DNA methyltransferases, and 5-aza-2'-deoxycytidine (5-Aza-dC, 2 µM). Among highly methylated genes, the combination of DHA and butyrate significantly reduced methylation of the proapoptotic Bcl2l11, Cideb, Dapk1, Ltbr, and Tnfrsf25 genes compared to untreated control cells. DHA treatment reduced the methylation of Cideb, Dapk1, and Tnfrsf25. These data suggest that the induction of apoptosis by DHA and butyrate is mediated, in part, through changes in the methylation state of apoptosis-related genes.

  17. Bile acids reduce the apoptosis-inducing effects of sodium butyrate on human colon adenoma (AA/C1) cells: implications for colon carcinogenesis.

    PubMed

    McMillan, L; Butcher, S; Wallis, Y; Neoptolemos, J P; Lord, J M

    2000-06-24

    Butyrate is produced in the colon by fermentation of dietary fibre and induces apoptosis in colon adenoma and cancer cell lines, which may contribute to the protective effect of a high fibre diet against colorectal cancer (CRC). However, butyrate is present in the colon together with unconjugated bile acids, which are tumour promoters in the colon. We show here that bile acids deoxycholate (DCA) and chenodeoxycholate (CDCA), at levels present in the colon, gave a modest increase in cell proliferation and decreased spontaneous apoptosis in AA/C1 adenoma cells. Bile acids significantly inhibited the induction of apoptosis by butyrate in AA/C1 cells. However, the survival-inducing effects of bile acids on AA/C1 cells could be overcome by increasing the concentration of sodium butyrate. These results suggest that dysregulation of apoptosis in colonic epithelial cells by dietary factors is a key factor in the pathophysiology of CRC.

  18. Occurrence and in Vivo Biosynthesis of Indole-3-Butyric Acid in Corn (Zea mays L.) 1

    PubMed Central

    Ludwig-Müller, Jutta; Epstein, Ephraim

    1991-01-01

    Indole-3-butyric acid (IBA) was identified as an endogenous compound in leaves and roots of maize (Zea mays L.) var Inrakorn by thin layer chromatography, high-performance liquid chromatography, and gas chromatography-mass spectrometry. Its presence was also confirmed in the variety Hazera 224. Indole-3-acetic acid (IAA) was metabolized to IBA in vivo by seedlings of the two maize varieties. The reaction product was identified by thin layer chromatography, high performance liquid chromatography, and gas chromatography-mass spectrometry after incubating the corn seedlings with [14C]IAA and [13C6]IAA. The in vivo conversion of IAA to IBA and the characteristics of IBA formation in two different maize varieties of Zea mays L. (Hazera 224 and Inrakorn) were investigated. IBA-forming activity was examined in the roots, leaves, and coleoptiles of both maize varieties. Whereas in the variety Hazera 224, IBA was formed mostly in the leaves, in the variety Inrakorn, IBA synthesis was detected in the roots as well as in the leaves. A time course study of IBA formation showed that maximum activity was reached in Inrakorn after 1 hour and in Hazera after 2 hours. The pH optimum for the uptake of IAA was 6.0, and that for IBA formation was 7.0. The Km value for IBA formation was 17 micromolar for Inrakorn and 25 micromolar for Hazera 224. The results are discussed with respect to the possible functions of IBA in the plant. ImagesFigure 5 PMID:16668464

  19. Novel mixed ligand complexes of bioactive Schiff base (E)-4-(phenyl (phenylimino) methyl) benzene-1,3-diol and 2-aminophenol/2-aminobenzoic acid: Synthesis, spectral characterization, antimicrobial and nuclease studies

    NASA Astrophysics Data System (ADS)

    Subbaraj, P.; Ramu, A.; Raman, N.; Dharmaraja, J.

    2014-01-01

    A novel bidentate Schiff base ligand has been synthesized using 2,4-dihydroxybenzophenone and aniline. Its mixed ligand complexes of MAB type [M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); HA = Schiff base and B = 2-aminophenol/2-aminobenzoic acid] have been synthesized and characterized on the basis of spectral data UV-Vis, IR, 1H NMR, FAB-Mass, EPR, SEM and magnetic studies. All the complexes were soluble in DMF and DMSO. Elemental analysis and molar conductance values indicate that the complexes are non-electrolytes. HA binds with M(II) ions through azomethine and deprotonated phenolic group and B binds through the primary amine group and deprotonated phenolic/carboxylic groups. Using FAB-Mass the cleavage pattern of the ligand (HA) has been established. All the complexes adopt octahedral geometry around the metal ions. It has been confirmed with the help of UV-Vis, IR, 1H NMR and FAB-Mass spectral data. DNA binding activities of the complexes 1d and 2d are studied by UV-Vis spectroscopy and cleavage studies of Schiff base ligand and its complexes 1d and 2d have been by agarose gel electrophoresis method. In vitro biological activities of the free ligand (HA) and their metal complexes (1a-1e and 2a-2e) were screened against few bacteria, Escherichia coli, Staphylococcus saphyphiticus, Staphylococcus aureus, Pseudomonas aeruginosa and fungi Aspergillus niger, Enterobacter species, Candida albicans by well diffusion technique.

  20. Rooting response of five pomegranate varieties to indole butyric acid concentration and cuttings age.

    PubMed

    Owais, Saed J

    2010-01-15

    The purpose of this study was to evaluate the effect of cutting age and Indole Butyric Acid (IBA) treatments on five pomegranate varieties propagation by stem cuttings. The experiment was carried out in a partially controlled glasshouse conditions at Mutah University, Jordan. The treatments comprised of two types of cuttings, i.e., hardwood and semi-hardwood; five concentrations of IBA, i.e., 3,000, 6,000, 9,000 and 12,000 ppm as quick dip (10 sec) as well as five Jordanian pomegranate varieties (Kdaree Hello, Hmadee Hmaree, Kdaree Sfaree, Zeklabi, Maleese). In this study, the percentage of cuttings that rooted, the number of roots produced per cutting, root length and diameter and root weight per cutting were recorded. It was obvious that the rootability of pomegranate is influenced by the interactive effect of cuttings age, IBA concentration and variety as well as by the single effect of either. The cuttings taken from hardwood stems had higher rooting percentage than those taken from semi-hardwood stems with a considerable differences in rootability between varieties under this study. The highest percentage of cuttings that rooted was observed in Hmadee Hmaree (70%), Zeklabee (69%) and Malesse (73%), while the lowest rooting percentage in Khdaree Hello (58%) and Kdaree Sfaree (49%) varieties. Zeklabee and Hmadee Hmaree varieties when compared with other varieties gave more favorable results at 6000 to 9000 ppm IBA in terms of the percentage of cuttings that rooted, the number of roots produced per cutting and root weight per cutting using both semi- and hard-wood cuttings. It was concluded that the increasing dose of IBA could be useful in increasing rooting potential and other root characteristics in pomegranate. PMID:20415137

  1. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  2. Butyric Acid- and Dimethyl Disulfide-Assimilating Microorganisms in a Biofilter Treating Air Emissions from a Livestock Facility▿

    PubMed Central

    Kristiansen, Anja; Lindholst, Sabine; Feilberg, Anders; Nielsen, Per H.; Neufeld, Josh D.; Nielsen, Jeppe L.

    2011-01-01

    Biofiltration has proven an efficient tool for the elimination of volatile organic compounds (VOCs) and ammonia from livestock facilities, thereby reducing nuisance odors and ammonia emissions to the local environment. The active microbial communities comprising these filter biofilms have not been well characterized. In this study, a trickle biofilter treating air from a pig facility was investigated and proved efficient in removing carboxylic acids (>70% reduction), mainly attributed to the primary filter section within which reduced organic sulfur compounds were also depleted (up to 50%). The secondary filter eliminated several aromatic compounds: phenol (81%), p-cresol (89%), 4-ethylphenol (68%), indole (48%), and skatole (69%). The active butyric acid degrading bacterial community of an air filter sample was identified by DNA stable-isotope probing (DNA-SIP) and microautoradiography, combined with fluorescence in situ hybridization (MAR-FISH). The predominant 16S rRNA gene sequences from a clone library derived from “heavy” DNA from [13C4]butyric acid incubations were Microbacterium, Gordonia, Dietzia, Rhodococcus, Propionibacterium, and Janibacter, all from the Actinobacteria. Actinobacteria were confirmed and quantified by MAR-FISH as being the major bacterial phylum assimilating butyric acid along with several Burkholderiales-related Betaproteobacteria. The active bacterial community assimilating dimethyl disulfide (DMDS) was characterized by DNA-SIP and MAR-FISH and found to be associated with the Actinobacteria, along with a few representatives of Flavobacteria and Sphingobacteria. Interestingly, ammonia-oxidizing Betaproteobacteria were also implicated in DMDS degradation, as were fungi. Thus, multiple isotope-based methods provided complementary data, enabling high-resolution identification and quantitative assessments of odor-eliminating Actinobacteria-dominated populations of these biofilter environments. PMID:22003018

  3. Simultaneous extraction and HPLC determination of 3-indole butyric acid and 3-indole acetic acid in pea plant by using ionic liquid-modified silica as sorbent.

    PubMed

    Sheikhian, Leila; Bina, Sedigheh

    2016-01-15

    In this study, ionic liquid-modified silica was used as sorbent for simultaneous extraction and preconcentration of 3-indole butyric acid and 3-indole acetic acid in pea plants. The effect of some parameters such as pH and ionic strength of sample solution, amount of sorbent, flow rate of aqueous sample solution and eluent solution, concentration of eluent solution, and temperature were studied for each hormone solution. Percent extraction of 3-indole butyric acid and 3-indole acetic acid was strongly affected by pH of aqueous sample solution. Ionic strength of aqueous phase and temperature showed no serious effects on extraction efficiency of studied plant hormones. Obtained breakthrough volume was 200mL for each of studied hormones. Preconcentration factor for spectroscopic and chromatographic determination of studied hormones was 100 and 4.0×10(3) respectively. Each solid sorbent phase was reusable for almost 10 times of extraction/stripping procedure. Relative standard deviations of extraction/stripping processes of 3-indole butyric acid and 3-indole acetic acid were 2.79% and 3.66% respectively. The calculated limit of detections for IBA and IAA were 9.1×10(-2)mgL(-1) and 1.6×10(-1)mgL(-1) respectively. PMID:26701202

  4. Simultaneous extraction and HPLC determination of 3-indole butyric acid and 3-indole acetic acid in pea plant by using ionic liquid-modified silica as sorbent.

    PubMed

    Sheikhian, Leila; Bina, Sedigheh

    2016-01-15

    In this study, ionic liquid-modified silica was used as sorbent for simultaneous extraction and preconcentration of 3-indole butyric acid and 3-indole acetic acid in pea plants. The effect of some parameters such as pH and ionic strength of sample solution, amount of sorbent, flow rate of aqueous sample solution and eluent solution, concentration of eluent solution, and temperature were studied for each hormone solution. Percent extraction of 3-indole butyric acid and 3-indole acetic acid was strongly affected by pH of aqueous sample solution. Ionic strength of aqueous phase and temperature showed no serious effects on extraction efficiency of studied plant hormones. Obtained breakthrough volume was 200mL for each of studied hormones. Preconcentration factor for spectroscopic and chromatographic determination of studied hormones was 100 and 4.0×10(3) respectively. Each solid sorbent phase was reusable for almost 10 times of extraction/stripping procedure. Relative standard deviations of extraction/stripping processes of 3-indole butyric acid and 3-indole acetic acid were 2.79% and 3.66% respectively. The calculated limit of detections for IBA and IAA were 9.1×10(-2)mgL(-1) and 1.6×10(-1)mgL(-1) respectively.

  5. The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T

    SciTech Connect

    Hatayama, Hajime; Iwashita, Jun; Kuwajima, Akiko; Abe, Tatsuya . E-mail: abetats@akita-pu.ac.jp

    2007-05-11

    The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells.

  6. Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors.

    PubMed

    Ho, Koc-Kan; Parnell, K Mark; Yuan, Yi; Xu, Yong; Kultgen, Steven G; Hamblin, Steven; Hendrickson, Thomas F; Luo, Bai; Foulks, Jason M; McCullar, Michael V; Kanner, Steven B

    2013-01-15

    A series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2- and Nck-interacting kinase (TNIK) activity are described. These compounds were used as tools to test the importance of TNIK kinase activity in signaling and proliferation in Wnt-activated colorectal cancer cells. The results indicate that pharmacological inhibition of TNIK kinase activity has minimal effects on either Wnt/TCF4/β-catenin-driven transcription or viability. The findings suggest that the kinase activity of TNIK may be less important to Wnt signaling than other aspects of TNIK function, such as its putative role in stabilizing the TCF4/β-catenin transcriptional complex. PMID:23232060

  7. Effect of different doses of coated butyric acid on growth performance and energy utilization in broilers.

    PubMed

    Kaczmarek, S A; Barri, A; Hejdysz, M; Rutkowski, A

    2016-04-01

    We recently applied four dietary treatments in experiments I and II to determine the effect of protected calcium butyrate (BP) on growth performance and nutrient digestibility in broiler chickens. A group of one-day-old male Ross 308 broiler chicks (total 960, 480 per trial) were used in the study. In experiment I, the basal diets were fed with protected BP inclusion (0.2, 0.3, or 0.4 g/kg of finished feed) (BP) or without (C). In experiment II, 4 different diets were tested: 1) basal diet with no supplementation (C), 2) basal diet supplemented with protected BP (0.3 g/kg) (BP), 3) basal diet supplemented with avilamycin (6 mg/kg, active substance) a common antibiotic growth promoter (AGP) (Av), and 4) basal diet supplemented with the combination of both avilaymicin and BP. In experiment I, considering the entire study period, the use of BP improved feed conversion ratio (P<0.05) irrespective of the dose. Apparent total tract crude fat digestibility and apparent metabolizable energy corrected for nitrogen (AMEN) were improved after BP supplementation (P<0.05). In experiment II, A or AB diets improved (P<0.05) body weight gain compared to the control treatment. The diets Av, BP, and AvB improved (P<0.05) feed conversion ratio compared to the control treatment. Birds from the treatment diet were characterized by having the thickest mucosa (P<0.05). On days 14, 35, and 42, the use of AB diets improved AMENcontent compared to the control treatment (P<0.05). The apparent ileal digestibility of amino acid data showed that Av or AvB treated birds were characterized by higher Asp, Glu, Cys, Gly, and Ala ileal digestibility than the control animals (P<0.05). The use of Av, BP, or AvB increased ileal digestibility of Thr, Ser, and Pro (P<0.05). There is an indication that BP, alone or in combination with avilamycin, improve the digestion and absorptive processes and consequently birds performance results. PMID:26740137

  8. Management of traveller's diarrhoea with a combination of sodium butyrate, organic acids, and A-300 silicon dioxide

    PubMed Central

    Mackiewicz, Jacek; Wejman-Matela, Anna; Krokowicz, Piotr; Drews, Michal; Banasiewicz, Tomasz

    2014-01-01

    Introduction Traveller's diarrhoea (TD), defined by UNICEF/WHO as three or more unformed stools with or without other symptoms, imposes a considerable burden on travellers from developed countries. Various efforts have focused on decreasing the prevalence and severity of this condition. Aim To assess the efficacy of a combination of sodium butyrate, organic acids, and A-300 silicon dioxide in treatment providing symptomatic relief of TD. Material and methods The study was conducted in accordance with a protocol presented to the Bioethical committee of Poznan University of Medical Sciences. A total of 278 patients travelling to countries with higher risk of diarrhoea for at least 10 days were divided into a study arm being administered, in case of TD, a combination of sodium butyrate, organic acids, and A-300 silicon dioxide (n = 139) and a placebo arm (n = 139) with placebo administration. Results Forty-seven patients completed the study (22 in the study arm and 25 in the placebo arm). The diarrhoea occurrence after initiation of treatment at first symptoms was significantly lower in the study arm as compared to the placebo arm (9% vs. 36%, p = 0.041). Also, subjects from the study arm more frequently reported that the regimen administered had been efficient for their symptoms in comparison to the placebo arm (72.7% vs. 32%, p = 0.008). No adverse effects of the administered medication were noted during the study. Conclusions Sodium butyrate, organic acids, and A-300 silicon dioxide can be successful in decreasing symptoms of TD. Because of its efficacy and lack of observed side effects it has a strong potential in the treatment of patients with TD. PMID:25396003

  9. Analysis of the key enzymes of butyric and acetic acid fermentation in biogas reactors

    PubMed Central

    Gabris, Christina; Bengelsdorf, Frank R; Dürre, Peter

    2015-01-01

    This study aimed at the investigation of the mechanisms of acidogenesis, which is a key process during anaerobic digestion. To expose possible bottlenecks, specific activities of the key enzymes of acidification, such as acetate kinase (Ack, 0.23–0.99 U mg−1 protein), butyrate kinase (Buk, < 0.03 U mg−1 protein) and butyryl-CoA:acetate-CoA transferase (But, 3.24–7.64 U mg−1 protein), were determined in cell free extracts of biogas reactor content from three different biogas reactors. Furthermore, the detection of Ack was successful via Western blot analysis. Quantification of corresponding functional genes encoding Buk (buk) and But (but) was not feasible, although an amplification was possible. Thus, phylogenetic trees were constructed based on respective gene fragments. Four new clades of possible butyrate-producing bacteria were postulated, as well as bacteria of the genera Roseburia or Clostridium identified. The low Buk activity was in contrast to the high specific But activity in the analysed samples. Butyrate formation via Buk activity does barely occur in the investigated biogas reactor. Specific enzyme activities (Ack, Buk and But) in samples drawn from three different biogas reactors correlated with ammonia and ammonium concentrations (NH3 and NH4+-N), and a negative dependency can be postulated. Thus, high concentrations of NH3 and NH4+-N may lead to a bottleneck in acidogenesis due to decreased specific acidogenic enzyme activities. PMID:26086956

  10. Analysis of the key enzymes of butyric and acetic acid fermentation in biogas reactors.

    PubMed

    Gabris, Christina; Bengelsdorf, Frank R; Dürre, Peter

    2015-09-01

    This study aimed at the investigation of the mechanisms of acidogenesis, which is a key process during anaerobic digestion. To expose possible bottlenecks, specific activities of the key enzymes of acidification, such as acetate kinase (Ack, 0.23-0.99 U mg(-1) protein), butyrate kinase (Buk, < 0.03 U mg(-1) protein) and butyryl-CoA:acetate-CoA transferase (But, 3.24-7.64 U mg(-1) protein), were determined in cell free extracts of biogas reactor content from three different biogas reactors. Furthermore, the detection of Ack was successful via Western blot analysis. Quantification of corresponding functional genes encoding Buk (buk) and But (but) was not feasible, although an amplification was possible. Thus, phylogenetic trees were constructed based on respective gene fragments. Four new clades of possible butyrate-producing bacteria were postulated, as well as bacteria of the genera Roseburia or Clostridium identified. The low Buk activity was in contrast to the high specific But activity in the analysed samples. Butyrate formation via Buk activity does barely occur in the investigated biogas reactor. Specific enzyme activities (Ack, Buk and But) in samples drawn from three different biogas reactors correlated with ammonia and ammonium concentrations (NH₃ and NH₄(+)-N), and a negative dependency can be postulated. Thus, high concentrations of NH₃ and NH₄(+)-N may lead to a bottleneck in acidogenesis due to decreased specific acidogenic enzyme activities.

  11. The interaction of propionic and butyric acids with ice and HNO₃-doped ice surfaces at 195-212 K.

    PubMed

    Romanias, Manolis N; Papadimitriou, Vassileios C; Papagiannakopoulos, Panos

    2014-12-01

    The interaction of propionic and butyric acids on ice and HNO3-doped ice were studied between 195 and 212 K and low concentrations, using a Knudsen flow reactor coupled with a quadrupole mass spectrometer. The initial uptake coefficients (γ0) of propionic and butyric acids on ice as a function of temperature are given by the expressions: γ0(T) = (7.30 ± 1.0) × 10(-10) exp[(3216 ± 478)/T] and γ0(T) = (6.36 ± 0.76) × 10(-11) exp[(3810 ± 434)/T], respectively; the quoted error limits are at 95% level of confidence. Similarly, γ0 of propionic acid on 1.96 wt % (A) and 7.69 wt % (B) HNO3-doped ice with temperature are given as γ(0,A)(T) = (2.89 ± 0.26) × 10(-8) exp[(2517 ± 266)/T] and γ(0,B)(T) = (2.77 ± 0.29) × 10(-7) exp[(2126 ± 206)/T], respectively. The results show that γ0 of C1 to C4 n-carboxylic acids on ice increase with the alkyl-group length, due to lateral interactions between alkyl-groups that favor a more perpendicular orientation and well packing of H-bonded monomers on ice. The high uptakes (>10(15) molecules cm(-2)) and long recovery signals indicate efficient growth of random multilayers above the first monolayer driven by significant van der Waals interactions. The heterogeneous loss of both acids on ice and HNO3-doped ice particles in dense cirrus clouds is estimated to take a few minutes, signifying rapid local heterogeneous removal by dense cirrus clouds.

  12. Driving carbon flux through exogenous butyryl-CoA: Acetate CoA-transferase to produce butyric acid at high titer in Thermobifida fusca.

    PubMed

    Deng, Yu; Mao, Yin; Zhang, Xiaojuan

    2015-12-20

    Butyric acid, a 4-carbon short chain fatty acid, is widely used in chemical, food, and pharmaceutical industries. The low activity of butyryl-CoA: acetate CoA-transferase in Thermobifida fusca muS, a thermophilic actinobacterium whose optimal temperature was 55°C, was found to hinder the accumulation of high yield of butyric acid. In order to solve this problem, an exogenous butyryl-CoA: acetate CoA-transferase gene (actA) from Thermoanaerobacterium thermosaccharolyticum DSM571 was integrated into the chromosome of T. fusca muS by replacing celR gene, forming T. fusca muS-1. We demonstrated that on 5g/L cellulose, the yield of butyric acid by the engineered muS-1 strain was increased by 42.9 % compared to the muS strain. On 100g/L of cellulose, the muS-1 strain could consume 90.5% of total cellulose in 144h, with 33.2g/L butyric acid produced. Furthermore, on the mix substrates including the major components of biomass: cellulose, xylose, mannose and galactose, 70.4g/L butyric acid was produced in 168h by fed-batch fermentation. To validate the ability of fermenting biomass, the muS-1 strain was grown on the milled corn stover ranging from 200 to 250μm. The muS-1 strain had the highest butyrate titer 17.1g/L on 90g/L corn stover. PMID:26535965

  13. Characterization and Rooting Ability of Indole-3-Butyric Acid Conjugates Formed during Rooting of Mung Bean Cuttings 1

    PubMed Central

    Wiesman, Zeev; Riov, Joseph; Epstein, Ephraim

    1989-01-01

    Indole-3-butyric acid (IBA) is rapidly metabolized by mung bean cuttings during rooting. Twenty-four hours after application, less than 20% of the applied IBA remained in the free form and its level decreased continuously in the later stages of rooting. Indole-3-butyrylaspartic acid (IBAsp) and at least two high molecular weight conjugates were the major metabolites in IBA-treated cuttings. In the latter conjugates, at least part of the IBA moiety is attached to a high molecular weight constituent in an amide linkage. IBAsp level peaked 24 hours after application of IBA to the cuttings and then declined. The level of the high molecular weight conjugates increased continuously throughout the rooting process. The conjugates were active in inducing rooting of cuttings, with IBAsp being superior to free IBA. It is suggested that IBA conjugates, and particularly IBAsp, serve as the source of auxin during the later stages of rooting. PMID:16667115

  14. Characterization and Rooting Ability of Indole-3-Butyric Acid Conjugates Formed during Rooting of Mung Bean Cuttings.

    PubMed

    Wiesman, Z; Riov, J; Epstein, E

    1989-11-01

    Indole-3-butyric acid (IBA) is rapidly metabolized by mung bean cuttings during rooting. Twenty-four hours after application, less than 20% of the applied IBA remained in the free form and its level decreased continuously in the later stages of rooting. Indole-3-butyrylaspartic acid (IBAsp) and at least two high molecular weight conjugates were the major metabolites in IBA-treated cuttings. In the latter conjugates, at least part of the IBA moiety is attached to a high molecular weight constituent in an amide linkage. IBAsp level peaked 24 hours after application of IBA to the cuttings and then declined. The level of the high molecular weight conjugates increased continuously throughout the rooting process. The conjugates were active in inducing rooting of cuttings, with IBAsp being superior to free IBA. It is suggested that IBA conjugates, and particularly IBAsp, serve as the source of auxin during the later stages of rooting. PMID:16667115

  15. A probe on the intermolecular forces in diisopropyl ether-n-butyric acid mixture by dielectric, FTIR studies and quantum chemical calculations.

    PubMed

    Arivazhagan, G; Shanmugam, R; Elangovan, A

    2013-03-15

    The results of FTIR spectral measurement on equimolar diisopropyl ether-butyric acid binary mixture and quantum chemical calculations on the complex molecule have been presented. Dielectric studies have been carried out on the binary mixture over the entire composition range and at four different temperatures 303 K, 308 K, 313 K and 318 K. n-Butyric acid seems to prefer less polar ether to interact with it. It appears that the usual interpretation of variation of static dielectric constant and positive deviation of excess permittivity from ideal mixture behavior needs to be relooked.

  16. Use of fluorescence-activated flow cytometry to determine membrane lipid peroxidation during hypothermic liquid storage and freeze-thawing of viable boar sperm loaded with 4, 4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid.

    PubMed

    Guthrie, H D; Welch, G R

    2007-06-01

    Part of the reduction in boar sperm motility and fertility associated with hypothermic liquid storage and cryopreservation may be due to membrane lipid peroxidation. Lipid peroxidation was monitored by the shift from red to green fluorescence emission of the lipophilic probe 4, 4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid, C(11)BODIPY(581/591) (BODIPY), as measured by fluorescence-activated flow cytometry in live sperm (negative for propidium iodide). Experiments were conducted with Percoll-washed sperm to determine the specificity of BODIPY oxidation in the presence of different reactive oxygen species generators and metal chelators. Compared with no FeSO(4) and Na ascorbate, the combination of FeSO(4) and Na ascorbate (FeAc) increased (P < 0.01) the percentage of sperm containing oxidized BODIPY from 70% and increased (P < 0.05) BOD-IPY fluorescence intensity/cell by 5- to 10-fold after a 30-min incubation. Motility was depressed (P < 0.05) after exposure to FeAc, but viability was not affected. Of the reactive oxygen species generators tested, BODIPY oxidation was specific for FeAc, because menadione and H(2)O(2) had little or no effect. The oxidization of hydroethidine to ethidium was specific for menadione and H(2)O(2); FeAc had no effect. The presence of the metal chelators EDTA or deferoxamine mesylate at 3 and 9 muM inhibited FeAc-induced BODIPY oxidation and maintained motility. Experiments were conducted to determine the effect of liquid storage at 17 degrees C for 1 and 5 d and the effect of freeze-thawing on basal and FeAc-induced BODIPY oxidation. Basal BODIPY oxidation (no FeAc) was low in liquid stored and thawed viable sperm (1.3 and 3.4%, respectively). Although the incidence of basal or spontaneous membrane lipid peroxidation was low during liquid storage and after freeze-thawing, viable boar sperm were susceptible to FeAc-induced lipid peroxidation. PMID:17296775

  17. A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR INTRAVENOUS AND INHALATION-ROUTE PHARMACOKINETICS OF BUTYL ACETATE AND METABOLITES N-BUTANOL AND N-BUTYRIC ACID

    EPA Science Inventory

    Risk assessment for n-butyl acetate and metabolites n-butanol and n-butyric acid (the butyl series) can be accomplished with limited toxicity data and pharmacokinetic data for each compound through application of the "family approach" (Barton et al., 2000). The necessary quantita...

  18. First European Report of Social Wasps Trapped in Response to Acetic acid, Isobutanol, 2-Methyl-2-propanol, and Heptyl butyrate in Tests Conducted in Hungary

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five species of social wasps were captured in trapping tests in Hungary that evaluated the attractiveness of acetic acid, isobutanol, 2-methyl-2-propanol, and heptyl butyrate to social wasps. Both Vespula vulgaris (L.) and Vespula germanica (Fabr.), were captured in traps baited with isobutanol, t...

  19. Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.

    PubMed

    Takuma, Kazuhiro; Hara, Yuta; Kataoka, Shunsuke; Kawanai, Takuya; Maeda, Yuko; Watanabe, Ryo; Takano, Erika; Hayata-Takano, Atsuko; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

    2014-11-01

    We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring. In the present study, we examined the effect of prenatal VPA on cognitive function and whether the effect is improved by chronic treatment with VPA and sodium butyrate, histone deacetylase inhibitors. In addition, we examined whether the cognitive dysfunction is associated with hippocampal dendritic morphological changes. Mice given prenatal exposure to VPA exhibited novel object recognition deficits at 9 weeks of age, and that the impairment was blocked by chronic (5-week) treatment with VPA (30 mg/kg/d, i.p.) or sodium butyrate (1.2g/kg/d, i.p.) starting at 4 weeks of age. In agreement with the behavioral findings, the mice prenatally exposed to VPA showed a decrease in dendritic spine density in the hippocampal CA1 region, and the spine loss was attenuated by chronic treatment with sodium butyrate or VPA. Furthermore, acute treatment with sodium butyrate, but not VPA, significantly increased acetylation of histone H3 in the hippocampus at 30 min, suggesting the difference in the mechanism for the effects of chronic VPA and sodium butyrate. These findings suggest that prenatal VPA-induced cognitive dysfunction is associated with changes in hippocampal dendritic spine morphology.

  20. The rib1 Mutant Is Resistant to Indole-3-Butyric Acid, an Endogenous Auxin in Arabidopsis1

    PubMed Central

    Poupart, Julie; Waddell, Candace S.

    2000-01-01

    The presence of indole-3-butyric acid (IBA) as an endogenous auxin in Arabidopsis has been recently demonstrated. However, the in vivo role of IBA remains to be elucidated. We present the characterization of a semi-dominant mutant that is affected in its response to IBA, but shows a wild-type response to indole-3-acetic acid (IAA), the predominant and most studied form of auxin. We have named this mutant rib1 for resistant to IBA. Root elongation assays show that rib1 is specifically resistant to IBA, to the synthetic auxin 2,4-dichlorophenoxyacetic acid, and to auxin transport inhibitors. rib1 does not display increased resistance to IAA, to the synthetic auxin naphthalene acetic acid, or to other classes of plant hormones. rib1 individuals also have other root specific phenotypes including a shortened primary root, an increased number of lateral roots, and a more variable response than wild type to a change in gravitational vector. Adult rib1 plants are morphologically indistinguishable from wild-type plants. These phenotypes suggest that rib1 alters IBA activity in the root, thereby affecting root development and response to environmental stimuli. We propose models in which RIB1 has a function in either IBA transport or response. Our experiments also suggest that IBA does not use the same mechanism to exit cells as does IAA and we propose a model for IBA transport. PMID:11115890

  1. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid.

    PubMed

    Duncan, Sylvia H; Russell, Wendy R; Quartieri, Andrea; Rossi, Maddalena; Parkhill, Julian; Walker, Alan W; Flint, Harry J

    2016-07-01

    Cereal fibres such as wheat bran are considered to offer human health benefits via their impact on the intestinal microbiota. We show here by 16S rRNA gene-based community analysis that providing amylase-pretreated wheat bran as the sole added energy source to human intestinal microbial communities in anaerobic fermentors leads to the selective and progressive enrichment of a small number of bacterial species. In particular, OTUs corresponding to uncultured Lachnospiraceae (Firmicutes) related to Eubacterium xylanophilum and Butyrivibrio spp. were strongly enriched (by five to 160 fold) over 48 h in four independent experiments performed with different faecal inocula, while nine other Firmicutes OTUs showed > 5-fold enrichment in at least one experiment. Ferulic acid was released from the wheat bran during degradation but was rapidly converted to phenylpropionic acid derivatives via hydrogenation, demethylation and dehydroxylation to give metabolites that are detected in human faecal samples. Pure culture work using bacterial isolates related to the enriched OTUs, including several butyrate-producers, demonstrated that the strains caused substrate weight loss and released ferulic acid, but with limited further conversion. We conclude that breakdown of wheat bran involves specialist primary degraders while the conversion of released ferulic acid is likely to involve a multi-species pathway. PMID:26636660

  2. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid.

    PubMed

    Duncan, Sylvia H; Russell, Wendy R; Quartieri, Andrea; Rossi, Maddalena; Parkhill, Julian; Walker, Alan W; Flint, Harry J

    2016-07-01

    Cereal fibres such as wheat bran are considered to offer human health benefits via their impact on the intestinal microbiota. We show here by 16S rRNA gene-based community analysis that providing amylase-pretreated wheat bran as the sole added energy source to human intestinal microbial communities in anaerobic fermentors leads to the selective and progressive enrichment of a small number of bacterial species. In particular, OTUs corresponding to uncultured Lachnospiraceae (Firmicutes) related to Eubacterium xylanophilum and Butyrivibrio spp. were strongly enriched (by five to 160 fold) over 48 h in four independent experiments performed with different faecal inocula, while nine other Firmicutes OTUs showed > 5-fold enrichment in at least one experiment. Ferulic acid was released from the wheat bran during degradation but was rapidly converted to phenylpropionic acid derivatives via hydrogenation, demethylation and dehydroxylation to give metabolites that are detected in human faecal samples. Pure culture work using bacterial isolates related to the enriched OTUs, including several butyrate-producers, demonstrated that the strains caused substrate weight loss and released ferulic acid, but with limited further conversion. We conclude that breakdown of wheat bran involves specialist primary degraders while the conversion of released ferulic acid is likely to involve a multi-species pathway.

  3. Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET

    PubMed Central

    Kim, Sung Won; Hooker, Jacob M.; Otto, Nicola; Win, Khaing; Muench, Lisa; Shea, Colleen; Carter, Pauline; King, Payton; Reid, Alicia E.; Volkow, Nora D.; Fowler, Joanna S.

    2013-01-01

    The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profile. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using 11CO2 and the appropriate Grignard reagents. [11C]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity was the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low (<0.006%ID/cc, BA>VPA>PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [11C]BA showed relatively high uptake in spleen and pancreas whereas [11C]PBA showed high uptake in liver and heart. Notably, [11C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of relevance in understanding their therapeutic and side effect profile including their teratogenic effects. PMID:23906667

  4. Structure, conformation and hydrogen bonding of 4-( N-methylpiperidinium)-butyric acid bromide

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Dulewicz, E.; Szafran, M.; Thaimattam, R.; Jaskolski, M.

    2007-02-01

    A 1:1 complex between 4-( N-methylpiperidinium)-butyrate inner salt (betaine) and hydrobromide, MPBUH·Br, has been characterized by single crystal X-ray analysis. The crystals are monoclinic, space group P2 1/c, with a = 8.284(1), b = 10.369(1), c = 13.809(2) Å, β = 92.26(1)°. The piperidine ring adopts a chair conformation with the (CH 2) 3COOH substituent in the axial and the CH 3 group in the equatorial positions. In the crystal, the Br - anion is engaged in a medium-strong hydrogen bond with the COOH group (O sbnd H⋯Br - = 3.141(1) Å), N +⋯Br - electrostatic interactions and in several C sbnd H⋯Br - contacts with the aliphatic groups forming a cavity in which it is enclosed. Three conformers ( 2- 4) were optimized by the B3LYP/6-31G (d, p) level of theory. The most stable is conformer 4 with the (CH 2) 3COOH substituent in the equatorial position and the CH 3 group in the axial position. The stability of the investigated conformers is controlled by electrostatic interactions between the oppositely charged groups. The FTIR spectrum of MPBUH·Br shows a strong band at 2941 cm -1 due to νOH and the νC dbnd O band at 1712 cm -1.

  5. LeProT1, a transporter for proline, glycine betaine, and gamma-amino butyric acid in tomato pollen.

    PubMed Central

    Schwacke, R; Grallath, S; Breitkreuz, K E; Stransky, E; Stransky, H; Frommer, W B; Rentsch, D

    1999-01-01

    During maturation, pollen undergoes a period of dehydration accompanied by the accumulation of compatible solutes. Solute import across the pollen plasma membrane, which occurs via proteinaceous transporters, is required to support pollen development and also for subsequent germination and pollen tube growth. Analysis of the free amino acid composition of various tissues in tomato revealed that the proline content in flowers was 60 times higher than in any other organ analyzed. Within the floral organs, proline was confined predominantly to pollen, where it represented >70% of total free amino acids. Uptake experiments demonstrated that mature as well as germinated pollen rapidly take up proline. To identify proline transporters in tomato pollen, we isolated genes homologous to Arabidopsis proline transporters. LeProT1 was specifically expressed both in mature and germinating pollen, as demonstrated by RNA in situ hybridization. Expression in a yeast mutant demonstrated that LeProT1 transports proline and gamma-amino butyric acid with low affinity and glycine betaine with high affinity. Direct uptake and competition studies demonstrate that LeProT1 constitutes a general transporter for compatible solutes. PMID:10072398

  6. Effect of iron on the sensitivity of hydrogen, acetate, and butyrate metabolism to inhibition by long-chain fatty acids in vegetable-oil-enriched freshwater sediments.

    PubMed

    Li, Zhengkai; Wrenn, Brian A; Venosa, Albert D

    2005-08-01

    Freshwater sediment microbial communities enriched by growth on vegetable oil in the presence of a substoichiometric amount of ferric hydroxide (sufficient to accept about 12% of the vegetable-oil-derived electrons) degrade vegetable oil to methane faster than similar microbial communities that develop when sediments are enriched by growth on vegetable oil in the absence of ferric hydroxide. This study examined the effects of enrichment in the presence of Fe(III) on the fatty-acid sensitivity of several important members of anaerobic triglyceride-degrading microbial communities in freshwater sediments. The fatty-acid sensitivity of three groups of microorganisms-hydrogenotrophic methanogens, acetate consumers, and hydrogen-producing acetogens-were investigated by comparing the rates of hydrogen, acetate, or butyrate consumption in the presence and absence of oleic acid. Methanogenesis from hydrogen was not affected by sediment enrichment conditions or by the presence of oleic acid, suggesting that hydrogenotrophic methanogens were insensitive to fatty acid inhibition in these sediments. Oleic acid inhibited the anaerobic degradation rates of acetate and butyrate by 38% and 63%, respectively, but enrichment in the presence of Fe(III) eliminated the fatty-acid sensitivity of acetate degradation and reduced the sensitivity of butyrate degradation by about half. These results suggest that iron-reducing bacteria may provide an alternative pathway through which vegetable oil can be converted to methane in anaerobic freshwater sediments.

  7. Synthesis and Characterization of a Novel Phenolic Lipid for Use as Potential Lipophilic Antioxidant and as a Prodrug of Butyric Acid.

    PubMed

    Kaki, Shiva Shanker; Kunduru, Konda Reddy; Kanjilal, Sanjit; Narayana Prasad, Rachapudi Badari

    2015-01-01

    Ferulic acid was modified to produce a novel phenolipid containing butyl chains. Ferulic acid was esterified with butanol to produce butyl ferulate which was further dihydroxylated followed by esterification with butyric anhydride to produce the phenolipid containing butyric acid. IR, NMR and MS techniques confirmed the structure of the synthesized structured lipophilic phenolic compound. The synthesized compound was tested for in vitro antioxidant and antimicrobial activities. The produced phenolipid showed moderate antioxidant activity in DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging assay but in linoleic acid oxidation method, it exhibited good activity compared with the parent compound and the reference compounds. The prepared derivative could find applications as antioxidant in lipophilic systems and also as a potential prodrug of butyric acid. It also showed antibacterial effect against the four bacterial strains studied. The drug-likeness properties of the prepared molecule calculated were in the acceptable ranges according to Lipinski's rule of 5 and suggest that it has potential to cross the blood-brain barrier.

  8. Synthesis and Characterization of a Novel Phenolic Lipid for Use as Potential Lipophilic Antioxidant and as a Prodrug of Butyric Acid.

    PubMed

    Kaki, Shiva Shanker; Kunduru, Konda Reddy; Kanjilal, Sanjit; Narayana Prasad, Rachapudi Badari

    2015-01-01

    Ferulic acid was modified to produce a novel phenolipid containing butyl chains. Ferulic acid was esterified with butanol to produce butyl ferulate which was further dihydroxylated followed by esterification with butyric anhydride to produce the phenolipid containing butyric acid. IR, NMR and MS techniques confirmed the structure of the synthesized structured lipophilic phenolic compound. The synthesized compound was tested for in vitro antioxidant and antimicrobial activities. The produced phenolipid showed moderate antioxidant activity in DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging assay but in linoleic acid oxidation method, it exhibited good activity compared with the parent compound and the reference compounds. The prepared derivative could find applications as antioxidant in lipophilic systems and also as a potential prodrug of butyric acid. It also showed antibacterial effect against the four bacterial strains studied. The drug-likeness properties of the prepared molecule calculated were in the acceptable ranges according to Lipinski's rule of 5 and suggest that it has potential to cross the blood-brain barrier. PMID:26179002

  9. Functional expression of γ-amino butyric acid transporter 2 in human and guinea pig airway epithelium and smooth muscle.

    PubMed

    Zaidi, Sarah; Gallos, George; Yim, Peter D; Xu, Dingbang; Sonett, Joshua R; Panettieri, Reynold A; Gerthoffer, William; Emala, Charles W

    2011-08-01

    γ-Amino butyric acid (GABA) is a primary inhibitory neurotransmitter in the central nervous system, and is classically released by fusion of synaptic vesicles with the plasma membrane or by egress via GABA transporters (GATs). Recently, a GABAergic system comprised of GABA(A) and GABA(B) receptors has been identified on airway epithelial and smooth muscle cells that regulate mucus secretion and contractile tone of airway smooth muscle (ASM). In addition, the enzyme that synthesizes GABA, glutamic acid decarboxylase, has been identified in airway epithelial cells; however, the mechanism(s) by which this synthesized GABA is released from epithelial intracellular stores is unknown. We questioned whether any of the four known isoforms of GATs are functionally expressed in ASM or epithelial cells. We detected mRNA and protein expression of GAT2 and -4, and isoforms of glutamic acid decarboxylase in native and cultured human ASM and epithelial cells. In contrast, mRNA encoding vesicular GAT (VGAT), the neuronal GABA transporter, was not detected. Functional inhibition of (3)H-GABA uptake was demonstrated using GAT2 and GAT4/betaine-GABA transporter 1 (BGT1) inhibitors in both human ASM and epithelial cells. These results demonstrate that two isoforms of GATs, but not VGAT, are expressed in both airway epithelial and smooth muscle cells. They also provide a mechanism by which locally synthesized GABA can be released from these cells into the airway to activate GABA(A) channels and GABA(B) receptors, with subsequent autocrine and/or paracrine signaling effects on airway epithelium and ASM. PMID:21057105

  10. Molecular structure of the 1:2 complex of 2-quinuclidinium-butyrate with p-hydroxybenzoic acid

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.

    2011-05-01

    The structure of the 1:2 complex of 2-quinuclidinium-butyrate, QNBu, with p-hydroxybenzoic acid, HBA, ( 1) has been determined by X-ray diffraction, DFT calculations, and the complex was characterized by FTIR and NMR spectroscopy. The crystals are triclinic, space group P1¯. The QNBu and HBA molecules are linked by medium-strong O sbnd H···O hydrogen bonds into a double strand related by two types of inversion centers, each inside different H-bonded rings. The O···O distances vary between 2.652(3) and 2.720(2) Å. The FTIR spectrum of the solid complex is consistent with the X-ray results. The second-derivative IR spectrum and calculated frequencies for the optimized structure of QNBu·2HBA were used to explain the FTIR spectrum in the carbonyl-carboxylate region. The interpretation of 1H and 13C NMR spectra has been based on 2D experiments and calculated GIAO/B3LYP/6-31G( d, p) magnetic isotropic shielding constants.

  11. Transcriptome analysis of indole-3-butyric acid-induced adventitious root formation in nodal cuttings of Camellia sinensis (L.).

    PubMed

    Wei, Kang; Wang, Li-Yuan; Wu, Li-Yun; Zhang, Cheng-Cai; Li, Hai-Lin; Tan, Li-Qiang; Cao, Hong-Li; Cheng, Hao

    2014-01-01

    Tea (Camellia sinensis L.) is a popular world beverage, and propagation of tea plants chiefly depends on the formation of adventitious roots in cuttings. To better understand potential mechanisms involved in adventitious root formation, we performed transcriptome analysis of single nodal cuttings of C. sinensis treated with or without indole-3-butyric acid (IBA) using the Illumina sequencing method. Totally 42.5 million RNA-Seq reads were obtained and these were assembled into 59,931 unigenes, with an average length of 732 bp and an N50 of 1292 bp. In addition, 1091 differentially expressed unigenes were identified in the tea cuttings treated with IBA compared to controls, including 656 up- and 435 down-regulated genes. Further real time RT-PCR analysis confirmed RNA-Seq data. Functional annotation analysis showed that many genes were involved in plant hormone signal transduction, secondary metabolism, cell wall organization and glutathione metabolism, indicating potential contributions to adventitious rooting. Our study presents a global view of transcriptome profiles of tea cuttings in response to IBA treatment and provides new insights into the fundamental mechanisms associated with auxin-induced adventitious rooting. Our data will be a valuable resource for genomic research about adventitious root formation in tea cuttings, which can be used to improve rooting for difficult-to-root varieties.

  12. Transcriptome Analysis of Indole-3-Butyric Acid-Induced Adventitious Root Formation in Nodal Cuttings of Camellia sinensis (L.)

    PubMed Central

    Wei, Kang; Wang, Li-Yuan; Wu, Li-Yun; Zhang, Cheng-Cai; Li, Hai-Lin; Tan, Li-Qiang; Cao, Hong-Li; Cheng, Hao

    2014-01-01

    Tea (Camellia sinensis L.) is a popular world beverage, and propagation of tea plants chiefly depends on the formation of adventitious roots in cuttings. To better understand potential mechanisms involved in adventitious root formation, we performed transcriptome analysis of single nodal cuttings of C. sinensis treated with or without indole-3-butyric acid (IBA) using the Illumina sequencing method. Totally 42.5 million RNA-Seq reads were obtained and these were assembled into 59,931 unigenes, with an average length of 732 bp and an N50 of 1292 bp. In addition, 1091 differentially expressed unigenes were identified in the tea cuttings treated with IBA compared to controls, including 656 up- and 435 down-regulated genes. Further real time RT-PCR analysis confirmed RNA-Seq data. Functional annotation analysis showed that many genes were involved in plant hormone signal transduction, secondary metabolism, cell wall organization and glutathione metabolism, indicating potential contributions to adventitious rooting. Our study presents a global view of transcriptome profiles of tea cuttings in response to IBA treatment and provides new insights into the fundamental mechanisms associated with auxin-induced adventitious rooting. Our data will be a valuable resource for genomic research about adventitious root formation in tea cuttings, which can be used to improve rooting for difficult-to-root varieties. PMID:25216187

  13. Transcriptome analysis of indole-3-butyric acid-induced adventitious root formation in nodal cuttings of Camellia sinensis (L.).

    PubMed

    Wei, Kang; Wang, Li-Yuan; Wu, Li-Yun; Zhang, Cheng-Cai; Li, Hai-Lin; Tan, Li-Qiang; Cao, Hong-Li; Cheng, Hao

    2014-01-01

    Tea (Camellia sinensis L.) is a popular world beverage, and propagation of tea plants chiefly depends on the formation of adventitious roots in cuttings. To better understand potential mechanisms involved in adventitious root formation, we performed transcriptome analysis of single nodal cuttings of C. sinensis treated with or without indole-3-butyric acid (IBA) using the Illumina sequencing method. Totally 42.5 million RNA-Seq reads were obtained and these were assembled into 59,931 unigenes, with an average length of 732 bp and an N50 of 1292 bp. In addition, 1091 differentially expressed unigenes were identified in the tea cuttings treated with IBA compared to controls, including 656 up- and 435 down-regulated genes. Further real time RT-PCR analysis confirmed RNA-Seq data. Functional annotation analysis showed that many genes were involved in plant hormone signal transduction, secondary metabolism, cell wall organization and glutathione metabolism, indicating potential contributions to adventitious rooting. Our study presents a global view of transcriptome profiles of tea cuttings in response to IBA treatment and provides new insights into the fundamental mechanisms associated with auxin-induced adventitious rooting. Our data will be a valuable resource for genomic research about adventitious root formation in tea cuttings, which can be used to improve rooting for difficult-to-root varieties. PMID:25216187

  14. Interactions between lead-zirconate titanate, polyacrylic acid, and polyvinyl butyral in ethanol and their influence on electrophoretic deposition behavior.

    PubMed

    Kuscer, Danjela; Bakarič, Tina; Kozlevčar, Bojan; Kosec, Marija

    2013-02-14

    Electrophoretic deposition (EPD) is an attractive method for the fabrication of a few tens of micrometer-thick piezoelectric layers on complex-shape substrates that are used for manufacturing high-frequency transducers. Niobium-doped lead-zirconate titanate (PZT Nb) particles were stabilized in ethanol using poly(acrylic acid) (PAA). With Fourier-transform infrared spectroscopy (FT-IR), we found that the deprotonated carboxylic group from the PAA is coordinated with the metal in the perovskite PZT Nb structure, resulting in a stable ethanol-based suspension. The hydroxyl group from the polyvinyl butyral added into the suspension to prevent the formation of cracks in the as-deposited layer did not interact with the PAA-covered PZT Nb particles. PVB acts as a free polymer in ethanol-based suspensions. The electrophoretic deposition of micro- and nanometer-sized PZT Nb particles from ethanol-based suspensions onto electroded alumina substrates was attempted in order to obtain uniform, crack-free deposits. The interactions between the PZT Nb particles, the PAA, and the PVB in ethanol will be discussed and related to the properties of the suspensions, the deposition yield and the morphology of the as-deposited PZT Nb thick film.

  15. Gamma-amino butyric acid (GABA) release in the ciliated protozoon Paramecium occurs by neuronal-like exocytosis.

    PubMed

    Ramoino, P; Milanese, M; Candiani, S; Diaspro, A; Fato, M; Usai, C; Bonanno, G

    2010-04-01

    Paramecium primaurelia expresses a significant amount of gamma-amino butyric acid (GABA). Paramecia possess both glutamate decarboxylase (GAD)-like and vesicular GABA transporter (vGAT)-like proteins, indicating the ability to synthesize GABA from glutamate and to transport GABA into vesicles. Using antibodies raised against mammalian GAD and vGAT, bands with an apparent molecular weight of about 67 kDa and 57 kDa were detected. The presence of these bands indicated a similarity between the proteins in Paramecium and in mammals. VAMP, syntaxin and SNAP, putative proteins of the release machinery that form the so-called SNARE complex, are present in Paramecium. Most VAMP, syntaxin and SNAP fluorescence is localized in spots that vary in size and density and are primarily distributed near the plasma membrane. Antibodies raised against mammal VAMP-3, sintaxin-1 or SNAP-25 revealed protein immunoblot bands having molecular weights consistent with those observed in mammals. Moreover, P. primaurelia spontaneously releases GABA into the environment, and this neurotransmitter release significantly increases after membrane depolarization. The depolarization-induced GABA release was strongly reduced not only in the absence of extracellular Ca(2+) but also by pre-incubation with bafilomycin A1 or with botulinum toxin C1 serotype. It can be concluded that GABA occurs in Paramecium, where it is probably stored in vesicles capable of fusion with the cell membrane; accordingly, GABA can be released from Paramecium by stimulus-induced, neuronal-like exocytotic mechanisms.

  16. Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone.

    PubMed

    Naik, S R; Naid, P R; Sheth, U K

    1978-04-14

    The effects of methaqualone on isonicotinic acid hydrazide, 6-mercapto propionic acid, picrotoxin, and strychnine-induced convulsion were studied in mice and the results compared with diazepam. Methaqualone, like diazepam, was found to be a selective antagonist of isoniazid-induced convulsion and a much less effective inhibitor of strychnine convulsion. Methaqualone elicits muscle-relaxant, sedative, and anticonvulsant effects at different dose levels. At low, nonsedative doses the drug produces anticonvulsant effects, and at higher doses, muscle-relaxant and sedative effects. It appears that the mechanism(s) of action of methaqualone in on GABA deficiency or receptor blockade, rather than on glycine receptors.

  17. Effect of Ethephon, Indole Butyric Acid, and Treatment Solution pH on Rooting and on Ethylene Levels within Mung Bean Cuttings.

    PubMed

    Mudge, K W; Swanson, B T

    1978-02-01

    Light-grown mung bean (Phaseolus aureus Roxb.) cuttings were treated with buffered and nonbuffered solutions of Ethephon, indole butyric acid (IBA), and the combination of both. Ethephon treatment resulted in increased tissue ethylene levels with increasing solution pH, but had no effect on rooting. IBA treatment had no effect on tissue ethylene levels, but strongly promoted rooting. Combinations of Ethephon and IBA had no effect on rooting of mung bean cuttings beyond that obtained by IBA alone. PMID:16660274

  18. Homology modeling of human γ-butyric acid transporters and the binding of pro-drugs 5-aminolevulinic acid and methyl aminolevulinic acid used in photodynamic therapy.

    PubMed

    Baglo, Yan; Gabrielsen, Mari; Sylte, Ingebrigt; Gederaas, Odrun A

    2013-01-01

    Photodynamic therapy (PDT) is a safe and effective method currently used in the treatment of skin cancer. In ALA-based PDT, 5-aminolevulinic acid (ALA), or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizer protoporphyrin IX (PpIX). Activation of PpIX by light causes the formation of reactive oxygen species (ROS) and toxic responses. Studies have indicated that ALA and its methyl ester (MAL) are taken up into the cells via γ-butyric acid (GABA) transporters (GATs). Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverse side effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes were constructed using three x-ray crystal structures of the homologous leucine transporter (LeuT) as templates. Binding of the native substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands into the central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs) of the putative substrate translocation pathway of each subtype were calculated using the outward-open and inward-open homology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3 and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. in outward-open conformations). Such differences may be exploited for development of inhibitors that selectively target specific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can be used to reduce ALA-induced pain. PMID:23762315

  19. Diet structure, butyric acid, and fermentable carbohydrates influence growth performance, gut morphology, and cecal fermentation characteristics in broilers.

    PubMed

    Qaisrani, S N; van Krimpen, M M; Kwakkel, R P; Verstegen, M W A; Hendriks, W H

    2015-09-01

    An experiment with 288 male (Ross 308) 1-d-old broilers was conducted to test the hypothesis that a coarse diet supplemented with butyric acid (BA) and fermentable carbohydrates (FC) improves performance of broilers with a poorly digestible protein source. The interaction effects of diet structure (fine or coarse), FC supplementation (with or without), and BA supplementation (with or without) in a poorly digestible diet based on rapeseed meal (RSM) were tested in a factorial arrangement of 8 (2×2×2) dietary treatments. The coarseness of the diet affected feed intake (FI) (P<0.001), BW gain (P=0.001), and the feed conversion ratio (FCR) (P=0.001) positively. Broilers fed the coarse diets had, on average, 14% heavier gizzards and 11, 7, 5, and 6% lower relative empty weights of the crop, duodenum, jejunum, and ileum, respectively, compared with those fed the fine diets. Dietary coarseness resulted in, on average, 6% greater ileal protein digestibility, 20% lower gizzard pH, 19% greater villus height, 18% lower crypt depth, and 23% reduced cecal branched chain fatty acids (BCFA) compared with chickens fed the fine diets. Broilers fed BA-supplemented diets had an improved FCR (P=0.004) and decreased crypt depth (P<0.001) compared with those fed diets without BA. Fermentable carbohydrate supplementation did not influence growth performance, gut development, or contents of total BCFA and total biogenic amines in the cecal digesta (P>0.05). Supplementation with FC, however, decreased the cecal concentration of spermine by approximately 31% compared with broilers fed diets without FC (P=0.002). In conclusion, feeding a coarse diet supplemented with BA improved performance of broilers fed a diet containing a poorly digestible protein source. The negative effects of a poorly digestible protein source can thus be partly counterbalanced by coarse grinding and BA supplementation in the diet.

  20. Diet structure, butyric acid, and fermentable carbohydrates influence growth performance, gut morphology, and cecal fermentation characteristics in broilers

    PubMed Central

    Qaisrani, S. N.; van Krimpen, M. M.; Kwakkel, R. P.; Verstegen, M. W. A.; Hendriks, W. H.

    2015-01-01

    An experiment with 288 male (Ross 308) 1-d-old broilers was conducted to test the hypothesis that a coarse diet supplemented with butyric acid (BA) and fermentable carbohydrates (FC) improves performance of broilers with a poorly digestible protein source. The interaction effects of diet structure (fine or coarse), FC supplementation (with or without), and BA supplementation (with or without) in a poorly digestible diet based on rapeseed meal (RSM) were tested in a factorial arrangement of 8 (2 × 2 × 2) dietary treatments. The coarseness of the diet affected feed intake (FI) (P < 0.001), BW gain (P = 0.001), and the feed conversion ratio (FCR) (P = 0.001) positively. Broilers fed the coarse diets had, on average, 14% heavier gizzards and 11, 7, 5, and 6% lower relative empty weights of the crop, duodenum, jejunum, and ileum, respectively, compared with those fed the fine diets. Dietary coarseness resulted in, on average, 6% greater ileal protein digestibility, 20% lower gizzard pH, 19% greater villus height, 18% lower crypt depth, and 23% reduced cecal branched chain fatty acids (BCFA) compared with chickens fed the fine diets. Broilers fed BA-supplemented diets had an improved FCR (P = 0.004) and decreased crypt depth (P < 0.001) compared with those fed diets without BA. Fermentable carbohydrate supplementation did not influence growth performance, gut development, or contents of total BCFA and total biogenic amines in the cecal digesta (P > 0.05). Supplementation with FC, however, decreased the cecal concentration of spermine by approximately 31% compared with broilers fed diets without FC (P = 0.002). In conclusion, feeding a coarse diet supplemented with BA improved performance of broilers fed a diet containing a poorly digestible protein source. The negative effects of a poorly digestible protein source can thus be partly counterbalanced by coarse grinding and BA supplementation in the diet. PMID:26175052

  1. Role of indole-3-butyric acid or/and putrescine in improving productivity of chickpea (Cicer arientinum L.) plants.

    PubMed

    Amin, A A; Gharib, F A; Abouziena, H F; Dawood, Mona G

    2013-12-15

    The response of chickpea (Cicer arientinum L. cv. Giza 3) to treatment with two plant growth regulators putrescine (Put) and Indole-3-butyric acid (IBA) at 25, 50 and 100 mg L(-1) applied either alone or in combinations was studied. Spraying of Put and IBA either individually or in combination significantly increased the plant height, number and dry weight of branches, leaves and pods/plant and leaf area/plant at the two growth stages. Total photosynthetic pigments in fresh leaves were significantly promoted as a result of application of Put or IBA. Generally, application of Put and/or IBA at 100 mg L(-1) produced the highest numbers of pods which resulted in substantially the highest seed yield. Put and IBA increased the seed yield by 21.3 and 19.2%, respectively, while the combination of Put at 100 mgL(-1) and IBA at 50 mgL(-1) increased it by 27.4%. Greatest increases in straw and biological yield/fed (38.3 and 30.4%, respectively) were noted with the combination treatment of IBA 100 mg L(-1) plus Put at 100 mg L(-1). Put and IBA significantly increased the nitrogen, phosphorus, potassium, total soluble sugars and total free amino acids in chickpea seeds over control, but the effects were less marked than those of their combination. This response was greater following treatment with IBA than with Put. It could be conclude that spraying Put or/and IBA on chickpea plants have promotion effects on the seeds yield criteria which have promising potential as sources of low-cost protein and minerals for possible use as food/feed supplements.

  2. Genetic differences in the modulation of accumbal glutamate and γ-amino butyric acid levels after cocaine-induced reinstatement.

    PubMed

    Miguéns, Miguel; Botreau, Fanny; Olías, Oscar; Del Olmo, Nuria; Coria, Santiago M; Higuera-Matas, Alejandro; Ambrosio, Emilio

    2013-07-01

    The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate and GABA responsiveness to cocaine-induced reinstatement remains unknown. To investigate this, we measured by in vivo microdialysis extracellular glutamate and GABA levels in the core division of the nucleus accumbens after extinction of cocaine self-administration and during cocaine-induced reinstatement (7.5mg/kg, i.p.) in these two strains of rats. No strain differences were evident in cocaine self-administration or extinction behavior, although cocaine priming did induce a higher rate of lever pressing in LEW compared with F344 rats. After extinction, F344 rats that self-administered cocaine had less GABA than the saline controls, while the glutamate levels remained constant in both strains. There was more accumbal glutamate after cocaine priming in LEW rats that self-administered cocaine, while GABA levels were unaffected. By contrast, GABA increased transiently in F344 rats that self-administered cocaine, while glutamate levels were unaltered. In F344 saline controls, cocaine priming provoked contrasting effects in glutamate and GABA levels, inducing a delayed increase in glutamate and a delayed decrease in GABA levels. These amino acids were unaffected by cocaine priming in LEW saline rats. Together, these results suggest that genetic differences in cocaine-induced reinstatement reflect different responses of the accumbal GABA and glutamate systems to cocaine priming.

  3. Hydrogen bonding and molecular association in 2-(quinuclidinium)-butyric acid bromide hydrate studied by X-ray diffraction, DFT calculations, FTIR and NMR spectroscopy, and potentiometric titration

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.; Barczyński, P.

    2010-06-01

    The structure of 2-(quinuclidinium)-butyric acid bromide hydrate (QNBu·H 2O·HBr, 3) has been determined by X-ray diffraction, DFT calculations and characterized by FTIR and NMR spectroscopy. Crystals of 3 are monoclinic, space group P2 1. The water molecule interacts with the carboxylic group of 2-(quinuclidinium)-butyric acid and with the bromide anion by the COOH⋯OH 2 and HOH⋯Br hydrogen bonds of 2.575(3) and 3.293(2) Å, respectively. The structures of monomer ( 4) and dimeric cation ( 5) of the title complex have been optimized by the B3LYP/6-31G(d,p) approach, yielding conformations consistent with this in the crystal. The solid-state FTIR spectra of 3 and its deuterated analogue have been measured and compared with the theoretical spectrum of 4. The assignments of the observed and predicted bands have been proposed. The molecule of 3 has a chiral center at the C(9) atom, which is responsible for the non-magnetically equivalence of the α-ring and C(11)H 2 methylene protons in 1H NMR spectrum. The values of p Ka of quinuclidinium-acetate (quinuclidine betaine), 2-(quinuclidinium)-propionate and 2-(quinuclidinium)-butyrate have been determined by the potentiometric titration of their hydrohalides.

  4. Plasmonic-based colorimetric and spectroscopic discrimination of acetic and butyric acids produced by different types of Escherichia coli through the different assembly structures formation of gold nanoparticles.

    PubMed

    La, Ju A; Lim, Sora; Park, Hyo Jeong; Heo, Min-Ji; Sang, Byoung-In; Oh, Min-Kyu; Cho, Eun Chul

    2016-08-24

    We present a plasmonic-based strategy for the colourimetric and spectroscopic differentiation of various organic acids produced by bacteria. The strategy is based on our discovery that particular concentrations of dl-lactic, acetic, and butyric acids induce different assembly structures, colours, and optical spectra of gold nanoparticles. We selected wild-type (K-12 W3110) and genetically-engineered (JHL61) Escherichia coli (E. coli) that are known to primarily produce acetic and butyric acid, respectively. Different assembly structures and optical properties of gold nanoparticles were observed when different organic acids, obtained after the removal of acid-producing bacteria, were mixed with gold nanoparticles. Moreover, at moderate cell concentrations of K-12 W3110 E. coli, which produce sufficient amounts of acetic acid to induce the assembly of gold nanoparticles, a direct estimate of the number of bacteria was possible based on time-course colour change observations of gold nanoparticle aqueous suspensions. The plasmonic-based colourimetric and spectroscopic methods described here may enable onsite testing for the identification of organic acids produced by bacteria and the estimation of bacterial numbers, which have applications in health and environmental sciences.

  5. Plasmonic-based colorimetric and spectroscopic discrimination of acetic and butyric acids produced by different types of Escherichia coli through the different assembly structures formation of gold nanoparticles.

    PubMed

    La, Ju A; Lim, Sora; Park, Hyo Jeong; Heo, Min-Ji; Sang, Byoung-In; Oh, Min-Kyu; Cho, Eun Chul

    2016-08-24

    We present a plasmonic-based strategy for the colourimetric and spectroscopic differentiation of various organic acids produced by bacteria. The strategy is based on our discovery that particular concentrations of dl-lactic, acetic, and butyric acids induce different assembly structures, colours, and optical spectra of gold nanoparticles. We selected wild-type (K-12 W3110) and genetically-engineered (JHL61) Escherichia coli (E. coli) that are known to primarily produce acetic and butyric acid, respectively. Different assembly structures and optical properties of gold nanoparticles were observed when different organic acids, obtained after the removal of acid-producing bacteria, were mixed with gold nanoparticles. Moreover, at moderate cell concentrations of K-12 W3110 E. coli, which produce sufficient amounts of acetic acid to induce the assembly of gold nanoparticles, a direct estimate of the number of bacteria was possible based on time-course colour change observations of gold nanoparticle aqueous suspensions. The plasmonic-based colourimetric and spectroscopic methods described here may enable onsite testing for the identification of organic acids produced by bacteria and the estimation of bacterial numbers, which have applications in health and environmental sciences. PMID:27497013

  6. Negative polarity of phenyl-C{sub 61} butyric acid methyl ester adjacent to donor macromolecule domains

    SciTech Connect

    Alley, Olivia J.; Dawidczyk, Thomas J.; Hardigree, Josué F. Martínez; Katz, Howard E.; Wu, Meng-Yin; Johns, Gary L.; Markovic, Nina; Arnold, Michael S.

    2015-01-19

    Interfacial fields within organic photovoltaics influence the movement of free charge carriers, including exciton dissociation and recombination. Open circuit voltage (V{sub oc}) can also be dependent on the interfacial fields, in the event that they modulate the energy gap between donor HOMO and acceptor LUMO. A rise in the vacuum level of the acceptor will increase the gap and the V{sub oc}, which can be beneficial for device efficiency. Here, we measure the interfacial potential differences at donor-acceptor junctions using Scanning Kelvin Probe Microscopy, and quantify how much of the potential difference originates from physical contact between the donor and acceptor. We see a statistically significant and pervasive negative polarity on the phenyl-C{sub 61} butyric acid methyl ester (PCBM) side of PCBM/donor junctions, which should also be present at the complex interfaces in bulk heterojunctions. This potential difference may originate from molecular dipoles, interfacial interactions with donor materials, and/or equilibrium charge transfer due to the higher work function and electron affinity of PCBM. We show that the contact between PCBM and poly(3-hexylthiophene) doubles the interfacial potential difference, a statistically significant difference. Control experiments determined that this potential difference was not due to charges trapped in the underlying substrate. The direction of the observed potential difference would lead to increased V{sub oc}, but would also pose a barrier to electrons being injected into the PCBM and make recombination more favorable. Our method may allow unique information to be obtained in new donor-acceptor junctions.

  7. Effects of ruminal ammonia and butyrate concentrations on reticuloruminal epithelial blood flow and volatile fatty acid absorption kinetics under washed reticulorumen conditions in lactating dairy cows.

    PubMed

    Storm, A C; Hanigan, M D; Kristensen, N B

    2011-08-01

    The effect of reticuloruminal epithelial blood flow on the absorption of propionate as a volatile fatty acid (VFA) marker in 8 lactating Holstein cows was studied under washed rumen conditions. The cows were surgically prepared with ruminal cannulas and permanent catheters in an artery and mesenteric, right ruminal, and hepatic portal veins. The experiment was designed with 2 groups of cows: 4 cows adapted to high crude protein (CP) and 4 to low CP. All cows were subjected to 3 buffers: butyric, ammonia, and control in a randomized replicated 3 × 3 incomplete Latin square design. The buffers (30 kg) were maintained in a temporarily emptied and washed rumen for 40 min. The initial concentration of VFA was 84.2 mmol/L. Butyrate was increased from 4 to 36 mmol/L in butyric buffer by replacement of acetate, and ammonia (NH(3)) was increased from 2.5 to 22.5 mmol/L in ammonia buffer by replacement of NaCl. Increasing amounts of deuterium oxide (D(2)O) were added to the buffers as the order of buffer sequence increased (6, 12, and 18 g of D(2)O). Ruminal clearance of D(2)O was used to estimate epithelial blood flow. To increase accuracy of the epithelial blood flow estimates, data of ruminal liquid marker (Cr-EDTA), and initial and final buffer volumes were fitted to a dynamic simulation model. The model was used to estimate ruminal liquid passages, residual liquid, and water influx (saliva and epithelia water) for each combination of cow and buffer (n=24). Epithelial blood flow increased 49±11% for butyric buffer compared with control. The ruminal disappearance of propionate (marker VFA) was affected by buffer and followed the same pattern as for epithelial blood flow. The correlation between ruminal disappearance of propionate and epithelial blood flow (r=0.56) indicates that the removal of propionate can be limited by epithelial blood flow. The ruminal disappearance of propionate increased 30±12% for the butyric compared with ammonia buffer and 12.5±8% when

  8. Effects of ruminal ammonia and butyrate concentrations on reticuloruminal epithelial blood flow and volatile fatty acid absorption kinetics under washed reticulorumen conditions in lactating dairy cows.

    PubMed

    Storm, A C; Hanigan, M D; Kristensen, N B

    2011-08-01

    The effect of reticuloruminal epithelial blood flow on the absorption of propionate as a volatile fatty acid (VFA) marker in 8 lactating Holstein cows was studied under washed rumen conditions. The cows were surgically prepared with ruminal cannulas and permanent catheters in an artery and mesenteric, right ruminal, and hepatic portal veins. The experiment was designed with 2 groups of cows: 4 cows adapted to high crude protein (CP) and 4 to low CP. All cows were subjected to 3 buffers: butyric, ammonia, and control in a randomized replicated 3 × 3 incomplete Latin square design. The buffers (30 kg) were maintained in a temporarily emptied and washed rumen for 40 min. The initial concentration of VFA was 84.2 mmol/L. Butyrate was increased from 4 to 36 mmol/L in butyric buffer by replacement of acetate, and ammonia (NH(3)) was increased from 2.5 to 22.5 mmol/L in ammonia buffer by replacement of NaCl. Increasing amounts of deuterium oxide (D(2)O) were added to the buffers as the order of buffer sequence increased (6, 12, and 18 g of D(2)O). Ruminal clearance of D(2)O was used to estimate epithelial blood flow. To increase accuracy of the epithelial blood flow estimates, data of ruminal liquid marker (Cr-EDTA), and initial and final buffer volumes were fitted to a dynamic simulation model. The model was used to estimate ruminal liquid passages, residual liquid, and water influx (saliva and epithelia water) for each combination of cow and buffer (n=24). Epithelial blood flow increased 49±11% for butyric buffer compared with control. The ruminal disappearance of propionate (marker VFA) was affected by buffer and followed the same pattern as for epithelial blood flow. The correlation between ruminal disappearance of propionate and epithelial blood flow (r=0.56) indicates that the removal of propionate can be limited by epithelial blood flow. The ruminal disappearance of propionate increased 30±12% for the butyric compared with ammonia buffer and 12.5±8% when

  9. All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification

    PubMed Central

    Kumar, Prerna; Periyasamy, Ramu; Das, Subhankar; Neerukonda, Smitha; Mani, Indra

    2014-01-01

    The objective of the present study was to delineate the mechanisms of GC-A/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) expression in vivo. We used all-trans retinoic acid (ATRA) and histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) to examine the expression and function of Npr1 using gene-disrupted heterozygous (1-copy; +/−), wild-type (2-copy; +/+), and gene-duplicated heterozygous (3-copy; ++/+) mice. Npr1+/− mice exhibited increased renal HDAC and reduced histone acetyltransferase (HAT) activity; on the contrary, Npr1++/+ mice showed decreased HDAC and enhanced HAT activity compared with Npr1+/+ mice. ATRA and NaBu promoted global acetylation of histones H3-K9/14 and H4-K12, reduced methylation of H3-K9 and H3-K27, and enriched accumulation of active chromatin marks at the Npr1 promoter. A combination of ATRA-NaBu promoted recruitment of activator-complex containing E26 transformation–specific 1, retinoic acid receptor α, and HATs (p300 and p300/cAMP response element–binding protein-binding protein–associated factor) at the Npr1 promoter, and significantly increased renal NPRA expression, GC activity, and cGMP levels. Untreated 1-copy mice showed significantly increased systolic blood pressure and renal expression of α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) compared with 2- and 3-copy mice. Treatment with ATRA and NaBu synergistically attenuated the expression of α-SMA and PCNA and reduced systolic blood pressure in Npr1+/− mice. Our findings demonstrate that epigenetic upregulation of Npr1 gene transcription by ATRA and NaBu leads to attenuation of renal fibrotic markers and systolic blood pressure in mice with reduced Npr1 gene copy number, which will have important implications in prevention and treatment of hypertension-related renal pathophysiological conditions. PMID:24714214

  10. Inhibition effects of benzylideneacetone, benzylacetone, and 4-phenyl-2-butanol on the activity of mushroom tyrosinase.

    PubMed

    Liu, Xuan; Jia, Yu-long; Chen, Jing-wei; Liang, Ge; Guo, Hua-yun; Hu, Yong-hua; Shi, Yan; Zhou, Han-Tao; Chen, Qing-Xi

    2015-03-01

    Tyrosinase (EC 1.14.18.1) is the key enzyme of melanin synthesis and fruit-vegetable browning. The inhibition of benzylideneacetone, benzylacetone, and 4-phenyl-2-butanol on mushroom tyrosinase was first investigated. The results shown that these three compounds could effectively inhibit the enzyme activity sharply and the inhibitory effects were determined to be reversible. Their inhibitor concentrations leading to 50% activity lost values were determined to be 1.5, 2.8, and 1.1 mM for monophenolase and 2.0, 0.6, and 0.8 mM for diphenolase, respectively. For the monophenolase activity, all of these three compounds were mixed-type inhibitors, however, only 4-phenyl-2-butanol obviously lengthened the lag time. For the diphenolase activity, benzylideneacetone and benzylacetone were mixed-type inhibitors, while 4-phenyl-2-butanol was a noncompetitive type inhibitor. In conclusion, these compounds exhibited potent antityrosinase activities. This research would provide scientific evidence for the use of benzylideneacetone, benzylacetone, and 4-phenyl-2-butanol as antityrosinase agents.

  11. Preparation of highly conjugated water-dispersible graphene-butyric acid for the enhancement of electron transfer within polyamic acid-benzoxazole: potential applications in electrochemical sensing.

    PubMed

    Chen, Hsiao-Chien; Chen, Yen-Hsuan; Chen, Shi-Liang; Chern, Yaw-Terng; Tsai, Rung-Ywan; Hua, Mu-Yi

    2013-08-15

    To break through the long time and complex procedures for the preparation of highly conjugated reduced graphene oxide (r-GO) in developing electrochemical sensor, a time-saving and simple method is investigated in this study. One novel step of the exfoliated accompanying carboxylated graphene sheet from pristine is achieved via Friedel-Crafts acylation. By electrophilic aromatic substitution, the succinic anhydride ring is opened and attaches covalently to the graphene sheet (Gs) to form exfoliated graphene with grafted 1-one-butyric acid (Gs-BA). The grafting chain converts anions in aqueous solution to maintain Gs-BA in a stable dispersion and noticeably decreases the π-π stacking of the exfoliated Gs during the drying process. The analytical results of the absorption spectroscopy demonstrate that the conjugation of Gs-BA is not significantly destroyed by this chemical modification; Gs-BA retains the Gs electrical properties favorable for developing electrochemical sensors. When polyamic acid-benzoxazole (PAA-BO), a hydrogen peroxide (H₂O₂)-sensitive probe, hybridizes with Gs-BA to form Gs-BA-PAA-BO, the electron transfer rate relating to the response time improves markedly from 1.09 s(-1) to 38.8 s(-1). Additionally, it offers a high performance for H₂O₂ sensing in terms of sensitivity and response time, making this method applicable for developing glucose and choline biosensors.

  12. Histone deacetylase inhibitors sodium butyrate and valproic acid delay spontaneous cell death in purified rat retinal ganglion cells

    PubMed Central

    Boyle, Jennifer; Pielen, Amelie; Lagrèze, Wolf Alexander

    2011-01-01

    Purpose Histone deacetylase inhibitors (HDACi) have neuroprotective effects under various neurodegenerative conditions, e.g., after optic nerve crush (ONC). HDACi-mediated protection of central neurons by increased histone acetylation has not previously been demonstrated in rat retinal ganglion cells (RGCs), although epigenetic changes were shown to be associated with cell death after ONC. We investigated whether HDACi can delay spontaneous cell death in purified rat RGCs and analyzed concomitant histone acetylation levels. Methods RGCs were purified from newborn (postnatal day [P] 0–P2) rat retinas by immunopanning with antibodies against Thy-1.1 and culturing in serum-free medium for 2 days. RGCs were treated with HDACi, each at several different concentrations: 0.1–10 mM sodium butyrate (SB), 0.1–2 mM valproic acid (VPA), or 0.5–10 nM trichostatin A (TSA). Negative controls were incubated in media alone, while positive controls were incubated in 0.05–0.4 IU/µl erythropoietin. Survival was quantified by counting viable cells using phase-contrast microscopy. The expression of acetylated histone proteins (AcH) 3 and 4 was analyzed in RGCs by immunohistochemistry. Results SB and VPA enhanced RGC survival in culture, with both showing a maximum effect at 0.1 mM (increase in survival to 188% and 163%, respectively). Their neuroprotective effect was comparable to that of erythropoietin at 0.05 IU/µl. TSA 0.5–1.0 nM showed no effect on RGC survival, and concentrations ≥5 nM increased RGC death. AcH3 and AcH4 levels were only significantly increased in RGCs treated with 0.1 mM SB. VPA 0.1 mM produced only a slight effect on histone acetylation. Conclusions Millimolar concentrations of SB and VPA delayed spontaneous cell death in purified RGCs; however, significantly increased histone acetylation levels were only detectable in RGCs after SB treatment. As the potent HDACi TSA was not neuroprotective, mechanisms other than histone acetylation may be the

  13. Molecular modeling study of agglomeration of [6,6]-phenyl-C61-butyric acid methyl ester in solvents.

    PubMed

    Mortuza, S M; Banerjee, Soumik

    2012-12-28

    The molecular interactions between solvent and nanoparticles during photoactive layer formation in organic photovoltaic (OPV) cells influence the morphology of the photoactive layer and hence determine the power conversion efficiency. Prediction of optimal synthesis parameters in OPVs, such as choice of solvent, processing temperature, and nanoparticle concentration, requires fundamental understanding of the mechanisms that govern the agglomeration of nanoparticles in solvents. In this study, we used molecular dynamics simulations to simulate a commonly used organic nanoparticle, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), in various solvents to correlate solvent-nanoparticle interactions with the size of the agglomerate structure of PCBM. We analyzed the effects of concentration of PCBM and operating temperature on the molecular rearrangement and agglomeration of PCBM in three solvents: (i) toluene, (ii) indane, and (iii) toluene-indane mixture. We evaluated the agglomeration behavior of PCBM by determining sizes of the largest clusters of PCBM and the corresponding size distributions. To obtain further insight into the agglomerate structure of PCBMs, we evaluated radial distribution functions (RDFs) and coordination numbers of the various moieties of PCBMs with respect to solvent atoms as well as with respect to that of other PCBMs. Our simulations demonstrate that PCBMs form larger clusters in toluene while they are relatively dispersed in indane, which indicates the greater solubility of PCBM in indane than in toluene. In toluene-indane mixture, PCBMs are clustered to a greater extent than in indane and less than that in toluene. To correlate agglomerate size to nanoparticle-solvent interactions, we also evaluated the potential of mean force (PMF) of the fullerene moiety of PCBM in toluene and indane. Our results also show that the cluster size of PCBM molecules increases with the increase of concentration of PCBM and the processing temperature. To

  14. Transport of Indole-3-Butyric Acid and Indole-3-Acetic Acid in Arabidopsis Hypocotyls Using Stable Isotope Labeling1[C][W][OA

    PubMed Central

    Liu, Xing; Barkawi, Lana; Gardner, Gary; Cohen, Jerry D.

    2012-01-01

    The polar transport of the natural auxins indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) has been described in Arabidopsis (Arabidopsis thaliana) hypocotyls using radioactive tracers. Because radioactive assays alone cannot distinguish IBA from its metabolites, the detected transport from applied [3H]IBA may have resulted from the transport of IBA metabolites, including IAA. To test this hypothesis, we used a mass spectrometry-based method to quantify the transport of IBA in Arabidopsis hypocotyls by following the movement of [13C1]IBA and the [13C1]IAA derived from [13C1]IBA. We also assayed [13C6]IAA transport in a parallel control experiment. We found that the amount of transported [13C1]IBA was dramatically lower than [13C6]IAA, and the IBA transport was not reduced by the auxin transport inhibitor N-1-naphthylphthalamic acid. Significant amounts of the applied [13C1]IBA were converted to [13C1]IAA during transport, but [13C1]IBA transport was independent of IBA-to-IAA conversion. We also found that most of the [13C1]IBA was converted to ester-linked [13C1]IBA at the apical end of hypocotyls, and ester-linked [13C1]IBA was also found in the basal end at a level higher than free [13C1]IBA. In contrast, most of the [13C6]IAA was converted to amide-linked [13C6]IAA at the apical end of hypocotyls, but very little conjugated [13C6]IAA was found in the basal end. Our results demonstrate that the polar transport of IBA is much lower than IAA in Arabidopsis hypocotyls, and the transport mechanism is distinct from IAA transport. These experiments also establish a method for quantifying the movement of small molecules in plants using stable isotope labeling. PMID:22323783

  15. Transcriptome characterization by deep-RNA-sequencing underlies the mechanisms of butyrate-induced epigenomic regulation in bovine cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Volatile short-chain fatty acids (SCFAs, acetate, propionate, and butyrate), especially butyrate, alter cell differentiation, proliferation, motility, and in particular, induce cell cycle arrest and apoptosis through its histone deacetylase (HDAC) inhibition activity. Butyrate is a great inducer of ...

  16. Fragrance material review on phenethyl butyrate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of phenethyl butyrate when used as a fragrance ingredient is presented. Phenethyl butyrate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenethyl butyrate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, and skin sensitization data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

  17. Fragrance material review on benzyl butyrate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of benzyl butyrate when used as a fragrance ingredient is presented. Benzyl butyrate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl butyrate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, skin sensitization, toxicokinetics, and repeated dose data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

  18. Selected biochemical properties of polyphenol oxidase in butter lettuce leaves (Lactuca sativa L. var. capitata) elicited with dl-β-amino-n-butyric acid.

    PubMed

    Złotek, Urszula; Gawlik-Dziki, Urszula

    2015-02-01

    The study concentrated on changes in certain biochemical parameters of polyphenol oxidase (PPO) from lettuce leaves caused by dl-β-amino-n-butyric acid (BABA) elicitation. PPO from control plants demonstrated the highest affinity toward catechol, whereas PPO from BABA-elicited lettuce showed the highest affinity to 4-methylcatechol. The optimum temperature for enzymes from control plants was 35°C, whereas from plants elicited with 1mM BABA this was 25°C. PPO from plants elicited with BABA was also more sensitive to the tested inhibitors than PPO from control plants. l-Cysteine was the most effective inhibitor. Native gel stained for PPO activity in control samples showed two isoforms. However, in BABA-treated lettuce three bands visualising PPO activity were observed. The information obtained in this study will be valuable for the development of treatment technology and storage conditions to control undesirable browning reactions in elicited lettuce.

  19. Poly-(3-hexylthiophene)/[6,6]-phenyl-C61-butyric-acid-methyl-ester bilayer deposition by matrix-assisted pulsed laser evaporation for organic photovoltaic applications

    NASA Astrophysics Data System (ADS)

    Caricato, A. P.; Cesaria, M.; Gigli, G.; Loiudice, A.; Luches, A.; Martino, M.; Resta, V.; Rizzo, A.; Taurino, A.

    2012-02-01

    A poly-(3-hexylthiophene) (P3HT)/[6,6]-phenyl-C61-butyric-acid-methyl-ester (PCBM) bilayer structure has been realized by single step matrix-assisted pulsed laser evaporation (ss-MAPLE) technique using the same solvent for both the polymers under vacuum conditions. Our ss-MAPLE procedure allows the fabrication of polymeric multilayer device stacks, which are very difficult to realize with the conventional solvent assisted deposition methods. A proof of concept bilayer P3HT/PCBM solar cell based on ss-MAPLE deposition has been realized and characterized. This demonstration qualifies ss-MAPLE as a general and alternative technique for the implementation of polymeric materials in hetero-structure device technology.

  20. 4,4,4-trifluoro-3-(indole-3-)butyric acid promotes root elongation in Lactuca sativa independent of ethylene synthesis and pH

    NASA Technical Reports Server (NTRS)

    Zhang, Nenggang; Hasenstein, Karl H.

    2002-01-01

    We studied the mode of action of 4,4,4-trifluoro-3- (indole-3-) butyric acid (TFIBA), a recently described root growth stimulator, on primary root growth of Lactuca sativa L. seedlings. TFIBA (100 micromoles) promoted elongation of primary roots by 40% in 72 h but inhibited hypocotyl growth by 35%. TFIBA induced root growth was independent of pH. TFIBA did not affect ethylene production, but reduced the inhibitory effect of ethylene on root elongation. TFIBA promoted root growth even in the presence of the ethylene biosynthesis inhibitor L-alpha-(2-aminoethoxyvinyl)glycine. TFIBA and the ethylene-binding inhibitor silver thiosulphate (STS) had a similar effect on root elongation. The results indicate that TFIBA-stimulated root elongation was neither pH-dependent nor related to inhibition of ethylene synthesis, but was possibly related to ethylene action.

  1. Broadband gain in poly(3-hexylthiophene):phenyl-C{sub 61}-butyric-acid-methyl-ester photodetectors enabled by a semicontinuous gold interlayer

    SciTech Connect

    Melancon, Justin M.; Živanović, Sandra R.

    2014-10-20

    Substantial broadband photoconductive gain has been realized for organic, thin-film photodetectors with a poly(3-hexylthiophene):phenyl-C{sub 61}-butyric-acid-methyl-ester (P3HT:PCBM) active layer at low bias voltages. External quantum efficiencies upwards of 1500% were achieved when a semicontinuous gold layer was introduced at the anode interface. Significant gain was also observed in the sub-band gap, near infrared region where the external quantum efficiency approached 100% despite the lack of a sensitizer. The gain response was highly dependent on the thickness of the active layer of the photodetector with the best results achieved with the thinnest devices. The gain is the result of the injection of secondary electrons due to hole charge trapping at the semicontinuous gold layer.

  2. Selected biochemical properties of polyphenol oxidase in butter lettuce leaves (Lactuca sativa L. var. capitata) elicited with dl-β-amino-n-butyric acid.

    PubMed

    Złotek, Urszula; Gawlik-Dziki, Urszula

    2015-02-01

    The study concentrated on changes in certain biochemical parameters of polyphenol oxidase (PPO) from lettuce leaves caused by dl-β-amino-n-butyric acid (BABA) elicitation. PPO from control plants demonstrated the highest affinity toward catechol, whereas PPO from BABA-elicited lettuce showed the highest affinity to 4-methylcatechol. The optimum temperature for enzymes from control plants was 35°C, whereas from plants elicited with 1mM BABA this was 25°C. PPO from plants elicited with BABA was also more sensitive to the tested inhibitors than PPO from control plants. l-Cysteine was the most effective inhibitor. Native gel stained for PPO activity in control samples showed two isoforms. However, in BABA-treated lettuce three bands visualising PPO activity were observed. The information obtained in this study will be valuable for the development of treatment technology and storage conditions to control undesirable browning reactions in elicited lettuce. PMID:25172730

  3. Thin film transistors based on poly(3-hexylthiophene)/[6,6]-phenyl C61 butyric acid methyl ester hetero-junction for ammonia detection

    NASA Astrophysics Data System (ADS)

    Chen, Yuyan; Xie, Guangzhong; Xie, Tao; Liu, Yanni; Du, Hongfei; Su, Yuanjie; Jiang, Yadong

    2015-10-01

    Composite film and bilayer film based on poly(3-hexylthiophene) (P3HT)/[6,6]-phenyl C61 butyric acid methyl ester(PC61BM) were firstly utilized as active layers of OTFT sensor. By comparing with electrical and sensing properties of these different devices for ammonia (NH3) at room temperature, the device based on PC61BM/P3HT composite film exhibited the optimum characteristics. The recovery value of PC61BM/P3HT composite film reached 93.9% of its initial value at 20 ppm NH3 within 9 min, which was improved by 75.5% in comparison with the one based on pristine P3HT film. In addition, the sensing mechanisms of all sensors were studied as well.

  4. Graphene composite for improvement in the conversion efficiency of flexible poly 3-hexyl-thiophene:[6,6]-phenyl C71 butyric acid methyl ester polymer solar cells

    NASA Astrophysics Data System (ADS)

    Chauhan, A. K.; Gusain, Abhay; Jha, P.; Koiry, S. P.; Saxena, Vibha; Veerender, P.; Aswal, D. K.; Gupta, S. K.

    2014-03-01

    The solution of thin graphene-sheets obtained from a simple ultrasonic exfoliation process was found to chemically interact with [6,6]-phenyl C71 butyric acid methyl ester (PCBM) molecules. The thinner graphene-sheets have significantly altered the positions of highest occupied molecular orbital and lowest unoccupied molecular orbital of PCBM, which is beneficial for the enhancement of the open circuit voltage of the solar cells. Flexible bulk heterojunction solar cells fabricated using poly 3-hexylthiophene (P3HT):PCBM-graphene exhibited a power conversion efficiency of 2.51%, which is a ˜2-fold increase as compared to those fabricated using P3HT:PCBM. Inclusion of graphene-sheets not only improved the open-circuit voltage but also enhanced the short-circuit current density owing to an improved electron transport.

  5. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease in zebrafish.

    PubMed

    Sarath Babu, Nukala; Murthy, Ch Lakshmi N; Kakara, Sameera; Sharma, Rahul; Brahmendra Swamy, Cherukuvada V; Idris, Mohammed M

    2016-05-01

    Parkinson's disease (PD) is the most common age associated neurodegenerative disease, which has been extensively studied for its etiology and phenotype. PD has been widely studied in alternate model system such as rodents towards understanding the role of neurotoxin by inducing PD. This study is aimed to understand the biomechanism of PD in zebrafish model system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The phenotype and role of various genes and proteins for Parkinsonism were tested and evaluated in this study using behavior, molecular and proteomic approaches. Zebrafish PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed a significant level of decrease in the movement with erratic swimming pattern and increased freezing bouts. CHCHD2, EEF2B, LRRK2, PARK7, PARK2, POLG, SNCGB and SYNB genes were differentially regulated at the transcript level in PD zebrafish. Similarly a total of 73 proteins were recognized as differentially expressed in the nervous system of zebrafish due to Parkinsonism based on quantitative proteomics approach. Proteins such as NEFL, MUNC13-1, NAV2 and GAPVD1 were down regulated in the zebrafish brain for the PD phenotype, which were associated with the neurological pathways. This zebrafish based PD model can be used as a potential model system for screening prospective drug molecules for PD. PMID:26959078

  6. Impact of mash feeding versus pellets on propionic/butyric acid levels and on total load in the gastrointestinal tract of growing pigs.

    PubMed

    Longpré, J; Fairbrother, J M; Fravalo, P; Arsenault, J; LeBel, P; Laplante, B; Surprenant, C; Massé, D; Letellier, A

    2016-03-01

    Feed characteristics may influence the bacterial community composition and metabolic activities in the pig gastrointestinal tract, known to be associated with positive effects on the gut. Use of mash feed is associated with reduced excretion, but little is known of its effect on the population or of the mechanism of action. Our objectives were to assess the effect of feed texture combined with feed particle size on VFA profiles and levels, total count, and the presence of genes encoding virulence factors of pathogenic strains in the digestive tract along with their impact on pig performance of fattening pigs. Pigs ( = 840) on a commercial farm received mash or pellet diets of different particle sizes during the fattening period. Caecal and colon contents from 164 pigs were sampled at the slaughterhouse for enumeration of by quantitative PCR (qPCR) and for VFA quantification by capillary gas chromatography. The gene was used to enumerate total . Improved pig performances associated with pellet texture and a 500-μm size were observed. Caecal ( = 0.02) and colon ( < 0.01) propionic acid concentrations were lower for pigs receiving pellet rather than mash feed. Similarly, caecal ( = 0.01) and colon ( < 0.001) butyric acid concentrations were also lower for pigs receiving pellet rather than mash feed, as determined by capillary gas chromatography. Moreover, caecal ( = 0.03) and colon ( < 0.001) butyric acid concentrations were higher for pigs receiving a feed with a 1,250-μm particle size rather than a 500-μm particle size. On the other hand, total caecal and colon levels were higher for pigs receiving pellet feed than for those receiving mash feed. For total enumeration, caecal ( < 0.01) and colon ( < 0.01) gene copies were higher for pigs receiving pellet rather than mash feed. No effect of particle size on fatty acid concentrations or on numbers was observed. Virulence gene quantification revealed no trend. Taken together, results showed that mash feed is

  7. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pretreatment attenuates methamphetamine-induced dopamine toxicity.

    PubMed

    Kita, Taizo; Saraya, Tutomu; Konishi, Noboru; Matsunari, Yasunori; Shimada, Keiji; Nakamura, Mitsutoshi; O'Hara, Kiichi; Wagner, George C; Nakashima, Toshikatsu

    2003-02-01

    The effects of pretreatment with MPTP (1-methyl4-phenyl-1,2,3,6-tetrahydropyridine) on the acute and long-term effects of methamphetamine on striatal dopamine were evaluated in BALB/c mice. Four subcutaneous injections of a non-toxic dose of MPTP (8 mg/kg, at 2 hr intervals) were followed three days later by a toxic regimen of methamphetamine (four injections of 4 mg/kg, at 2 hr intervals) and mice were sacrificed immediately or three days later. Control mice received saline in place of the MPTP or methamphetamine and mice were observed for acute changes in body temperature, self-injurious behaviour, and striatal dopamine metabolites, or long-term changes in striatal dopamine levels, tyrosine hydroxylase immunoreactivity and glial fibrillary acidic protein. It was observed that pretreatment with MPTP protected mice against the acute increase in body temperature caused by the methamphetamine but, at the same time, delayed the occurrence of self-injurious behaviour following the repeated injections of methamphetamine. Likewise, pretreatment with MPTP attenuated the long-term depletion of striatal dopamine induced by the methamphetamine as well as the large increase in glial fibrillary acidic protein and the reduction in tyrosine hydroxylase immunoreactivity. The MPTP-treatment itself did not alter any of these neurotoxic markers. Finally, the acute decrease in 3,4-dihydroxyphenyacetic acid levels and increased ratio of 3-methoxytyramine/dopamine observed 60 min. after a single injection of methamphetamine (4 mg/kg) were also attenuated in MPTP-treated mice. These results are discussed in the context of the hypothesis that the low-dose treatment with MPTP may modify exchange diffusion across the striatal cell membrane thereby altering the acute and long-lasting effects of methamphetamine.

  8. High butyric acid amounts induce oxidative stress, alter calcium homeostasis, and cause neurite retraction in nerve growth factor-treated PC12 cells.

    PubMed

    Cueno, Marni E; Kamio, Noriaki; Seki, Keisuke; Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu

    2015-07-01

    Butyric acid (BA) is a common secondary metabolite by-product produced by oral pathogenic bacteria and is detected in high amounts in the gingival tissue of patients with periodontal disease. Previous works have demonstrated that BA can cause oxidative stress in various cell types; however, this was never explored using neuronal cells. Here, we exposed nerve growth factor (NGF)-treated PC1(2) cells to varying BA concentrations (0.5, 1.0, 5.0 mM). We measured total heme, H(2)O(2), catalase, and calcium levels through biochemical assays and visualized the neurite outgrowth after BA treatment. Similarly, we determined the effects of other common periodontal short-chain fatty acids (SCFAs) on neurite outgrowth for comparison. We found that high (1.0 and 5.0 mM) BA concentrations induced oxidative stress and altered calcium homeostasis, whereas low (0.5 mM) BA concentration had no significant effect. Moreover, compared to other SCFAs, we established that only BA was able to induce neurite retraction.

  9. Synthesis, molecular modeling and biological evaluation of novel 2-allyl amino 4-methyl sulfanyl butyric acid as α-amylase and α-glucosidase inhibitor

    NASA Astrophysics Data System (ADS)

    Balan, Kannan; Perumal, Perumal; Sundarabaalaji, Narayanan; Palvannan, Thayumanavan

    2015-02-01

    In the present study 2-allyl amino 4-methyl sulfanyl butyric acid (AMSB) was synthesized in good yield. AMSB was characterized by Fourier transforms infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR) (1H and 13C) and Liquid chromatography mass spectrometry (LCMS). The radical scavenging activity and reducing power assay of AMSB was assessed using 1-1-diphenyl 2-picryl hydrazyl (DPPH), 2,2‧-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power assay (FRAP) and was found to be 44.1, 34.71 and 41.7 μg/ml respectively. The compound showed effective inhibition against α-amylase and α-glucosidase. AMSB was identified to be a reversible mixed noncompetitive inhibitor of α-amylase and α-glucosidase. The molecular docking study was carried out to evaluate the specific groove binding properties and affords valuable information of AMSB binding mode in the active site of α-glucosidase the study may lead to the which leads to the rational design of new class of antidiabetic drugs targeting α-glucosidase based on AMSB in near future.

  10. Perturbation of Indole-3-Butyric Acid Homeostasis by the UDP-Glucosyltransferase UGT74E2 Modulates Arabidopsis Architecture and Water Stress Tolerance[W

    PubMed Central

    Tognetti, Vanesa B.; Van Aken, Olivier; Morreel, Kris; Vandenbroucke, Korneel; van de Cotte, Brigitte; De Clercq, Inge; Chiwocha, Sheila; Fenske, Ricarda; Prinsen, Els; Boerjan, Wout; Genty, Bernard; Stubbs, Keith A.; Inzé, Dirk; Van Breusegem, Frank

    2010-01-01

    Reactive oxygen species and redox signaling undergo synergistic and antagonistic interactions with phytohormones to regulate protective responses of plants against biotic and abiotic stresses. However, molecular insight into the nature of this crosstalk remains scarce. We demonstrate that the hydrogen peroxide–responsive UDP-glucosyltransferase UGT74E2 of Arabidopsis thaliana is involved in the modulation of plant architecture and water stress response through its activity toward the auxin indole-3-butyric acid (IBA). Biochemical characterization of recombinant UGT74E2 demonstrated that it strongly favors IBA as a substrate. Assessment of indole-3-acetic acid (IAA), IBA, and their conjugates in transgenic plants ectopically expressing UGT74E2 indicated that the catalytic specificity was maintained in planta. In these transgenic plants, not only were IBA-Glc concentrations increased, but also free IBA levels were elevated and the conjugated IAA pattern was modified. This perturbed IBA and IAA homeostasis was associated with architectural changes, including increased shoot branching and altered rosette shape, and resulted in significantly improved survival during drought and salt stress treatments. Hence, our results reveal that IBA and IBA-Glc are important regulators of morphological and physiological stress adaptation mechanisms and provide molecular evidence for the interplay between hydrogen peroxide and auxin homeostasis through the action of an IBA UGT. PMID:20798329

  11. Characterization of antiproliferative potential and biological targets of a copper compound containing 4'-phenyl terpyridine.

    PubMed

    Mendo, Ana Soraia; Figueiredo, Sara; Roma-Rodrigues, Catarina; Videira, Paula A; Ma, Zhen; Diniz, Mário; Larguinho, Miguel; Costa, Pedro M; Lima, João C; Pombeiro, Armando J L; Baptista, Pedro V; Fernandes, Alexandra R

    2015-09-01

    Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

  12. Comparative studies of the release of 1-methyl-4-phenyl-pyridinium species (MPP/sup +/) from rat and mouse brain synaptosomes

    SciTech Connect

    Abell, C.W.; Shen, R.S.; Gessner, W.; Brossi, A.

    1986-05-01

    The parkinsonian producing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), selectively destroys nigrostriatal neurons in humans and primates and depletes striatal dopamine in mice but not in rats. MPTP is oxidized by monoamine oxidase B (MAO B) in glial cells and/or serotonergic neurons to form a 1-methyl-4-phenyl pyridinium species (MPP/sup +/), which accumulates in dopaminergic neurons in the substantia nigra and is thought to cause cell destruction. The authors compared the spontaneous release of MPP/sup +/ in striatal and hypothalamic synaptosomes prepared from male Sprague-Dawley rats and male C57BL mice. Synaptosomes were preloaded with (/sup 3/H)-MPP/sup +/ (final concentration of 0.8 ..mu..M, 265 ..mu..Ci/..mu..mol) in physiological Tris containing 0.02% ascorbic acid for 7.5 min at 37/sup 0/C. Hypothalamic, but not striatal, (/sup 3/H)-MPP/sup +/ release from rat and mouse brain was directly proportional to its initial loading concentration (0.008-0.8 ..mu..M). Striatal synaptosomes from rats and mice gave identical rates of spontaneous release of (/sup 3/H)- MPP/sup +/, but the rate of release of hypothalamus is 60% faster in rats than in mice. (/sup 3/H)-MPP/sup +/ release from rat and mouse striatum, but not hypothalamus, was stimulated by monoamines and MAO substrates and inhibitors, a finding that suggests a role for MAO in the intraneuronal transport of MPP/sup +/.

  13. Acarbose enhances human colonic butyrate production.

    PubMed

    Weaver, G A; Tangel, C T; Krause, J A; Parfitt, M M; Jenkins, P L; Rader, J M; Lewis, B A; Miller, T L; Wolin, M J

    1997-05-01

    Earlier studies suggest that butyrate has colonic differentiating and nutritional effects and that acarbose increases butyrate production. To determine the effects of acarbose on colonic fermentation, subjects were given 50-200 mg acarbose or placebo (cornstarch), three times per day, with meals in a double-blind crossover study. Fecal concentrations of starch and starch-fermenting bacteria were measured and fecal fermentation products determined after incubation of fecal suspensions with and without added substrate for 6 and 24 h. Substrate additions were cornstarch, cornstarch plus acarbose and potato starch. Dietary starch consumption was similar during acarbose and placebo treatment periods, but fecal starch concentrations were found to be significantly greater with acarbose treatment. Ratios of starch-fermenting to total anaerobic bacteria were also significantly greater with acarbose treatment. Butyrate in feces, measured either as concentration or as percentage of total short-chain fatty acids, was significantly greater with acarbose treatment than with placebo treatment. Butyrate ranged from 22.3 to 27.5 mol/100 mol for the 50-200 mg, three times per day doses of acarbose compared with 18.3-19.3 mol/100 mol for the comparable placebo periods. The propionate in fecal total short-chain fatty acids was significantly less with acarbose treatment (10.7-12.1 mol/100 mol) than with placebo treatment (13.7-14.2 mol/100 mol). Butyrate production was significantly greater in fermentations in samples collected during acarbose treatment, whereas production of acetate and propionate was significantly less. Fermentation decreased when acarbose was added directly to cornstarch fermentations. Acarbose effectively augmented colonic butyrate production by several mechanisms; it reduced starch absorption, expanded concentrations of starch-fermenting and butyrate-producing bacteria and inhibited starch use by acetate- and propionate-producing bacteria.

  14. Effect of Exogenous Indole-3-Acetic Acid and Indole-3-Butyric Acid on Internal Levels of the Respective Auxins and Their Conjugation with Aspartic Acid during Adventitious Root Formation in Pea Cuttings.

    PubMed

    Nordström, A C; Jacobs, F A; Eliasson, L

    1991-07-01

    The influence of exogenous indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) on the internal levels of these auxins was studied during the first 4 days of adventitious root formation in cuttings of Pisum sativum L. The quantitations were done by high performance liquid chromatography with spectrofluorometric detection. IBA, identified by combined gas chromatography-mass spectrometry (GC-MS), was found to naturally occur in this plant material. The root inducing ability of exogenous IBA was superior to that of IAA. The IAA level in the tissue increased considerably on the first day after application of IAA, but rapidly decreased again, returning to a level twice the control by day 3. The predominant metabolic route was conjugation with aspartic acid, as reflected by the increase in the level of indole-3-acetylaspartic acid. The IBA treatment resulted in increases in the levels of IBA, IAA, and indole-3-acetylaspartic acid. The IAA content rapidly returned to control levels, whereas the IBA level remained high throughout the experimental period. High amounts of indole-3-butyrylaspartic acid were found in the tissue after feeding with IBA. The identity of the conjugate was confirmed by (1)H-nuclear magnetic resonance and GC-MS. IBA was much more stable in solution than IAA. No IAA was detected after 48 hours, whereas 70% IBA was still recovered after this time. The relatively higher root inducing ability of IBA is ascribed to the fact that its level remained elevated longer than that of IAA, even though IBA was metabolized in the tissue. Adventitious root formation is discussed on the basis of these findings. PMID:16668265

  15. Identification of genes involved in indole-3-butyric acid-induced adventitious root formation in nodal cuttings of Camellia sinensis (L.) by suppression subtractive hybridization.

    PubMed

    Wei, Kang; Wang, Liyuan; Cheng, Hao; Zhang, Chengcai; Ma, Chunlei; Zhang, Liqun; Gong, Wuyun; Wu, Liyun

    2013-02-10

    The plant hormone auxin plays a key role in adventitious rooting. To increase our understanding of genes involved in adventitious root formation, we identified transcripts differentially expressed in single nodal cuttings of Camellia sinensis treated with or without indole-3-butyric acid (IBA) by suppressive subtractive hybridization (SSH). A total of 77 differentially expressed transcripts, including 70 up-regulated and 7 down-regulated sequences, were identified in tea cuttings under IBA treatment. Seven candidate transcripts were selected and analyzed for their response to IBA, and IAA by real time RT-PCR. All these transcripts were up regulated by at least two folds one day after IBA treatment. Meanwhile, IAA showed less positive effects on the expression of candidate transcripts. The full-length cDNA of a F-box/kelch gene was also isolated and found to be similar to a group of At1g23390 like genes. These unigenes provided a new source for mining genes related to adventitious root formation, which facilitate our understanding of relative fundamental metabolism.

  16. Identification of genes involved in indole-3-butyric acid-induced adventitious root formation in nodal cuttings of Camellia sinensis (L.) by suppression subtractive hybridization.

    PubMed

    Wei, Kang; Wang, Liyuan; Cheng, Hao; Zhang, Chengcai; Ma, Chunlei; Zhang, Liqun; Gong, Wuyun; Wu, Liyun

    2013-02-10

    The plant hormone auxin plays a key role in adventitious rooting. To increase our understanding of genes involved in adventitious root formation, we identified transcripts differentially expressed in single nodal cuttings of Camellia sinensis treated with or without indole-3-butyric acid (IBA) by suppressive subtractive hybridization (SSH). A total of 77 differentially expressed transcripts, including 70 up-regulated and 7 down-regulated sequences, were identified in tea cuttings under IBA treatment. Seven candidate transcripts were selected and analyzed for their response to IBA, and IAA by real time RT-PCR. All these transcripts were up regulated by at least two folds one day after IBA treatment. Meanwhile, IAA showed less positive effects on the expression of candidate transcripts. The full-length cDNA of a F-box/kelch gene was also isolated and found to be similar to a group of At1g23390 like genes. These unigenes provided a new source for mining genes related to adventitious root formation, which facilitate our understanding of relative fundamental metabolism. PMID:23201417

  17. Influence of indole-butyric acid and electro-pulse on in vitro rooting and development of olive (Olea europea L.) microshoots.

    PubMed

    Padilla, Isabel Maria Gonzalez; Vidoy, I; Encina, C L

    2009-09-01

    The effects of indole-butyric acid (IBA) and electro-pulses on rooting and shoot growth were studied in vitro, using olive shoot cultures. Tested shoots were obtained from seedlings belonging to three Spanish cultivars, 'Arbequina', 'Manzanilla de Sevilla' and 'Gordal Sevillana', which have easy-, medium- and difficult-to-root rooting abilities, respectively. The standard two-step rooting method (SRM), consisting of root induction in olive rooting medium supplemented with 0, 0.1 or 1 mg/l IBA followed by root elongation in the same rooting medium without IBA, was compared with a novel one-step method consisting of shoot electro-pulses of 250, 1,250 or 2,500 V in a solution of IBA (0, 0.1 or 1 mg/l) and direct transferral to root elongation medium. The rooting percentage of the seedling-derived shoots obtained with the SRM was 76% for 'Arbequina' and 'Gordal Sevillana' cultivars and 100% for 'Manzanilla de Sevilla' cultivar, whereas with the electro-pulse method, the rooting percentages were 68, 64 and 88%, respectively. IBA dipping without pulse produced 0% rooting in 'Arbequina' seedling-derived shoots. The electroporation in IBA not only had an effect on shoot rooting but also on shoot growth and development, with longer shoots and higher axillary shoot sprouting and growth after some of the treatments. These effects were cultivar-dependent. The electro-pulse per se could explain some of these effects on shoot development. PMID:19655148

  18. Traceable atomic force microscopy of high-quality solvent-free crystals of [6,6]-phenyl-C61-butyric acid methyl ester

    NASA Astrophysics Data System (ADS)

    Lazzerini, Giovanni Mattia; Paternò, Giuseppe Maria; Tregnago, Giulia; Treat, Neil; Stingelin, Natalie; Yacoot, Andrew; Cacialli, Franco

    2016-02-01

    We report high-resolution, traceable atomic force microscopy measurements of high-quality, solvent-free single crystals of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). These were grown by drop-casting PCBM solutions onto the spectrosil substrates and by removing the residual solvent in a vacuum. A home-built atomic force microscope featuring a plane mirror differential optical interferometer, fiber-fed from a frequency-stabilized laser (emitting at 632.8 nm), was used to measure the crystals' height. The optical interferometer together with the stabilized laser provides traceability (via the laser wavelength) of the vertical measurements made with the atomic force microscope. We find that the crystals can conform to the surface topography, thanks to their height being significantly smaller compared to their lateral dimensions (namely, heights between about 50 nm and 140 nm, for the crystals analysed, vs. several tens of microns lateral dimensions). The vast majority of the crystals are flat, but an isolated, non-flat crystal provides insights into the growth mechanism and allows identification of "molecular terraces" whose height corresponds to one of the lattice constants of the single PCBM crystal (1.4 nm) as measured with X-ray diffraction.

  19. Enteric Bacterial Metabolites Propionic and Butyric Acid Modulate Gene Expression, Including CREB-Dependent Catecholaminergic Neurotransmission, in PC12 Cells - Possible Relevance to Autism Spectrum Disorders

    PubMed Central

    Nankova, Bistra B.; Agarwal, Raj; MacFabe, Derrick F.; La Gamma, Edmund F.

    2014-01-01

    Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA) like propionic (PPA), and butyric acid (BA), which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD). Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal) or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH) mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s) was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals such as

  20. Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain

    SciTech Connect

    Riachi, N.J.; LaManna, J.C.; Harik, S.I.

    1989-06-01

    We studied blood-to-brain entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+) and butanol in anesthetized rats using the indicator-fractionation method with right atrial bolus injection. Minimal amounts of MPP+, which has low octanol/water partition coefficient, crossed the blood-brain barrier. MPTP and butanol, both of which have high octanol/water partition coefficients, were almost completely extracted by all regions of the brain on the first pass. The main difference between the MPTP and butanol tracers is that butanol rapidly left the brain with an exponential rate constant of 1.24 min-1, whereas MPTP was avidly retained by the brain with a washout rate constant of 0.10 min-1 (mean values for the four brain regions that we studied). Early retention of MPTP by the brain was not due to its rapid metabolism by monoamine oxidase because pargyline pretreatment did not affect this rate constant. However, 30 min after (/sup 3/H)MPTP injection, brain retention of the 3H tracer was reduced significantly by pargyline treatment, and the ratio of brain MPTP/MPP+ was increased markedly.

  1. O-Ethyl S-{(S)-1-oxo-1-[(R)-2-oxo-4-phenyl-oxazolidin-3-yl]propan-2-yl} carbonodi-thio-ate.

    PubMed

    García-Merinos, J Pablo; López-Ruiz, Heraclio; López, Yliana; Rojas-Lima, Susana

    2014-05-01

    In the title compound, C15H17NO4S2, synthesized by addition of O-ethylxanthic acid potassium salt to a diastereomeric mixture of (4R)-3-(2-chloro-propano-yl)-4-phenyl-oxazolidin-2-one, the oxazolidinone ring has a twist conformation on the C-C bond. The phenyl ring is inclined to the mean plane of the oxazolidinone ring by 76.4 (3)°. In the chain the methine H atom is involved in a C-H⋯S and a C-H⋯O intra-molecular inter-action. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming chains along [001]. The S configuration at the C atom to which the xanthate group is attached was determined by comparison to the known R configuration of the C atom to which the phenyl group is attached.

  2. Quantification of transcriptome responses of the rumen epithelium to butyrate infusion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Short-chain fatty acids (SCFAs), such as butyrate, produced by gut microorganisms play an important role in energy metabolism and physiology in ruminants as well as in human health. Butyrate is a preferred substrate in the rumen epithelium where approximately 90% of butyrate is metabolized. Additi...

  3. Isolation of Functional Components β-Glucan and γ-Amino Butyric Acid from Raw and Germinated Barnyard Millet (Echinochloa frumentaceae) and their Characterization.

    PubMed

    Sharma, Seema; Saxena, Dharmesh C; Riar, Charanjit S

    2016-09-01

    The study was carried out to analyze the characteristics of two functional constituents' viz. γ-amino butyric acid (GABA) and β-glucan extracted from raw and germination barnyard millet (var. PRJ-1). A significant (P ≤ 0.05) effect of germination (sprouting) was observed in yield, chemical composition, functional, rheological and antioxidant properties of β-glucan and GABA. The yield of GABA extract was 12.34 % and the content increased from 6.37 mg/100 g in raw to 35.70 mg/100 g in germinated sample. The DPPH, total antioxidant and hydrogen peroxide scavenging activities of GABA extract increased after germination from 45.34 to 65.34 %, 15.3 to 33.3 millimole/g and 38.4 to 64.7 millimole/g, respectively. The yield of β-glucan extract of raw and germinated flour was 6.05 and 5.01 % whereas the β-glucan contents were 83.30 and 79.64 %, respectively. The functional properties of β-glucan i.e., swelling power, water binding capacity and DPPH scavenging activity increased from 1.45 to 1.76 g/g, 2.13 to 2.32 g/g and 44.39 to 57.42 %, respectively, after germination. Similarly there was an increase in the storage modulus after germination process which attributes a better viscoelastic capacity of β-glucan at low frequencies. The results exploit that the β-glucan and GABA might promise a polymeric incipient to be implemented as food additives with variable functional and structural characteristics. PMID:27245684

  4. Micron-sized [6,6]-phenyl C61 butyric acid methyl ester crystals grown by dip coating in solvent vapour atmosphere: interfaces for organic photovoltaics.

    PubMed

    Dabirian, R; Feng, X; Ortolani, L; Liscio, A; Morandi, V; Müllen, K; Samorì, P; Palermo, V

    2010-05-01

    We have devised a novel dip coating procedure to form highly crystalline and macroscopic pi-conjugated architectures on solid surfaces. We have employed this approach to a technologically relevant system, i.e. the electron-acceptor [6,6]-phenyl C61 butyric acid methyl ester molecule (PCBM), which is the most commonly used electron-acceptor in organic photovoltaics. Highly ordered, hexagonal shaped crystals of PCBM, ranging between 1 to 80 mum in diameter and from 20 to 500 nm in thickness, have been grown by dip coating the substrates into a solution containing the fullerene derivative. These crystals have been found to possess a monocrystalline character, to exhibit a hexagonal symmetry and to display micron sized molecularly flat terraces. The crystals have been prepared on a wide variety of surfaces such as SiO(x), silanized SiO(x), Au, graphite, amorphous carbon-copper grids and ITO. Their multiscale characterization has been performed by atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM), X-ray diffraction (XRD), optical microscopy, scanning and transmission electron microscopy (SEM, TEM).To test the stability of these electron accepting PCBM crystals, they have been coated with a complementary, electron donor hexa-peri-hexabenzocoronene (HBC) derivative by solution processing from acetone and chloroform-methanol blends. The HBC self assembles in a well-defined network of nanofibers on the PCBM substrate, and the two materials can be clearly resolved by AFM and KPFM.Due to its structural precision on the macroscopic scale, the PCBM crystals appear as ideal interface to perform fundamental photophysical studies in electron-acceptor and -donor blends, as well as workbench for unravelling the architecture vs. function relationship in organic solar cells prototypes.

  5. Ectopic expression of UGT75D1, a glycosyltransferase preferring indole-3-butyric acid, modulates cotyledon development and stress tolerance in seed germination of Arabidopsis thaliana.

    PubMed

    Zhang, Gui-Zhi; Jin, Shang-Hui; Jiang, Xiao-Yi; Dong, Rui-Rui; Li, Pan; Li, Yan-Jie; Hou, Bing-Kai

    2016-01-01

    The formation of auxin glucose conjugate is proposed to be one of the molecular modifications controlling auxin homeostasis. However, the involved mechanisms and relevant physiological significances are largely unknown or poorly understood. In this study, Arabidopsis UGT75D1 was at the first time identified to be an indole-3-butyric acid (IBA) preferring glycosyltransferase. Assessment of enzyme activity and IBA conjugates in transgenic plants ectopically expressing UGT75D1 indicated that the UGT75D1 catalytic specificity was maintained in planta. It was found that the expression pattern of UGT75D1 was specific in germinating seeds. Consistently, we found that transgenic seedlings with over-produced UGT75D1 exhibited smaller cotyledons and cotyledon epidermal cells than the wild type. In addition, UGT75D1 was found to be up-regulated under mannitol, salt and ABA treatments and the over-expression lines were tolerant to osmotic and salt stresses during germination, resulting in an increased germination rate. Quantitative RT-PCR analysis revealed that the mRNA levels of ABA INSENSITIVE 3 (ABI3) and ABI5 gene in ABA signaling were substantially down-regulated in the transgenic lines under stress treatments. Interestingly, AUXIN RESPONSE FACTOR 16 (ARF16) gene of transgenic lines was also dramatically down-regulated under the same stress conditions. Since ARF16 functions as an activator of ABI3 transcription, we supposed that UGT75D1 might play a role in stress tolerance during germination through modulating ARF16-ABI3 signaling. Taken together, our work indicated that, serving as the IBA preferring glycosyltransferase but distinct from other auxin glycosyltransferases identified so far, UGT75D1 might be a very important player mediating a crosstalk between cotyledon development and stress tolerance of germination at the early stage of plant growth.

  6. Ectopic expression of UGT75D1, a glycosyltransferase preferring indole-3-butyric acid, modulates cotyledon development and stress tolerance in seed germination of Arabidopsis thaliana.

    PubMed

    Zhang, Gui-Zhi; Jin, Shang-Hui; Jiang, Xiao-Yi; Dong, Rui-Rui; Li, Pan; Li, Yan-Jie; Hou, Bing-Kai

    2016-01-01

    The formation of auxin glucose conjugate is proposed to be one of the molecular modifications controlling auxin homeostasis. However, the involved mechanisms and relevant physiological significances are largely unknown or poorly understood. In this study, Arabidopsis UGT75D1 was at the first time identified to be an indole-3-butyric acid (IBA) preferring glycosyltransferase. Assessment of enzyme activity and IBA conjugates in transgenic plants ectopically expressing UGT75D1 indicated that the UGT75D1 catalytic specificity was maintained in planta. It was found that the expression pattern of UGT75D1 was specific in germinating seeds. Consistently, we found that transgenic seedlings with over-produced UGT75D1 exhibited smaller cotyledons and cotyledon epidermal cells than the wild type. In addition, UGT75D1 was found to be up-regulated under mannitol, salt and ABA treatments and the over-expression lines were tolerant to osmotic and salt stresses during germination, resulting in an increased germination rate. Quantitative RT-PCR analysis revealed that the mRNA levels of ABA INSENSITIVE 3 (ABI3) and ABI5 gene in ABA signaling were substantially down-regulated in the transgenic lines under stress treatments. Interestingly, AUXIN RESPONSE FACTOR 16 (ARF16) gene of transgenic lines was also dramatically down-regulated under the same stress conditions. Since ARF16 functions as an activator of ABI3 transcription, we supposed that UGT75D1 might play a role in stress tolerance during germination through modulating ARF16-ABI3 signaling. Taken together, our work indicated that, serving as the IBA preferring glycosyltransferase but distinct from other auxin glycosyltransferases identified so far, UGT75D1 might be a very important player mediating a crosstalk between cotyledon development and stress tolerance of germination at the early stage of plant growth. PMID:26496910

  7. Seed priming with BABA (β-amino butyric acid): a cost-effective method of abiotic stress tolerance in Vigna radiata (L.) Wilczek.

    PubMed

    Jisha, K C; Puthur, Jos T

    2016-03-01

    The effects of β-amino butyric acid (BABA) on abiotic stress tolerance potential of three Vigna radiata varieties were studied. The reduction in the growth of seedlings subjected to NaCl/polyethylene glycol (PEG) stress is alleviated by BABA seed priming, which also enhanced photosynthetic pigment content and photosynthetic and mitochondrial activities, and also modified the chlorophyll a fluorescence-related parameters. Moreover, BABA seed priming reduced malondialdehyde content in the seedlings and enhanced the accumulation of proline, total protein, total carbohydrate, nitrate reductase activity, and activities of antioxidant enzymes like guaiacol peroxidase and superoxide dismutase. Most of these positive features of BABA priming were predominantly exhibited when the plants were encountered with stress (NaCl/PEG). The BABA content in the BABA-treated green gram seeds and seedlings was also detected and quantified with high-performance thin layer chromatography (HPTLC), and it revealed that the priming effect of BABA initiated in seeds and further gets carried over to the seedlings. It was concluded that BABA seed priming improved the drought and salinity stress tolerance potential of all the three green gram varieties, and it was evident in the NaCl-tolerant variety Pusa Vishal as compared to Pusa Ratna (abiotic stress sensitive) and Pusa 9531(drought tolerant). Dual mode in cost effectiveness of BABA priming is evident from: (1) the positive features of priming are being exhibited more during the exposure of plants to stress, and (2) priming of seedlings can be carried out by BABA application to seeds at very low concentration and volume.

  8. Accumulation, selection and covariation of amino acids in sieve tube sap of tansy (Tanacetum vulgare) and castor bean (Ricinus communis): evidence for the function of a basic amino acid transporter and the absence of a γ-amino butyric acid transporter.

    PubMed

    Bauer, Susanne N; Nowak, Heike; Keller, Frank; Kallarackal, Jose; Hajirezaei, Mohamad-Reza; Komor, Ewald

    2014-09-01

    Sieve tube sap was obtained from Tanacetum by aphid stylectomy and from Ricinus after apical bud decapitation. The amino acids in sieve tube sap were analyzed and compared with those from leaves. Arginine and lysine accumulated in the sieve tube sap of Tanacetum more than 10-fold compared to the leaf extracts and they were, together with asparagine and serine, preferably selected into the sieve tube sap, whereas glycine, methionine/tryptophan and γ-amino butyric acid were partially or completely excluded. The two basic amino acids also showed a close covariation in sieve tube sap. The acidic amino acids also grouped together, but antagonistic to the other amino acids. The accumulation ratios between sieve tube sap and leaf extracts were smaller in Ricinus than in Tanacetum. Arginine, histidine, lysine and glutamine were enriched and preferentially loaded into the phloem, together with isoleucine and valine. In contrast, glycine and methionine/tryptophan were partially and γ-amino butyric acid almost completely excluded from sieve tube sap. The covariation analysis grouped arginine together with several neutral amino acids. The acidic amino acids were loaded under competition with neutral amino acids. It is concluded from comparison with the substrate specificities of already characterized plant amino acid transporters, that an AtCAT1-like transporter functions in phloem loading of basic amino acids, whereas a transporter like AtGAT1 is absent in phloem. Although Tanacetum and Ricinus have different minor vein architecture, their phloem loading specificities for amino acids are relatively similar.

  9. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibits proton motive force in energized liver mitochondria

    SciTech Connect

    Singh, Y.; Bhatnagar, R.; Sidhu, G.S.; Batra, J.K.; Krishna, G. )

    1989-05-15

    It is known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like disease in primates and humans, depletes hepatocytes of ATP and subsequently causes cell death. Incubation of rat liver mitochondria with MPTP and 1-methyl-4-phenyl pyridinium ion (MPP+) significantly inhibited incorporation of {sup 32}Pi into ATP. MPTP and MPP+ inhibited the development of membrane potential and pH gradient in energized rat liver mitochondria, suggesting that reduction of the proton motive force may have reduced ATP synthesis. Since deprenyl, an inhibitor of monoamine oxidase, prevented the formation of MPP+ and inhibited the decrease in membrane potential caused by MPTP, but not that caused by MPP+, these effects of MPTP, as well as cell death, probably were mediated by MPP+. This mechanism may play a role in the specific loss of dopaminergic neurons resulting in MPTP-induced Parkinson's disease.

  10. TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse cortical neurons

    PubMed Central

    Zhang, Qi-Shan; Liao, Yuan-Gao; Ji, Zhong; Gu, Yong; Jiang, Hai-Shan; Xie, Zuo-Shan; Pan, Su-Yue; Hu, Ya-Fang

    2016-01-01

    The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups. MPP+ was then applied to all groups, with the exception of the control group, and neurons were cultured for an additional 24 h. Neuron viability was evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism underlying the protective effects of TFP5, the expression levels of p35, p25 and phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell membranes and distribute around the nucleus. CCK8 assay showed that neuronal apoptosis was dependent on MPP+ concentration and exposure time. Cell viability decreased significantly in the model group compared with the control group (55±7 vs. 100±0%; P<0.01), and increased significantly in the TFP5 group compared with the model group (98±2 vs. 55±5%; P<0.01) and Scb group (98±2 vs. 54±4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+-induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical neurons, possibly through inhibiting the MPP+-induced formation and elevated kinase activity of a cyclin-dependent kinase 5/p25 complex.

  11. Synthesis, characterization, thermal properties and antiproliferative potential of copper(II) 4'-phenyl-terpyridine compounds.

    PubMed

    Ma, Zhen; Zhang, Bian; Guedes da Silva, M Fátima C; Silva, Joana; Mendo, Ana Soraia; Baptista, Pedro Viana; Fernandes, Alexandra R; Pombeiro, Armando J L

    2016-03-28

    Reactions between 4'-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o-OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]4·MeOH (·MeOH) and [Cu(p-OCOC6H4OH)2L]5·2H2O (·2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2-5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π···π stacking interactions could also be found in 2-5 (in the 3.569-3.651 Å range and involving solely the pyridyl rings). Medium-strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.

  12. TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse cortical neurons

    PubMed Central

    Zhang, Qi-Shan; Liao, Yuan-Gao; Ji, Zhong; Gu, Yong; Jiang, Hai-Shan; Xie, Zuo-Shan; Pan, Su-Yue; Hu, Ya-Fang

    2016-01-01

    The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups. MPP+ was then applied to all groups, with the exception of the control group, and neurons were cultured for an additional 24 h. Neuron viability was evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism underlying the protective effects of TFP5, the expression levels of p35, p25 and phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell membranes and distribute around the nucleus. CCK8 assay showed that neuronal apoptosis was dependent on MPP+ concentration and exposure time. Cell viability decreased significantly in the model group compared with the control group (55±7 vs. 100±0%; P<0.01), and increased significantly in the TFP5 group compared with the model group (98±2 vs. 55±5%; P<0.01) and Scb group (98±2 vs. 54±4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+-induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical neurons, possibly through inhibiting the MPP+-induced formation and elevated kinase activity of a cyclin-dependent kinase 5/p25 complex. PMID:27698762

  13. Butyrate increases IL-23 production by stimulated dendritic cells.

    PubMed

    Berndt, Bradford E; Zhang, Min; Owyang, Stephanie Y; Cole, Tyler S; Wang, Teresa W; Luther, Jay; Veniaminova, Natalia A; Merchant, Juanita L; Chen, Chun-Chia; Huffnagle, Gary B; Kao, John Y

    2012-12-15

    The gut microbiota is essential for the maintenance of intestinal immune homeostasis and is responsible for breaking down dietary fiber into short-chain fatty acids (SCFAs). Butyrate, the most abundant bioactive SCFA in the gut, is a histone deacetylase inhibitor (HDACi), a class of drug that has potent immunomodulatory properties. This characteristic of butyrate, along with our previous discovery that conventional dendritic cells (DCs) are required for the development of experimental colitis, led us to speculate that butyrate may modulate DC function to regulate gut mucosal homeostasis. We found that butyrate, in addition to suppressing LPS-induced bone marrow-derived DC maturation and inhibiting DC IL-12 production, significantly induced IL-23 expression. The upregulation of mRNA subunit IL-23p19 at the pretranslational level was consistent with the role of HDACi on the epigenetic modification of gene expression. Furthermore, the mechanism of IL-23p19 upregulation was independent of Stat3 and ZBP89. Coculture of splenocytes with LPS-stimulated DCs pretreated with or without butyrate was performed and showed a significant induction of IL-17 and IL-10. We demonstrated further the effect of butyrate in vivo using dextran sulfate sodium (DSS)-induced colitis and found that the addition of butyrate in the drinking water of mice worsened DSS-colitis. This is in contrast to the daily intraperitoneal butyrate injection of DSS-treated mice, which mildly improved disease severity. Our study highlights a novel effect of butyrate in upregulating IL-23 production of activated DCs and demonstrates a difference in the host response to the oral vs. systemic route of butyrate administration.

  14. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

    PubMed

    Vieira, Erica L M; Leonel, Alda J; Sad, Alexandre P; Beltrão, Nathália R M; Costa, Thaís F; Ferreira, Talita M R; Gomes-Santos, Ana C; Faria, Ana M C; Peluzio, Maria C G; Cara, Denise C; Alvarez-Leite, Jacqueline I

    2012-05-01

    Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

  15. Barley malt increases hindgut and portal butyric acid, modulates gene expression of gut tight junction proteins and Toll-like receptors in rats fed high-fat diets, but high advanced glycation end-products partially attenuate the effects.

    PubMed

    Zhong, Yadong; Teixeira, Cristina; Marungruang, Nittaya; Sae-Lim, Watina; Tareke, Eden; Andersson, Roger; Fåk, Frida; Nyman, Margareta

    2015-09-01

    Barley malt, a product of controlled germination, has been shown to produce high levels of butyric acid in the cecum and portal serum of rats and may therefore have anti-inflammatory effects. The aim of the study was to investigate how four barley malts, caramelized and colored malts, 50-malt and 350-malt, differing in functional characteristics concerning beta-glucan content and color, affect short-chain fatty acids (SCFA), barrier function and inflammation in the hindgut of rats fed high-fat diets. Male Wistar rats were given malt-supplemented high-fat diets for four weeks. Low and high-fat diets containing microcrystalline cellulose were incorporated as controls. All diets contained 70 g kg(-1) dietary fiber. The malt-fed groups were found to have had induced higher amounts of butyric and propionic acids in the hindgut and portal serum compared with controls, while cecal succinic acid only increased to a small extent. Fat increased the mRNA expression of tight junction proteins and Toll-like receptors (TLR) in the small intestine and distal colon of the rats, as well as the concentration of some amino acids in the portal plasma, but malt seemed to counteract these adverse effects to some extent. However, the high content of advanced glycation end-products (AGE) in caramelized malt tended to prohibit the positive effects on occludin in the small intestine and plasma amino acids seen with the other malt products. In conclusion, malting seems to be an interesting process for producing foods with positive health effects, but part of these effects may be destroyed if the malt contains a high content of AGE. PMID:26227569

  16. Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a high affinity niacin receptor.

    PubMed

    Kim, Hyeon Young; Jadhav, Vithal B; Jeong, Dae Young; Park, Woo Kyu; Song, Jong-Hwan; Lee, Sunkyung; Cho, Heeyeong

    2015-06-01

    Even though nicotinic acid (niacin) appears to have beneficial effects on human lipid profiles, niacin-induced cutaneous vasodilatation called flushing limits its remedy to patient. GPR109A is activated by niacin and mediates the anti-lipolytic effects. Based on the hypothesis that β-arrestin signaling mediates niacin-induced flushing, but not its anti-lipolytic effect, we tried to find GPR109A agonists which selectively elicit Gi-protein-biased signaling devoid of β-arrestin internalization using a β-lactamase assay. We identified a 4-(phenyl)thio-1H-pyrazole as a novel scaffold for GPR109A agonist in a high throughput screen, which has no carboxylic acid moiety known to be important for binding. While 1-nicotinoyl derivatives (5a-g, 6a-e) induced β-arrestin recruitment, 1-(pyrazin-2-oyl) derivatives were found to play as G-protein-biased agonists without GPR109A receptor internalization. The activity of compound 5a (EC50 = 45 nM) was similar to niacin (EC50 = 52 nM) and MK-6892 (EC50 = 74 nM) on calcium mobilization assay, but its activity at 10 μM on β-arrestin recruitment were around two and five times weaker than niacin and MK-6892, respectively. The development of G-protein biased GPR109A ligands over β-arrestin pathway is attainable and might be important in differentiation of pharmacological efficacy.

  17. In vitro and in vivo study of transcriptome alternation induced by butyrate in cattle using deep RNA-seq

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Short-chain fatty acids (SCFAs,), especially butyrate, affect cell differentiation, proliferation, and motility. Furthermore, butyrate induces cell cycle arrest and apoptosis through its inhibition on histone deacetylases (HDACs). Butyrate is a potent inducer of histone hyper-acetylation in cells a...

  18. Copper(II) and nickel(II) complexes of benzyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone: Synthesis, characterization and biological activity

    NASA Astrophysics Data System (ADS)

    Prathima, B.; Subba Rao, Y.; Adinarayana Reddy, S.; Reddy, Y. P.; Varada Reddy, A.

    2010-09-01

    Benzyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone ligand (L) has been synthesized from benzyloxybenzaldehyde and 4-phenyl-3-thiosemicarbazide. Complexes of this ligand with chlorides of Cu(II) and Ni(II) have been prepared. The structure of the ligand (L) is proposed based on elemental analysis, IR and 1H NMR spectra. Its complexes with Cu(II) and Ni(II) ions are characterized from the studies of electronic as well as EPR spectra. On the basis of electronic and EPR studies, rhombically distorted octahedral structure has been proposed for Cu(II) complex while the Ni(II) complex has been found to acquire an octahedral structure. The ligand and their metal complexes have been tested in vitro for their biological effects. Their antibacterial activities against Gram-negative bacteria ( Escherichia coli and Klebsiella pneumoniae) and Gram-positive bacteria ( Staphylococcus aureus and Bacillus subtilis) have been investigated. The prepared metal complexes exhibit higher antibacterial activities than the parent ligand. The in vitro antioxidant activity of free ligand and its metal(II) complexes have also been investigated and the results however reveal that the ligand exhibits greater antioxidant activity than its complexes.

  19. Effect of butyrate on immune response of a chicken macrophage cell line

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyric acid is a major short chain fatty acid (SCFA) produced in the gastrointestinal tract by anaerobic bacterial fermentation which has been demonstrated to have beneficial health effects in many species including poultry. To understand the immunomodulating effects of butyrate on chicken macropha...

  20. Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism.

    PubMed

    Singhal, Naveen Kumar; Agarwal, Swati; Bhatnagar, Priyanka; Tiwari, Manindra Nath; Tiwari, Shashi Kant; Srivastava, Garima; Kumar, Pradeep; Brashket, Seth; Patel, Devendra Kumar; Chaturvedi, Rajnish Kumar; Singh, Mahendra Pratap; Gupta, Kailash Chand

    2015-12-01

    The study aimed to measure the neuroprotective efficacy of caffeine-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles over bulk and to delineate the mechanism of improvement in efficacy both in vitro and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinsonism. Caffeine-encapsulated PLGA nanoparticles exhibited more pronounced increase in the endurance of dopaminergic neurons, fibre outgrowth and expression of tyrosine hydroxylase (TH) and growth-associated protein-43 (GAP-43) against 1-methyl-4-phenylpyridinium (MPP+)-induced alterations in vitro. Caffeine-encapsulated PLGA nanoparticles also inhibited MPP(+)-mediated nuclear translocation of nuclear factor-kappa B (NF-κB) and augmented protein kinase B phosphorylation more potentially than bulk counterpart. Conversely, MPTP reduced the striatal dopamine and its metabolites and nigral TH immunoreactivity whereas augmented the nigral microglial activation and nigrostriatal lipid peroxidation and nitrite content, which were shifted towards normalcy by caffeine. The modulations were more evident in caffeine-encapsulated PLGA nanoparticles treated animals as compared with bulk. Moreover, the striatal caffeine and its metabolites were found to be significantly higher in caffeine-encapsulated PLGA nanoparticles-treated mice as compared with bulk. The results thus suggest that nanotization improves the protective efficacy of caffeine against MPTP-induced Parkinsonism owing to enhanced bioavailability, inhibition of the nuclear translocation of NF-κB and activation of protein kinase B phosphorylation.

  1. (1)H NMR-based metabolomics study on a goldfish model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

    PubMed

    Lu, Zhaoguang; Wang, Junsong; Li, Minghui; Liu, Qingwang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

    2014-11-01

    A goldfish (Carassius auratus) model of Parkinson's disease (PD) was constructed by a single dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to previously reported methods. Global metabolite changes in brain of the MPTP induced goldfish model of PD were investigated. (1)H NMR-based metabolomics combined with various statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) found significant increase of leucine, isoleucine, valine, alanine, alanylalanine, creatinine, myo-inositol, 18:2 fatty acid, total fatty acids, arachic alcohol, taurine and significant decrease of N-acetylaspartate, (phospho)creatine, (phospho)choline, betaine, glutamine, 3-hexenedioate, acetamide, malonate, isocitrate, scyllo-inositol, phosphatidylcholines, cholesterols, n-3 fatty acids, polyunsaturated fatty acids (PUFAs) in brain of MPTP induced PD goldfish. These disturbed metabolite levels were involved in oxidative stress, energy failure, neuronal cell injury and death, consistent with those observed in clinical PD patients, and rodents and primates model of PD, indicating that the acute MPTP model of goldfish was an ideal and valuable model for PD research. In addition, several unusual metabolites in brain were significantly changed between MPTP induced PD and control goldfish, which might also play an important role in the pathogenesis of PD. This study also demonstrated the applicability and potential of (1)H NMR-based metabolomics approach for evaluation of animal models of disease induced by chemicals, such as MPTP-induced PD goldfish. PMID:25242684

  2. Transcriptional attenuation in colon carcinoma cells in response to butyrate.

    PubMed

    Daroqui, Maria C; Augenlicht, Leonard H

    2010-10-01

    The short-chain fatty acid sodium butyrate (NaB), produced in the colonic lumen, induces cell cycle arrest, differentiation, and/or apoptosis in colorectal carcinoma cells in vitro, establishing a potential role for NaB in colon cancer prevention. We have previously shown that butyrate decreases cyclin D1 and c-myc expression, each essential for intestinal tumor development, by transcriptional attenuation. Here, we determined that butyrate-induced transcriptional attenuation of the cyclin D1 and c-myc genes in SW837 human colorectal adenocarcinoma cells occurs at ∼100 nucleotides downstream of the transcription start site, with a similar positioning in Caco-2 cells. A concomitant decrease in RNA polymerase II occupancy at the 5' end of each gene was observed. Because transcriptional regulation is associated with chromatin remodeling, we investigated by chromatin immunoprecipitation whether the histone deacetylase inhibitory activity of butyrate altered chromatin structure at the attenuated loci. Although the distributions of histone H3 trimethylated on K4 and K36 along the cyclin D1 and c-myc genes were consistent with current models, butyrate induced only modest decreases in these modifications, with a similar effect on acetylated H3 and a modest increase in histone H3 trimethylated on K27. Finally, transcriptome analysis using novel microarrays showed that butyrate-induced attenuation is widespread throughout the genome, likely independent of transcriptional initiation. We identified 42 loci potentially paused by butyrate and showed that the transcription patterns are gene specific. The biological functions of these loci encompass a number of effects of butyrate on the physiology of intestinal epithelial cells.

  3. Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

    PubMed

    Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

    2015-01-01

    Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture. PMID:25265058

  4. Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

    PubMed

    Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

    2015-01-01

    Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture.

  5. Graphene composite for improvement in the conversion efficiency of flexible poly 3-hexyl-thiophene:[6,6]-phenyl C{sub 71} butyric acid methyl ester polymer solar cells

    SciTech Connect

    Chauhan, A. K. E-mail: akc.barc@gmail.com; Gusain, Abhay; Jha, P.; Koiry, S. P.; Saxena, Vibha; Veerender, P.; Aswal, D. K.; Gupta, S. K.

    2014-03-31

    The solution of thin graphene-sheets obtained from a simple ultrasonic exfoliation process was found to chemically interact with [6,6]-phenyl C{sub 71} butyric acid methyl ester (PCBM) molecules. The thinner graphene-sheets have significantly altered the positions of highest occupied molecular orbital and lowest unoccupied molecular orbital of PCBM, which is beneficial for the enhancement of the open circuit voltage of the solar cells. Flexible bulk heterojunction solar cells fabricated using poly 3-hexylthiophene (P3HT):PCBM-graphene exhibited a power conversion efficiency of 2.51%, which is a ∼2-fold increase as compared to those fabricated using P3HT:PCBM. Inclusion of graphene-sheets not only improved the open-circuit voltage but also enhanced the short-circuit current density owing to an improved electron transport.

  6. Synthesis, structure and solvatochromic properties of some novel 5-arylazo-6-hydroxy-4-phenyl-3-cyano-2-pyridone dyes

    PubMed Central

    2012-01-01

    Background A series of some novel arylazo pyridone dyes was synthesized from the corresponding diazonium salt and 6-hydroxy-4-phenyl-3-cyano-2-pyridone using a classical reaction for the synthesis of the azo compounds. Results The structure of the dyes was confirmed by UV-vis, FT-IR, 1H NMR and 13C NMR spectroscopic techniques and elemental analysis. The solvatochromic behavior of the dyes was evaluated with respect to their visible absorption properties in various solvents. Conclusions The azo-hydrazone tautomeric equilibration was found to depend on the substituents as well as on the solvent. The geometry data of the investigated dyes were obtained using DFT quantum-chemical calculations. The obtained calculational results are in very good agreement with the experimental data. PMID:22824496

  7. Copper(II) complexes derived from di-2-pyridyl ketone- N4-phenyl-3-semicarbazone: Synthesis and spectral studies

    NASA Astrophysics Data System (ADS)

    Reena, T. A.; Kurup, M. R. Prathapachandra

    2010-08-01

    Five copper(II) complexes [CuLCl] 2·CuCl 2·4H 2O ( 1), [CuLOAc] ( 2), [CuLNO 3] 2 ( 3), [CuLN 3] ( 4) and [CuLNCS]·3/2H 2O ( 5) of di-2-pyridyl ketone- N4-phenyl-3-semicarbazone (HL) were synthesized and characterized by elemental analyses and electronic, infrared and EPR spectral techniques. In all these complexes the semicarbazone undergoes deprotonation and coordinates through enolate oxygen, azomethine and pyridyl nitrogen atoms. All the complexes are EPR active due to the presence of an unpaired electron. EPR spectra of all the complexes in DMF at 77 K suggest axial symmetry and the presence of half field signals for the complexes 1 and 3 indicates dimeric structures.

  8. Butyrate and propionate: important components of toxic dental plaque extracts.

    PubMed Central

    Singer, R E; Buckner, B A

    1981-01-01

    Extracts of in vitro-cultured human dental plaque contain factors toxic to mammalian cells. Previous studies demonstrated that those toxic factors most readily released from cultured plaque had very low molecular weights and were heat stable. Studies reported here demonstrate that metabolic end products including short-chain fatty acids were present in fractions containing the low-molecular-weight, heat-stable factors. The salts of two of these acids, butyrate and propionate, inhibited proliferation of both mouse L929 cells and human gingival fibroblasts. Furthermore, when tested at concentrations present in plaque extracts, the inhibitory effects of butyrate and propionate accounted for essentially all the inhibitory potential of the extracts. These findings, taken together with those of other groups, suggest that butyrate and propionate, end products of dental plaque metabolism, may have an etiological role in periodontal disease. PMID:7251132

  9. Butyrate supplementation to gestating sows and piglets induces muscle and adipose tissue oxidative genes and improves growth performance.

    PubMed

    Lu, H; Su, S; Ajuwon, K M

    2012-12-01

    Weaned pigs often experience growth reduction immediately after weaning due to multiple stress factors associated with weaning. We tested the effect of prenatal and postnatal butyrate supplementation on growth performance of piglets. In study 1, piglets were orally gavaged with 0.3% butyrate from day 4 after birth to weaning (day 21). Butyrate increased ADG by 13% compared to saline treated control. Expression of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α) was higher in muscle, adipose tissue, and ileum of butyrate-supplemented animals. Also, peroxisome proliferator activated receptor alpha (PPARα) was induced (P < 0.05) in the subcutaneous adipose tissue (SCAT) and muscle (longissimus dorsi [LD]) of butyrate-supplemented piglets. In vitro, butyrate increased (P < 0.05) fatty acid oxidation in primary adipocytes and suppressed basal lipolysis by 62% compared to untreated cells. Butyrate suppressed (P < 0.05) lipogenesis ((14)C-glucose incorporation into lipids) in adipocytes. This was accompanied by an approximately 30% reduction in the mRNA expression of fatty acid synthase (P < 0.05) in butyrate-treated cells vs. controls. Piglets born to sows that were supplemented with 0.3% butyrate during the last trimester of gestation had a 15% higher (P < 0.05) body weight at 12 wk than controls. In summary, butyrate supplementation to gestating sows and piglets enhanced postweaning growth performance, which may be mediated by increased substrate oxidation in butyrate treated animals.

  10. Consequences of manganese administration for striatal dopamine and motor behavior in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed C57BL/6 mice.

    PubMed

    Dodd, C A; Bloomquist, J R; Klein, B G

    2013-08-01

    Environmental compounds may be important contributors to Parkinson's disease etiology. Epidemiological and experimental evidence for the facilitation of parkinsonism by manganese is equivocal. This work addressed methodological concerns in the few studies of manganese modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in C57BL/6 mice. Male, retired breeder mice received 0 or 100 mg/kg of manganese chloride (MnCl₂; subcutaneously on days 1, 4 and 7) and 0 or 20 mg/kg of MPTP (intraperitoneally on day 8) and survived up to day 15 or 22. On the day of sacrificing, horizontal (grid crossing) and vertical (rearing) open field movement, swimming, grip strength and grip fatigue were examined. Striata were analyzed for dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) using high-performance liquid chromatography. MPTP produced a main effect decrease in striatal dopamine (48.8%) and DOPAC (38.1%), but there was no main effect of MnCl₂ or MnCl₂ x MPTP interaction. However, modulatory interactions were observed between the effects of MnCl₂ and MPTP for grid crossing, rearing and grip strength. Interestingly, these interactions reduced the severity of behavioral deficits attributable to either of these compounds alone. For rearing and grip strength, the MnCl₂ x MPTP interaction was dependent upon survival time. The mechanistic nature of the MnCl₂ x MPTP interaction upon these behaviors, in the absence of such an interaction for striatal dopamine and DOPAC, remains to be clarified.

  11. Neurochemical and toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridine to rat serotonin neurons in dissociated cell cultures

    SciTech Connect

    Friedman, L.K.; Mytilineou, C. )

    1990-05-01

    Dissociated cell cultures from the pontine area of embryonic rat brain were used to study the sensitivity of serotonin (5-hydroxy-tryptamine (5-HT)) neurons to the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+). Treatment with MPTP (up to 100 microM) for 7 days did not cause degeneration of 5-HT neurons. A 50% inhibition of (3H)5-HT uptake caused by 100 microM MPTP was a direct effect on the 5-HT uptake carrier, reversed by washing for 7 days. Incubation of cultures with MPTP increased the intraneuronal levels of 5-HT and reduced the levels of 5-hydroxyindoleacetic acid, suggesting a reduction in 5-HT metabolism. MPTP reduced monoamine oxidase activity in the cultures, which probably led to the reduction in 5-HT metabolism. Exposure to MPP+ (0.5-10 microM) for 4 to 7 days decreased (3H)5-HT uptake and induced loss of neurons stained with antibodies against 5-HT. Comparison between 5-HT and dopamine (DA) neurons indicated a differential sensitivity to MPP+ toxicity with DA neurons being more susceptible. Analysis of the competition of MPP+ with the natural substrates for uptake sites of 5-HT and DA neurons demonstrated higher affinity of MPP+ for DA compared to 5-HT neurons. The lower affinity of MPP+ for 5-HT neurons could be responsible for the accumulation of lower MPP+ levels observed in pontine cultures and explain the resistance of 5-HT neurons to this toxin.

  12. Fast Hetero-Diels-Alder Reactions Using 4-Phenyl-1,2,4-Triazoline-3,5-Dione (PTAD) as the Dienophile

    ERIC Educational Resources Information Center

    Celius, Tevye C.

    2010-01-01

    A hetero-Diels-Alder reaction that proceeds rapidly and only requires a simple filtration to purify the product is presented. The dienophile, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), is prepared by the heterogeneous oxidation of 4-phenylurazole by the bromenium ion, Br[superscript +], generated in situ by the oxidation of potassium bromide by…

  13. Biosynthesis of heparin. Effects of n-butyrate on cultured mast cells

    SciTech Connect

    Jacobsson, K.G.; Riesenfeld, J.; Lindahl, U.

    1985-10-05

    Murine mastocytoma cells were incubated in vitro with inorganic (TVS)sulfate, in the absence or presence of 2.5 mM n-butyrate, and labeled heparin was isolated. The polysaccharide produced in the presence of butyrate showed a lower charge density on anion exchange chromatography than did the control material and a 3-fold increased proportion of components with high affinity for antithrombin. Structural analysis of heparin labeled with (TH) glucosamine in the presence of butyrate showed that approximately 35% of the glucosamine units were N-acetylated, as compared to approximately 10% in the control material; the nonacetylated glucosamine residues were N-sulfated. The presence of butyrate thus leads to an inhibition of the N-deacetylation/N-sulfation process in heparin biosynthesis, along with an augmented formation of molecules with high affinity for antithrombin. Preincubation of the mastocytoma cells with butyrate was required for manifestation of either effect; when the preincubation period was reduced from 24 to 10 h the effects of butyrate were no longer observed. A polysaccharide formed on incubating mastocytoma microsomal fraction with UDP-(TH)glucuronic acid, UDP-N-acetylglucosamine, and 3'-phosphoadenylylsulfate in the presence of 5 mM butyrate showed the same N-acetyl/N-sulfate ratio as did the corresponding control polysaccharide, produced in the absence of butyrate. These findings suggest that the effect of butyrate on heparin biosynthesis depends on the integrity of the cell.

  14. Inhibitory effects of butyrate on biological hydrogen production with mixed anaerobic cultures.

    PubMed

    Zheng, Xian-Jun; Yu, Han-Qing

    2005-01-01

    In this study batch experiments were conducted to investigate the inhibitory effects of butyrate addition on hydrogen production from glucose by using anaerobic mixed cultures. Experimental results showed that addition of butyrate at 4.18 and 6.27 g/l only slightly inhibited hydrogen production, and addition of butyrate at 8.36-12.54 g/l imposed a moderate inhibitory effect on hydrogen production. At addition of 25.08 g/l, butyrate had a strong inhibitory influence on substrate degradation and hydrogen production. The distribution of the volatile fatty acids produced from the acidogeneisis of glucose was significantly influenced by the addition of butyrate. The inhibition of butyrate addition on hydrogen production was described well by a non-competitive and non-linear inhibition model, with the maximum hydrogen production rate of 59.3 ml/g-SS/h, critical added butyrate concentration of 25.08 g/l, and inhibition degree of 0.323, respectively. The C(I,50) values (the butyrate concentration at which bioactivity is reduced by 50%) for hydrogen production rate and yield were estimated as 19.39 and 20.78 g/l of added butyrate, respectively.

  15. Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3.

    PubMed

    Li, Huating; Gao, Zhanguo; Zhang, Jin; Ye, Xin; Xu, Aimin; Ye, Jianping; Jia, Weiping

    2012-04-01

    Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator-activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3.

  16. Conformation and tautomerism of methoxy-substituted 4-phenyl-4-thiazoline-2-thiones: a combined crystallographic and ab initio investigation.

    PubMed

    Balti, Monaem; Norberg, Bernadette; Efrit, Mohamed Lotfi; Lanners, Steve; Wouters, Johan

    2016-05-01

    4-Phenyl-4-thiazoline-2-thiol is an active pharmaceutical compound, one of whose activities is as a human indolenamine dioxygenase inhibitor. It has been shown recently that in both the solid state and the gas phase, the thiazolinethione tautomer should be preferred. As part of both research on this lead compound and a medicinal chemistry program, a series of substituted arylthiazolinethiones have been synthesized. The molecular conformations and tautomerism of 4-(2-methoxyphenyl)-4-thiazoline-2-thione and 4-(4-methoxyphenyl)-4-thiazoline-2-thione, both C10H9NOS2, are reported and compared with the geometry deduced from ab initio calculations [PBE/6-311G(d,p)]. Both the crystal structure analyses and the calculations establish the thione tautomer for the two substituted arylthiazolinethiones. In the crystal structure of the 2-methoxyphenyl regioisomer, the thiazolinethione unit was disordered over two conformations. Both isomers exhibit similar hydrogen-bond patterns [R2(2)(8) motif] and form dimers. The crystal packing is further reinforced by short S...S interactions in the 2-methoxyphenyl isomer. The conformations of the two regioisomers correspond to stable geometries calculated from an ab initio energy-relaxed scan. PMID:27146572

  17. Dextromethorphan prevents the diethyldithiocarbamate enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice.

    PubMed

    Vaglini, Francesca; Pardini, Carla; Bonuccelli, Ubaldo; Maggio, Roberto; Corsini, Giovanni U

    2003-05-30

    In this report we show that dextromethorphan, a non-opioid cough suppressant, prevents the neurodegeneration of dopaminergic neurons in the substantia nigra of mice treated with diethyldithiocarbamate (DDC) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This effect is further substantiated by the assessment of dopamine (DA) content in the striatum of these animals. Dextromethorphan does not attenuate the striatal DA fall induced by MPTP alone but completely prevents DDC-induced enhancement after the combined treatment. Moreover, a study of DA metabolites has confirmed this neuroprotective property. The striatal levels of serotonin, which were studied as a control neuronal marker, did not change with any of the treatments administered. Furthermore, we show that dextromethorphan reduces the toxicity of glutamate against dopamine neurons in mesencephalic cell cultures. In line with previous data suggesting that dextromethorphan can prevent neuronal damage, our observations supply new evidence regarding the possibility of this compound being of therapeutic use in neurodegenerative diseases. PMID:12738074

  18. Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice☆

    PubMed Central

    Wang, Tao; Liu, Yanyong; Yang, Nan; Ji, Chao; Chan, Piu; Zuo, Pingping

    2012-01-01

    Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson's disease. Oral administration of octacosanol (100 mg/kg) significantly improved behavioral impairments in mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signal transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson's disease. PMID:25722698

  19. Nonclassical antifolates, part 4. 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: synthesis, biological evaluation and molecular modeling study.

    PubMed

    Hassan, Ghada S; El-Messery, Shahenda M; Al-Omary, Fatmah A M; Al-Rashood, Sarah T; Shabayek, Marwa I; Abulfadl, Yasmin S; Habib, El-Sayed E; El-Hallouty, Salwa M; Fayad, Walid; Mohamed, Khaled M; El-Menshawi, Bassem S; El-Subbagh, Hussein I

    2013-08-01

    A new series of compounds possessing 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol skeleton was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, antitumor and schistosomicidal activities. Four active compounds were allocated, the antibacterial 22 (comparable to gentamicin and ciprofloxacin), the schistosomicidal 29 (comparable to praziquantel), the DHFR inhibitor 34 (IC₅₀ 0.03 μM, 2.7 fold more active than MTX), and the antitumor 36 (comparable to doxorubicin). Molecular modeling studies concluded that recognition with key amino acid Leu4 and Val1 is essential for DHFR binding. Flexible alignment and surface mapping revealed that the obtained model could be useful for the development of new class of DHFR inhibitors.

  20. The synthesis and crystal structure of 2-[4(S)-4,5-dihydro-4-phenyl-2-oxazolinyl]-benzenamine, and 2-[4(S)-4,5-dihydro-4-benzyl-2-oxazolinyl]-benzenamine

    NASA Astrophysics Data System (ADS)

    Mei, Luo; Hai, Zhang Jia; Hao, Yin; Min, Pang Wei; Liang, Hu Ke

    2010-12-01

    Two oxazolines compound 1a and 1b, 2-[4( S)-4,5-dihydro-4-phenyl-2-ozazolinyl-benzenamine, and (C15H14N2O), 2-[4( S)-4,5-dihydro-4-benzyl-2-ozazolinyl-benzenamine (C16H16N2O) were obtained in moderate yield from the reactions of 2-aminobenzonitrile with optically active L-(+)-Phenylglycinol and L-(+)-Phenylalaninol, respectively, in chlorobenzene under dry, anaerobic conditions. ZnCl2 was dried under vacuum and acted as a Lewis acid catalyst in this reaction. The structures of 1a and 1b were determined by X-ray diffraction and NMR. There exist intra- and intermolecular N-H…N hydrogen bonds in the crystal structure.

  1. Presence of insulin receptors in cultured glial C6 cells. Regulation by butyrate.

    PubMed Central

    Montiel, F; Ortiz-Caro, J; Villa, A; Pascual, A; Aranda, A

    1989-01-01

    The presence of insulin receptor and its regulation by butyrate and other short-chain fatty acids was studied in C6 cells, a rat glioma cell line. Intact C6 cells bind 125I-insulin in a rapid, reversible and specific manner. Scatchard analysis of the binding data gives typical curvilinear plots with apparent affinities of approx. 6 nM and 70 nM for the low-affinity (approx. 90% of total) and high-affinity (approx. 10% of total) sites respectively. Incubation with butyrate results in a time- and dose-dependent decrease of insulin binding to C6 cells. A maximal effect was found with 2 mM-butyrate that decreased the receptor by 40-70% after 48 h. Butyrate decreased numbers of receptors of both classes, but did not significantly alter receptor affinity. Other short-chain fatty acids, as well as keto acids, had a similar effect, but with a lower potency. Cycloheximide caused an accumulation of insulin receptors at the cell surface, since insulin binding increased and receptor affinity did not change after incubation with the inhibitor. Simultaneous addition of butyrate and cycloheximide abolished the loss of receptors produced by the fatty acid. In cells preincubated with butyrate, cycloheximide also produced a large increase in receptor numbers, showing that in the absence of new receptor synthesis a large pool of receptors re-appears at the surface of butyrate-treated cells. PMID:2930502

  2. Butyrate as preferred substrate for polyhydroxybutyrate production.

    PubMed

    Marang, Leonie; Jiang, Yang; van Loosdrecht, Mark C M; Kleerebezem, Robbert

    2013-08-01

    In this study, the suitability of butyrate as substrate for polyhydroxyalkanoate (PHA) production by microbial enrichment cultures was assessed. Two sequencing batch reactors were operated under feast-famine conditions: one fed with butyrate, and another with mixed acetate and butyrate. The obtained results were compared to previous results with acetate as sole substrate. In all three reactors Plasticicumulans acidivorans dominated the enrichment culture. The carbon uptake rate and PHA yield were significantly higher on butyrate than on acetate, resulting in a higher PHA production rate. When both substrates were available the bacteria strongly preferred the uptake of butyrate. Only after butyrate depletion acetate was taken up at a high rate. The molar substrate uptake rate remained the same, suggesting that substrate uptake is the rate-limiting step. The results show that for optimized waste-based PHA production the pre-fermentation process should be directed towards butyrate production.

  3. Induction of peroxisomes by butyrate-producing probiotics.

    PubMed

    Weng, Huachun; Endo, Kosuke; Li, Jiawei; Kito, Naoko; Iwai, Naoharu

    2015-01-01

    We previously found that peroxisomal biogenesis factor 11a (Pex11a) deficiency is associated with a reduction in peroxisome abundance and impaired fatty acid metabolism in hepatocytes, and results in steatosis. In the present study, we investigated whether butyrate induces Pex11a expression and peroxisome proliferation, and studied its effect on lipid metabolism. C57BL/6 mice fed standard chow or a high-fat diet (HFD) were treated with tributyrin, 4-phelybutyrate acid (4-PBA), or the butyrate-producing probiotics (Clostridium butyricum MIYAIRI 588 [CBM]) plus inulin (dietary fiber), and the body weight, white adipose tissue, serum triglycerides, mRNA expression, and peroxisome abundance were evaluated. Tributyrin or 4-PBA treatment significantly decreased body weight and increased hepatic mRNA expression of peroxisome proliferator-activated receptor-α (PPARα) and Pex11a. In addition, 4-PBA treatment increased peroxisome abundance and the expression of genes involved in peroxisomal fatty acid β-oxidation (acyl-coenzyme A oxidase 1 and hydroxysteroid [17-beta] dehydrogenase 4). CBM and inulin administration reduced adipose tissue mass and serum triglycerides, induced Pex11a, acyl-coenzyme A oxidase 1, and hydroxysteroid (17-beta) dehydrogenase 4 genes, and increased peroxisome abundance in mice fed standard chow or an HFD. In conclusion, elevation of butyrate availability (directly through administration of butyrate or indirectly via administration of butyrate-producing probiotics plus fiber) induces PPARα and Pex11a and the genes involved in peroxisomal fatty acid β-oxidation, increases peroxisome abundance, and improves lipid metabolism. These results may provide a new therapeutic strategy against hyperlipidemia and obesity.

  4. Models construction for acetone-butanol-ethanol fermentations with acetate/butyrate consecutively feeding by graph theory.

    PubMed

    Li, Zhigang; Shi, Zhongping; Li, Xin

    2014-05-01

    Several fermentations with consecutively feeding of acetate/butyrate were conducted in a 7 L fermentor and the results indicated that exogenous acetate/butyrate enhanced solvents productivities by 47.1% and 39.2% respectively, and changed butyrate/acetate ratios greatly. Then extracellular butyrate/acetate ratios were utilized for calculation of acids rates and the results revealed that acetate and butyrate formation pathways were almost blocked by corresponding acids feeding. In addition, models for acetate/butyrate feeding fermentations were constructed by graph theory based on calculation results and relevant reports. Solvents concentrations and butanol/acetone ratios of these fermentations were also calculated and the results of models calculation matched fermentation data accurately which demonstrated that models were constructed in a reasonable way.

  5. Cellular Metabolism and Dose Reveal Carnitine-Dependent and -Independent Mechanisms of Butyrate Oxidation in Colorectal Cancer Cells.

    PubMed

    Han, Anna; Bennett, Natalie; MacDonald, Amber; Johnstone, Megan; Whelan, Jay; Donohoe, Dallas R

    2016-08-01

    Dietary fiber has been suggested to suppress colorectal cancer development, although the mechanisms contributing to this beneficial effect remain elusive. Butyrate, a fermentation product of fiber, has been shown to have anti-proliferative and pro-apoptotic effects on colorectal cancer cells. The metabolic fate of butyrate in the cell is important in determining whether, it acts as an HDAC inhibitor or is consumed as a short-chain fatty acid. Non-cancerous colonocytes utilize butyrate as the primary energy source whereas cancerous colonocytes increase glucose utilization through the Warburg effect. In this study, we show that butyrate oxidation is decreased in cancerous colonocytes compared to non-cancerous colonocytes. We demonstrate that colorectal cancer cells utilize both a carnitine-dependent and carnitine-independent mechanism that contributes to butyrate oxidation. The carnitine-dependent mechanism is contingent on butyrate concentration. Knockdown of CPT1A in colorectal cancer cells abolishes butyrate oxidation. In terms of selectivity, the carnitine-dependent mechanism only regulated butyrate oxidation, as acetate and propionate oxidation were carnitine-independent. Carnitine decreased the action of butyrate as an HDAC inhibitor and suppressed induction of H3 acetylation by butyrate in colorectal cancer cells. Thus, diminished oxidation of butyrate is associated with decreased HDAC inhibition and histone acetylation. In relation to the mechanism, we find that dichloroacetate, which decreases phosphorylation of pyruvate dehydrogenase, increased butyrate oxidation and that this effect was carnitine-dependent. In conclusion, these data suggest that colorectal cancer cells decrease butyrate oxidation through inhibition of pyruvate dehydrogenase, which is carnitine-dependent, and provide insight into why butyrate shows selective effects toward colorectal cancer cells. J. Cell. Physiol. 231: 1804-1813, 2016. © 2015 Wiley Periodicals, Inc.

  6. Acetylcarnitine potentiates the anticarcinogenic effects of butyrate on SW480 colon cancer cells.

    PubMed

    Elimrani, Ihsan; Dionne, Serge; Saragosti, Dan; Qureshi, Ijaz; Levy, Emile; Delvin, Edgar; Seidman, Ernest G

    2015-08-01

    Butyrate is a potent anticarcinogenic compound against colon cancer cells in vitro. However, its rapid metabolism is hypothesized to limit its anticancer benefits in colonic epithelial cells. Carnitine, a potent antioxidant, is essential to fatty acid oxidation. The aims of this study were to identify a colon cancer cell line capable of transporting carnitine. We evaluated the effect of carnitine and acetylcarnitine (ALCAR) on the response of colon carcinoma cells to butyrate. We explored the mechanisms underlying the anticarcinogenic benefit. SW480 cells were incubated with butyrate ± carnitine or ALCAR. Carnitine uptake was assessed using [3H]-carnitine. Apoptosis and cell viability were assessed using an ELISA kit and flow cytometry, respectively. Modulation of proteins implicated in carnitine transport, cell death and proliferation were assessed by western blotting. SW480 cells were found to transport carnitine primarily via the OCTN2 transporter. Butyrate induced SW480 cell death occurred at concentrations of 2 mM and higher. Cells treated with the combination of butyrate (3 mM) with ALCAR exhibited increased mortality. The addition of carnitine or ALCAR also increased butyrate-induced apoptosis. Butyrate increased levels of cyclin D1, p21 and PARP p86, but decreased Bcl-XL and survivin levels. Butyrate also downregulated dephospho-β-catenin and increased acetylated histone H4 levels. Butyrate and carnitine decreased survivin levels by ≥25%. ALCAR independently induced a 20% decrease in p21. These results demonstrate that butyrate and ALCAR are potentially beneficial anticarcinogenic nutrients that inhibit colon cancer cell survival in vitro. The combination of both agents may have superior anticarcinogenic properties than butyrate alone.

  7. Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages.

    PubMed

    Fernando, Maria R; Saxena, Alpana; Reyes, José-Luis; McKay, Derek M

    2016-05-15

    The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4)s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibition of histone deacetylation. Functionally, M(IL-4)s treated with butyrate showed increased phagocytosis and killing of bacteria, compared with M(IL-4) and this was not accompanied by enhanced proinflammatory cytokine production. Culture of regulatory T cells with M(IL-4)s and M(IL-4 + butyrate)s revealed that both macrophage subsets suppressed expression of the regulatory T-cell marker Foxp3. However, Tregs cocultured with M(IL-4 + butyrate) produced less IL-17A than Tregs cocultured with M(IL-4). These data illustrate the importance of butyrate, a microbial-derived metabolite, in the regulation of gut immunity: the demonstration that butyrate promotes phagocytosis in M(IL-4)s that can limit T-cell production of IL-17A reveals novel aspects of bacterial-host interaction in the regulation of intestinal homeostasis.

  8. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    PubMed

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development.

  9. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    PubMed

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development. PMID:25478867

  10. The Dependence of Donor:Acceptor Ratio on the Photovoltaic Performances of Blended poly (3-octylthiophene-2,5-diyl) and (6,6)-phenyl C{sub 71} butyric acid methyl ester Bulk Heterojunction Organic Solar Cells

    SciTech Connect

    Fauzia, Vivi; Umar, Akrajas Ali; Salleh, Muhamad Mat; Yahya, Muhammad

    2010-10-24

    Bulk heterojunction organic solar cells using blended poly (3-octylthiophene-2,5-diyl)(P3OT) and (6,6)-phenyl C{sub 71} butyric acid methyl ester (PC{sub 71}BM) have been fabricated. P3OT and PC{sub 71}BM were used as the electron donor (D) and acceptor (A), respectively. Both materials were mixed and dissolved in dichlorobenzene with three different D:A ratios i.e. 1:3, 1:1 and 3:1 (weight) while maintained at the concentration of 2 wt%(26 mg/ml). The blended thin films were sandwiched between the indium tin oxide (ITO) coated glass and the aluminum film. This paper reports the influence of donor:acceptor ratio on the performance of solar cell devices measured by current-voltage measurement both in the dark and under 1.5 AM solar illumination. It was found that all devices showed the photovoltaic effect with poor diode behavior and the donor:acceptor ratio significantly influenced on the performance of bulk heterojunction organic solar cells.

  11. Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases?

    PubMed

    Brahe, L K; Astrup, A; Larsen, L H

    2013-12-01

    It is increasingly recognized that there is a connection between diet, intestinal microbiota, intestinal barrier function and the low-grade inflammation that characterizes the progression from obesity to metabolic disturbances, making dietary strategies to modulate the intestinal environment relevant. In this context, the ability of some Gram-positive anaerobic bacteria to produce the short-chain fatty acid butyrate is interesting. A lower abundance of butyrate-producing bacteria has been associated with metabolic risk in humans, and recent studies suggest that butyrate might have an anti-inflammatory potential that can alleviate obesity-related metabolic complications, possibly due to its ability to enhance the intestinal barrier function. Here, we review and discuss the potential of butyrate as an anti-inflammatory mediator in metabolic diseases, and the potential for dietary interventions increasing the intestinal availability of butyrate.

  12. Theoretical investigation on the isomerization reaction of 4-phenyl-hexa-1,5-enyne catalyzed by homogeneous Au catalysts.

    PubMed

    Liu, Yuxia; Zhang, Dongju; Bi, Siwei

    2010-12-16

    By carrying out density functional theory calculations, we have performed a detailed mechanism study for the cycloisomerization reaction of 4-phenyl-hexa-1,5-enyne catalyzed by homogeneous gold to better understand the observed different catalytic activity of several catalysts, including (PPh(3))AuBF(4), (PPh(3))AuCl, AuCl(3), and AuCl. In all situations, the reaction is found to involve two major steps: the initial nucleophilic addition of the alkynyl onto the alkene group and the subsequent 1,2-H migration. It is found that the potential energy surface profiles of systems are very different when different catalysts are used. For (PMe(3))AuBF(4)- and (PMe(3))AuCl-mediated systems, the nucleophilic addition is the rate-determining step, and the calculated free energy barriers are 15.2 and 41.9 kcal/mol, respectively. In contrast, for AuCl(3)- and AuCl-mediated systems, the reactions are controlled by the dissociations of catalysts from the product-like intermediates, and the calculated dissociation energies are 18.1 and 21.7 kcal/mol, respectively, which are larger than both the corresponding free energy barriers of the nucleophilic addition and the H-migration processes (8.5 and 7.3 kcal/mol for the AuCl(3)-mediated reaction, and 16.9 and 11.3 kcal/mol for the AuCl-mediated reaction). These results can rationalize the early experimental observations that the reactant conversion rates are 100, 0, and 50% when using (PPh(3))AuBF(4), (PPh(3))AuCl, and AuCl(3) as catalysts, respectively. The present study indicates that both the ligand and counterion of homogeneous Au catalysts importantly influence their catalytic activities, whereas the oxidation state of Au is not a crucial factor controlling the reactivity.

  13. Optimized butyl butyrate synthesis catalyzed by Thermomyces lanuginosus lipase.

    PubMed

    Martins, Andréa B; Friedrich, John L R; Rodrigues, Rafael C; Garcia-Galan, Cristina; Fernandez-Lafuente, Roberto; Ayub, Marco A Z

    2013-01-01

    Butyl butyrate is an ester present in pineapple flavor, which is very important for the food and beverages industries. In this work, the optimization of the reaction of butyl butyrate synthesis catalyzed by the immobilized lipase Lipozyme TL-IM was performed. n-Hexane was selected as the most appropriate solvent. Other reaction parameters such as temperature, substrate molar ratio, biocatalyst content and added water, and their responses measured as yield, were evaluated using a fractional factorial design, followed by a central composite design (CCD) and response surface methodology. In the fractional design 2(4-1) , the four variables were tested and temperature and biocatalyst content were statistically significant and then used for optimization on CCD. The optimal conditions for butyl butyrate synthesis were found to be 48°C; substrate molar ratio 3:1 (butanol:butyric acid); biocatalyst content of 40% of acid mass. Under these conditions, over 90% of yield was obtained in 2 h. Enzyme reuse was tested by washing the biocatalyst with n-hexane or by direct reuse. The direct reuse produced a rapid decrease on enzyme activity, while washing with n-hexane allowed reusing the enzyme for five reactions cycles keeping approximately 85% of its activity.

  14. Sodium hydroxide catalyzed N-alkylation of (hetero) aromatic primary amines and N1,C5-dialkylation of 4-phenyl-2-aminothiazoles with benzyl alcohols.

    PubMed

    Donthiri, Ramachandra Reddy; Pappula, Venkatanarayana; Mohan, Darapaneni Chandra; Gaywala, Hiren H; Adimurthy, Subbarayappa

    2013-07-01

    In the presence of a catalytic amount of NaOH, the selective N-alkylation of various heteroaromatic primary amines is reported. With 1 equiv of NaOH, N1,C5-dialkylation of 4-phenyl-2-aminothiazoles has been investigated. Reaction of in situ generated aldehyde with amine yields the N-alkylated and N1,C5-dialkylated products through hydride ion transformation from alcohol.

  15. Crystal structure and spectroscopic study on photochromism of 1,3-diphenyl-4-(4‧-fluoro)benzal-5-pyrazolone N(4)-phenyl semicarba-zone

    NASA Astrophysics Data System (ADS)

    Chai, Hui; Liu, Guangfei; Liu, Lang; Jia, Dianzeng; Guo, Zaiping; Lang, Jianping

    2005-10-01

    A novel compound 1,3-diphenyl-4-(4'-fluoro)benzal-5-pyrazolone N(4)-phenyl semicarbazone (DP4FBP-PSC) has been synthesized. X-ray single crystal structure analysis shows that the compound has interlaced structure linked by intermolecular hydrogen bonds. The results of fluorescence emission spectroscopy, UV-Vis reflection spectroscopy and the reaction rate constant indicate that DP4FBP-PSC is photochromic material. Its photochromic mechanism was investigated by structure analysis.

  16. The important role of caspase-10 in sodium butyrate-induced apoptosis.

    PubMed

    Nohara, Kazunari; Yokoyama, Yoshiko; Kano, Kazutaka

    2007-01-01

    Butyrate, a short chain fatty acid, exhibits a wide variety of biological effects including the inhibition of cell growth, change of cellular morphology and the induction of apoptosis. Sodium butyrate-induced apoptosis has been reported to associate with the up-regulation of pro-apoptotic Bax expression, and the down-regulation of anti-apoptotic Bcl-2 and Bcl-XL expressions. However, in some cases, butyrate has also been shown to cause apoptosis without change in Bcl-2, Bcl-XL and/or Bax. This study investigates the detailed mechanisms of sodium butyrate-induced apoptosis. The effect of sodium butyrate was analyzed in the induction of caspase activities, formation of caspase active forms and mRNA levels in human breast cancer cell line MRK-nu-1. Induction of activities of caspase-3, -10 and, to some extent, -8 and formation of DNA fragmentation were observed with sodium butyrate in a dose- and/or time-dependent manner. The levels of caspase-10 mRNA expression markedly increased in a time-dependent manner by the treatment of sodium butyrate, whereas caspase-8 mRNA expression was not changed. Inhibitors of caspase-8 and caspase-10 reduced caspase-3 activity and subsequent DNA fragmentation induced by sodium butyrate. These caspase inhibitors also inhibited the cleavage of pro-caspase-3 to the active forms indicated by Western blotting analysis. Pyrrolidine dithiocarbamate also inhibited the induction of caspase-10 mRNA expression and caspase-3 activation. Contrary to other reports, levels of Bcl-2, Bcl-XL and Bax mRNA expressions were not distinctly changed by even 5 mM sodium butyrate treatment. Our results suggest that sodium butyrate may trigger apoptosis via the induction of the caspase-10 expression.

  17. Preventive effects of butyric acid, nicotinamide, calcium glucarate alone or in combination during the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis via modulation of K-Ras-PI3K-AKTpathway and associated micro RNAs.

    PubMed

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2016-02-01

    Skin cancer is among the most common cancers worldwide and identifiable molecular changes for early and late stage of skin tumorigenesis can suggest the better targets for its control. In this study, we investigated the status of K-Ras-PI3K-AKTpathway followed by NF-κB, cyclin D1, MMP-9 and regulatory micro RNA during 7, 12-dimethylbenz[a]anthracene (DMBA) induced mouse skin tumorigenesis and its prevention by butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG), individually or in combination with respect to time. DMBA upregulated the K-Ras, PI3K, Akt, NF-κB, cyclin D1 and MMP-9, but downregulated the PTEN in a time dependent manner. DMBA also reduced the levels of micoRNA let-7a but induced the levels of miR-21 and miR-20a as a function of time. BA, NA and CAG were found to prevent DMBA induced changes, but they were most effective when used together in a combination. Reduced let-7a and miR-211 were correlated with the overexpression of K-Ras and MMP-9. Overexpression of miR-21 and miR-20a was correlated with the down regulation of PTEN and overexpression of Cyclin D1. Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management.

  18. Preventive effects of butyric acid, nicotinamide, calcium glucarate alone or in combination during the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis via modulation of K-Ras-PI3K-AKTpathway and associated micro RNAs.

    PubMed

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2016-02-01

    Skin cancer is among the most common cancers worldwide and identifiable molecular changes for early and late stage of skin tumorigenesis can suggest the better targets for its control. In this study, we investigated the status of K-Ras-PI3K-AKTpathway followed by NF-κB, cyclin D1, MMP-9 and regulatory micro RNA during 7, 12-dimethylbenz[a]anthracene (DMBA) induced mouse skin tumorigenesis and its prevention by butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG), individually or in combination with respect to time. DMBA upregulated the K-Ras, PI3K, Akt, NF-κB, cyclin D1 and MMP-9, but downregulated the PTEN in a time dependent manner. DMBA also reduced the levels of micoRNA let-7a but induced the levels of miR-21 and miR-20a as a function of time. BA, NA and CAG were found to prevent DMBA induced changes, but they were most effective when used together in a combination. Reduced let-7a and miR-211 were correlated with the overexpression of K-Ras and MMP-9. Overexpression of miR-21 and miR-20a was correlated with the down regulation of PTEN and overexpression of Cyclin D1. Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management. PMID:26655363

  19. Efficient bulk heterojunction solar cells with poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] and 6,6-phenyl C61 butyric acid methyl ester blends and their application in tandem cells.

    PubMed

    Zhao, Dewei; Tang, Weihua; Ke, Lin; Tan, Swee Tiam; Sun, Xiao Wei

    2010-03-01

    We present herein efficient bulk heterojunction (BHJ) solar cells via mixing poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] (F6T2) and 6,6-phenyl C61 butyric acid methyl ester (PCBM) with variable weight ratios. The photo-physics and morphology of F6T2:PCBM blend films and the electrical characteristics of their corresponding single cells were studied in details by changing PCBM concentration. The complete photoluminescence quenching of F6T2 emission occurs with only a small fraction of PCBM blended, demonstrating effective photoinduced charge transfer between F6T2 and PCBM. Morphology images from atomic force microscopy and scanning electron microscopy (SEM) reveal that the phase separation in F6T2:PCBM blend films becomes pronounced with the increase of PCBM concentration, resulting in the increased fill factor from 25.2% (1:1) to 56.9% (1:6). A SEM image also shows the phase separation is within the range of 10 - 20 nm. With the optimized F6T2:PCBM weight ratio (1:2), the single cell exhibits a highest power conversion efficiency of 2.46% due to the balance of light absorption and charge transport. Finally, the polymer-small molecule tandem cells are constructed using F6T2:PCBM BHJ as the bottom cell and copper phthalocyanine (CuPc):fullerene (C(60)) as the top cell. The open-circuit voltage (V(oc)) of tandem cell (1.27 V) is equal to the summation of the V(oc) values of the bottom cell (0.86 V) and the top cell (0.43 V). PMID:20356288

  20. Gamma-amino butyric acid inhibits the nicotine-imposed stimulatory challenge in xenograft models of non-small cell lung carcinoma.

    PubMed

    Al-Wadei, H A N; Al-Wadei, M H; Ullah, M F; Schuller, H M

    2012-02-01

    Non-small cell lung carcinoma (NSCLC) is the leading type of lung cancer; smoking is a documented risk factor. Nicotinic acetylcholine receptor (nAChR)-mediated intracellular signaling in response to nicotine has recently been implicated in the growth regulation of NSCLC. In the current study nude mice carrying xenografts of the human lung NSCLC cell lines NCI-H322 or NCI-H441 were used as animal models. Nicotine administration and gamma aminobutyric acid (GABA) treatment lasted for 30 days. Catecholamines, cortisol, GABA, and cAMP were analyzed in blood and tumor tissues by immunoassays. Expression of nicotinic receptors and effector proteins in the xenografts was assessed by Western blotting. Our data indicate that nicotine stimulated the growth of NSCLC xenografts via modulation of nAChR upregulation and activation of cAMP signaling. The nicotine-treated group showed an enhanced level of stress neurotransmitters and second messenger cAMP in serum, blood cellular fraction, and xenograft tissues. Activation of critical proteins in the oncogenic pathway, including CREB, ERK, Akt, and Src, and upregulation of α-4 and α-7 subunits of nAChR provided mechanistic insight for the observed stimulatory effect of nicotine. Interestingly, GABA, being an antagonist to cAMP signaling, showed a promising intervention by reversing the stimulatory effect of nicotine on cancer growth and all signaling pathways. GABA has potential to lower the risk of NSCLC among smokers and could be used to enhance the clinical outcome of standard cancer intervention strategies.

  1. Comparative Analysis of Protocols to Induce Human CD4+Foxp3+ Regulatory T Cells by Combinations of IL-2, TGF-beta, Retinoic Acid, Rapamycin and Butyrate.

    PubMed

    Schmidt, Angelika; Eriksson, Matilda; Shang, Ming-Mei; Weyd, Heiko; Tegnér, Jesper

    2016-01-01

    Regulatory T cells (Tregs) suppress other immune cells and are critical mediators of peripheral tolerance. Therapeutic manipulation of Tregs is subject to numerous clinical investigations including trials for adoptive Treg transfer. Since the number of naturally occurring Tregs (nTregs) is minute, it is highly desirable to develop a complementary approach of inducing Tregs (iTregs) from naïve T cells. Mouse studies exemplify the importance of peripherally induced Tregs as well as the applicability of iTreg transfer in different disease models. Yet, procedures to generate iTregs are currently controversial, particularly for human cells. Here we therefore comprehensively compare different established and define novel protocols of human iTreg generation using TGF-β in combination with other compounds. We found that human iTregs expressed several Treg signature molecules, such as Foxp3, CTLA-4 and EOS, while exhibiting low expression of the cytokines Interferon-γ, IL-10 and IL-17. Importantly, we identified a novel combination of TGF-β, retinoic acid and rapamycin as a robust protocol to induce human iTregs with superior suppressive activity in vitro compared to currently established induction protocols. However, iTregs generated by these protocols did not stably retain Foxp3 expression and did not suppress in vivo in a humanized graft-versus-host-disease mouse model, highlighting the need for further research to attain stable, suppressive iTregs. These results advance our understanding of the conditions enabling human iTreg generation and may have important implications for the development of adoptive transfer strategies targeting autoimmune and inflammatory diseases. PMID:26886923

  2. Comparative Analysis of Protocols to Induce Human CD4+Foxp3+ Regulatory T Cells by Combinations of IL-2, TGF-beta, Retinoic Acid, Rapamycin and Butyrate

    PubMed Central

    Schmidt, Angelika; Eriksson, Matilda; Shang, Ming-Mei; Weyd, Heiko; Tegnér, Jesper

    2016-01-01

    Regulatory T cells (Tregs) suppress other immune cells and are critical mediators of peripheral tolerance. Therapeutic manipulation of Tregs is subject to numerous clinical investigations including trials for adoptive Treg transfer. Since the number of naturally occurring Tregs (nTregs) is minute, it is highly desirable to develop a complementary approach of inducing Tregs (iTregs) from naïve T cells. Mouse studies exemplify the importance of peripherally induced Tregs as well as the applicability of iTreg transfer in different disease models. Yet, procedures to generate iTregs are currently controversial, particularly for human cells. Here we therefore comprehensively compare different established and define novel protocols of human iTreg generation using TGF-β in combination with other compounds. We found that human iTregs expressed several Treg signature molecules, such as Foxp3, CTLA-4 and EOS, while exhibiting low expression of the cytokines Interferon-γ, IL-10 and IL-17. Importantly, we identified a novel combination of TGF-β, retinoic acid and rapamycin as a robust protocol to induce human iTregs with superior suppressive activity in vitro compared to currently established induction protocols. However, iTregs generated by these protocols did not stably retain Foxp3 expression and did not suppress in vivo in a humanized graft-versus-host-disease mouse model, highlighting the need for further research to attain stable, suppressive iTregs. These results advance our understanding of the conditions enabling human iTreg generation and may have important implications for the development of adoptive transfer strategies targeting autoimmune and inflammatory diseases. PMID:26886923

  3. Sodium butyrate mitigates in vitro ammonia generation in cecal content of laying hens.

    PubMed

    Wang, Anping; Wang, Yan; Di Liao, Xin; Wu, Yinbao; Liang, Juan Boo; Laudadio, Vito; Tufarelli, Vincenzo

    2016-08-01

    One of the environmental challenges that modern poultry industry faced is odor pollution caused by ammonia emission. The objectives of the study were to determine the effect of sodium butyrate on the production of ammonia in the cecal contents of laying hens using in vitro gas production study and to elucidate the mechanism behind it. The study consisted of a control (without sodium butyrate), and three experimental groups added with 10, 15, and 20 mg of sodium butyrate, respectively. Results showed that ammonia production in headspace of the syringe decreased by 8.2, 23, and 23 %, respectively, while ammonium production from the fermentation broth decreased by 6.3, 14.4, and 13.7 %, respectively. Sodium butyrate had no significant effect on the contents of uric acid and urea, nitrate-N, or total N in all treatments. However, sodium butyrate decreased the urease and uricase activities (P < 0.05) in the fermentation broth. Sodium butyrate also altered volatile fatty acids profile of the fermentation broth by decreasing the production of isovalerate (P < 0.05) and increasing those of acetate, butyrate, and isobutyrate (P < 0.05). The MiSeq System Sequencing results showed that sodium butyrate increased the relative abundance of Bacteroides and Faecalibacterium (P < 0.05) and decreased the relative abundance of Desulfovibrio, Helicobacter, and Campylobacter (P < 0.05).Our results concluded that sodium butyrate changes the diversity and relative abundance of the microbes which altered the fermentation characteristics leading to reduction in ammonia production. PMID:27154844

  4. Sodium butyrate mitigates in vitro ammonia generation in cecal content of laying hens.

    PubMed

    Wang, Anping; Wang, Yan; Di Liao, Xin; Wu, Yinbao; Liang, Juan Boo; Laudadio, Vito; Tufarelli, Vincenzo

    2016-08-01

    One of the environmental challenges that modern poultry industry faced is odor pollution caused by ammonia emission. The objectives of the study were to determine the effect of sodium butyrate on the production of ammonia in the cecal contents of laying hens using in vitro gas production study and to elucidate the mechanism behind it. The study consisted of a control (without sodium butyrate), and three experimental groups added with 10, 15, and 20 mg of sodium butyrate, respectively. Results showed that ammonia production in headspace of the syringe decreased by 8.2, 23, and 23 %, respectively, while ammonium production from the fermentation broth decreased by 6.3, 14.4, and 13.7 %, respectively. Sodium butyrate had no significant effect on the contents of uric acid and urea, nitrate-N, or total N in all treatments. However, sodium butyrate decreased the urease and uricase activities (P < 0.05) in the fermentation broth. Sodium butyrate also altered volatile fatty acids profile of the fermentation broth by decreasing the production of isovalerate (P < 0.05) and increasing those of acetate, butyrate, and isobutyrate (P < 0.05). The MiSeq System Sequencing results showed that sodium butyrate increased the relative abundance of Bacteroides and Faecalibacterium (P < 0.05) and decreased the relative abundance of Desulfovibrio, Helicobacter, and Campylobacter (P < 0.05).Our results concluded that sodium butyrate changes the diversity and relative abundance of the microbes which altered the fermentation characteristics leading to reduction in ammonia production.

  5. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

    PubMed

    Stilling, Roman M; van de Wouw, Marcel; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2016-10-01

    Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication.

  6. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

    PubMed

    Stilling, Roman M; van de Wouw, Marcel; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2016-10-01

    Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication. PMID:27346602

  7. Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion.

    PubMed

    Liu, Bin; Qian, Jianmin; Wang, Qingbao; Wang, Fangrui; Ma, Zhenyu; Qiao, Yingli

    2014-01-01

    Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

  8. In vivo measurement of colonic butyrate metabolism in patients with quiescent ulcerative colitis

    PubMed Central

    Simpson, E; Chapman, M; Dawson, J; Berry, D; Macdonald, I; Cole, A

    2000-01-01

    BACKGROUND—Butyrate, a short chain fatty acid produced by bacterial fermentation, is a major fuel source for the colonocyte. In vitro work has shown that ulcerative colitis may be characterised by a metabolic defect in colonocyte butyrate oxidation.
AIMS—To investigate the rate of metabolism of rectally administered butyrate in patients with quiescent colitis.
METHODS—[1-13C]-butyrate enemas were administered to 11 patients with long standing quiescent ulcerative colitis and to 10 control patients. The rate of production of 13CO2 in exhaled breath over four hours was measured by isotope ratio mass spectrometry combined with indirect calorimetry in order to measure CO2 production. This allowed calculation of the patients' resting energy expenditure and respiratory quotient.
RESULTS—Over a four hour period, 325 (SEM 21) µmol 13CO2 was recovered in breath samples from the colitis group compared with 322 (17) µmol from the control group (NS). The respiratory quotient of the colitic group was significantly lower than that of the control group.
CONCLUSION—There was no difference in the rate of metabolism of butyrate between the two groups. It is unlikely that there is a primary metabolic defect of butyrate metabolism in patients with quiescent ulcerative colitis.


Keywords: ulcerative colitis; in vivo butyrate metabolism PMID:10601058

  9. Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate.

    PubMed

    Vrba, J; Dolezel, P; Ulrichova, J

    2010-01-01

    Differentiation of myeloid leukemic cells may result in less sensitivity to various apoptotic stimuli. We examined whether human leukemia HL-60 cells differentiating by all-trans retinoic acid (ATRA) acquired resistance to the apoptogenic activity of two histone deacetylase (HDAC) inhibitors, butyrate and valproate. In undifferentiated cells, the cytotoxicity of both butyrate and valproate was associated with activation of the intrinsic apoptotic pathway since we observed dissipation of mitochondrial membrane potential, induction of caspase-9 and caspase-3 activities, appearance of sub-G1 DNA and loss of plasma membrane asymmetry and/or integrity. Both HDAC inhibitors were also able to induce accumulation of undifferentiated cells in the G0/G1 phase of the cell cycle. ATRA was found to enhance the apoptotic effect of both butyrate and valproate in undifferentiated cells. This aside, ATRA appeared to synergize with butyrate in the induction of the G0/G1 cell cycle arrest. In cells pretreated for 72 h with ATRA, butyrate and valproate in combination with ATRA induced lower dissipation of mitochondrial membrane potential and weaker apoptotic and/or necrotic changes in plasma membrane, whereas DNA fragmentation was not diminished compared to undifferentiated cells. Similar results were also obtained when butyrate or valproate were combined with another neutrophilic differentiation inducer, dimethyl sulfoxide. We conclude that neutrophilic differentiation modulates but does not abrogate the apoptotic response of HL-60 cells to butyrate and valproate, and nuclei are preferentially affected during apoptosis in differentiated cells.

  10. Sodium butyrate maintains growth performance by regulating the immune response in broiler chickens.

    PubMed

    Zhang, W H; Jiang, Y; Zhu, Q F; Gao, F; Dai, S F; Chen, J; Zhou, G H

    2011-06-01

    1. The experiment was conducted to investigate the effects of dietary sodium butyrate on the growth performance and immune response of broiler chickens. In experiment 1, 240 1-d-old chickens were allocated into 4 dietary groups (0, 0·25, 0·50 or 1·00 g sodium butyrate/kg) with 6 replicates each. In experiment 2, 120 1-d-old chickens were fed a control diet (without sodium butyrate) or 1·00 g sodium butyrate/kg diet. Half of the chickens fed on each diet were injected intra-peritoneally with 0·5 g/kg body weight of Escherichia coli lipopolysaccharide (LPS) at 16, 18 and 20 d of age. 2. There was no effect of dietary sodium butyrate on growth performance. On d 21, serum interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) were decreased in chickens given 1·00 g sodium butyrate/kg, serum superoxide dismutase (SOD) and catalase activities were significantly increased, and malondialdehyde (MDA) was decreased by dietary sodium butyrate at 0·50 or 1·00 g/kg. On d 42, serum IL-6 was markedly decreased by dietary sodium butyrate, while 1·00 g sodium butyrate/kg greatly reduced MDA and increased catalase. 3. LPS challenge significantly reduced the growth performance of chickens. Serum IL-1β, IL-6, TNF-α, corticosterone, alpha-1 acid glycoprotein (AGP) and prostaglandin E(2) (PGE(2)) were increased in LPS-challenged chickens. Dietary sodium butyrate supplementation maintained the body weight gain and feed intake. Sodium butyrate supplementation inhibited the increase in IL-6 and AGP in serum at 16 d of age and TNF-α, corticosterone, AGP and PGE(2) at 20 d of age. Similar inhibitory effects of sodium butyrate in serum glucose and total protein concentrations were also found at 20 d of age. 4. The results indicated that dietary sodium butyrate supplementation can improve the growth performance in chickens under stress and that this may be used to moderate the immune response and reduce tissue damage.

  11. Effect of butyrate on immune response of a chicken macrophage cell line.

    PubMed

    Zhou, Z Y; Packialakshmi, B; Makkar, S K; Dridi, S; Rath, N C

    2014-11-15

    Butyric acid is a major short chain fatty acid (SCFA), produced in the gastrointestinal tract by anaerobic bacterial fermentation, that has beneficial health effects in many species including poultry. To understand the immunomodulating effects of butyrate on avian macrophage, we treated a naturally transformed line of chicken macrophage cells named HTC with Na-butyrate in the absence or presence of Salmonella typhimurium lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA), a metabolic activator, evaluating its various functional parameters. The results demonstrate that, butyrate by itself had no significant effect on variables such as nitric oxide (NO) production and the expression of genes associated with various inflammatory cytokines but it inhibited NO production, and reduced the expression of cytokines such as IL-1β, IL-6, IFN-γ, and IL-10 in LPS-stimulated cells. Butyrate decreased the expression of TGF-β3 in the presence or absence of LPS, while it had no effect on IL-4, Tβ4, and MMP2 gene expression. In addition, butyrate augmented PMA induced oxidative burst indicated by DCF-DA oxidation and restored LPS induced attenuation of tartrate resistant acid phosphatase (TRAP) activity. Although butyrate had no significant effect on phagocytosis or matrix metalloproteinase (MMP) activities of resting macrophages, it significantly suppressed the effects induced by their respective stimulants such as LPS induced phagocytosis and PMA induced MMP expression. These results suggest that butyrate has immunomodulatory property in the presence of agents that incite the cells thus, has potential to control inflammation and restore immune homeostasis.

  12. Lactobacillus acidophilus counteracts enteropathogenic E. coli-induced inhibition of butyrate uptake in intestinal epithelial cells.

    PubMed

    Kumar, Anoop; Alrefai, Waddah A; Borthakur, Alip; Dudeja, Pradeep K

    2015-10-01

    Butyrate, a key short-chain fatty acid metabolite of colonic luminal bacterial action on dietary fiber, serves as a primary fuel for the colonocytes, ameliorates mucosal inflammation, and stimulates NaCl absorption. Absorption of butyrate into the colonocytes is essential for these intracellular effects. Monocarboxylate transporter 1 (MCT1) plays a major role in colonic luminal butyrate absorption. Previous studies (Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. Adv Immunol 121: 91-119, 2014.) showed decreased MCT1 expression and function in intestinal inflammation. We have previously shown (Borthakur A, Gill RK, Hodges K, Ramaswamy K, Hecht G, Dudeja PK. Am J Physiol Gastrointest Liver Physiol 290: G30-G35, 2006.) impaired butyrate absorption in human intestinal epithelial Caco-2 cells due to decreased MCT1 level at the apical cell surface following enteropathogenic E. coli (EPEC) infection. Current studies, therefore, examined the potential role of probiotic Lactobacilli in stimulating MCT1-mediated butyrate uptake and counteracting EPEC inhibition of MCT1 function. Of the five species of Lactobacilli, short-term (3 h) treatment with L. acidophilus (LA) significantly increased MCT1-mediated butyrate uptake in Caco-2 cells. Heat-killed LA was ineffective, whereas the conditioned culture supernatant of LA (LA-CS) was equally effective in stimulating MCT1 function, indicating that the effects are mediated by LA-secreted soluble factor(s). Furthermore, LA-CS increased apical membrane levels of MCT1 protein via decreasing its basal endocytosis, suggesting that LA-CS stimulation of butyrate uptake could be secondary to increased levels of MCT1 on the apical cell surface. LA-CS also attenuated EPEC inhibition of butyrate uptake and EPEC-mediated endocytosis of MCT1. Our studies highlight distinct role of specific LA-secreted molecules in modulating colonic butyrate absorption. PMID:26272259

  13. Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages

    PubMed Central

    Millard, A L; Mertes, P M; Ittelet, D; Villard, F; Jeannesson, P; Bernard, J

    2002-01-01

    We studied the in vitro effects of butyric acid on differentiation, maturation and function of dendritic cells (DC) and macrophages (MΦ) generated from human monocytes. A non-toxic dose of butyrate was shown to alter the phenotypic differentiation process of DC as assessed by a persistence of CD14, and a decreased CD54, CD86 and HLA class II expression. The more immature differentiation stage of treated cells was confirmed further by their increased phagocytic capability, their altered capacity to produce IL-10 and IL-12, and their weak allostimulatory abilities. Butyrate also altered DC terminal maturation, regardless of the maturation inducer, as demonstrated by a strong down-regulation of CD83, a decreased expression of CD40, CD86 and HLA class II. Similarly, butyrate altered MΦ differentiation, down-regulating the expression of the restricted membrane antigens and reducing the phagocytic capacity of treated cells. To investigate further the mechanism by which butyrate hampers the monocyte dual differentiation pathway, we studied the effects of 1,25(OH)2D3 alone or in combination with butyrate on the phenotypic features of DC. Unlike 1,25(OH)2D3, butyrate inhibited DC differentiation without redirecting it towards MΦ. Combined treatment gave rise to a new cell subset (CD14high, CD86 and HLA-DRlow) phenotypically distinct from monocytes. These results reveal an alternative mechanism of inhibition of DC and MΦ differentiation. Altogether, our data demonstrate a novel immune suppression property of butyrate that may modulate both inflammatory and immune responses and support further the interest for butyrate and its derivatives as new immunotherapeutic agents. PMID:12390312

  14. The role of butyrate, a histone deacetylase inhibitor in diabetes mellitus: experimental evidence for therapeutic intervention.

    PubMed

    Khan, Sabbir; Jena, Gopabandhu

    2015-01-01

    The contribution of epigenetic mechanisms in diabetes mellitus (DM), β-cell reprogramming and its complications is an emerging concept. Recent evidence suggests that there is a link between DM and histone deacetylases (HDACs), because HDAC inhibitors promote β-cell differentiation, proliferation, function and improve insulin resistance. Moreover, gut microbes and diet-derived products can alter the host epigenome. Furthermore, butyrate and butyrate-producing microbes are decreased in DM. Butyrate is a short-chain fatty acid produced from the fermentation of dietary fibers by microbiota and has been proven as an HDAC inhibitor. The present review provides a pragmatic interpretation of chromatin-dependent and independent complex signaling/mechanisms of butyrate for the treatment of Type 1 and Type 2 DM, with an emphasis on the promising strategies for its drugability and therapeutic implication.

  15. n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells

    SciTech Connect

    Diakos, Christos; Prieschl, Eva E.; Saeemann, Marcus D.; Boehmig, Georg A.; Csonga, Robert; Sobanov, Yury; Baumruker, Thomas; Zlabinger, Gerhard J. . E-mail: gerhard.zlabinger@meduniwien.ac.at

    2006-10-20

    Mast cells are well known to contribute to type I allergic conditions but only recently have been brought in association with chronic relapsing/remitting autoimmune diseases such as celiac disease and ulcerative colitis. Since the bacterial metabolite n-butyrate is considered to counteract intestinal inflammation we investigated the effects of this short chain fatty acid on mast cell activation. Using RNAse protection assays and reporter gene technology we show that n-butyrate downregulates TNF-{alpha} transcription. This correlates with an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a consequence, we observed a decreased nuclear activity of AP-1 and NF-AT transcription factors. These results indicate that n-butyrate inhibits critical inflammatory mediators in mast cells by relatively selectively targeting the JNK signalling.

  16. Varying butyric acid amounts induce different stress- and cell death-related signals in nerve growth factor-treated PC12 cells: implications in neuropathic pain absence during periodontal disease progression.

    PubMed

    Seki, Keisuke; Cueno, Marni E; Kamio, Noriaki; Saito, Yuko; Kamimoto, Atsushi; Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu

    2016-06-01

    Neuropathic pain is absent from the early stages of periodontal disease possibly due to neurite retraction. Butyric acid (BA) is a periodontopathic metabolite that activates several stress-related signals and, likewise, induce neurite retraction. Neuronal cell death is associated to neurite retraction which would suggest that BA-induced neurite retraction is ascribable to neuronal cell death. However, the underlying mechanism of BA-related cell death signaling remains unknown. In this study, we exposed NGF-treated PC12 cells to varying BA concentrations [0 (control), 0.5, 1.0, 5.0 mM] and determined selected stress-related (H2O2, glutathione reductase, calcium (Ca(2+)), plasma membrane Ca(2+) ATPase (PMCA), and GADD153/CHOPS) and cell death-associated (extrinsic: FasL, TNF-α, TWEAK, and TRAIL; intrinsic: cytochrome C (CytC), NF-kB, CASP8, CASP9, CASP10, and CASP3) signals. Similarly, we confirmed cell death execution by chromatin condensation. Our results showed that low (0.5 mM) and high (1.0 and 5.0 mM) BA levels differ in stress and cell death signaling. Moreover, at periodontal disease-level BA concentration (5 mM), we observed that only FasL amounts were affected and occurred concurrently with chromatin condensation insinuating that cells have fully committed to neurodegeneration. Thus, we believe that both stress and cell death signaling in NGF-treated PC12 cells are affected differently depending on BA concentration. In a periodontal disease scenario, we hypothesize that during the early stages, low BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurite non-proliferation, whereas, during the later stages, high BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurodegeneration. More importantly, we propose that neuropathic pain absence at any stage of periodontal disease progression is ascribable to BA accumulation regardless of amount. PMID:26994613

  17. Derivation of a human equivalent concentration for n-butanol using a physiologically based pharmacokinetic model for n-butyl acetate and metabolites n-butanol and n-butyric acid

    SciTech Connect

    Teeguarden, Justin G.; Deisinger, P. J.; Poet, Torka S.; English, J C.; Faber, W D.; Barton, H. A.; Corley, Rick A.; Clewell, III, H. J.

    2005-05-01

    The metabolic series (family) approach for risk assessment uses a dosimetry-based analysis to develop toxicity information for a group of metabolically linked compounds using pharmacokinetic (PK) data for each compound and toxicity data for the parent compound. An initial physiologically-based pharmacokinetic (PBPK) model was developed to support the implementation of the metabolic series approach for n-butyl acetate and its subsequent metabolites, n-butanol, and n-butyric acid (the butyl series) (Barton et al. 2000). In conjunction with pilot pharmacokinetic studies, the model was used to design the definitive intravenous (i.v.) PK studies. Rats were implanted with dual indwelling cannulae and administered test compounds by i.v. bolus dose, i.v. infusion, or by inhalation in a recirculating closed chamber. Hepatic, vascular and extravascular metabolic constants for metabolism were estimated by fitting the model to the blood time course data from these experiments. The respiratory bioavailability of n-butyl acetate and n-butanol was estimated from closed chamber inhalation studies and measured ventilation rates. The resulting butyl series PBPK model successfully reproduces the blood time course of these compounds following i.v. administration, and inhalation exposure to n-butyl acetate and n-butanol. A fully scaled human version of the model successfully reproduces arterial blood n-butanol kinetics following inhalation exposure to n-butanol. These validated i.v (rat) and inhalation route models (rat, butyl acetate, n-butanol; human, butanol only) can be used to support species and dose-route extrapolations required for risk assessment of butyl series family of compounds. Further, this work demonstrates the usefulness of i.v. kinetic data for parameterization of systemic metabolism and the value of collaboration between experimentalists and kineticists in the development of PBPK models. The product of this effort, validated rat and human PBPK models for the butyl

  18. Effect of partially protected butyrate used as feed additive on growth and intestinal metabolism in sea bream (Sparus aurata).

    PubMed

    Robles, R; Lozano, A B; Sevilla, A; Márquez, L; Nuez-Ortín, W; Moyano, F J

    2013-12-01

    Butyrate is a short-chain fatty acid extensively used in animal nutrition since it promotes increases in body weight and other multiple beneficial effects on the intestinal tract. Although such effects have been demonstrated in several species, very few studies have assessed them in fish. On the other hand, little is known about the metabolic processes underlying these effects. In the present work, growth parameters and changes in more than 80 intestinal metabolites (nucleotides, amino acids and derivatives, glycolytic intermediates, redox coenzymes and lipid metabolism coenzymes) have been quantified in juvenile sea bream fed a butyrate-supplemented diet. Results showed a significant increase in the weight of fish receiving butyrate, while metabolomics provided some clues on the suggested effects of this feed additive. It seems that butyrate increased the availability of several essential amino acids and nucleotide derivatives. Also, the energy provision for enteric cells might have been enhanced by a decrease in glucose and amino acid oxidation related to the use of butyrate as fuel. Additionally, butyrate might have increased transmethylation activity. This work represents an advance in the knowledge of the metabolic consequences of using butyrate as an additive in fish diets.

  19. Crystal structure of catena-poly[bis(formato-κO)bis-[μ2-1,1'-(1,4-phenyl-ene)bis-(1H-imidazole)-κ(2) N (3):N (3')]cobalt(II)].

    PubMed

    Xu, Guo-Wang; Wang, Ye-Nan; Xia, Hong-Xu; Wang, Zhong-Long

    2015-09-01

    A red block-shaped crystal of the title compound, [Co(HCOO)2(C12H10N4)2] n , was obtained by the reaction of cobalt(II) nitrate hexa-hydrate, formic acid and 1,1'-(1,4-phenyl-ene)bis-(1H-imidazole) (bib) mol-ecules. The asymmetric unit consists of one Co(II) cation, one formate ligand and two halves of a bib ligand. The central Co(II) cation, located on an inversion centre, is coordinated by two carboxyl-ate O atoms and four N atoms from bib ligands, completing an octa-hedral coordination geometry. The Co(II) centres are bridged by bib ligands, giving a two-dimensional net. Topologically, taking the Co(II) atoms as nodes and the bib ligands as linkers, the two-dimensional structure can be simplified as a typical sql/Shubnikov tetra-gonal plane network. The structure features C-H⋯O hydrogen-bonding inter-actions between formate and bib ligands, resulting in a three-dimensional supra-molecular network. PMID:26396863

  20. O-Ethyl S-{(S)-1-oxo-1-[(R)-2-oxo-4-phenyl­oxazolidin-3-yl]propan-2-yl} carbonodi­thio­ate

    PubMed Central

    García-Merinos, J. Pablo; López-Ruiz, Heraclio; López, Yliana; Rojas-Lima, Susana

    2014-01-01

    In the title compound, C15H17NO4S2, synthesized by addition of O-ethylxanthic acid potassium salt to a diastereomeric mixture of (4R)-3-(2-chloro­propano­yl)-4-phenyl­oxazolidin-2-one, the oxazolidinone ring has a twist conformation on the C—C bond. The phenyl ring is inclined to the mean plane of the oxazolidinone ring by 76.4 (3)°. In the chain the methine H atom is involved in a C—H⋯S and a C—H⋯O intra­molecular inter­action. In the crystal, mol­ecules are linked by C—H⋯π inter­actions, forming chains along [001]. The S configuration at the C atom to which the xanthate group is attached was determined by comparison to the known R configuration of the C atom to which the phenyl group is attached. PMID:24860384

  1. Unusual aggregation of bis(2-quinuclidinium-butyrate) hydrobromides

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.

    2010-12-01

    The molecular structure of di-[bis(2-quinuclidinium-butyrate) hydrobromide], [(QNBu) 2HBr] 2 ( 1), has been characterized by single-crystal X-ray diffraction, infrared spectroscopy and DFT calculations. The crystals ( 1) are monoclinic, space group P2 1/c with [(QNBu) 2HBr] 2 symmetry-independent units. The complex 1 consists of two independent homoconjugated cations, in which two ( S) QNBu semications, and ( S) and ( R) QNBu semications are joined by short, symmetrical O⋯H⋯O hydrogen bonds of 2.418(12) and 2.411(13) Å, respectively. The bromide anions interact electrostatically with the one positively charged nitrogen atom of each cation. The presence of short OHO hydrogen bonds is confirmed by the broad absorption in the 1500-400 cm -1 region, with the center of gravity, νH, at ca. 900 cm -1, in the solid-state FTIR spectrum. In the structure of [(QNBu) 2HBr] 2 ( 2) optimized at the B3LYP/6-31G(d,p) level of theory, the 2-quinuclidinium-butyrate units are non-equivalent. In each homoconjugated cation the 2-quinuclidinium-butyric acid interacts with the QNBu inner salt by the short, asymmetric O-H···O hydrogen bonds of 2.440 and 2.446 Å, respectively. Each bromide anion interacts electrostatically with the positively charged nitrogen atoms from both homoconjugated cations, which fold into a globular supramolecular aggregate.

  2. Transcriptome characterization by RNA-seq unravels the mechanisms of butyrate-induced epigenomic regulation in bovine cells.

    PubMed

    Wu, Sitao; Li, Robert W; Li, Weizhong; Li, Cong-Jun

    2012-01-01

    Short-chain fatty acids (SCFAs), especially butyrate, affect cell differentiation, proliferation, and motility. Butyrate also induces cell cycle arrest and apoptosis through its inhibition of histone deacetylases (HDACs). In addition, butyrate is a potent inducer of histone hyper-acetylation in cells. Therefore, this SCFA provides an excellent in vitro model for studying the epigenomic regulation of gene expression induced by histone acetylation. In this study, we analyzed the differential in vitro expression of genes induced by butyrate in bovine epithelial cells by using deep RNA-sequencing technology (RNA-seq). The number of sequences read, ranging from 57,303,693 to 78,933,744, were generated per sample. Approximately 11,408 genes were significantly impacted by butyrate, with a false discovery rate (FDR) <0.05. The predominant cellular processes affected by butyrate included cell morphological changes, cell cycle arrest, and apoptosis. Our results provided insight into the transcriptome alterations induced by butyrate, which will undoubtedly facilitate our understanding of the molecular mechanisms underlying butyrate-induced epigenomic regulation in bovine cells.

  3. Butyrate suppresses proliferation and migration of RKO colon cancer cells though regulating endocan expression by MAPK signaling pathway.

    PubMed

    Zuo, Li; Lu, Man; Zhou, Qing; Wei, Wei; Wang, Yuan

    2013-12-01

    Butyrate is a short-chain fatty acid produced by colonic bacterial fermentation. In colon cancer cells butyrate is able to suppress cell growth, induce apoptosis. It also inhibits tumor growth in vivo. However, the underlying mechanism is still not fully understood. We hypothesize that butyrate regulates the growth and migration of colon cancer cells by altering endocan expression. To test this hypothesis, we performed quantitative real time RT–PCR and Western blots, and found that butyrate increased endocan expression of colon cancer cell RKO. Moreover, endocan over-expression inhibited RKO proliferation, migration and colony formation. Functionally, butyrate significantly suppressed RKO proliferation, migration, and colony formation, as well as induced apoptosis. Knocking down endogenous endocan was able to attenuate the inhibitory role of butyrate in RKO migration and proliferation. Since our results showed that butyrate inhibited MAPK/ERK2 phosphorylation. To determine whether ERK2 signaling is associated with endocan expression, we knocked down endogenous ERK2 expression. Our results showed that knocking down ERK2 expression up-regulated endocan expression. Taken together, these results suggested that butyrate suppressed RKO proliferation, colony formation, migration through up-regulating endocan expression via ERK2/MAPK signaling pathway.

  4. Butyrate: A dietary inhibitor of histone deacetylases and an epigenetic regulator

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The short-chain fatty acids (SCFAs) acetate, propionate and butyrate, also known as volatile fatty acids (VFA), are produced in the gastrointestinal tract by microbial fermentation. Consumption of dietary fibers has been shown to have positive metabolic health effects, such as increasing satiety, an...

  5. Perturbation dynamics of the rumen microbiota in response to exogenous butyrate.

    PubMed

    Li, Robert W; Wu, Sitao; Baldwin, Ransom L; Li, Weizhong; Li, Congjun

    2012-01-01

    The capacity of the rumen microbiota to produce volatile fatty acids (VFAs) has important implications in animal well-being and production. We investigated temporal changes of the rumen microbiota in response to butyrate infusion using pyrosequencing of the 16S rRNA gene. Twenty one phyla were identified in the rumen microbiota of dairy cows. The rumen microbiota harbored 54.5±6.1 genera (mean ± SD) and 127.3±4.4 operational taxonomic units (OTUs), respectively. However, the core microbiome comprised of 26 genera and 82 OTUs. Butyrate infusion altered molar percentages of 3 major VFAs. Butyrate perturbation had a profound impact on the rumen microbial composition. A 72 h-infusion led to a significant change in the numbers of sequence reads derived from 4 phyla, including 2 most abundant phyla, Bacteroidetes and Firmicutes. As many as 19 genera and 43 OTUs were significantly impacted by butyrate infusion. Elevated butyrate levels in the rumen seemingly had a stimulating effect on butyrate-producing bacteria populations. The resilience of the rumen microbial ecosystem was evident as the abundance of the microorganisms returned to their pre-disturbed status after infusion withdrawal. Our findings provide insight into perturbation dynamics of the rumen microbial ecosystem and should guide efforts in formulating optimal uses of probiotic bacteria treating human diseases.

  6. Oral supplementation of butyrate reduces mucositis and intestinal permeability associated with 5-Fluorouracil administration.

    PubMed

    Ferreira, Talita Mayra; Leonel, Alda Jusceline; Melo, Marco Antônio; Santos, Rosana R G; Cara, Denise Carmona; Cardoso, Valbert N; Correia, Maria I T D; Alvarez-Leite, Jacqueline I

    2012-07-01

    Mucositis affects about 40 % of patients undergoing chemotherapy. Short chain fatty acids (SCFA), mainly butyrate, are claimed to improve mucosal integrity, reduce intestinal permeability and act as anti-inflammatory agents for the colon mucosa. We evaluated the effects of oral administration of SCFA or butyrate in the 5FU-induced mucositis. Mice received water, SCFA or butyrate during all experiment (10 days) and a single dose of 5FU (200 mg/kg) 3 days before euthanasia. We evaluated inflammatory and histological score by morphometry, and by activity of enzymes specific to neutrophil, eosinophil and macrophage and TLR-4, TNF-alpha and IL6 expressions. Intestinal permeability and tight junction protein ZO-1 expression were evaluated. Mice from the 5FU (5-Fluorouracil) group presented weight loss, ulcerations and inflammatory infiltration of neutrophils and eosinophils, increased expression of IL6 and TNF-alpha and increased intestinal permeability. SCFA minimized intestinal damage, reduced ulcerations without affecting intestinal permeability. Butyrate alone was more efficient at improving those parameters than in SCFA solution and also reduced intestinal permeability. The expression of pro-inflammatory cytokines and ZO-1 tended to be higher in the SCFA supplemented but not in the butyrate supplemented group. We showed the beneficial effects of butyrate on intestinal mucositis and its promising function as an adjuvant in the treatment of diseases not only of the colon, but also of the small intestine.

  7. ANGPTL4 expression induced by butyrate and rosiglitazone in human intestinal epithelial cells utilizes independent pathways.

    PubMed

    Korecka, Agata; de Wouters, Tomas; Cultrone, Antonietta; Lapaque, Nicolas; Pettersson, Sven; Doré, Joël; Blottière, Hervé M; Arulampalam, Velmurugesan

    2013-06-01

    Short-chain fatty acids (SCFAs), such as butyrate and propionate, are metabolic products of carbohydrate fermentation by the microbiota and constitute the main source of energy for host colonocytes. SCFAs are also important for gastrointestinal health, immunity, and host metabolism. Intestinally produced angiopoietin-like protein 4 (ANGPTL4) is a secreted protein with metabolism-altering properties and may offer a route by which microbiota can regulate host metabolism. Peroxisome proliferator-activated receptor (PPAR)-γ has previously been shown to be involved in microbiota-induced expression of intestinal ANGPTL4, but the role of bacterial metabolites in this process has remained elusive. Here, we show that the SCFA butyrate regulates intestinal ANGPTL4 expression in a PPAR-γ-independent manner. Although PPAR-γ is not required for butyrate-driven intestinal ANGPTL4 expression, costimulating with PPAR-γ ligands and SCFAs leads to additive increases in ANGPTL4 levels. We suggest that PPAR-γ and butyrate rely on two separate regulatory sites, a PPAR-responsive element downstream the transcription start site and a butyrate-responsive element(s) within the promoter region, 0.5 kb upstream of the transcription start site. Furthermore, butyrate gavage and colonization with Clostridium tyrobutyricum, a SCFA producer, can independently induce expression of intestinal ANGPTL4 in germ-free mice. Thus, oral administration of SCFA or use of SCFA-producing bacteria may be additional routes to maintain intestinal ANGPTL4 levels for preventive nutrition or therapeutic purposes.

  8. Biochemical and morphological effects of sodium butyrate on Dictyostelium discoideum development.

    PubMed

    Boto, L; Cano, A; Pestaña, A

    1987-04-01

    Pretreatment of proliferating D. discoideum amoebae with 10 mM butyrate for at least 8 h (one duplicating time) induced a reversible and dose dependent premature expression of several developmental parameters when the cells were starved in the absence of the fatty acid. The aggregative phase of the morphogenetic cycle was reduced in 2 h and the appearance of mature fruiting bodies and spores took place 4 h earlier as a result of butyrate pretreatment. Some developmentally regulated proteins, such as contact-sites A, cell surface lectins and cyclic AMP phosphodiesterase were also expressed 2 h earlier in butyrate pretreated cells than in controls. The level of extracellular cyclic AMP was reduced in butyrate pretreated cells, while other parameters of cyclic AMP metabolism were not affected. Butyrate also caused a partial inhibition of growth and the hyperacetylation of histone H4 in growing amoeba. These results suggest that butyrate acts as an inducer of differentiation in D. discoideum and can therefore be used as an experimental tool in order to explore regulatory mechanisms operating in slime mold differentiation. PMID:3037305

  9. Butyrate-mediated acquisition of chemoresistance by human colon cancer cells.

    PubMed

    Kang, Hyang Ri; Choi, Hyeon Gyeom; Jeon, Chae Kyung; Lim, Soo-Jeong; Kim, So Hee

    2016-08-01

    Butyrate is a short-chain fatty acid produced by the intestinal microflora and it not only induces apoptosis but also inhibits the proliferation of cancer cells. Recently, it has been reported that butyrate may cause resistance in colon cancer cells. Therefore, we investigated the effects of increased resistance to butyrate in HCT116 colon cancer cells. We established HCT116 cells resistant to butyrate (HCT116/BR) by treating HCT116 parental cells (HCT116/PT) with increasing concentrations of butyrate to a maximum of 1.6 mM for 3 months. The butyrate concentrations that inhibited cell growth by 50% (IC50) were 0.508 and 5.50 mM in HCT116/PT and HCT116/BR cells. The values after treatment with paclitaxel, 5-fluorouracil (5-FU), doxorubicin and trichostatin A (TSA) were 2.42, 2.36, 4.31 and 11.3-fold higher, respectively, in HCT116/BR cells compared with HCT116/PT cells. The protein expression of drug efflux pumps, such as P-glycoprotein (P-gp), breast cancer-resistant protein (BCRP) and the multidrug resistance associated protein 1 (MRP1), did not differ between HCT116/PT and HCT116/BR cells. The expression level of the anti-apoptotic Bcl-xL protein was increased while those of pro-apoptotic Bax and Bim proteins were reduced in HCT116/BR cells. There were no significant differences in cell motility and invasion. This study suggests that exposure of colon cancer cells to butyrate results in development of resistance to butyrate, which may play a role in the acquisition of chemoresistance in colon cancer. PMID:27277338

  10. Characterization of butyrate transport across the luminal membranes of equine large intestine.

    PubMed

    Nedjadi, Taoufik; Moran, Andrew W; Al-Rammahi, Miran A; Shirazi-Beechey, Soraya P

    2014-10-01

    The diet of the horse, pasture forage (grass), is fermented by the equine colonic microbiota to short-chain fatty acids, notably acetate, propionate and butyrate. Short-chain fatty acids provide a major source of energy for the horse and contribute to many vital physiological processes. We aimed to determine both the mechanism of butyrate uptake across the luminal membrane of equine colon and the nature of the protein involved. To this end, we isolated equine colonic luminal membrane vesicles. The abundance and activity of cysteine-sensitive alkaline phosphatase and villin, intestinal luminal membrane markers, were significantly enriched in membrane vesicles compared with the original homogenates. In contrast, the abundance of GLUT2 protein and the activity of Na(+)-K(+)-ATPase, known markers of the intestinal basolateral membrane, were hardly detectable. We demonstrated, by immunohistochemistry, that monocarboxylate transporter 1 (MCT1) protein is expressed on the luminal membrane of equine colonocytes. We showed that butyrate transport into luminal membrane vesicles is energized by a pH gradient (out < in) and is not Na(+) dependent. Moreover, butyrate uptake is time and concentration dependent, with a Michaelis-Menten constant of 5.6 ± 0.45 mm and maximal velocity of 614 ± 55 pmol s(-1) (mg protein)(-1). Butyrate transport is significantly inhibited by p-chloromercuribenzoate, phloretin and α-cyano-4-hydroxycinnamic acid, all potent inhibitors of MCT1. Moreover, acetate and propionate, as well as the monocarboxylates pyruvate and lactate, also inhibit butyrate uptake. Data presented here support the conclusion that transport of butyrate across the equine colonic luminal membrane is predominantly accomplished by MCT1.

  11. Synthesis, characterization, and crystal structure of 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c] pyran-3-carbonitrile

    SciTech Connect

    Sharma, S.; Banerjee, B.; Brahmachari, G.; Kant, Rajni; Gupta, V. K.

    2015-12-15

    2-Amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c] pyran-3-carbonitrile, C{sub 16}H{sub 12}N{sub 2}O{sub 3} is synthesized via one-pot multi-component reaction at room temperature using commercially available urea as inexpensive and environmentally benign organo-catalyst. Its structure is determined by single-crystal X-ray diffraction technique The crystals are monoclinic, a = 10.7357(12), b = 8.7774(8), c = 15.0759(16) Å, β = 103.575(11)°, Z = 4, sp. gr. P2{sub 1}/n, R = 0.0551 for 1696 observed reflections. The crystal structure is stabilized by N–H···N, C–H···O, and C–H···π interactions.

  12. Detoxification of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by cytochrome P450 enzymes: A theoretical investigation.

    PubMed

    Li, Xiao-Xi; Wang, Yong; Zheng, Qing-Chuan; Zhang, Hong-Xing

    2016-01-01

    Two types of detoxification routes, N-demethylation to form 4-phenyl-1,2,3,6-tetrahydropyridine (PTP) and aromatic hydroxylation to generate 4-(4'-hydroxyphenyl)-1-methyl-1,2,3,6-tetrahydropyridine (MPTP-OH), for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mediated by Compound I (Cpd I) of cytochrome P450 are investigated theoretically using hybrid density functional calculations. Quantum chemical results reveal that for the N-demethylation, the initial C-H bond activation is achieved via a hydrogen atom transfer (HAT) mechanism. This is followed by a subsequent O-rebound to yield the carbinolamine intermediate. Due to the nature of pericyclic reaction, the generated carbinolamine decomposes in a non-enzymatic aqueous environment with the assistance of water molecules, forming amine and hydrated formaldehyde. For the aromatic hydroxylation, an initial addition of Cpd I to the substrate occurs mainly through a side-on approach with a subsequent proton shuttle to form the phenol product. A comparison of the energy barriers for both routes indicates that the N-demethylation (7.5/5.7kcal/mol for the quartet/doublet state in solvent) is thermodynamically more favorable than the aromatic hydroxylation process (14.9/14.8kcal/mol for the quartet/doublet state in solvent). This trend is in good agreement with the experimental product distribution, viz., the N-demethylation product PTP is more than the aromatic hydroxylation product MPTP-OH. Taken together, these observations not only enrich our knowledge on the mechanistic details of the N-dealkylation and the aromatic hydroxylation by P450s, but also provide certain insights into the metabolism of other analogous toxins. PMID:26544505

  13. Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model.

    PubMed

    Yadav, Satyndra Kumar; Prakash, Jay; Chouhan, Shikha; Westfall, Susan; Verma, Mradul; Singh, Tryambak Deo; Singh, Surya Pratap

    2014-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In Ayurveda, Mucuna pruriens (Mp), a leguminous plant, is used as an anti-inflammatory drug. In this study, the neuroprotective effect of an ethanolic extract of Mp seed is evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and compared to estrogen, a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+Mp and MPTP+estrogen. The behavioural recovery in both Mp and estrogen treated mice was investigated using the rotarod, foot printing and hanging tests. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by tyrosine hydroxylase (TH), immunostaining. Additionally inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity was evaluated to assess the level of oxidative damage and glial activation respectively. The levels of dopamine and its metabolite in the nigrostriatal region were measured by HPLC. Mp treatment restored all the deficits induced by MPTP more effectively than estrogen. Mp treatment recovered the number of TH-positive cells in both the SN region and the striatum while reducing the expression of iNOS and GFAP in the SN. Treatment with Mp significantly increased the levels of dopamine, DOPAC and homovanillic acid compared to MPTP intoxicated mice. Notably, the effect of Mp was greater than that elicited by estrogen. Mp down regulates NO production, neuroinflammation and microglial activation and all of these actions contribute to Mp's neuroprotective activity. These results suggest that Mp can be an effective treatment for neurodegenerative diseases, especially PD by decreasing oxidative stress and possibly by

  14. Butyrate delivered by butyrylated starch increases distal colonic epithelial apoptosis in carcinogen-treated rats.

    PubMed

    Clarke, Julie M; Young, Graeme P; Topping, David L; Bird, Anthony R; Cobiac, Lynne; Scherer, Benjamin L; Winkler, Jessica G; Lockett, Trevor J

    2012-01-01

    Animal studies show that increasing large bowel butyrate concentration through ingestion of butyrylated or resistant starches opposes carcinogen-induced tumorigenesis, which is consistent with population data linking greater fiber consumption with lowered colorectal cancer (CRC) risk. Butyrate has been shown to regulate the apoptotic response to DNA damage. This study examined the impact of increasing large bowel butyrate concentration by dietary butyrylated starch on the colonic epithelium of rats treated with the genotoxic carcinogen azoxymethane (AOM). Four groups of 10 male rats were fed AIN-93G based-diets containing either low amylose maize starch (LAMS), LAMS with 3% tributyrin, 10% high amylose maize starch (HAMS) or 10% butyrylated HAMS (HAMSB). HAMS and HAMSB starches were cooked by heating in water. After 4 weeks, rats were injected once with AOM and killed 6 h later. Rates of apoptosis and proliferation were measured in colonic epithelium. Short-chain fatty acid concentrations in large bowel digesta and hepatic portal venous plasma were higher in HAMSB than all other groups. Apoptotic rates in the distal colon were increased by HAMSB and correlated with luminal butyrate concentrations but cellular proliferation rates were unaffected by diet. The increase in apoptosis was most marked in the base and proliferative zone of the crypt. Regulation of luminal butyrate using HAMSB increases the rates of apoptotic deletion of DNA-damaged colonocytes. We propose this pro-apoptotic function of butyrate plays a major role reducing tumour formation in the AOM-treated rat and that these data support a potential protective role of butyrate in CRC.

  15. Short communication: Interrelationship between butyrate and glucose supply on butyrate and glucose oxidation by ruminal epithelial preparations.

    PubMed

    Wiese, B I; Górka, P; Mutsvangwa, T; Okine, E; Penner, G B

    2013-09-01

    The aim of this study was to determine whether dietary Na-butyrate supplementation affects butyrate and glucose oxidation by ruminal epithelial preparations and whether this effect can be acutely modulated by substrate (glucose and butyrate) supply. Eighteen Suffolk wether lambs (6 lambs/treatment) were blocked by body weight and, within block, randomly assigned to the control treatment (CON) or to diets containing differing Na-butyrate inclusion rates (1.58 or 3.16%) equating to 1.25 (B1.25), and 2.50% (B2.50) butyrate on a dry matter basis, respectively. All lambs received their diet for a period of 14 d. After dietary adaptation, lambs were killed and the ruminal epithelium was harvested from the ventral sac, minced finely, and used for in vitro incubations. Incubation medium contained either a constant concentration of glucose (4 mM) with increasing butyrate concentrations (0, 5, 15, 25, or 40 mM) or a constant butyrate concentration (15 mM) with increasing glucose concentrations (0, 1, 2, 4, or 8 mM) to allow for the evaluation of whether acute changes in the concentration of metabolic substrates affect the oxidation of glucose and butyrate. We observed no interactions between the in vivo and in vitro treatments. Increasing dietary butyrate supplementation linearly decreased glucose oxidation by ruminal epithelial preparations, but had no effect on butyrate oxidation. Increasing butyrate concentration in vitro decreased (cubic effect) glucose oxidation when butyrate concentration ranged between 5 and 15 mM; however, glucose oxidation was increased with a butyrate concentration of 40 mM. Butyrate oxidation decreased (cubic effect) as glucose concentration increased from 1 to 4 mM; however, butyrate oxidation increased when glucose was included at 8mM. The results of this study demonstrate that dietary butyrate supplementation can decrease glucose oxidation by the ruminal epithelium, but the relative supply of glucose and butyrate has a pronounced effect on

  16. Fluoro-Jade C can specifically stain the degenerative neurons in the substantia nigra of the 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine-treated C57BL/6 mice.

    PubMed

    Bian, Gan-Lan; Wei, Li-Chun; Shi, Mei; Wang, Yan-Qin; Cao, Rong; Chen, Liang-Wei

    2007-05-30

    Fluoro-Jade C, a new-developed fluorescent dye, has been successfully applied for identification of neuronal degeneration in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated mice in the present study. The animal model was first prepared by intraperitoneal injection of neurotoxicant MPTP that can specifically induce degeneration of dopamine neurons in the substantia nigra of C57BL/6 mice. Fluoro-Jade C was then utilized to stain the midbrain sections and semiquantitation analysis was carried out in comparison with controls. It revealed that Fluoro-Jade C-positive cells showed strong green color in neuronal profile and were observed in the substantia nigra of MPTP-treated mice whereas they were not detected in that of controls. The Fluoro-Jade C-positive cells were mostly shrunken or smaller-sized in their cell bodies in comparing with that of normal dopamine neurons of controls. In the midbrain of MPTP-treated mice, Fluoro-Jade C-positive neuronal cells were exclusively distributed in the substantia nigra pars compacta, but rarely seen in the ventral tegemental area where dopamine neurons were numerously distributed. Double-labeling experiments indicated that a population of Fluoro-Jade C-positive cells (23%) exhibited neuron-specific nuclear protein-immunoreactivity and none of them showed immunoreactivity to glial cell marker glial fibrillary acid protein. However, most of Fluoro-Jade C-positive degenerative neurons (98%) lost their immunoreactivity to dopaminergic marker tyrosine hydroxylase in the substantia nigra of MPTP-treated mice. Taken together with previous observations, this study has presented that Fluoro-Jade C can be sensitively and specifically utilized to identify the neuronal degeneration in the substantia nigra of rodent animals receiving MPTP insult.

  17. Perturbation dynamics of the rumen microbiota in response to exogenous butyrate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The capacity of the rumen microbiota to produce volatile fatty acids (VFA) has important implications in animal well-being and production. We investigated temporal changes of the rumen microbiota in response to butyrate infusion using pyrosequencing of the 16S rRNA gene. Phyla were identified in ...

  18. Feeding trial in pigs with a diet containing sodium n-butyrate.

    PubMed

    Gálfi, P; Bokori, J

    1990-01-01

    Pigs weighing 7 to 102 kg were fed a diet containing 0.17% sodium n-butyrate. The diet increased the average daily body mass gain of pigs by 23.5%. Due to its dietetic effect, feed consumption increased by 8.9%. However, owing to the higher feed conversion, specific feed utilization was reduced by 11.8%. The experimental diet markedly reduced the percentile proportion of coliform bacteria in the ileum as compared to Lactobacillus ssp.: it decreased the coliform count and increased the counts of Lactobacillus spp. The diet increased the length of ileal microvilli and the depth of caecal crypts. It raised the concentration of immunoreactive insulin in the blood plasma. The feed supplemented with sodium butyrate did not alter adversely the clinical indices tested. It reduced feed costs by 9% and increased the returns from sales by 13%. As the additive is normally produced by microbial fermentation in the large intestine, it is not alien to the body. Sodium butyrate exerted its favourable effect in 3.6- to 24.2-fold lower concentrations than the organic acids (citric acid, fumaric acid, propionic acid) used earlier. With respect to its favourable biological and economic effect, sodium n-butyrate can be recommended for use in pig feeding as a growth promoter.

  19. Enzymology of butyrate formation by Butyrivibrio fibrisolvens.

    PubMed

    Miller, T L; Jenesel, S E

    1979-04-01

    Butyrivibrio fibrisolvens is a major butyrate-forming species in the bovine and ovine rumen. The enzymology of butyrate formation from pyruvate was investigated in cell-free extracts of B. fibrisolvens D1. Pyruvate owas oxidized to acetylcoenzyme A (CoA) in the presence of CoA.SH and benzyl viologen or flavin nucleotides. The bacterium uses thiolase, beta-hydroxybutyryl-CoA dehydrogenase, crotonase, and crotonyl-CoA reductase to form butyryl-CoA from acetyl-CoA. Reduction of acetoacetyl-CoA to beta-hydroxybutyryl-CoA was faster with NADH than with NADPH. Crotonyl-CoA was reduced to butyryl-CoA by NADH, but not by NADPH, only in the presence of flavin nucleotides. Reduction of flavin nucleotides by NADH was much slower than the flavin-dependent reduction of crotonyl-CoA. This indicates that flavoproteins rather than free flavin participated in the reduction of crotonyl-CoA. Butyryl-CoA was converted to butyrate by phosphate butyryl transferase and butyrate kinase.

  20. Searching for Synbiotics to increase Colonic Butyrate Concentration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate is produced by microbial fermentation of plant fiber in the gut and a preferred substrate for gut epithelial cells. In ruminants, butyrate contributes to 70% of energy metabolism. In monogastric species, butyrate also plays an important role in energy metabolism in the hindgut. Moreover, bu...

  1. Enhancement of the Power Conversion Efficiency in the Inverted Organic Solar Cells Fabricated Utilizing a CeO2 Interlayer Between the Poly(3-hexylthiophene) (P3HT):[6,6]-Phenyl C6 Butyric Acid Methyl Ester and the Cathode.

    PubMed

    Arul, N Sabari; Lee, Yong Hun; Lee, Dea Uk; Kim, Tae Whan

    2015-01-01

    CeO2 nanoparticles were synthesized by using a precipitation method. High-resolution transmission electron microscopy images, X-ray diffraction patterns, energy dispersive X-ray spectroscopy spectra, and UV-Visible absorption spectroscopy spectra showed that the formed samples were CeO2 polycrystalline nanoparticles. Inverted organic solar cells with a structure of indium-tin-oxide/CeO2/poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C61 butyric acid methyl ester (PCBM)/MoO3/Ag were fabricated. Current density-voltage results showed that the power conversion efficiency of the device of the fabricated inverted OPV cells with a CeO2 interlayer between the P3HT:PCBM and the cathode was 0.39% larger than that without a CeO2 interlayer.

  2. Poly[diaqua-[μ6-4,4'-(1,4-phenyl-ene)bis-(2,6-dimethyl-pyridine-3,5-dicarboxyl-ato)]dilead(II)].

    PubMed

    Zhu, Yi; Zhang, Ming-Xing; Yang, Shan-Shan; Xiao, Feng; Zhang, Xiao-Ping; Gao, Yuan-Yuan; Li, Bing-Jie; Huang, Kun-Lin

    2013-04-01

    The asymmetric unit of the title Pb-based coordination polymer, [Pb2(C24H16N2O8)(H2O)2] n , consists of one Pb(II) cation, half of a 4,4'-(1,4-phenyl-ene)bis-(2,6-dimethyl-pyridine-3,5-di-carb-oxyl-ate (L (4-)) ligand and one coordinating water mol-ecule. The centers of the benzene ring of the ligand and the four-membered Pb/O/Pb/O ring are located on centers of inversion. The Pb(II) ion is coordinated in form of a distorted polyhedron by seven O atoms from four separate L (4-) ligands and by one water O atom. The PbO7 polyhedra share O atoms, forming infinite zigzag [PbO4(H2O)] n chains along [100] that are bridged by L (4-) ligands, forming a two-dimensional coordination network parallel to (001). O-H⋯O hydrogen bonds involving the water mol-ecule are observed. PMID:23634022

  3. Clean photodecomposition of 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thiones to carbodiimides proceeds via a biradical

    PubMed Central

    Alawode, Olajide E.; Robinson, Colette; Rayat, Sundeep

    2010-01-01

    The photochemistry of 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thione (1a) and 1-(3-methoxyphenyl)-4-methyl-1H-tetrazole-5(4H)-thione (1b) was studied in acetonitrile at 254 and 300 nm which involves expulsion of dinitrogen and sulfur to form the respective carbodiimides 5a – b as sole photoproducts. Photolysis of the title compounds in the presence of 1,4-cyclohexadiene trap led to the formation of respective thioureas, providing strong evidence for the intermediacy of a 1,3-biradical formed by the loss of dinitrogen. In contrast, a trapping experiment with cyclohexene provided no evidence to support an alternative pathway of photodecomposition involving initial desulfurization followed by loss of dinitrogen via the intermediacy of a carbene. Triplet sensitization and triplet quenching studies argue against the involvement of a triplet excited state. While the quantum yields for the formation of the carbodiimides 5a – b were modest, and showed little change on going from a C6H5 (1a) to mOMeC6H4 (1b) substituent on the tetrazolethione ring, the highly clean photodecomposition of these compounds to a photostable end product makes them promising lead structures for industrial, agricultural and medicinal applications. PMID:21142194

  4. Growth, spectral, optical, thermal, surface analysis and third order nonlinear optical properties of an organic single crystal: 1-(2-Methyl-6-nitro-4-phenyl-3-quinolyl) ethanone

    NASA Astrophysics Data System (ADS)

    Nirosha, M.; Kalainathan, S.; Sarveswari, S.; Vijayakumar, V.; Srikanth, A.

    2015-02-01

    Single crystal of 1-(2-Methyl-6-nitro-4-phenyl-3-quinolyl) ethanone was grown using slow evaporation solution growth technique. Single crystal X-ray diffraction study reveals the lattice parameters of the grown crystal. The modes of vibration of different molecular groups present in 2M6NQE were identified by FTIR spectral analysis. Its optical behavior was examined through UV-vis-NIR absorption and PL emission spectrum. They signify that the crystal has transparency in the region between 383 and 1100 nm. The PL spectrum of the title compound shows green emission in the crystal. From the thermal analysis, 2M6NQE has found to be thermally stable up to 263 °C, and the melting point of the material is 170 °C. The estimations of third order non-linear optical properties like non-linear absorption coefficient (β), non-linear refractive index (n2) and susceptibility [χ(3)] were calculated using Z-scan technique. It has observed that, crystal exhibits reverse saturation absorption and self-defocusing performance. Etching study was carried out for the grown crystal using different solvents.

  5. Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

    PubMed Central

    2014-01-01

    Background Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Results Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Conclusion Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment. PMID:24965042

  6. Executive function deficits and glutamatergic protein alterations in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

    PubMed

    Pflibsen, Lacey; Stang, Katherine A; Sconce, Michelle D; Wilson, Vanessa B; Hood, Rebecca L; Meshul, Charles K; Mitchell, Suzanne H

    2015-12-01

    Changes in executive function are at the root of most cognitive problems associated with Parkinson's disease. Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of neurotransmitters/systems other than dopamine (DA) may be associated with this decrease in cognitive function. We have reported decreases in motor function and dopaminergic/glutamatergic biomarkers in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinson's mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has not previously been explored in our model. Our results show progressive behavioral decline in a cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice that had been given MPTP showed a 63% and 83% loss of tyrosine hydroxylase and dopamine transporter expression, respectively, there were no changes in the nucleus accumbens or medial prefrontal cortex (mPFC). Furthermore, dopamine-1 receptor and vesicular glutamate transporter (VGLUT)-1 expression increased in the mPFC following DA loss. There were significant MPTP-induced decreases and increases in VGLUT-1 and VGLUT-2 expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change not only in cortical-cortical (VGLUT-1) glutamate function but also in striatal DA and glutamate (VGLUT-1/VGLUT-2) input.

  7. Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys

    SciTech Connect

    Porrino, L.J.; Burns, R.S.; Crane, A.M.; Palombo, E.; Kopin, I.J.; Sokoloff, L.

    1987-08-01

    The quantitative 2-deoxy(/sup 14/C) glucose autoradiographic method was used to map the distribution of alterations in local cerebral glucose utilization that accompanies clinically effective chronic L-dopa therapy of rhesus monkeys made parkinsonian by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This pattern of changes was compared to the effects of a similar treatment regimen in normal monkeys. L-Dopa was administered orally to normal and parkinsonian monkeys 3 times daily for 60-120 days prior to measurement of local cerebral glucose utilization. In parkinsonian monkeys treated with L-dopa, signs and symptoms of parkinsonism were controlled or suppressed, and widespread increases in glucose utilization were seen throughout the brain. Cerebral metabolic activity was increased both in areas rich in dopaminergic receptors, such as the caudate and putamen, and in nondopaminergic areas involved in motor functions. In many structures the rates of glucose utilization in L-dopa-treated parkinsonian monkeys were increased to levels that far exceeded rates measured in normal monkeys. In sharp contrast, similar treatment with L-dopa in normal monkeys had little if any effect on local cerebral glucose utilization. L-Dopa, then, appears to have an action in animals with selective lesions of the substantia nigra pars compacta produced by MPTP that is distinctly different from its effects in the normal monkey.

  8. Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity

    SciTech Connect

    Kalaria, R.N.; Mitchell, M.J.; Harik, S.I.

    1987-05-01

    Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and subhuman primates, but not in rats and many other laboratory animals; mice are intermediate in their susceptibility. Since MPTP causes selective dopaminergic neurotoxicity when infused directly into rat substantia nigra, the authors hypothesized that systemic MPTP may be metabolized by monoamine oxidase and/or other enzymes in rat brain capillaries and possibly other peripheral organs and thus prevented from reaching its neuronal sites of toxicity. They tested this hypothesis by assessing monoamine oxidase in isolated cerebral microvessels of humans, rats, and mice by measuring the specific binding of (/sup 3/H)pargyline, an irreversible monoamine oxidase inhibitor, and by estimating the rates of MPTP and benzylamine oxidation. (/sup 3/H)Pargyline binding to rat cerebral microvessels was about 10-fold higher than to human or mouse microvessels. Also, MPTP oxidation by rat brain microvessels was about 30-fold greater than by human microvessels; mouse microvessels yielded intermediate values. These results may explain, at least in part, the marked species differences in susceptibility to systemic MPTP. They also suggest the potential importance of enzyme barriers at the blood-brain interface that can metabolize toxins not excluded by structural barriers, and may provide biological bases for developing therapeutic strategies for the prevention of MPTP-induced neurotoxicity and other neurotoxic conditions including, possibly, Parkinson's disease.

  9. Dietary Supplementation of Walnut Partially Reverses 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induced Neurodegeneration in a Mouse Model of Parkinson's Disease.

    PubMed

    Essa, Musthafa Mohamed; Subash, Selvaraju; Dhanalakshmi, Chinnasamy; Manivasagam, Thamilarasan; Al-Adawi, Samir; Guillemin, Gilles J; Justin Thenmozhi, Arokiasamy

    2015-06-01

    Numerous studies indicating that natural plant sources and their active phytochemicals offer protection to the pathological processes related to the development of neurogenerative diseases including Parkinson's disease (PD). In the present study, the neuro protective efficacy of dietary supplementation of walnut (6 %) for 28 days was examined in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (i.p., 20 mg/kg body weight/day) for last four consecutive days. MPTP injection diminished the levels of GSH, dopamine and metabolites along with decreased activities of GPx and mitochondrial complex I. Further, the levels of TBARS and enzymatic antioxidants such as SOD and catalase, MAO-B activities were enhanced by MPTP treatment. Behavioral deficits and lowered TH expression are also proved MPTP induced neurotoxicity. Dietary supplementation of walnut attenuated MPTP-induced impairment in PD mice might be by its MAO-B inhibitory, antioxidant and mitochondrial protective actions. To find out the exact mechanism of action walnut on PD mice warrants further extensive studies.

  10. Naphthazarin has a protective effect on the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson's disease model.

    PubMed

    Choi, Seon Young; Son, Tae Gen; Park, Hee Ra; Jang, Young Jung; Oh, Shin Bi; Jin, Bora; Lee, Jaewon

    2012-09-01

    "Neurohormesis" refers to a response to a moderate level of stress that enhances the ability of the nervous systems to resist more severe stress that might be lethal or cause dysfunction or disease. Neurohormetic phytochemicals, such as, resveratrol, sulforaphane, curcumin, and catechins, protect neurons against injury and disease. Naphthoquinones, such as, juglone and plumbagin, induce robust hormetic stress responses. However, the possibility that subtoxic dose of 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin) may protect against brain diseases via the activation of an adaptive stress response pathway in the brain has not been investigated. In this study, we examined the neurohormetic effect of a subtoxic dose of naphthazarin in a Parkinson's disease model. It was found that, under these conditions, naphthazarin enhanced movement ability, prevented loss of dopaminergic neurons, and attenuated neuroinflammation in a 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson's disease model. Furthermore, it was found that the neuroprotective effect of naphthazarin was mediated by the suppression of astroglial activation in response to 1-methyl-4-phenylpyridine treatment. In conclusion, we suggest that naphthazarin, in view of its hormetic effect on neuroprotection, be viewed as a potential treatment for Parkinson's disease and other neurodegenerative diseases associated with neuroinflammation.

  11. Chronic dietary supplementation with turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated neurotoxicity in vivo: implications for Parkinson's disease.

    PubMed

    Mythri, Rajeswara Babu; Veena, Jayagopalan; Harish, G; Shankaranarayana Rao, B S; Srinivas Bharath, M M

    2011-07-01

    Multiple pathways including oxidative stress and mitochondrial damage are implicated in neurodegeneration during Parkinson's disease (PD). The current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Therefore, there is a demand for novel compound(s)/products that could target multiple pathways and protect the dying midbrain dopaminergic neurons, with potential utility as adjunctive therapy along with conventional drugs. Turmeric is a spice used in traditional Indian cuisine and medicine with antioxidant, anti-inflammatory and potential neuroprotective properties. To explore the neuroprotective property of turmeric in PD, mice were subjected to dietary supplementation with aqueous suspensions of turmeric for 3 months, mimicking its chronic consumption and challenged in vivo with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain samples from untreated and treated groups were characterised based on mitochondrial complex I (CI) activity, protein nitration and tyrosine hydroxylase immunoreactivity. Chronic turmeric supplementation induced the enzyme activity of γ-glutamyl cysteine ligase, which in turn increased glutathione levels and protected against peroxynitrite-mediated inhibition of brain CI. These mice were also protected against MPTP-mediated protein nitration, CI inhibition and degeneration of substantia nigra neurons in the brain. We conclude that chronic dietary consumption of turmeric protects the brain against neurotoxic insults, with potential application in neurodegeneration. Further characterisation of the active constituents of turmeric that potentially promote neuroprotection could improve the utility of dietary turmeric in brain function and disease. PMID:21473798

  12. Evaluation of DNA-binding, DNA cleavage, antioxidant and cytotoxic activity of mononuclear ruthenium(II) carbonyl complexes of benzaldehyde 4-phenyl-3-thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Sampath, Krishnan; Sathiyaraj, Subbaiyan; Jayabalakrishnan, Chinnasamy

    2013-11-01

    Two 4-phenyl-3-thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-phenylhydrazinecarbothioamide (HL1) and (E)-2-(2-nitrobenzylidene)-N-phenylhydrazinecarbothioamide (HL2), and its ruthenium(II) complexes were synthesized and characterized by physico-chemical and spectroscopic methods. The Schiff bases act as bidentate, monobasic chelating ligands with S and N as the donor sites and are preferably found in the thiol form in all the complexes studied. The molecular structure of HL1 and HL2 were determined by single crystal X-ray diffraction method. DNA binding of the compounds was investigated by absorption spectroscopy which indicated that the compounds bind to DNA via intercalation. The oxidative cleavage of the complexes with CT-DNA inferred that the effects of cleavage are dose dependent. Antioxidant study of the ligands and complexes showed significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of the ligands and complexes assayed against HeLa and MCF-7 cell lines showed higher cytotoxic activity with the lower IC50 values indicating their efficiency in killing the cancer cells even at low concentrations.

  13. Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

    PubMed Central

    Mounsey, Ross B.; Mustafa, Sarah; Robinson, Lianne; Ross, Ruth A.; Riedel, Gernot; Pertwee, Roger G.; Teismann, Peter

    2015-01-01

    Parkinson's disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain. Symptomatic therapies are available but no treatment slows or prevents the loss of neurons. Neuroinflammation has been implicated in its pathogenesis. To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients. Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated. The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5 mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death. Furthermore, the addition of DFU (25 mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects. Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits. The results expand the current understanding of the role that this signalling system has and its potential influence in PD. PMID:26244281

  14. Both butyrate incubation and hypoxia upregulate genes involved in the ruminal transport of SCFA and their metabolites.

    PubMed

    Dengler, F; Rackwitz, R; Benesch, F; Pfannkuche, H; Gäbel, G

    2015-04-01

    Butyrate modulates the differentiation, proliferation and gene expression profiles of various cell types. Ruminal epithelium is exposed to a high intraluminal concentration and inflow of n-butyrate. We aimed to investigate the influence of n-butyrate on the mRNA expression of proteins involved in the transmembranal transfer of n-butyrate metabolites and short-chain fatty acids in ruminal epithelium. N-butyrate-induced changes were compared with the effects of hypoxia because metabolite accumulation after O2 depletion is at least partly comparable to the accumulation of metabolites after n-butyrate exposure. Furthermore, in various tissues, O2 depletion modulates the expression of transport proteins that are also involved in the extrusion of metabolites derived from n-butyrate breakdown in ruminal epithelium. Sheep ruminal epithelia mounted in Ussing chambers were exposed to 50 mM n-butyrate or incubated under hypoxic conditions for 6 h. Electrophysiological measurements showed hypoxia-induced damage in the epithelia. The mRNA expression levels of monocarboxylate transporters (MCT) 1 and 4, anion exchanger (AE) 2, downregulated in adenoma (DRA), putative anion transporter (PAT) 1 and glucose transporter (GLUT) 1 were assessed by RT-qPCR. We also examined the mRNA expression of nuclear factor (NF) κB, cyclooxygenase (COX) 2, hypoxia-inducible factor (HIF) 1α and acyl-CoA oxidase (ACO) to elucidate the possible signalling pathways involved in the modulation of gene expression. The mRNA expression levels of MCT 1, MCT 4, GLUT 1, HIF 1α and COX 2 were upregulated after both n-butyrate exposure and hypoxia. ACO and PAT 1 were upregulated only after n-butyrate incubation. Upregulation of both MCT isoforms and NFκB after n-butyrate incubation could be detected on protein level as well. Our study suggests key roles for MCT 1 and 4 in the adaptation to an increased intracellular load of metabolites, whereas an involvement of PAT 1 in the transport of n-butyrate also

  15. Effect of sodium butyrate on growth performance and response to lipopolysaccharide in weanling pigs.

    PubMed

    Weber, T E; Kerr, B J

    2008-02-01

    Two experiments were conducted to determine the effects of dietary sodium butyrate on growth performance and response to Escherichia coli lipopolysaccharide (LPS) in weanling pigs. In a 28-d experiment, 180 pigs (initial BW 6.3 kg) were fed 0, 0.05, 0.1, 0.2, or 0.4% sodium butyrate, or 110 mg/kg of dietary tylosin. There was no effect of dietary sodium butyrate or tylosin on overall G:F, but there was a linear trend (P < 0.07) toward decreased ADFI and ADG as levels of sodium butyrate increased. In a second 28-d experiment, 108 pigs (initial BW 6.3 kg) were assigned to 1 of 3 dietary treatments: 1) no antibiotics, 2) 0.2% sodium butyrate, or 3) 55 mg/kg of carbadox. On d 14, a subset of pigs from the no-antibiotic and butyrate treatment groups was challenged with E. coli LPS or injected with sterile saline in a 2 x 2 factorial arrangement (+/-LPS challenge; +/-dietary butyrate; n = 6 pigs/treatment group). Four hours after LPS challenge, blood samples were obtained, and samples of LM, liver, and ileum were collected for gene expression analysis. Serum samples were analyzed for IL-6, tumor necrosis factor alpha (TNFalpha), alpha(1)-acid glycoprotein, cortisol, IGF-I, insulin, and metabolites. The relative abundance of tissue cytokine and IGF-I mRNA was measured by real-time PCR. Feeding diets containing sodium butyrate or carbadox did not alter ADG or ADFI compared with pigs fed the control diet. From d 0 to 14, pigs fed diets containing 0.2% sodium butyrate had decreased (P < 0.05) ADG and tended (P < 0.06) to have decreased G:F compared with animals fed diets containing carbadox. Challenge with LPS increased (P < 0.05) serum cytokines and cortisol and decreased (P < 0.05) serum glucose and triglycerides. Injection with LPS increased (P < 0.05) the relative abundance of hepatic IL-6 and TNFalpha mRNA, increased (P < 0.05) LM TNFalpha mRNA content, and decreased (P < 0.05) IGF-I mRNA in LM. For serum cortisol, there was an interaction (P < 0.05) between dietary

  16. The enhancement of phase 2 enzyme activities by sodium butyrate in normal intestinal epithelial cells is associated with Nrf2 and p53.

    PubMed

    Yaku, Keisuke; Enami, Yuka; Kurajyo, Chika; Matsui-Yuasa, Isao; Konishi, Yotaro; Kojima-Yuasa, Akiko

    2012-11-01

    Dietary fiber fermentation by the colonic bacterial flora produces short-chain fatty acids, acetate, propionate and butyrate. Among them, butyrate is considered to be the major energy substrate for colonocytes and, at least in rats, seems to protect against colonic carcinogenesis. In this study, we examined the effect and the mechanisms of short-chain fatty acids on the activity of phase 2 enzymes. Sodium butyrate increased phase 2 enzyme activities in normal rat small intestine epithelial cells, Glutathione S-transferase and NAD(P)H:quinone oxidoreductase (NQO) in a dose-dependent manner(;) however, other short-chain fatty acids did not increase them. The mechanism of the induction of phase 2 enzymes with sodium butyrate sodium butyrate, but not other short-chain fatty acids was related to the increase of NF-E2-related factor 2 (Nrf2) nuclear translocation and the decrease in the levels of nuclear fraction p53. Sodium butyrate also caused enhancement of Nrf2 mRNA levels and suppression of p53 mRNA levels. Sodium butyrate enhances the activities of phase 2 enzymes via an increase in the Nrf2 protein levels in the nucleus and a decrease in the mRNA and protein levels of p53.

  17. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.

    PubMed

    Furusawa, Yukihiro; Obata, Yuuki; Fukuda, Shinji; Endo, Takaho A; Nakato, Gaku; Takahashi, Daisuke; Nakanishi, Yumiko; Uetake, Chikako; Kato, Keiko; Kato, Tamotsu; Takahashi, Masumi; Fukuda, Noriko N; Murakami, Shinnosuke; Miyauchi, Eiji; Hino, Shingo; Atarashi, Koji; Onawa, Satoshi; Fujimura, Yumiko; Lockett, Trevor; Clarke, Julie M; Topping, David L; Tomita, Masaru; Hori, Shohei; Ohara, Osamu; Morita, Tatsuya; Koseki, Haruhiko; Kikuchi, Jun; Honda, Kenya; Hase, Koji; Ohno, Hiroshi

    2013-12-19

    Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.

  18. Fragrance material review on 1,1-dimethyl-2-phenylethyl butyrate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 1,1-dimethyl-2-phenylethyl butyrate when used as a fragrance ingredient is presented. 1,1-Dimethyl-2-phenylethyl butyrate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1,1-dimethyl-2-phenylethyl butyrate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, and genotoxicity data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

  19. Mesencephalic dopamine neurons become less sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity during development in vitro.

    PubMed

    Danias, P; Nicklas, W J; Ofori, S; Shen, J; Mytilineou, C

    1989-10-01

    The in vitro development of monoamine oxidase (MAO) activity and [3H]dopamine (DA) uptake capacity of dissociated cell cultures from rat embryo mesencephalon were correlated with the potency of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) neurotoxicity. Specific activities of both MAO-A and MAO-B increased during in vitro development of the cultures, with MAO-B activity increasing 20-fold between the first and fourth week. Similarly, [3H]DA accumulation increased 2.6-fold between the first and third week in vitro, when it reached a plateau. Unexpectedly, the toxicities of MPTP and MPP+ were substantially decreased in the older cultures. Exposure to MPTP reduced [3H]DA accumulation per culture by 77% in 1-week-old cultures and by 36% in 4-week-old cultures. Similarly, damage caused by MPPT was reduced from 84% of control in the first week to 34% of control in the fourth week. The attenuation of neurotoxicity was not due to an increase in storage of MPP+ in the synaptic vesicles of DA neurons, nor to a change in the distribution of MPP+ between dopaminergic and other cellular components of the cultures. The damage to DA neurons caused by the mitochondrial toxin, rotenone, also showed a similar reduction in the older cultures. These observations coupled with an increase in lactate formation and glucose consumption during the in vitro development of the cultures suggest a shift toward increased glycolysis and decreased dependence on aerobic metabolism. This would render the cells more resistant to the inhibition of mitochondrial function by MPP+. PMID:2788714

  20. Crystal structures, spectra properties and DFT calculations studies on 4-phenyl-1-(3-phenylallylidene)thiosemicarbazide and its Ni(II) complex.

    PubMed

    Song, Jie; Zhu, Fengxia; Wang, Hongyan; Zhao, Pusu

    2014-08-14

    4-Phenyl-1-(3-phenylallylidene)thiosemicarbazide (HL) and its metal complex of NiL2 have been synthesized. For them, elemental analysis, IR and X-ray single crystal diffraction have been carried out. In complex NiL2, the central Ni(2+) ion coordinates with two deprotonated ligands of L(-) and adopts a distorted square planar configuration with the Ni(2+) ion being located at the inversion center. The thermal analyses result shows that complex NiL2 undergoes two decomposition processes. For the title compounds, DFT calculations of the structures and natural population analysis (NPA) have been performed at B3LYP/LANL2DZ level of theory. The predicted geometric parameters are compared with the experimental values and they are supported each other. By using TD-DFT method, electron spectra of ligand HL and complex NiL2 have been predicted, which suggest the B3LYP/LANL2DZ method can approximately simulate the electron spectra for the system presented here. The NPA results indicate that, for ligand HL, the electronic absorption spectra are mainly assigned to n-π(∗) and π-π(∗) electron transitions, while for the complex NiL2, the electronic transitions are mainly derived from the contribution of an intra-ligand (IL) transition, a metal-to-ligand charge transfer (MLCT) transition and a d-d transition. Based on vibrational analysis, thermodynamic properties for ligand HL and complex NiL2 at different temperatures have been obtained. PMID:24735780

  1. Metabolism of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine by Mitochondrion-targeted Cytochrome P450 2D6

    PubMed Central

    Bajpai, Prachi; Sangar, Michelle C.; Singh, Shilpee; Tang, Weigang; Bansal, Seema; Chowdhury, Goutam; Cheng, Qian; Fang, Ji-Kang; Martin, Martha V.; Guengerich, F. Peter; Avadhani, Narayan G.

    2013-01-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4-phenylpyridinium ion (MPP+), which then targets the dopaminergic neurons causing neuronal death. Here, we demonstrate that mitochondrion-targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adrenodoxin reductase, can efficiently catalyze the metabolism of MPTP to MPP+, as shown with purified enzymes and also in cells expressing mitochondrial CYP2D6. Neuro-2A cells stably expressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondrial respiratory dysfunction and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels of reactive oxygen species and showed abnormal mitochondrial structures. MPTP treatment also induced mitochondrial translocation of an autophagic marker, Parkin, and a mitochondrial fission marker, Drp1, in differentiated neurons expressing mitochondrial CYP2D6. MPTP-mediated toxicity in primary dopaminergic neurons was attenuated by CYP2D6 inhibitor, quinidine, and also partly by monoamine oxidase B inhibitors deprenyl and pargyline. These studies show for the first time that dopaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine. PMID:23258538

  2. Long-lasting transcriptional refractoriness triggered by a single exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine.

    PubMed

    Pattarini, R; Rong, Y; Shepherd, K R; Jiao, Y; Qu, C; Smeyne, R J; Morgan, J I

    2012-07-12

    Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is thought to have environmental (toxin) and genetic contributions. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) induces pathological features of PD including loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatal dopamine (DA) depletion. We previously described the striatal transcriptional response following acute MPTP administration in MPTP-sensitive C57BL/6J mice. We identified three distinct phases: early (5h), intermediate (24h) and late (72h) and reported that the intermediate and late responses were absent in MPTP-resistant Swiss-Webster (SWR) mice. Here we show that C57BL/6J mice pre-treated with a single 40 mg/kg dose of MPTP and treated 9 days later with 4×20 mg/kg MPTP, display a striatal transcriptional response similar to that of MPTP-resistant SWR mice, i.e. a robust acute response but no intermediate or late response. Transcriptional refractoriness is dependent upon the dose of the priming challenge with as little as 10mg/kg MPTP being effective and can persist for more than 28 days. Priming of SWR mice has no effect on their response to subsequent challenge with MPTP. We also report that paraquat, another free radical producer, also elicits striatal transcriptional alterations but these are largely distinct from those triggered by MPTP. Paraquat-induced changes are also refractory to priming with paraquat. However neither paraquat nor MPTP elicits cross-attenuation. Thus exposure to specific toxins triggers distinct transcriptional responses in striatum that are influenced by prior exposure to the same toxin. The prolonged refractory period described here for MPTP could explain at the molecular level the reported discrepancies between different MPTP administration regimens and may have implications for our understanding of the relationship between environmental toxin exposure and PD.

  3. Fish oil, melatonin and vitamin E attenuates midbrain cyclooxygenase-2 activity and oxidative stress after the administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine.

    PubMed

    Ortiz, Genaro Gabriel; Pacheco-Moisés, Fermín P; Gómez-Rodríguez, Víctor M; González-Renovato, Erika D; Torres-Sánchez, Erandhis D; Ramírez-Anguiano, Ana C

    2013-12-01

    Parkinson's disease is a neurodegenerative disease whose hallmark pathological features include a selective loss of dopaminergic neurons in the midbrain. Ciclooxygenase-2 activity induction and oxidative stress have been implicated in the aetiology of Parkinson's disease and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Upon administration of fish oil, melatonin and vitamin E, neuroprotective effects on MPTP-induced neurotoxicity have been indicated. The aim of this study was to investigate the time course and compare the potency of these agents alone, on several parameters such as COX-2 and lipid peroxides (LPO) products associated with MPTP neurotoxicity in midbrain homogenates of C57BL/6 mice. Using fish oil (0.0368 g EPA and 0.0184 g DHA, per day), melatonin (10 mg/kg/day), and vitamin E (50 mg/Kg/day) we have now shown that COX-2 activity, LPO and nitrite/nitrate levels were significantly increased in MPTP treated mice (p < 0.001) while fish oil, melatonin and vitamin E treatment were capable of decreasing significantly the outcome of all above noted parameters (p < 0.05). The effect of fish oil on COX-2 activity and nitrite/nitrate levels was more profound than that of vitamin E or melatonin while the latter was more effective on reducing the LPO levels compared to fish oil and vitamin E. In conclusion, the outcome of the neuroprotective effects of these agents is long lasting and of variable potency indicating a different anti-inflammatory mode of action. PMID:23703110

  4. Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice

    PubMed Central

    Shi, Xiaojin; Chen, Yu-Hua; Liu, Hao; Qu, Hong-Dang

    2016-01-01

    Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is known for its antioxidant, anti-inflammatory and antitumor properties. The present study was designed to investigate the therapeutic potential and underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease (PD). MPTP (25 mg/kg), followed by probenecid (250 mg/kg), was administered via i.p. injection for five consecutive days to induce the mouse model of PD. Paeonol (20 mg/kg) was administrated orally for 21 days. Behavior was assessed using the rotarod performance and open-field tests. Additionally, the levels of tyrosine hydroxylase (TH), microglia, interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) in the substantia nigra pars compacta (SNpc) were evaluated by immunohistochemical staining. MPTP/p-induced motor deficits were observed to be significantly improved following long-term treatment with paeonol. Paeonol treatment decreased MPTP/p-induced oxidative stress, as determined by evaluating the activity levels of superoxide dismutase, catalase and glutathione. Additionally, MPTP/p-induced neuroinflammation was assessed by examining the levels of microglia and IL-1β, which were significantly decreased following paeonol treatment. Paeonol treatment improved the MPTP/p-induced dopaminergic neurodegeneration, as measured by observing the increased TH level in the SNpc. Furthermore, the BDNF level was significantly elevated in the paeonol treatment group compared with mice treated with MPTP/p only. In conclusion, paeonol exerted therapeutic effects in the MPTP/p-induced mouse model of PD, possibly by decreasing the damage from oxidative stress and neuroinflammation, and by enhancing the neurotrophic effect on dopaminergic neurons. The results demonstrate paeonol as a potential novel treatment for PD. PMID:27484986

  5. Development of highly sensitive extractive spectrophotometric determination of nickel(II) in medicinal leaves, soil, industrial effluents and standard alloy samples using pyridoxal-4-phenyl-3-thiosemicarbazone.

    PubMed

    Sarma, Loka Subramanyam; Kumar, Jyothi Rajesh; Reddy, Koduru Janardhan; Thriveni, Thenepalli; Reddy, Ammireddy Varada

    2008-01-01

    Pyridoxal-4-phenyl-3-thiosemicarbazone (PPT) is proposed as a new sensitive reagent for the extractive spectrophotometric determination of nickel(II). PPT reacts with nickel(II) in the pH range 4.0-6.0 to form a reddish brown colored complex, which was well-extracted into n-butanol. The absorbance value of the Ni(II)-PPT complex was measured at different time intervals at 430nm, to ascertain the stability of the complex. The system obeyed Beer's law up to 0.5-5.0microgmL(-1) of nickel(II), with an excellent linearity in terms of the correlation coefficient value of 0.99. The molar absorptivity and Sandell's sensitivity of the extracted species are 1.92 x 10(4)Lmol(-1)cm(-1) and 0.003057microgcm(-2) respectively at 430nm. The detection limit of the method is 0.069microgmL(-1). To assess precision and accuracy of the developed method, determinations were carried out at different concentrations. The relative standard deviation of all measurements does not exceed 2.62%. The developed method has been satisfactorily applied for the determination of nickel(II), when present alone or in the presence of diverse ions, which are usually associated with nickel(II) in medicinal leaves, soil and industrial effluent samples. Various standard and certified reference materials (CM 247 LC, IN 718, BCS 233, 266, 253 and 251) have also been tested for the determination of nickel for the purpose of validation of the present method. The results of the proposed method are compared with those obtained from an atomic absorption spectrometer (AAS).

  6. Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention.

    PubMed

    Bultman, Scott J

    2014-02-15

    Gene-environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low-moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression.

  7. Butyrate produced by commensal bacteria potentiates phorbol esters induced AP-1 response in human intestinal epithelial cells.

    PubMed

    Nepelska, Malgorzata; Cultrone, Antonietta; Béguet-Crespel, Fabienne; Le Roux, Karine; Doré, Joël; Arulampalam, Vermulugesan; Blottière, Hervé M

    2012-01-01

    The human intestine is a balanced ecosystem well suited for bacterial survival, colonization and growth, which has evolved to be beneficial both for the host and the commensal bacteria. Here, we investigated the effect of bacterial metabolites produced by commensal bacteria on AP-1 signaling pathway, which has a plethora of effects on host physiology. Using intestinal epithelial cell lines, HT-29 and Caco-2, stably transfected with AP-1-dependent luciferase reporter gene, we tested the effect of culture supernatant from 49 commensal strains. We observed that several bacteria were able to activate the AP-1 pathway and this was correlated to the amount of short chain fatty acids (SCFAs) produced. Besides being a major source of energy for epithelial cells, SCFAs have been shown to regulate several signaling pathways in these cells. We show that propionate and butyrate are potent activators of the AP-1 pathway, butyrate being the more efficient of the two. We also observed a strong synergistic activation of AP-1 pathway when using butyrate with PMA, a PKC activator. Moreover, butyrate enhanced the PMA-induced expression of c-fos and ERK1/2 phosphorylation, but not p38 and JNK. In conclusion, we showed that SCFAs especially butyrate regulate the AP-1 signaling pathway, a feature that may contribute to the physiological impact of the gut microbiota on the host. Our results provide support for the involvement of butyrate in modulating the action of PKC in colon cancer cells.

  8. Steering Endogenous Butyrate Production in the Intestinal Tract of Broilers as a Tool to Improve Gut Health.

    PubMed

    Onrust, Lonneke; Ducatelle, Richard; Van Driessche, Karolien; De Maesschalck, Celine; Vermeulen, Karen; Haesebrouck, Freddy; Eeckhaut, Venessa; Van Immerseel, Filip

    2015-01-01

    The ban on antimicrobial growth promoters and efforts to reduce therapeutic antibiotic usage has led to major problems of gastrointestinal dysbiosis in livestock production in Europe. Control of dysbiosis without the use of antibiotics requires a thorough understanding of the interaction between the microbiota and the host mucosa. The gut microbiota of the healthy chicken is highly diverse, producing various metabolic end products, including gases and fermentation acids. The distal gut knows an abundance of bacteria from within the Firmicutes Clostridium clusters IV and XIVa that produce butyric acid, which is one of the metabolites that are sensed by the host as a signal. The host responds by strengthening the epithelial barrier, reducing inflammation, and increasing the production of mucins and antimicrobial peptides. Stimulating the colonization and growth of butyrate-producing bacteria thus may help optimizing gut health. Various strategies are available to stimulate butyrate production in the distal gut. These include delivery of prebiotic substrates that are broken down by bacteria into smaller molecules which are then used by butyrate producers, a concept called cross-feeding. Xylo-oligosaccharides (XOS) are such compounds as they can be converted to lactate, which is further metabolized to butyrate. Probiotic lactic acid producers can be supplied to support the cross-feeding reactions. Direct feeding of butyrate-producing Clostridium cluster IV and XIVa strains are a future tool provided that large scale production of strictly anaerobic bacteria can be optimized. Current results of strategies that promote butyrate production in the gut are promising. Nevertheless, our current understanding of the intestinal ecosystem is still insufficient, and further research efforts are needed to fully exploit the capacity of these strategies. PMID:26734618

  9. Steering Endogenous Butyrate Production in the Intestinal Tract of Broilers as a Tool to Improve Gut Health

    PubMed Central

    Onrust, Lonneke; Ducatelle, Richard; Van Driessche, Karolien; De Maesschalck, Celine; Vermeulen, Karen; Haesebrouck, Freddy; Eeckhaut, Venessa; Van Immerseel, Filip

    2015-01-01

    The ban on antimicrobial growth promoters and efforts to reduce therapeutic antibiotic usage has led to major problems of gastrointestinal dysbiosis in livestock production in Europe. Control of dysbiosis without the use of antibiotics requires a thorough understanding of the interaction between the microbiota and the host mucosa. The gut microbiota of the healthy chicken is highly diverse, producing various metabolic end products, including gases and fermentation acids. The distal gut knows an abundance of bacteria from within the Firmicutes Clostridium clusters IV and XIVa that produce butyric acid, which is one of the metabolites that are sensed by the host as a signal. The host responds by strengthening the epithelial barrier, reducing inflammation, and increasing the production of mucins and antimicrobial peptides. Stimulating the colonization and growth of butyrate-producing bacteria thus may help optimizing gut health. Various strategies are available to stimulate butyrate production in the distal gut. These include delivery of prebiotic substrates that are broken down by bacteria into smaller molecules which are then used by butyrate producers, a concept called cross-feeding. Xylo-oligosaccharides (XOS) are such compounds as they can be converted to lactate, which is further metabolized to butyrate. Probiotic lactic acid producers can be supplied to support the cross-feeding reactions. Direct feeding of butyrate-producing Clostridium cluster IV and XIVa strains are a future tool provided that large scale production of strictly anaerobic bacteria can be optimized. Current results of strategies that promote butyrate production in the gut are promising. Nevertheless, our current understanding of the intestinal ecosystem is still insufficient, and further research efforts are needed to fully exploit the capacity of these strategies. PMID:26734618

  10. Alternative splicing regulated by butyrate in bovine epithelial cells.

    PubMed

    Wu, Sitao; Li, Congjun; Huang, Wen; Li, Weizhong; Li, Robert W

    2012-01-01

    As a signaling molecule and an inhibitor of histone deacetylases (HDACs), butyrate exerts its impact on a broad range of biological processes, such as apoptosis and cell proliferation, in addition to its critical role in energy metabolism in ruminants. This study examined the effect of butyrate on alternative splicing in bovine epithelial cells using RNA-seq technology. Junction reads account for 11.28 and 12.32% of total mapped reads between the butyrate-treated (BT) and control (CT) groups. 201,326 potential splicing junctions detected were supported by ≥ 3 junction reads. Approximately 94% of these junctions conformed to the consensus sequence (GT/AG) while ~3% were GC/AG junctions. No AT/AC junctions were observed. A total of 2,834 exon skipping events, supported by a minimum of 3 junction reads, were detected. At least 7 genes, their mRNA expression significantly affected by butyrate, also had exon skipping events differentially regulated by butyrate. Furthermore, COL5A3, which was induced 310-fold by butyrate (FDR <0.001) at the gene level, had a significantly higher number of junction reads mapped to Exon#8 (Donor) and Exon#11 (Acceptor) in BT. This event had the potential to result in the formation of a COL5A3 mRNA isoform with 2 of the 69 exons missing. In addition, 216 differentially expressed transcript isoforms regulated by butyrate were detected. For example, Isoform 1 of ORC1 was strongly repressed by butyrate while Isoform 2 remained unchanged. Butyrate physically binds to and inhibits all zinc-dependent HDACs except HDAC6 and HDAC10. Our results provided evidence that butyrate also regulated deacetylase activities of classical HDACs via its transcriptional control. Moreover, thirteen gene fusion events differentially affected by butyrate were identified. Our results provided a snapshot into complex transcriptome dynamics regulated by butyrate, which will facilitate our understanding of the biological effects of butyrate and other HDAC inhibitors.

  11. Isobaric vapor liquid equilibria data for the binary system (glycidyl butyrate + acetone, glycidyl butyrate + carbon tetrachloride, glycidyl butyrate + chloroform) at atmospheric pressure 101 kPa

    NASA Astrophysics Data System (ADS)

    Huang, Qiang; Meng, Qingyi; Ban, Chunlan; Zhang, Rui; Gao, Yingyu

    2016-09-01

    Isobaric vapor liquid equilibria (VLE) for the binary mixtures of glycidyl butyrate(1) + acetone(2), glycidyl butyrate(1) + carbon tetrachloride(2) and glycidyl butyrate(1) + chloroform(2) at 101 kPa were studied. The experimental data were satisfactorily correlated with the models of Wilson, NRTL and UNIQUAC activity coefficients. The activity coefficients for the equilibrium data were obtained by the nonlinear least square method. The average relative deviations between experimental temperatures and calculated temperatures by the Wilson, NRTL and UNIQUAC models were 0.16, 0.16, 0.23% for glycidyl butyrate(1) + chloroform( 2), 0.38, 0.12, 0.27% for glycidylbutyrate(1) + carbon tetrachloride(2), and 0.67, 0.13, 0.54% for glycidyl butyrate(1) + acetone(2). Azeotrope behavior was not found for these systems. The thermodynamic consistency of the correlations was checked by the Herrington's area test.

  12. Butyrate production in engineered Escherichia coli with synthetic scaffolds.

    PubMed

    Baek, Jang-Mi; Mazumdar, Suman; Lee, Sang-Woo; Jung, Moo-Young; Lim, Jae-Hyung; Seo, Sang-Woo; Jung, Gyoo-Yeol; Oh, Min-Kyu

    2013-10-01

    Butyrate pathway was constructed in recombinant Escherichia coli using the genes from Clostridium acetobutylicum and Treponema denticola. However, the pathway constructed from exogenous enzymes did not efficiently convert carbon flux to butyrate. Three steps of the productivity enhancement were attempted in this study. First, pathway engineering to delete metabolic pathways to by-products successfully improved the butyrate production. Second, synthetic scaffold protein that spatially co-localizes enzymes was introduced to improve the efficiency of the heterologous pathway enzymes, resulting in threefold improvement in butyrate production. Finally, further optimizations of inducer concentrations and pH adjustment were tried. The final titer of butyrate was 4.3 and 7.2 g/L under batch and fed-batch cultivation, respectively. This study demonstrated the importance of synthetic scaffold protein as a useful tool for optimization of heterologous butyrate pathway in E. coli.

  13. Butyricicoccus pullicaecorum, a butyrate producer with probiotic potential, is intrinsically tolerant to stomach and small intestine conditions.

    PubMed

    Geirnaert, Annelies; Steyaert, Alix; Eeckhaut, Venessa; Debruyne, Bo; Arends, Jan B A; Van Immerseel, Filip; Boon, Nico; Van de Wiele, Tom

    2014-12-01

    Butyrate has several beneficial properties that are essential to maintain gastrointestinal health. Therefore butyrate-producing bacteria are seen as the next generation of probiotics. The butyrate-producing bacterium Butyricicoccus pullicaecorum (a clostridial cluster IV strain) is such a promising probiotic candidate for people suffering from inflammatory bowel disease. To exert its beneficial properties, it is crucial that B. pullicaecorum survives the harsh conditions of the upper gastrointestinal tract to arrive in the colon in a viable and metabolically active state. Before developing a stable formulation of B. pullicaecorum for oral administration, it is important to know its intrinsic acid and bile tolerance. We monitored the survival during and short chain fatty acid production after incubation in conditions simulating the stomach and small intestine using in vitro batch experiments. In case of acid conditions (pH 2 and pH 3), B. pullicaecorum was viable and active but not cultivable. Cultivability was restored during subsequent small intestine conditions. Importantly, bile and pancreatic juice had no lethal effect. Milk, as a suspension medium, only had a protective effect on the cultivability during the first hour at pH 2. B. pullicaecorum was still metabolically active after upper gastrointestinal conditions and produced short chain fatty acids, but a shift from butyrate to acetate production was observed. Although the butyrate-producing anaerobe B. pullicaecorum showed good intrinsic acid and bile tolerance in terms of viability and metabolic activity, colonization efficiency and butyrate production under colon conditions is needed to further evaluate its probiotic potential.

  14. Dietary sodium gluconate protects rats from large bowel cancer by stimulating butyrate production.

    PubMed

    Kameue, Chiyoko; Tsukahara, Takamitsu; Yamada, Kouji; Koyama, Hironari; Iwasaki, Yoshie; Nakayama, Keizo; Ushida, Kazunari

    2004-04-01

    Butyrate has an antitumorigenic effect on colorectal cancer cell lines. Dietary sodium gluconate (GNA) promotes butyrate production in the large intestine. Accordingly, we examined the effect of dietary GNA on tumorigenesis in the large intestine in rats. Male Fisher-344 rats (n = 32) were divided into 4 groups: 2 diets (with or without 50 g GNA/kg basal diet) x 2 treatments (with or without carcinogen administration). Colonic tumors were induced by 3 intraperitoneal injections of azoxymethane (15 mg/kg body wt, 1 time/wk) and dietary deoxycholic acid (2 g/kg basal diet). The experiment was conducted for 33 wk except for a few rats. Ingestion of GNA increased cecal butyrate concentration at the end of experiment (P < 0.01). No tumor development occurred in the untreated groups. Ingestion of GNA decreased the incidence of tumors in rats administered the carcinogen (37.5 vs. 100%, P < 0.05). Ingestion of GNA also decreased the mean number of tumors per rat (0.5 +/- 0.8 vs. 2.8 +/- 1.5, P < 0.01). beta-Catenin accumulation and TdT-mediated dUTP nick end labeling (TUNEL) positive cells in tumors were histochemically examined. The results of this study suggested that the antitumorigenic effect of GNA may involve the stimulation of apoptosis through enhanced butyrate production in the large intestine.

  15. Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis.

    PubMed

    Rios-Covian, David; Gueimonde, Miguel; Duncan, Sylvia H; Flint, Harry J; de los Reyes-Gavilan, Clara G

    2015-11-01

    Cross-feeding is an important metabolic interaction mechanism of bacterial groups inhabiting the human colon and includes features such as the utilization of acetate by butyrate-producing bacteria as may occur between Bifidobacterium and Faecalibacterium genera. In this study, we assessed the utilization of different carbon sources (glucose, starch, inulin and fructooligosaccharides) by strains of both genera and selected the best suited combinations for evidencing this cross-feeding phenomenon. Co-cultures of Bifidobacterium adolescentis L2-32 with Faecalibacterium prausnitzii S3/L3 with fructooligosaccharides as carbon source, as well as with F. prausnitzii A2-165 in starch, were carried out and the production of short-chain fatty acids was determined. In both co-cultures, acetate levels decreased between 8 and 24 h of incubation and were lower than in the corresponding B. adolescentis monocultures. In contrast, butyrate concentrations were higher in co-cultures as compared to the respective F. prausnitzii monocultures, indicating enhanced formation of butyrate by F. prausnitzii in the presence of the bifidobacteria. Variations in the levels of acetate and butyrate were more pronounced in the co-culture with fructooligosaccharides than with starch. Our results provide a clear demonstration of cross-feeding between B. adolescentis and F. prausnitzii.

  16. Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India

    PubMed Central

    Kumari, Reena; Ahuja, Vineet; Paul, Jaishree

    2013-01-01

    AIM: To study the interplay between butyrate concentration and butyrate-producing bacteria in fecal samples of ulcerative colitis (UC) patients vs control individuals. METHODS: Fecal samples were collected from 14 control individuals (hemorrhoid patients only) and 26 UC patients (severe: n = 12, moderate: n = 6, remission: n = 8), recruited by the gastroenterologist at the Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Disease activity in UC patients was determined by clinical colitis activity index. We employed fluorescent in situ hybridization in combination with flow cytometry to enumerate the clostridium cluster population targeted by 16S rRNA gene probe. Major butyrate-producing species within this cluster were quantified to see if any change existed in control vs UC patients with different disease activity. This observed change was further validated by quantitative polymerase chain reaction. In addition to this, we carried out gas chromatography to evaluate the changes in concentration of major short chain fatty acids (SCFAs), namely acetate, n-butyrate, iso-butyrate, in the above samples. Student t test and Graph pad prism-6 were used to compare the data statistically. RESULTS: There was a significant decrease of Clostridium coccoides (control, 25.69% ± 1.62% vs severe, 9.8% ± 2.4%, P = 0.0001) and Clostridium leptum clusters (control, 13.74% ± 1.05% vs severe, 6.2% ± 1.8%, P = 0.0001) in fecal samples of UC patients. Furthermore, we demonstrated that some butyrate-producing members of the clostridial cluster, like Fecalibacterium prausnitzii (control, 11.66% ± 1.55% vs severe, 6.01% ± 1.6%, P = 0.0001) and Roseburia intestinalis (control, 14.48% ± 1.52% vs severe, 9% ± 1.83%, P = 0.02) were differentially present in patients with different disease activity. In addition, we also demonstrated decreased concentrations of fecal SCFAs, especially of n-butyrate (control, 24.32 ± 1.86 mmol/μL vs severe, 12.74

  17. Germinated barley foodstuff increases fecal volume and butyrate production in humans.

    PubMed

    Kanauchi, O; Mitsuyama, K; Saiki, T; Fushikia, T; Iwanaga, T

    1998-06-01

    Germinated barley foodstuff (GBF), derived from the aleurone layer, scutellum and germ of germinated barley, contains a large quantity of fermentable dietary fibers, especially hemicellulose. Ten grams of GBF were given to 10 healthy volunteers 3 times a day (30 g/day/person) for 28 consecutive days. Fecal weight, water contents and short chain fatty acid content were measured before GBF administration and from days 25 to 28 after initiation of GBF administration. GBF intake significantly increased fecal butyrate content as well as fecal weight and water content. No significant change in body weight resulted from consumption of GBF for 28 days. No major laboratory abnormalities were found in hematologic and urinary analysis. These findings indicate that GBF promotes defecation, produces bacterial short chain fatty acids, especially butyrate, without adverse effects, and is a safe foodstuff for humans.

  18. Ultrasound assisted synthesis of methyl butyrate using heterogeneous catalyst.

    PubMed

    Dange, P N; Kulkarni, A V; Rathod, V K

    2015-09-01

    Ultrasound assisted esterification of butyric acid with methanol was investigated in an ultrasound irradiated isothermal batch reactor using acid ion-exchange resin (amberlyst-15) as a catalyst. Effect of parameters such as temperature (323-353 K), catalyst loading (0-8.5%w/w), alcohol to acid ratio, M (2-6), ultrasound power (0-145 W), duty cycle (0-85%) and amount of molecular sieves added (0-11%w/w) on the rate of reaction was studied. At optimized parameters, a maximum conversion of 91.64% was obtained in 120 min in presence of ultrasound. Experimental kinetic data were correlated by using Eley-Rideal (ER) and Langmuir-Hinshelwood-Hougen-Watson (LHH W) models taking into account reverse reaction. Studies showed that single site LHHW with reactants and products both adsorbing on catalyst surface was most suited for the obtained experimental data. Activation energy determined based on heterogeneous kinetics was in the range 49.31-57.54 kJ/mol while it was 18.29 kJ/mol using homogeneous model.

  19. Control of placental alkaline phosphatase gene expression in HeLa cells: induction of synthesis by prednisolone and sodium butyrate

    SciTech Connect

    Chou, J.Y.; Takahashi, S.

    1987-06-16

    HeLa S/sub 3/ cells produce an alkaline phosphatase indistinguishable from the enzyme from human term placenta. The phosphatase activity in these cells was induced by both prednisolone and sodium butyrate. Both agents stimulated de novo synthesis of the enzyme. The increase in phosphatase activity paralleled the increase in immunoactivity and biosynthesis of placental alkaline phosphatase. The fully processed phosphatase monomer in control, prednisolone-treated or butyrate-treated cells was a 64.5 K polypeptide, measured by both incorporation of L-(/sup 35/S)methionine into enzyme protein and active-site labeling. The 64.5K polypeptide was formed by the incorporation of additional N-acetylneuraminic acid moieties to a precursor polypeptide of 61.5K. However, this biosynthetic pathway was identified only in butyrate-treated cells. In prednisolone-treated cells, the processing of 61.5K to 64.5K monomer was accelerated, and the presence of the 61.5 precursor could only be detected by either neuraminidase or monensin treatment. Phosphatase mRNA which comigrated with the term placental alkaline phosphatase mRNA of 2.7 kilobases was induced in the presence of either prednisolone or butyrate. Alkaline phosphatase mRNA is untreated HeLa S/sub 3/ cells migrated slightly faster than the term placental alkaline phosphatase mRNA. Butyrate also induced a second still faster migrating alkaline phosphatase mRNA. Both prednisolone and butyrate increased the steady-state levels of placental alkaline phosphatase mRNA. The data indicate that the increase in phosphatase mRNA by prednisolone and butyrate resulted in the induction of alkaline phosphatase activity and biosynthesis in HeLa S/sub 3/ cells. Furthermore, both agents induced the expression of different alkaline phosphatase gene transcripts without altering its protein product.

  20. The synergistic effect of 1'-acetoxychavicol acetate and sodium butyrate on the death of human hepatocellular carcinoma cells.

    PubMed

    Kato, Rie; Matsui-Yuasa, Isao; Azuma, Hideki; Kojima-Yuasa, Akiko

    2014-04-01

    It has been suggested that the combined effect of natural products may improve the effect of treatment against the proliferation of cancer cells. In this study, we evaluated the combination of 1'-acetoxychavicol acetate (ACA), obtained from Alpinia galangal, and sodium butyrate, a major short chain fatty acid, on the growth of HepG2 human hepatocellular carcinoma cells and found that treatment had a synergistic inhibitory effect. The number of HepG2 cells was synergistically decreased via apoptosis induction when cells were treated with both ACA and sodium butyrate. In ACA- and sodium butyrate-treated cells, intracellular reactive oxygen species (ROS) levels and NADPH oxidase activities were increased significantly. The decrease in cell number after combined treatment of ACA and sodium butyrate was diminished when cells were pretreated with catalase. These results suggest that an increase in intracellular ROS levels is involved in cancer cell death. AMP-activated protein kinase (AMPK), a cellular energy sensor, plays an essential role in controlling processes related to tumor development. In ACA- and sodium butyrate-treated cells, AMPK phosphorylation was induced significantly, and this induction improved when cells were pretreated with catalase. These results suggest that the increase in intracellular ROS is involved in the increase of AMPK phosphorylation. In normal hepatocyte cells, treatment with ACA and sodium butyrate did not decrease cell numbers or increase ROS levels. In conclusion, combined treatment with ACA and sodium butyrate synergistically induced apoptotic cell death via an increase in intracellular ROS and phosphorylation of AMPK. Our findings may provide new insight into the development of novel combination therapies against hepatocellular carcinoma.

  1. Isolation of unique butyrate-producing bacteria from swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate-producing bacteria in humans contribute to a healthy gastrointestinal tract and are known to be species from clostridial clusters IV, IX, XIVa, and XVI - with the community dominated by clusters XIVa and IV. However, the composition of the butyrate-producing bacterial community in swine is...

  2. Increasing butyrate concentration in the distal colon by accelerating intestinal transit

    PubMed Central

    Lewis, S; Heaton, K

    1997-01-01

    Background—Populations at low risk of colonic cancer consume large amounts of fibre and starch and pass acid, bulky stools. One short chain fatty acid (SCFA), butyrate, is the colon's main energy source and inhibits malignant transformation in vitro. 
Aim—To test the hypothesis that altering colonic transit rate alters colonic pH and the SCFA content of the stools. 
Patients—Thirteen healthy adults recruited by advertisement. 
Methods—Volunteers consumed, in turn, wheat bran, senna and loperamide, each for nine days with a two week washout period between study periods, dietary intake being unchanged. Before, and in the last four days of each intervention, whole gut transit time (WGTT), defaecation frequency, stool form, stool β-glucuronidase activity, stool pH, stool SCFA concentrations and intracolonic pH (using a radiotelemetry capsule for continuous monitoring) were assessed. 
Results—WGTT decreased, stool output and frequency increased with wheat bran and senna, vice versa with loperamide. The pH was similar in the distal colon and stool. Distal colonic pH fell with wheat bran and senna and tended to increase with loperamide. Faecal SCFA concentrations, including butyrate, increased with senna and fell with loperamide. With wheat bran the changes were non-significant, possibly because of the short duration of the study. Baseline WGTT correlated with faecal SCFA concentration (r=−0.511, p=0.001), with faecal butyrate (r=−0.577, p<0.001) and with distal colonic pH (r=0.359, p=0.029). 
Conclusion—Bowel transit rate is a determinant of stool SCFA concentration including butyrate and distal colonic pH. This may explain the inter-relations between colonic cancer, dietary fibre intake, stool output, and stool pH. 

 Keywords: bowel cancer; colonic pH; fibre; intestinal transit; pH; short chain fatty acids PMID:9301506

  3. LeuO enhances butyrate-induced virulence expression through a positive regulatory loop in enterohaemorrhagic Escherichia coli.

    PubMed

    Takao, Miyuki; Yen, Hilo; Tobe, Toru

    2014-09-01

    Enterohaemorrhagic Escherichia coli (EHEC) causes bloody diarrhoea and other severe symptoms such as haemorrhagic uraemic syndrome. The expression of virulence genes on the locus for enterocyte effacement (LEE) and associated genes is regulated by a variety of factors, including transcriptional regulators and environmental signals. Butyrate, one of the major short-chain fatty acids present in the intestine, enhances expression of LEE genes and flagella biosynthesis genes in EHEC O157:H7, resulting in increased bacterial adherence and motility. Here, we show that expression of the leuO gene, which encodes a LysR-type transcriptional regulator, is enhanced by butyrate via Lrp, which is also necessary for butyrate-induced responses of LEE genes. LeuO expression induces prolonged activation of the promoter of LEE1 operon, including the ler gene, as well as virulence mechanisms such as microcolony formation. Activation of the LEE1 promoter by LeuO depends on another regulator, called Pch. The response of the leuO promoter to butyrate requires two virulence regulators, Pch and Ler, in addition to Lrp. Pch, Ler and Lrp bind the upstream region of the leuO promoter. Thus, leuO is involved in butyrate-enhanced expression of LEE genes through a positive feedback mechanism, but its expression and action on the LEE1 promoter are dependent on the virulence regulators Pch and Ler.

  4. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes.

    PubMed

    Mali, Prashant; Chou, Bin-Kuan; Yen, Jonathan; Ye, Zhaohui; Zou, Jizhong; Dowey, Sarah; Brodsky, Robert A; Ohm, Joyce E; Yu, Wayne; Baylin, Stephen B; Yusa, Kosuke; Bradley, Allan; Meyers, David J; Mukherjee, Chandrani; Cole, Philip A; Cheng, Linzhao

    2010-04-01

    We report here that butyrate, a naturally occurring fatty acid commonly used as a nutritional supplement and differentiation agent, greatly enhances the efficiency of induced pluripotent stem (iPS) cell derivation from human adult or fetal fibroblasts. After transient butyrate treatment, the iPS cell derivation efficiency is enhanced by 15- to 51-fold using either retroviral or piggyBac transposon vectors expressing 4 to 5 reprogramming genes. Butyrate stimulation is more remarkable (>100- to 200-fold) on reprogramming in the absence of either KLF4 or MYC transgene. Butyrate treatment did not negatively affect properties of iPS cell lines established by either 3 or 4 retroviral vectors or a single piggyBac DNA transposon vector. These characterized iPS cell lines, including those derived from an adult patient with sickle cell disease by either the piggyBac or retroviral vectors, show normal karyotypes and pluripotency. To gain insights into the underlying mechanisms of butyrate stimulation, we conducted genome-wide gene expression and promoter DNA methylation microarrays and other epigenetic analyses on established iPS cells and cells from intermediate stages of the reprogramming process. By days 6 to 12 during reprogramming, butyrate treatment enhanced histone H3 acetylation, promoter DNA demethylation, and the expression of endogenous pluripotency-associated genes, including DPPA2, whose overexpression partially substitutes for butyrate stimulation. Thus, butyrate as a cell permeable small molecule provides a simple tool to further investigate molecular mechanisms of cellular reprogramming. Moreover, butyrate stimulation provides an efficient method for reprogramming various human adult somatic cells, including cells from patients that are more refractory to reprogramming. PMID:20201064

  5. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes.

    PubMed

    Mali, Prashant; Chou, Bin-Kuan; Yen, Jonathan; Ye, Zhaohui; Zou, Jizhong; Dowey, Sarah; Brodsky, Robert A; Ohm, Joyce E; Yu, Wayne; Baylin, Stephen B; Yusa, Kosuke; Bradley, Allan; Meyers, David J; Mukherjee, Chandrani; Cole, Philip A; Cheng, Linzhao

    2010-04-01

    We report here that butyrate, a naturally occurring fatty acid commonly used as a nutritional supplement and differentiation agent, greatly enhances the efficiency of induced pluripotent stem (iPS) cell derivation from human adult or fetal fibroblasts. After transient butyrate treatment, the iPS cell derivation efficiency is enhanced by 15- to 51-fold using either retroviral or piggyBac transposon vectors expressing 4 to 5 reprogramming genes. Butyrate stimulation is more remarkable (>100- to 200-fold) on reprogramming in the absence of either KLF4 or MYC transgene. Butyrate treatment did not negatively affect properties of iPS cell lines established by either 3 or 4 retroviral vectors or a single piggyBac DNA transposon vector. These characterized iPS cell lines, including those derived from an adult patient with sickle cell disease by either the piggyBac or retroviral vectors, show normal karyotypes and pluripotency. To gain insights into the underlying mechanisms of butyrate stimulation, we conducted genome-wide gene expression and promoter DNA methylation microarrays and other epigenetic analyses on established iPS cells and cells from intermediate stages of the reprogramming process. By days 6 to 12 during reprogramming, butyrate treatment enhanced histone H3 acetylation, promoter DNA demethylation, and the expression of endogenous pluripotency-associated genes, including DPPA2, whose overexpression partially substitutes for butyrate stimulation. Thus, butyrate as a cell permeable small molecule provides a simple tool to further investigate molecular mechanisms of cellular reprogramming. Moreover, butyrate stimulation provides an efficient method for reprogramming various human adult somatic cells, including cells from patients that are more refractory to reprogramming.

  6. ALA-Butyrate prodrugs for Photo-Dynamic Therapy

    NASA Astrophysics Data System (ADS)

    Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

    2010-05-01

    The use of 5-aminolevulinic acid (ALA) administration has led to many applications of photodynamic therapy (PDT) in cancer. However, the hydrophilic nature of ALA limits its ability to penetrate the cells and tissues, and therefore the need for ALA derivatives became an urgent research target. In this study we investigated the activity of novel multifunctional acyloxyalkyl ester prodrugs of ALA that upon metabolic hydrolysis release active components such as, formaldehyde, and the histone deacetylase inhibitory moiety, butyric acid. Evaluation of these prodrugs under photo-irradiation conditions showed that butyryloxyethyl 5-amino-4-oxopentanoate (ALA-BAC) generated the most efficient photodynamic destruction compared to ALA. ALA-BAC stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells which resulted in generation of intracellular ROS, reduction of mitochondrial activity, leading to apoptotic and necrotic death of the cells. The apoptotic cell death induced by ALA / ALA-BAC followed by PDT equally activate intrinsic and extrinsic apoptotic signals and both pathways may occur simultaneously. The main advantage of ALA-BAC over ALA stems from its ability to induce photo-damage at a significantly lower dose than ALA.

  7. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

    PubMed

    Chang, Pamela V; Hao, Liming; Offermanns, Stefan; Medzhitov, Ruslan

    2014-02-11

    Given the trillions of microbes that inhabit the mammalian intestines, the host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria. Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. The mechanisms by which the immune system maintains this critical balance remain largely undefined. Here, we demonstrate that the short-chain fatty acid n-butyrate, which is secreted in high amounts by commensal bacteria, can modulate the function of intestinal macrophages, the most abundant immune cell type in the lamina propria. Treatment of macrophages with n-butyrate led to the down-regulation of lipopolysaccharide-induced proinflammatory mediators, including nitric oxide, IL-6, and IL-12, but did not affect levels of TNF-α or MCP-1. These effects were independent of toll-like receptor signaling and activation of G-protein-coupled receptors, two pathways that could be affected by short-chain fatty acids. In this study, we provide several lines of evidence that suggest that these effects are due to the inhibition of histone deacetylases by n-butyrate. These findings elucidate a pathway in which the host may maintain tolerance to intestinal microbiota by rendering lamina propria macrophages hyporesponsive to commensal bacteria through the down-regulation of proinflammatory effectors.

  8. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

    PubMed

    Chang, Pamela V; Hao, Liming; Offermanns, Stefan; Medzhitov, Ruslan

    2014-02-11

    Given the trillions of microbes that inhabit the mammalian intestines, the host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria. Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. The mechanisms by which the immune system maintains this critical balance remain largely undefined. Here, we demonstrate that the short-chain fatty acid n-butyrate, which is secreted in high amounts by commensal bacteria, can modulate the function of intestinal macrophages, the most abundant immune cell type in the lamina propria. Treatment of macrophages with n-butyrate led to the down-regulation of lipopolysaccharide-induced proinflammatory mediators, including nitric oxide, IL-6, and IL-12, but did not affect levels of TNF-α or MCP-1. These effects were independent of toll-like receptor signaling and activation of G-protein-coupled receptors, two pathways that could be affected by short-chain fatty acids. In this study, we provide several lines of evidence that suggest that these effects are due to the inhibition of histone deacetylases by n-butyrate. These findings elucidate a pathway in which the host may maintain tolerance to intestinal microbiota by rendering lamina propria macrophages hyporesponsive to commensal bacteria through the down-regulation of proinflammatory effectors. PMID:24390544

  9. [Isolation and identification of a lactate-utilizing, butyrate-producing bacterium and its primary metabolic characteristics].

    PubMed

    Liu, Wei; Zhu, Wei-yun; Yao, Wen; Mao, Sheng-yong

    2007-06-01

    The distal mammalian gut harbors prodigiously abundant microbes, which provide unique metabolic traits to host. A lactate-utilizing, butyrate-producing bacterium, strain LB01, was isolated from adult swine feces by utilizing modified Hungate technique with rumen liquid-independent YCFA medium supplemented with lactate as the single carbon source. It was an obligate anaerobic, Gram positive bacterium, and could utilize glucose, fructose, maltose and lactate with a large amount of gas products. 16S rRNA sequence analysis revealed that it had the high similarity with members of the genus Megasphaera. The metabolic characteristics of strain LB01 was investigated by using in vitro fermentation system. Lactate at the concentration of 65 mmol/L in YCFA medium was rapidly consumed within 9 hours and was mainly converted to propionate and butyrate after 24h. As the level of acetate declined, the concentration of butyrate rose only in the presence of glucose, suggesting that butyrate could possibly be synthesized by the acetyl CoA: butyryl CoA transferase. When co-cultured with lactic acid bacteria strain K9, strain LB01 evidently reduced the concentration of lactate produced by strain K9 and decelerated the rapid pH drop, finally producing 12.11 mmol/L butyrate and 4.06 mmol/L propionate. The metabolic characteristics that strain LB01 efficiently converts toxic lactate and excessive acetate to butyrate can prevent lactate and acetate accumulation in the large intestine and maintain the slightly acidic environment of the large intestine, consequently revealing that stain LB01 could act as a potential probiotics.

  10. Butyrate Infusions in the Ovine Fetus Delay the Biologic Clock for Globin Gene Switching

    NASA Astrophysics Data System (ADS)

    Perrine, Susan P.; Rudolph, Abraham; Faller, Douglas V.; Roman, Christine; Cohen, Ruth A.; Chen, Shao-Jing; Kan, Yuet Wai

    1988-11-01

    The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal β -globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching.

  11. Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells.

    PubMed

    Rosignoli, P; Fabiani, R; De Bartolomeo, A; Spinozzi, F; Agea, E; Pelli, M A; Morozzi, G

    2001-10-01

    Epidemiological studies support the involvement of short-chain fatty acids (SCFA) in colon physiology and the protective role of butyrate on colon carcinogenesis. Among the possible mechanisms by which butyrate may exert its anti-carcinogenicity an antioxidant activity has been recently suggested. We investigated the effects of butyrate and mixtures of SCFA (butyrate, propionate and acetate) on DNA damage induced by H(2)O(2) in isolated human colonocytes and in two human colon tumour cell lines (HT29 and HT29 19A). Human colonocytes were isolated from endoscopically obtained samples and the DNA damage was assessed by the comet assay. H(2)O(2) induced DNA damage in normal colonocytes in a dose-dependent manner which was statistically significant at concentrations over 10 microM. At 15 microM H(2)O(2) DNA damage in HT29 and HT29 19A cells was significantly lower than that observed in normal colonocytes (P < 0.01). Pre-incubation of the cells with physiological concentrations of butyrate (6.25 and 12.5 mM) reduced H(2)O(2) (15 microM) induced damage by 33 and 51% in human colonocytes, 45 and 75% in HT29 and 30 and 80% in HT29 19A, respectively. Treatment of cells with a mixture of 25 mM acetate + 10.4 mM propionate + 6.25 mM butyrate did not induce DNA damage, while a mixture of 50 mM acetate + 20.8 mM propionate + 12.5 mM butyrate was weakly genotoxic only towards normal colonocytes. However, both mixtures were able to reduce the H(2)O(2)-induced DNA damage by about 50% in all cell types. The reported protective effect of butyrate might be important in pathogenetic mechanisms mediated by reactive oxygen species, and aids understanding of the apparent protection toward colorectal cancer exerted by dietary fibres, which enhance the butyrate bioavailability in the colonic mucosa. PMID:11577008

  12. Specific cell cycle synchronization with butyrate and cell cycle analysis.

    PubMed

    Li, Congjun

    2011-01-01

    Synchronized cells have been invaluable in many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in Madin Darby Bovine Kidney (MDBK) cells. We explore the possibility of using butyrate-blocked cells to obtain synchronized cells and we characterize the properties of butyrate-induced cell cycle arrest. The site of growth inhibition and cell cycle arrest was analyzed using 5-bromo-2'-deoxyuridine (BrdU) incorporation and flow cytometry analyses. Exposure of MDBK cells to 10 mM butyrate caused growth inhibition and cell cycle arrest in a reversible manner. Butyrate affected the cell cycle at a specific point both immediately after mitosis and at a very early stage of the G1 phase. After release from butyrate arrest, MDBK cells underwent synchronous cycles of DNA synthesis and transited through the S phase. It takes at least 8 h for butyrate-induced G1-synchronized cells to begin the progression into the S phase. One cycle of cell division for MDBK cells is about 20 h. By combining BrdU incorporation and DNA content analysis, not only can the overlapping of different cell populations be eliminated, but the frequency and nature of individual cells that have synthesized DNA can also be determined.

  13. Molecular structure, vibrational and electronic properties of 4-Phenyl-3H-1,3-thiazol-2-ol using density functional theory and comparison of drug efficacy of keto and enol forms by QSAR analysis

    NASA Astrophysics Data System (ADS)

    Sachan, Alok K.; Pathak, Shilendra K.; Chand, Satish; Srivastava, Ruchi; Prasad, Onkar; Belaidi, Salah; Sinha, Leena

    2014-11-01

    4-Phenyl-3H-1,3-thiazol-2-ol can exist in two tautomeric forms - keto and enol. Comprehensive investigation of molecular geometry and electronic structure in ground as well as in the first excited state of 4-Phenyl-3H-1,3-thiazol-2-ol (enol) has been carried out. To determine lowest-energy molecular conformation of the title molecule, the selected torsion angles were varied in steps of 10° and molecular energy profile was calculated from -180° to +180°. Experimental FT-IR and FT-Raman spectra of title compound were compared with the spectral data obtained by DFT/B3LYP method. Dipole moment, polarizability, first static hyperpolarizability and molecular electrostatic potential surface map have been calculated to get a better insight of the properties of title molecule. Natural bond orbital (NBO) analysis has been done to study the stability of the molecule arising from charge delocalization. UV-Vis spectrum of the title compound was also recorded and electronic properties such as frontier orbitals and band gap energies were calculated by TD-DFT approach. To compare the drug efficacy of enolic and keto forms, QSAR properties of both forms have also been computed and discussed.

  14. Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents.

    PubMed

    Herraiz, Tomás

    2012-12-01

    Monoamine oxidase (MAO) enzymes catalyze the oxidative deamination of amines and neurotransmitters and inhibitors of MAO are useful as neuroprotectants. This work evaluates the human MAO-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a dopaminergic neurotoxin, to the directly-acting neurotoxic metabolites, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP(+)) and 1-methyl-4-phenylpyridinium (MPP(+)) measured by High-Performance Liquid Chromatography (HPLC), and this approach is subsequently used as a new method for screening of MAO inhibitors and protective agents. Oxidation of MPTP by human MAO-B was more efficient than by MAO-A. R-Deprenyl, a known neuroprotectant, norharman (β-carboline), 5-nitroindazole and menadione (vitamin K3) inhibited MAO-B and reduced the formation of toxic pyridinium cations. Clorgyline and the β-carbolines, harman and norharman, inhibited the oxidation of MPTP by MAO-A. Cigarette smoke, as well as the naturally occurring β-carbolines (norharman and harman) isolated from smoke and coffee inhibited the oxidation of MPTP by MAO-B and/or MAO-A, suggesting protective effects against MPTP. The results show the suitability of the approach used to search for new MAO inhibitors with eventual neuroprotective activity.

  15. Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice.

    PubMed

    Singh, Alpana; Verma, Poonam; Balaji, Gillela; Samantaray, Supriti; Mohanakumar, Kochupurackal P

    2016-10-01

    Parkinson's disease (PD), the most common progressive neurodegenerative movement disorder, results from loss of dopaminergic neurons of substantia nigra pars compacta. These neurons exhibit Cav1.3 channel-dependent pacemaking activity. Epidemiological studies suggest reduced risk for PD in population under long-term antihypertensive therapy with L-type calcium channel antagonists. These prompted us to investigate nimodipine, an L-type calcium channel blocker for neuroprotective effect in cellular and animal models of PD. Nimodipine (0.1-10 μM) significantly attenuated 1-methyl-4-phenyl pyridinium ion-induced loss in mitochondrial morphology, mitochondrial membrane potential and increases in intracellular calcium levels in SH-SY5Y neuroblastoma cell line as measured respectively employing Mitotracker green staining, TMRM, and Fura-2 fluorescence, but only a feeble neuroprotective effect was observed in MTT assay. Nimodipine dose-dependently reduced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian syndromes (akinesia and catalepsy) and loss in swimming ability in Balb/c mice. It attenuated MPTP-induced loss of dopaminergic tyrosine hydroxylase positive neurons in substantia nigra, improved mitochondrial oxygen consumption and inhibited reactive oxygen species production in the striatal mitochondria measured using dichlorodihydrofluorescein fluorescence, but failed to block striatal dopamine depletion. These results point to an involvement of L-type calcium channels in MPTP-induced dopaminergic neuronal death in experimental parkinsonism and more importantly provide evidences for nimodipine to improve mitochondrial integrity and function.

  16. Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice.

    PubMed

    Singh, Alpana; Verma, Poonam; Balaji, Gillela; Samantaray, Supriti; Mohanakumar, Kochupurackal P

    2016-10-01

    Parkinson's disease (PD), the most common progressive neurodegenerative movement disorder, results from loss of dopaminergic neurons of substantia nigra pars compacta. These neurons exhibit Cav1.3 channel-dependent pacemaking activity. Epidemiological studies suggest reduced risk for PD in population under long-term antihypertensive therapy with L-type calcium channel antagonists. These prompted us to investigate nimodipine, an L-type calcium channel blocker for neuroprotective effect in cellular and animal models of PD. Nimodipine (0.1-10 μM) significantly attenuated 1-methyl-4-phenyl pyridinium ion-induced loss in mitochondrial morphology, mitochondrial membrane potential and increases in intracellular calcium levels in SH-SY5Y neuroblastoma cell line as measured respectively employing Mitotracker green staining, TMRM, and Fura-2 fluorescence, but only a feeble neuroprotective effect was observed in MTT assay. Nimodipine dose-dependently reduced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian syndromes (akinesia and catalepsy) and loss in swimming ability in Balb/c mice. It attenuated MPTP-induced loss of dopaminergic tyrosine hydroxylase positive neurons in substantia nigra, improved mitochondrial oxygen consumption and inhibited reactive oxygen species production in the striatal mitochondria measured using dichlorodihydrofluorescein fluorescence, but failed to block striatal dopamine depletion. These results point to an involvement of L-type calcium channels in MPTP-induced dopaminergic neuronal death in experimental parkinsonism and more importantly provide evidences for nimodipine to improve mitochondrial integrity and function. PMID:27395789

  17. Liquid Crystals and Glasses in Binary Systems from Sodium and Alkali-Earth Metal Butyrates

    NASA Astrophysics Data System (ADS)

    Mirnaya, T. A.; Bereznitski, Y. V.; Volkov, S. V.

    1996-07-01

    The temperature and composition ranges of liquid crystal and glass formation have been established for the binary mixtures of mesogenic sodium butyrate with non-mesogenic magnesium, calcium and strontium butyrates by means of differential thermal analysis and hot stage polarization microscopy. The formation of a vitreous optically anisotropic mesophase has been found for binaries of sodium butyrate with calcium and strontium butyrates.

  18. Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring

    PubMed Central

    Adamu, Hadiza Altine; Imam, Mustapha Umar; Ooi, Der-Jiun; Esa, Norhaizan Mohd; Rosli, Rozita; Ismail, Maznah

    2016-01-01

    Background Evidence suggests perinatal environments influence the risk of developing insulin resistance. Objective The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR) and GBR-derived gamma (γ) aminobutyric acid (GABA) extract on epigenetically mediated high fat diet–induced insulin resistance. Design Pregnant Sprague Dawley rats were fed high-fat diet (HFD), HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4) were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. Results Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. Conclusions These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis. PMID:26842399

  19. Local uptake of (14)C-labeled acetate and butyrate in rat brain in vivo during spreading cortical depression.

    PubMed

    Dienel, G A; Liu, K; Cruz, N F

    2001-12-01

    Spreading depression severely disrupts ion homeostasis, causes sensory neglect and motor impairment, and is associated with stroke and migraine. Glucose utilization (CMR(glc)) and lactate production rise during spreading depression, but the metabolic changes in different brain cell types are unknown. Uptake of (14)C-labeled compounds known to be preferentially metabolized by the glial tricarboxylic acid cycle was, therefore, examined during unilateral KCl-induced spreading cortical depression in conscious, normoxic rats. [(14)C]Metabolites derived from [(14)C]butyrate in K+ -treated tissue rose 21% compared to that of untreated contralateral control cortex, whereas incorporation of H(14)CO(3) into metabolites in K+ -treated tissue was reduced to 86% of control. Autoradiographic analysis showed that laminar labeling of cerebral cortex by both (14)C-labeled acetate and butyrate was elevated heterogeneously throughout cortex by an average of 23%; the increase was greatest (approximately 40%) in tissue adjacent to the K+ application site. Local uptake of acetate, butyrate, and deoxyglucose showed similar patterns, and monocarboxylic acid uptake was highest in the structures in which apparent loss of labeled metabolites of [6-(14)C]glucose was greatest. Enhancement of net uptake of acetate and butyrate in cerebral cortex during spreading depression is tentatively ascribed to increased astrocyte metabolism.

  20. Quantitative influences of butyrate or propionate on thermophilic production of methane from biomass

    SciTech Connect

    Henson, J.M.; Bordeaux, F.M.; Rivards, C.J.; Smith, P.H.

    1986-02-01

    Sodium butyrate and sodium propionate were continuously infused into separate 4-liter thermophilic digesters. These digesters were operated at 55/sup 0/C, had a retention time of 20 days, and had a pH of 7.8. Infusion rates were started at 10 mM day/sup -1/ and were increased incrementally when new stable external organic acid pool sizes and new stable gas production rates were observed. Stable conditions were obtained in both digesters at an infusion rate of 15 mM day/sup -1/, with methanogenesis elevated over that of control digesters. Calculations based on expected CH/sub 4/ at this infusion rate and measured CH/sub 4/ production in the treated and control digesters, however, showed an approximately 25% inhibition of methanogenesis in both digesters. A digester infused with sodium chloride showed little or no inhibition at this infusion rate, but was totally inhibited when its infusion rate was increased to 20 mM day/sup -1/, and cumulative added NaCl reached 0.38 M. The butyrate and propionate-amended digesters tolerated addition rates of 20 mM day/sup -1/, but both failed when they were increased to 25 mM day/sup -1/. These results indicate that the thermophilic digesters could function stably at higher external pool sizes of butyrate or propionate than routinely observed.

  1. Quantitative Influences of Butyrate or Propionate on Thermophilic Production of Methane from Biomass †

    PubMed Central

    Henson, J. Michael; Bordeaux, F. M.; Rivard, Christopher J.; Smith, P. H.

    1986-01-01

    Sodium butyrate and sodium propionate were continuously infused into separate 4-liter thermophilic digesters. These digesters were operated at 55°C, had a retention time of 20 days, and had a pH of 7.8. Infusion rates were started at 10 mM day−1 and were increased incrementally when new stable external organic acid pool sizes and new stable gas production rates were observed. Stable conditions were obtained in both digesters at an infusion rate of 15 mM day−1, with methanogenesis elevated over that of control digesters. Calculations based on expected CH4 at this infusion rate and measured CH4 production in the treated and control digesters, however, showed an approximately 25% inhibition of methanogenesis in both digesters. A digester infused with sodium chloride showed little or no inhibition at this infusion rate, but was totally inhibited when its infusion rate was increased to 20 mM day−1, and cumulative added NaCl reached 0.38 M. The butyrate and propionate-amended digesters tolerated addition rates of 20 mM day−1, but both failed when they were increased to 25 mM day−1. These results indicate that the thermophilic digesters could function stably at higher external pool sizes of butyrate or propionate than routinely observed. PMID:16346985

  2. Nonprotein Amino Acids in the Murchison Meteorite

    PubMed Central

    Kvenvolden, Keith A.; Lawless, James G.; Ponnamperuma, Cyril

    1971-01-01

    Twelve nonprotein amino acids appear to be present in the Murchison meteorite. The identity of eight of them has been conclusively established as N-methylglycine, β-alanine, 2-methylalanine, α-amino-n-butyric acid, β-amino-n-butyric acid, γ-amino-n-butyric acid, isovaline, and pipecolic acid. Tentative evidence is presented for the presence of N-methylalanine, N-ethylglycine, β-aminoisobutyric acid, and norvaline. These amino acids appear to be extraterrestrial in origin and may provide new evidence for the hypothesis of chemical evolution. PMID:16591908

  3. Crystal structure of catena-poly[bis(formato-κO)bis­[μ2-1,1′-(1,4-phenyl­ene)bis­(1H-imidazole)-κ2 N 3:N 3′]cobalt(II)

    PubMed Central

    Xu, Guo-Wang; Wang, Ye-Nan; Xia, Hong-Xu; Wang, Zhong-Long

    2015-01-01

    A red block-shaped crystal of the title compound, [Co(HCOO)2(C12H10N4)2]n, was obtained by the reaction of cobalt(II) nitrate hexa­hydrate, formic acid and 1,1′-(1,4-phenyl­ene)bis­(1H-imidazole) (bib) mol­ecules. The asymmetric unit consists of one CoII cation, one formate ligand and two halves of a bib ligand. The central CoII cation, located on an inversion centre, is coordinated by two carboxyl­ate O atoms and four N atoms from bib ligands, completing an octa­hedral coordination geometry. The CoII centres are bridged by bib ligands, giving a two-dimensional net. Topologically, taking the CoII atoms as nodes and the bib ligands as linkers, the two-dimensional structure can be simplified as a typical sql/Shubnikov tetra­gonal plane network. The structure features C—H⋯O hydrogen-bonding inter­actions between formate and bib ligands, resulting in a three-dimensional supra­molecular network. PMID:26396863

  4. Colonic mucin synthesis is increased by sodium butyrate.

    PubMed

    Finnie, I A; Dwarakanath, A D; Taylor, B A; Rhodes, J M

    1995-01-01

    The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of beta oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial biopsy specimens were incubated for 16 hours in RPMI 1640 with glutamine, supplemented with 10% fetal calf serum and N-acetyl-[3H]-glucosamine ([3H]-Glc NAc), and differing concentrations of sodium butyrate. Incorporation of [3H] Glc NAc into mucin by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens = 24 from six patients, p < 0.001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the beta oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis. PMID:7890244

  5. Colonic mucin synthesis is increased by sodium butyrate.

    PubMed

    Finnie, I A; Dwarakanath, A D; Taylor, B A; Rhodes, J M

    1995-01-01

    The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of beta oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial biopsy specimens were incubated for 16 hours in RPMI 1640 with glutamine, supplemented with 10% fetal calf serum and N-acetyl-[3H]-glucosamine ([3H]-Glc NAc), and differing concentrations of sodium butyrate. Incorporation of [3H] Glc NAc into mucin by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens = 24 from six patients, p < 0.001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the beta oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis.

  6. Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells.

    PubMed

    Andrade, F O; Nagamine, M K; Conti, A De; Chaible, L M; Fontelles, C C; Jordão Junior, A A; Vannucchi, H; Dagli, M L Z; Bassoli, B K; Moreno, F S; Ong, T P

    2012-09-01

    The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10(4) cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21WAF1 by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered.

  7. Performance, intestinal microflora, and wall morphology of weanling pigs fed sodium butyrate.

    PubMed

    Biagi, G; Piva, A; Moschini, M; Vezzali, E; Roth, F X

    2007-05-01

    Adding organic acids to piglet diets is known to be helpful in overcoming postweaning syndrome, and butyric acid is known to be the main energy source for the epithelial cells of the large intestine and the terminal ileum. This study investigated the effect of sodium butyrate (SB) on in vitro and in vivo swine microflora, piglet growth performance, and intestinal wall morphology. During a 24-h in vitro cecal fermentation, total gas production and maximal rate of gas production were reduced linearly by SB (P < 0.001). Ammonia in cecal liquor was increased linearly by SB after 4, 8, and 24 h of fermentation (P < 0.001). In the in vivo study, 48 piglets housed in individual crates were allotted to 4 treatment groups (12 animals per treatment) for 6 wk. Piglets received a basal diet with a) no addition (control), or with SB at b) 1,000 ppm, c) 2,000 ppm, or d) 4,000 ppm. After 6 wk, 6 animals per treatment were killed, and samples of intestinal content and mucosa were collected. Sodium butyrate did not improve the animal growth performance. In the cecum, SB increased pH and isobutyric acid concentration (linear, P < 0.05) and tended to increase ammonia concentration (P = 0.056). Intestinal counts of clostridia, enterobacteriaceae, and lactic acid bacteria as well as intestinal mucosal morphology were not affected by feeding SB. This study showed that SB influenced the cecal microflora in an in vitro system, reducing the total gas production but increasing ammonia concentrations. When fed to piglets, SB did not improve the animal growth performance, increased cecal pH, and tended to increase cecal ammonia concentrations. Further studies will be needed to better understand the mechanisms underlying the effects observed when SB is fed to piglets.

  8. Relationship of Enhanced Butyrate Production by Colonic Butyrate-Producing Bacteria to Immunomodulatory Effects in Normal Mice Fed an Insoluble Fraction of Brassica rapa L.

    PubMed Central

    Tanaka, Sachi; Yamamoto, Kana; Yamada, Kazuki; Furuya, Kanon

    2016-01-01

    This study was performed to determine the effects of feeding a fiber-rich fraction of Brassica vegetables on the immune response through changes in enteric bacteria and short-chain fatty acid (SCFA) production in normal mice. The boiled-water-insoluble fraction of Brassica rapa L. (nozawana), which consists mainly of dietary fiber, was chosen as a test material. A total of 31 male C57BL/6J mice were divided into two groups and housed in a specific-pathogen-free facility. The animals were fed either a control diet or the control diet plus the insoluble B. rapa L. fraction for 2 weeks and sacrificed to determine microbiological and SCFA profiles in lower-gut samples and immunological molecules. rRNA-based quantification indicated that the relative population of Bacteroidetes was markedly lower in the colon samples of the insoluble B. rapa L. fraction-fed group than that in the controls. Populations of the Eubacterium rectale group and Faecalibacterium prausnitzii, both of which are representative butyrate-producing bacteria, doubled after 2 weeks of fraction intake, accompanying a marginal increase in the proportion of colonic butyrate. In addition, feeding with the fraction significantly increased levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and tended to increase splenic regulatory T cell numbers but significantly reduced the population of cells expressing activation markers. We demonstrated that inclusion of the boiled-water-insoluble fraction of B. rapa L. can alter the composition of the gut microbiota to decrease the numbers of Bacteroidetes and to increase the numbers of butyrate-producing bacteria, either of which may be involved in the observed shift in the production of splenic IL-10. PMID:26921420

  9. Relationship of Enhanced Butyrate Production by Colonic Butyrate-Producing Bacteria to Immunomodulatory Effects in Normal Mice Fed an Insoluble Fraction of Brassica rapa L.

    PubMed

    Tanaka, Sachi; Yamamoto, Kana; Yamada, Kazuki; Furuya, Kanon; Uyeno, Yutaka

    2016-05-01

    This study was performed to determine the effects of feeding a fiber-rich fraction of Brassica vegetables on the immune response through changes in enteric bacteria and short-chain fatty acid (SCFA) production in normal mice. The boiled-water-insoluble fraction of Brassica rapa L. (nozawana), which consists mainly of dietary fiber, was chosen as a test material. A total of 31 male C57BL/6J mice were divided into two groups and housed in a specific-pathogen-free facility. The animals were fed either a control diet or the control diet plus the insoluble B. rapa L. fraction for 2 weeks and sacrificed to determine microbiological and SCFA profiles in lower-gut samples and immunological molecules. rRNA-based quantification indicated that the relative population of Bacteroidetes was markedly lower in the colon samples of the insoluble B. rapa L. fraction-fed group than that in the controls. Populations of the Eubacterium rectale group and Faecalibacterium prausnitzii, both of which are representative butyrate-producing bacteria, doubled after 2 weeks of fraction intake, accompanying a marginal increase in the proportion of colonic butyrate. In addition, feeding with the fraction significantly increased levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and tended to increase splenic regulatory T cell numbers but significantly reduced the population of cells expressing activation markers. We demonstrated that inclusion of the boiled-water-insoluble fraction of B. rapa L. can alter the composition of the gut microbiota to decrease the numbers of Bacteroidetes and to increase the numbers of butyrate-producing bacteria, either of which may be involved in the observed shift in the production of splenic IL-10. PMID:26921420

  10. Relationship of Enhanced Butyrate Production by Colonic Butyrate-Producing Bacteria to Immunomodulatory Effects in Normal Mice Fed an Insoluble Fraction of Brassica rapa L.

    PubMed

    Tanaka, Sachi; Yamamoto, Kana; Yamada, Kazuki; Furuya, Kanon; Uyeno, Yutaka

    2016-05-01

    This study was performed to determine the effects of feeding a fiber-rich fraction of Brassica vegetables on the immune response through changes in enteric bacteria and short-chain fatty acid (SCFA) production in normal mice. The boiled-water-insoluble fraction of Brassica rapa L. (nozawana), which consists mainly of dietary fiber, was chosen as a test material. A total of 31 male C57BL/6J mice were divided into two groups and housed in a specific-pathogen-free facility. The animals were fed either a control diet or the control diet plus the insoluble B. rapa L. fraction for 2 weeks and sacrificed to determine microbiological and SCFA profiles in lower-gut samples and immunological molecules. rRNA-based quantification indicated that the relative population of Bacteroidetes was markedly lower in the colon samples of the insoluble B. rapa L. fraction-fed group than that in the controls. Populations of the Eubacterium rectale group and Faecalibacterium prausnitzii, both of which are representative butyrate-producing bacteria, doubled after 2 weeks of fraction intake, accompanying a marginal increase in the proportion of colonic butyrate. In addition, feeding with the fraction significantly increased levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and tended to increase splenic regulatory T cell numbers but significantly reduced the population of cells expressing activation markers. We demonstrated that inclusion of the boiled-water-insoluble fraction of B. rapa L. can alter the composition of the gut microbiota to decrease the numbers of Bacteroidetes and to increase the numbers of butyrate-producing bacteria, either of which may be involved in the observed shift in the production of splenic IL-10.

  11. Effects of acetate, propionate, and butyrate on the thermophilic anaerobic degradation of propionate by methanogenic sludge and defined cultures

    SciTech Connect

    Lier, J.B. van; Grolle, K.C.F.; Frijters, C.T.M.J.; Stams, A.J.M.; Lettinga, G. )

    1993-04-01

    Acetate, propionate, and butyrate are intermediate products in the anaerobic bioconversion of organic matter to methane and carbon dioxide. This study examines the effects of acetate, propionate, and butyrate on the thermophilic oxidation of propionate in continuous-flow methanogenic sludge bed systems and in defined propionate-oxidizing cultures. Volatile fatty acids (VFA) in sludge inhibit thermophilic anaerobic oxidation of propionate, dependent on the concentration and on the pH. Addition of butyrate-oxidizing acetogens to the media eliminate the inhibitory effect of butyrate and stimulated propionate conversion. In the propionate-oxidizing enrichment, and to a lesser extent in the UASB reactor, culture growth was affected by acetate. However, the relationship between acetate concentrations and propionate degradation was not clear. Hydrogen is an important intermediate of thermophilic propionate conversion. This study found that propionate oxidation was severely inhibited with no increase in the hydrogen partial pressure in the biogas. As a result, the authors conclude the suitability of hydrogen as a n overall control parameter for anaerobic digestion has to be reconsidered. 29 refs., 6 figs., 2 tabs.

  12. catena-Poly[[tetra­aqua­cadmium]-μ-5,5′-(1,4-phenyl­ene)di(tetra­zol-2-ido)-κ2 N 2:N 2′

    PubMed Central

    Dang, Qinqin; Caiyun, Han

    2013-01-01

    In the title compound, [Cd(C8H4N8)(H2O)4]n, 5,5′-(1,4-phenyl­ene)di(tetra­zol-2-ide) (L) ligands bridge CdII atoms into polymeric chains along [201]. The CdII atom is situated on an inversion centre and is coordinated by two N atoms from two L ligands and by four water O atoms in a distorted octa­hedral geometry. In the L ligand, the benzene ring resides on an inversion centre and the tetra­zole rings are twisted from its plane by 22.3 (1)°. An extensive hydrogen-bonding network formed by classical O—H⋯N and O—H⋯O inter­actions consolidates the crystal packing, linking the poymeric chains into a three-dimensional structure. PMID:23723784

  13. Reduced information transmission in the internal segment of the globus pallidus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced rhesus monkey models of Parkinson's disease☆

    PubMed Central

    He, Yan; Wang, Jue; Gao, Guodong; Zhang, Guangjun

    2012-01-01

    Rhesus monkey models of Parkinson’s disease were induced by injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neural firings were recorded using microelectrodes placed in the internal segment of the globus pallidus. The wavelets and power spectra show gradual power reduction during the disease process along with increased firing rates in the Parkinson’s disease state. Singular values of coefficients decreased considerably during tremor-related activity as well as in the Parkinson’s disease state compared with normal signals, revealing that higher-frequency components weaken when Parkinson’s disease occurs. We speculate that the death of neurons could be reflected by irregular frequency spike trains, and that wavelet packet decomposition can effectively detect the degradation of neurons and the loss of information transmission in the neural circuitry. PMID:25624834

  14. In Vitro Effects of Dietary Inulin on Human Fecal Microbiota and Butyrate Production.

    PubMed

    Jung, Tae-Hwan; Jeon, Woo-Min; Han, Kyoung-Sik

    2015-09-01

    Administration of dietary fibers has various health benefits, mainly by increasing numbers of beneficial bacteria and enhancing production of short-chain fatty acids in the colon. There has been growing interest in the addition of dietary fiber to human diet, due to its prebiotic effects. This study aimed to evaluate the prebiotic activity of inulin using an in vitro batch fermentation system with human fecal microbiota. Fermentation of inulin resulted in a significantly greater ratio of Lactobacillus or Bifidobacteria to Enterobacteria strains as an index of healthy human intestine and elevated butyrate concentration, which are related to improvement of gut health.

  15. Enhanced third-order nonlinear optical properties determined in thin films using the Z-scan technique: bis(μ-4,4'-oxydibenzoato)bis[(4'-phenyl-2,2':6',2''-terpyridine)cobalt(II)].

    PubMed

    Liu, Runqiang; Zhao, Ning; Liu, Ping; An, Caixia; Lian, Zhaoxun

    2016-05-01

    π-Conjugated organic materials exhibit high and tunable nonlinear optical (NLO) properties, and fast response times. 4'-Phenyl-2,2':6',2''-terpyridine (PTP) is an important N-heterocyclic ligand involving π-conjugated systems, however, studies concerning the third-order NLO properties of terpyridine transition metal complexes are limited. The title binuclear terpyridine Co(II) complex, bis(μ-4,4'-oxydibenzoato)-κ(3)O,O':O'';κ(3)O'':O,O'-bis[(4'-phenyl-2,2':6',2''-terpyridine-κ(3)N,N',N'')cobalt(II)], [Co2(C14H8O5)2(C21H15N3)2], (1), has been synthesized under hydrothermal conditions. In the crystal structure, each Co(II) cation is surrounded by three N atoms of a PTP ligand and three O atoms, two from a bidentate and one from a symmetry-related monodentate 4,4'-oxydibenzoate (ODA(2-)) ligand, completing a distorted octahedral coordination geometry. Neighbouring [Co(PTP)](2+) units are bridged by ODA(2-) ligands to form a ring-like structure. The third-order nonlinear optical (NLO) properties of (1) and PTP were determined in thin films using the Z-scan technique. The title compound shows a strong third-order NLO saturable absorption (SA), while PTP exhibits a third-order NLO reverse saturable absorption (RSA). The absorptive coefficient β of (1) is -37.3 × 10(-7) m W(-1), which is larger than that (8.96 × 10(-7) m W(-1)) of PTP. The third-order NLO susceptibility χ((3)) values are calculated as 6.01 × 10(-8) e.s.u. for (1) and 1.44 × 10(-8) e.s.u. for PTP. PMID:27146576

  16. Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells.

    PubMed

    Sun, Suxia; Li, Wenjun; Zhang, He; Zha, Longying; Xue, Yong; Wu, Xianbo; Zou, Fei

    2012-02-01

    The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis.

  17. Fermentative effluents from hydrogen producing bioreactor as substrate for poly(beta-OH) butyrate production with simultaneous treatment: an integrated approach.

    PubMed

    Venkata Mohan, S; Reddy, M Venkateswar; Subhash, G Venkata; Sarma, P N

    2010-12-01

    The feasibility of bioplastics production as poly(beta-OH)butyrate (PHB) was studied with individual volatile fatty acids (VFA) and acid-rich effluents from a biohydrogen producing reactor (HBR) as primary substrates employing aerobic consortia as biocatalyst under anoxic microenvironment. Butyrate as substrate showed higher PHB productivity (33%) followed by acetate (32%), acids mixture (16%) and propionate (11%) among synthetic VFA studied. Acid-rich effluents from HBR yielded higher PHB productivity (25%) especially at lower substrate loading conditions. Decrement observed in PHB production (from 25% to 6%) with increase in substrate load might be due to the presence of high concentration of residual carbon along with acid metabolites. Neutral redox operation showed effective PHB production compared to acidic and basic conditions due to associated higher metabolic activity of the biocatalyst. The integrated approach helped to treat additional COD from acid-rich HBR effluents apart from by-product recovery. PMID:20667721

  18. 1-(4-Carb­oxy­butan-2-yl­idene)-4-phenyl­thio­semicarbazide

    PubMed Central

    Mendoza-Meroño, Rafael; Menéndez-Taboada, Laura; García-Granda, Santiago

    2012-01-01

    The mol­ecule of the title compound, C12H15N3O2S, which belongs to the family of thio­semicarbazones, containing an acid group, adopts a semi-closed conformation with an intramolecular N—H⋯N hydrogen bond. In the crystal, molecules are linked by strong N—H⋯O and O—H⋯S hydrogen bonds between the acid group and thiosemicarbazone unit, with one additional intermolecular hydrogen C—H⋯O interaction. These three interactions form R 2 2(8) and a R 2 1(7) rings and the molecules related by the c-glide plane are linked into a zigzag chain along [001]. PMID:22719696

  19. Sodium Butyrate, a Histone Deacetylase Inhibitor, Reverses Behavioral and Mitochondrial Alterations in Animal Models of Depression Induced by Early- or Late-life Stress.

    PubMed

    Valvassori, Samira S; Resende, Wilson R; Budni, Josiane; Dal-Pont, Gustavo C; Bavaresco, Daniela V; Réus, Gislaine Z; Carvalho, André F; Gonçalves, Cinara L; Furlanetto, Camila B; Streck, Emilio L; Quevedo, João

    2015-01-01

    The aim of the present study was to evaluate the effects of sodium butyrate on depressive-like behavior and mitochondrial alteration parameters in animal models of depression induced by maternal deprivation or chronic mild stress in Wistar rats. maternal deprivation was established by separating pups from their mothers for 3 h daily from postnatal day 1 to day 10. Chronic mild stress was established by water deprivation, food deprivation, restraint stress, isolation and flashing lights. Sodium butyrate or saline was administered twice a day for 7 days before the behavioral tests. Depressive behavior was evaluated using the forced swim test. The activity of tricarboxylic acid cycle enzymes (succinate dehydrogenase and malate dehydrogenase) and of mitochondrial chain complexes (I, II, II-III and IV) was measured in the striatum of rats. From these analyses it can be observed that sodium butyrate reversed the depressive-like behavior observed in both animal models of depression. Additionally, maternal deprivation and chronic mild stress inhibited mitochondrial respiratory chain complexes and increased the activity of tricarboxylic acid cycle enzymes. Sodium butyrate treatment reversed -maternal deprivation and chronic mild stress- induced dysfunction in the striatum of rats. In conclusion, sodium butyrate showed antidepressant effects in maternal deprivation and chronic mild stress-treated rats, and this effect can be attributed to its action on the neurochemical pathways related to depression.

  20. N-Butyrate alters chromatin accessibility to DNA repair enzymes

    SciTech Connect

    Smith, P.J.

    1986-03-01

    Current evidence suggests that the complex nature of mammalian chromatin can result in the concealment of DNA damage from repair enzymes and their co-factors. Recently it has been proposed that the acetylation of histone proteins in chromatin may provide a surveillance system whereby damaged regions of DNA become exposed due to changes in chromatin accessibility. This hypothesis has been tested by: (i) using n-butyrate to induce hyperacetylation in human adenocarcinoma (HT29) cells; (ii) monitoring the enzymatic accessibility of chromatin in permeabilised cells; (iii) measuring u.v. repair-associated nicking of DNA in intact cells and (iv) determining the effects of n-butyrate on cellular sensitivity to DNA damaging agents. The results indicate that the accessibility of chromatin to Micrococcus luteus u.v. endonuclease is enhanced by greater than 2-fold in n-butyrate-treated cells and that there is a corresponding increase in u.v. repair incision rates in intact cells exposed to the drug. Non-toxic levels of n-butyrate induce a block to G1 phase transit and there is a significant growth delay on removal of the drug. Resistance of HT29 cells to u.v.-radiation and adriamycin is enhanced in n-butyrate-treated cells whereas X-ray sensitivity is increased. Although changes in the responses of cells to DNA damaging agents must be considered in relation to the effects of n-butyrate on growth rate and cell-cycle distribution, the results are not inconsistent with the proposal that increased enzymatic-accessibility/repair is biologically favourable for the resistance of cells to u.v.-radiation damage. Overall the results support the suggested operation of a histone acetylation-based chromatin surveillance system in human cells.

  1. Leptin counteracts sodium butyrate-induced apoptosis in human colon cancer HT-29 cells via NF-kappaB signaling.

    PubMed

    Rouet-Benzineb, Patricia; Aparicio, Thomas; Guilmeau, Sandra; Pouzet, Cécile; Descatoire, Véronique; Buyse, Marion; Bado, André

    2004-04-16

    This study shows that leptin induced a rapid phosphorylation of p42/44 mitogen-activated protein kinase, an enhancement of both NF-kappaB DNA binding and transcriptional activities, and a concentration-dependent increase of HT-29 cell proliferation. These effects are consistent with the presence of leptin receptors on cell membranes. The leptin induction of cell growth was associated with an increase of cell population in S and G2/M phase compared with control cells found in G0/G1 phase of the cell cycle. Moreover, cyclin D1 immunoreactivity was enhanced in leptin-treated HT-29 cells and this increase was essentially associated with cell population in G0/G1 phase. On the other hand, we observed that sodium butyrate inhibited cell proliferation by blocking HT-29 cells in G0/G1 phase of the cell cycle. Interestingly, at physiological concentration, leptin prevented sodium butyrate-induced morphological nucleus changes, DNA laddering and suppressed butyrate-induced cell cycle arrest. This anti-apoptotic effect of leptin was associated with HT-29 cell proliferation and activation NF-kappaB pathways. However, the phosphorylation of p42/44 MAP kinase in response to leptin was reduced in butyrate-treated cells. These data demonstrated that leptin is a potent mitogenic factor for intestinal epithelial cells through the MAP kinase and NF-kappaB pathways. They also showed, for the first time, that leptin promotes colon cancer HT-29 cell survival upon butyrate challenge by counteracting the apoptotic programs initiated by this short chain fatty acid probably through the NF-kappaB pathways. Although further studies are required to unravel the precise mechanism, these data may have significance in the pathogenesis of colorectal cancer and ulcerative colitis diseases.

  2. Transport of butyrate across the isolated bovine rumen epithelium--interaction with sodium, chloride and bicarbonate.

    PubMed

    Sehested, J; Diernaes, L; Møller, P D; Skadhauge, E

    1999-08-01

    The Ussing chamber technique was used for studying unidirectional fluxes of 14C-butyrate across the bovine rumen epithelium in vitro. Significant amounts of butyrate were absorbed across the bovine rumen epithelium in vitro, without any external driving force. The paracellular pathway was quantitatively insignificant. The transcellular pathway was predominately voltage-insensitive. The serosal to mucosal (SM) pathway was regulated by mass action, whereas the mucosal to serosal (MS) pathway further includes a saturable process, which accounted for 30 to 55% of the MS flux. The studied transport process for 14C-butyrate across the epithelium could include metabolic processes and transport of 14C-labelled butyrate metabolites. The transport of butyrate interacted with Na+, Cl- and HCO3-, and there was a linear relationship between butyrate and sodium net transport. Lowering the sodium concentration from 140 to 10 mmol l-1 decreased the butyrate MS flux significantly. Amiloride (1 mmol l-1) did, however, not reduce the butyrate flux significantly. Chloride concentration in itself did not seem to influence the transport of butyrate, but chloride-free conditions tended to increase the MS and SM flux of butyrate by a DIDS-sensitive pathway. DIDS (bilateral 0.5 mmol l-1) did further decrease the butyrate SM flux significantly at all chloride concentrations. Removing bicarbonate from the experimental solutions decreased the MS and increased the SM flux of butyrate significantly, and abolished net butyrate flux. There were no significant effects of the carbonic anhydrase inhibitor Acetazolamide (bilateral 1.0 mmol l-1). The results can be explained by a model where butyrate and butyrate metabolites are transported both by passive diffusion and by an electroneutral anion-exchange with bicarbonate. The model couples sodium and butyrate via CO2 from metabolism of butyrate, and intracellular pH.

  3. Effect of abomasal butyrate infusion on net nutrient flux across the portal-drained viscera and liver of growing lambs.

    PubMed

    Foote, A P; Freetly, H C

    2016-07-01

    The purpose of this experiment was to determine if supplying butyrate to the postruminal gastrointestinal tract of growing lambs alters blood flow and nutrient flux across the portal-drained viscera (PDV) and hepatic tissues. Polled Dorset wether lambs ( = 10; initial BW = 55 ± 3.3 kg) had catheters surgically implanted into the portal vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta. A cannula was placed in the abomasum to deliver the treatment. Lambs were fed a pelleted ration once daily consisting of 69.7% dehydrated alfalfa, 30.0% ground corn, and 0.3% salt at 1.3 × NE requirement. The experimental design was a crossover balanced in time, so that each lamb received both treatments. Treatments consisted of either a pulse dose infusion of butyrate (buffered solution) to supply butyrate (10 mg/kg BW) or a buffered saline solution (1 mL/kg BW) once daily at the time of feeding. On d 14 of the treatment period, nutrient fluxes were measured using para-aminohippuric acid as a blood flow marker. Blood samples were collected from the aorta, portal vein, and hepatic vein every hour for 9 h beginning at 30 min prior to treatment/feeding. There was a tendency for a treatment × time interaction ( = 0.05) for portal vein blood flow, indicating that blood flow began to decrease earlier postprandial in lambs receiving butyrate. The butyrate treatment tended to increase the uptake of O ( = 0.07) and increased the uptake of glucose ( = 0.002), glutamate ( = 0.04), and glutamine ( = 0.02) by the PDV. There was a treatment × time interaction ( < 0.01) for flux of acetate, propionate, butyrate, isobutyrate, and valerate across the PDV. The interaction was mainly due to an earlier postprandial peak and associated decrease in the flux rate of the VFA. The alteration in timing of the postprandial peak of VFA flux was also observed in hepatic fluxes of VFA. It appears that supplying butyrate to the postruminal tissues through an abomasal cannula

  4. Effect of abomasal butyrate infusion on net nutrient flux across the portal-drained viscera and liver of growing lambs.

    PubMed

    Foote, A P; Freetly, H C

    2016-07-01

    The purpose of this experiment was to determine if supplying butyrate to the postruminal gastrointestinal tract of growing lambs alters blood flow and nutrient flux across the portal-drained viscera (PDV) and hepatic tissues. Polled Dorset wether lambs ( = 10; initial BW = 55 ± 3.3 kg) had catheters surgically implanted into the portal vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta. A cannula was placed in the abomasum to deliver the treatment. Lambs were fed a pelleted ration once daily consisting of 69.7% dehydrated alfalfa, 30.0% ground corn, and 0.3% salt at 1.3 × NE requirement. The experimental design was a crossover balanced in time, so that each lamb received both treatments. Treatments consisted of either a pulse dose infusion of butyrate (buffered solution) to supply butyrate (10 mg/kg BW) or a buffered saline solution (1 mL/kg BW) once daily at the time of feeding. On d 14 of the treatment period, nutrient fluxes were measured using para-aminohippuric acid as a blood flow marker. Blood samples were collected from the aorta, portal vein, and hepatic vein every hour for 9 h beginning at 30 min prior to treatment/feeding. There was a tendency for a treatment × time interaction ( = 0.05) for portal vein blood flow, indicating that blood flow began to decrease earlier postprandial in lambs receiving butyrate. The butyrate treatment tended to increase the uptake of O ( = 0.07) and increased the uptake of glucose ( = 0.002), glutamate ( = 0.04), and glutamine ( = 0.02) by the PDV. There was a treatment × time interaction ( < 0.01) for flux of acetate, propionate, butyrate, isobutyrate, and valerate across the PDV. The interaction was mainly due to an earlier postprandial peak and associated decrease in the flux rate of the VFA. The alteration in timing of the postprandial peak of VFA flux was also observed in hepatic fluxes of VFA. It appears that supplying butyrate to the postruminal tissues through an abomasal cannula

  5. Proliferation of human colonic mucosa as an intermediate biomarker of carcinogenesis: effects of butyrate, deoxycholate, calcium, ammonia, and pH.

    PubMed

    Bartram, H P; Scheppach, W; Schmid, H; Hofmann, A; Dusel, G; Richter, F; Richter, A; Kasper, H

    1993-07-15

    A high-fat/high-protein diet has been reported to promote colon cancer by increasing luminal bile acid and ammonia concentrations, whereas butyrate, calcium, and low colonic pH may have protective effects. In this study, bromodeoxyuridine labeling of colonic epithelium was investigated after incubating biopsies from the ascending colon of 70 patients with HCl (20 mM, pH 6.0), butyric acid (H-BUT, 20 mM, pH 6.0), sodium butyrate (Na-BUT, 10 mM, pH 8.0), CaCl2 (10 mM), calcium butyrate (Ca-BUT, 10 mM), ammonium butyrate (NH4-BUT, 10 mM), deoxycholic acid (DCA, 5 microM), and a combination of DCA and Na-BUT (DCA/Na-BUT, 5 microM/10 mM). Compared to NaCl, H-BUT and Na-BUT increased the whole crypt-labeling index significantly, whereas HCl and CaCl2 had no effect. Reduced labeling, however, occurred with Ca-BUT in comparison to equimolar Na-BUT. No differences in the labeling indexes were found for NH4-BUT compared to Na-BUT, but increased labeling with expansion of the proliferative zone to the upper 40% of the crypt was seen with DCA compared to NaCl. DCA-induced hyperproliferation was abolished by coincubation with DCA/Na-BUT. These data suggest that butyrate, calcium, and DCA have complex influences on mucosal proliferation. Since luminal concentrations of these compounds are influenced by dietary interventions, the findings of this study may be of particular interest with regard to colon cancer development and prevention.

  6. Postnatal development of the myenteric glial network and its modulation by butyrate.

    PubMed

    Cossais, François; Durand, Tony; Chevalier, Julien; Boudaud, Marie; Kermarrec, Laetitia; Aubert, Philippe; Neveu, Isabelle; Naveilhan, Philippe; Neunlist, Michel

    2016-06-01

    The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fatty acids on their maturation. We showed an increased expression of the glial markers GFAP and S100β during the first postnatal week. As demonstrated by immunohistochemistry, a structured myenteric glial network was observed at 36 days in the rat colons. Butyrate inhibited EGC proliferation in vivo and in vitro but had no effect on glial marker expression. These results indicate that the EGC myenteric network continues to develop after birth, and luminal factors such as butyrate endogenously produced in the colon may affect this development. PMID:27056724

  7. Development of a specific radioimmunoassay for cortisol 17-butyrate

    SciTech Connect

    Smith, G.N.; Lee, Y.F.; Bu'Lock, D.E.; August, P.; Anderson, D.C.

    1983-07-01

    We describe the development and validation of an assay for cortisol 17-butyrate in blood in which there is no significant cross reaction with endogenous corticosteroids at levels encountered normally in man. Preliminary data on blood levels of the drug in absorption studies are presented.

  8. Alternate splicing regulated by butyrate in the bovine epithelial cell

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As a signaling molecule and a potent inhibitor of histone deacetylases (HADCs), butyrate exerts its impacts on a broad range of biological processes, such as apoptosis and cell proliferation, in addition to its critical role in energy metabolism in ruminants. In this study, we examined the effect of...

  9. Effect of microencapsulated sodium butyrate in the close-up diet on performance of dairy cows in the early lactation period.

    PubMed

    Kowalski, Z M; Górka, P; Flaga, J; Barteczko, A; Burakowska, K; Oprządek, J; Zabielski, R

    2015-05-01

    Two trials were conducted to determine the effect of sodium butyrate microencapsulated within triglyceride matrix (Na-butyrate) in the close-up period on performance of dairy cows and rumen papillae development. In trial 1, 26 Holstein-Friesian cows were randomly allocated to 2 groups (13 cows/group) and fed prepartum a total mixed ration (TMR) without or with 300g of Na-butyrate/d from 30 d before expecting calving to parturition. After calving, the same lactational TMR without Na-butyrate was offered to both treatments. Dry matter intake and milk yield were monitored daily to 60 d in milk, and body condition of cows was scored on d 30, 21, and 4 before parturition and d 14, 31, and 60 after parturition. On d 15, 10, and 5 before parturition blood samples were collected from 6 cows randomly chosen from each group and analyzed for plasma β-hydroxybutyrate and nonesterified fatty acids concentrations. No differences in dry matter (DM) intake, milk yield, body condition score, or plasma β-hydroxybutyrate and nonesterified fatty acids concentrations was observed between treatments; however, in the last 5 d before parturition the cows receiving Na-butyrate ate 1.7kg of DM/d more, on average, as compared with control cows. In trial 2, 12 Holstein-Friesian growing bulls (404±48; body weight ± SD) were used to determine the effect of Na-butyrate inclusion in the diet on rumen papillae development. Bulls were randomly allocated to 2 groups (6 bulls/group) and fed TMR without or with 2% (on a dry matter basis) of Na-butyrate for 21 d. At the end of the study, bulls were killed and rumen fluid and rumen tissue samples from dorsal and ventral sac of the rumen were collected. No effect of Na-butyrate supplementation on BW of bulls and DMI during the trial period was observed. Sodium butyrate supplementation increased total short-chain fatty acid concentration in the rumen but had no effect on rumen pH, molar proportions of short-chain fatty acids, and NH3-N concentration

  10. Effects of butyrate on ouabain-sensitive respiration of hamster brown adipocytes.

    PubMed

    O'Donnell, M E; Horwitz, B A

    1982-01-01

    Brown adipose tissue is an important site of cold-induced nonshivering thermogenesis in many mammals. The plasma membrane-bound Na+-K+-ATPase has been shown to be significantly involved in this thermogenesis although its exact role is unknown at present. Evidence that coupling of oxidative phosphorylation to electron transport may become loosened during thermogenesis has prompted an investigation of potential roles of the Na+-K+ pump that would be compatible with altered respiratory coupling. One such role is that of modulating norepinephrine (NE)-induced lipolysis and hence provision of free fatty acids to the mitochondria. Under such conditions, inhibition of the pump would reduce NE-induced respiration by limiting substrate availability. If, in fact, the primary role of the pump in NE-induced thermogenesis is to facilitate substrate availability, provision of exogenous substrate should bypass this involvement and ameliorate the ouabain inhibition of respiration. In the present study, this possibility was examined by determining the effect of an exogenous substrate, butyrate, on the contribution of the Na+-K+ pump to NE-stimulated respiration of isolated hamster brown adipocytes. Although exogenous butyrate was able to serve as a substrate for brown adipocyte respiration, its presence had no significant effect on the ouabain sensitivity of NE-induced rates of oxygen consumption. That is, ouabain (1 mM) inhibited the NE-evoked thermogenesis of the adipocytes by 77.7 +/- 6.5% in the absence of butyrate (2 mM) and by 73.4 +/- 9.9% in its presence. It appears, therefore, that the contribution of the Na+-K+ membrane pump to brown fat thermogenesis does not simply reflect modulation of NE-evoked lipolysis.

  11. Flow cytometry analysis of cell cycle and specific cell synchronization with butyrate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synchronized cells have been invaluable in many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in MDBK cells. The possibility of using butyrate-blocked cells to obtain synchronized cells was explored and the properties of butyrate-induced cell ...

  12. Butyrate-producing bacteria, including mucin degraders, from the swine intestinal tract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate-producing microbes promote gastrointestinal health in the human gut, and similar benefits are likely derived from butyrate-producing microbes in other animal hosts. Consequently, there is considerable potential for butyrate-producing microbes to be utilized in health-promoting application...

  13. Role of rumen butyrate in regulation of nitrogen utilization and urea nitrogen kinetics in growing sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate, a major rumen VFA, has been indirectly linked to enhancement of urea recycling based on increased expression of urea transporter (UT-B) in the rumen epithelia of steers fed a rumen butyrate-enhancing diet. Two studies were conducted to quantify the effect of elevated rumen butyrate concent...

  14. Phase Diagrams of Binary Systems of Some Alkali Iso-Butyrates with One Mesogenic Component

    NASA Astrophysics Data System (ADS)

    Mirnaya, T. A.; Yaremchuk, G. G.; Volkov, S. V.

    1995-09-01

    The phase diagrams of the binary mixtures of mesogenic potassium iso-butyrate with non-mesogenic lithium-, sodium-, and caesium iso-butyrate have been investigated by differential thermal analysis and hot stage polarization microscopy. The temperature and concentration ranges of liquid crystal formation have been established. Sodium and caesium iso-butyrate have been found to possess latent mesogenic properties.

  15. ION-EXCLUSION CHROMATOGRAPHIC DETERMINATION OF CARBOXYLIC ACIDS USED TO SUPPORT THE MICROBIALLY MEDIATED REDUCTIVE DECHLORINATION OF TETRACHLOROETHENE

    EPA Science Inventory

    An analytical method was developed for the determination of lactic acid, formic acid, acetic acid, propionic acid, and butyric acid in environmental microcosm samples using ion-exclusion chromatography. The chromatographic behavior of various eluents was studied to determine the ...

  16. Performance and plasma metabolites of dairy calves fed starter containing sodium butyrate, calcium propionate or sodium monensin.

    PubMed

    Ferreira, L S; Bittar, C M M

    2011-02-01

    This study was conducted to examine the influence of supplementation of sodium butyrate, sodium monensin or calcium propionate in a starter diet on the performance and selected plasma metabolites (plasma glucose, non-esterified fatty acids and β-hydroxybutyrate) of Holstein calves during pre- and post-weaning periods. Twenty-four newborn Holstein calves were housed in individual hutches until 10 weeks of life, receiving water free choice, and fed four liters of milk daily. Calves were blocked according to weight and date of birth, and allocated to one of the following treatments, according to the additive in the starter: (i) sodium butyrate (150 g/kg); (ii) sodium monensin (30 mg/kg); and (iii) calcium propionate (150 g/kg). During 10 weeks, calves received starter ad libitum, while coast cross hay (Cynodon dactylon (L.) pers.) was offered after weaning, which occurred at the 8th week of age. Weekly, calves were weighted and evaluated for body measurements. Blood samples were taken weekly after the fourth week of age, 2 hours after the morning feeding, for determination of plasma metabolites. No differences were observed among treatments for starter or hay intake, BW and daily gain of the animals. Mean concentrations of selected plasma metabolites were similar in calves fed a starter supplemented with sodium butyrate, sodium monensin and calcium propionate. There was significant reduction in the concentrations of plasma glucose as calves aged. The inclusion of sodium butyrate, calcium propionate or sodium monensin as additives in starter feeds resulted in equal animal performance, before and after weaning, suggesting that sodium monensin may be replaced by organic acid salts.

  17. The Bacterial Fermentation Product Butyrate Influences Epithelial Signaling via Reactive Oxygen Species-Mediated Changes in Cullin-1 Neddylation1

    PubMed Central

    Kumar, Amrita; Wu, Huixia; Collier-Hyams, Lauren S.; Kwon, Young-Man; Hanson, Jason M.; Neish, Andrew S.

    2010-01-01

    The human enteric flora plays a significant role in intestinal health and disease. Populations of enteric bacteria can inhibit the NF-κB pathway by blockade of IκB-α ubiquitination, a process catalyzed by the E3-SCFβ-TrCP ubiquitin ligase. The activity of this ubiquitin ligase is regulated via covalent modification of the Cullin-1 subunit by the ubiquitin-like protein NEDD8. We previously reported that interaction of viable commensal bacteria with mammalian intestinal epithelial cells resulted in a rapid and reversible generation of reactive oxygen species (ROS) that modulated neddylation of Cullin-1 and resulted in suppressive effects on the NF-κB pathway. Herein, we demonstrate that butyrate and other short chain fatty acids supplemented to model human intestinal epithelia in vitro and human tissue ex vivo results in loss of neddylated Cul-1 and show that physiological concentrations of butyrate modulate the ubiquitination and degradation of a target of the E3-SCFβ-TrCP ubiquitin ligase, the NF-κB inhibitor IκB-α. Mechanistically, we show that physiological concentrations of butyrate induces reactive oxygen species that transiently alters the intracellular redox balance and results in inactivation of the NEDD8-conjugating enzyme Ubc12 in a manner similar to effects mediated by viable bacteria. Because the normal flora produces significant amounts of butyrate and other short chain fatty acids, these data provide a functional link between a natural product of the intestinal normal flora and important epithelial inflammatory and proliferative signaling pathways. PMID:19109186

  18. Diet and carcinogen alter luminal butyrate concentration and intracellular pH in isolated rat colonocytes.

    PubMed

    Zoran, D L; Barhoumi, R; Burghardt, R C; Chapkin, R S; Lupton, J R

    1997-01-01

    A 2 x 2 factorial experiment was conducted to examine the effects of two different dietary fibers and carcinogen treatment on colonic luminal short-chain fatty acid (SCFA) concentrations and intracellular pH (pHi) in rats. Twenty-four male Sprague-Dawley rats were divided into four groups, injected with a carcinogen [azoxymethane (AOM)] or normal saline (Sal), and fed one of two diets differing only in the type of dietary fiber [cellulose (Cell) or pectin (Pect)]. After 38 weeks of consuming these diets, the rats were euthanized, luminal contents were collected for analysis of SCFA concentrations, and colonocytes were isolated from the proximal and distal colon for subsequent determination of pHi. Changes in pHi after the addition of exogenous sodium butyrate to the culture medium were also tested. The highest concentrations of SCFAs were produced by the control rats (saline injected) consuming the pectin diet. Luminal butyrate concentrations were reduced in three of four colonic segments of carcinogen-injected groups [proximal and distal cellulose (Prox Cell and Dist Cell) and distal pectin (Dist Pect)] compared with saline controls. The pHi was consistently higher in colonocytes isolated from carcinogen-injected rats (Prox Cell/AOM = 6.95 vs. Prox Cell/Sal = 6.65, Prox Pect/AOM = 6.75 vs. Prox Pect/Sal = 6.65, Dist Cell/AOM = 6.94 vs. Dist Cell/AOM = 6.85, Dist Pect/AOM = 6.92 vs. Dist Pect/Sal = 6.79) than in cells from saline-injected rats. Furthermore, in the majority of rats, pHi was lower in the proximal than in the distal colon. Addition of butyrate to cultured colonocytes consistently lowered pHi, but the effect was more pronounced in the carcinogen-injected animals. These data identify changes that occur intraluminally and intracellularly in colons of rats injected with AOM and suggest that, during tumorigenesis, alterations in butyrate production and basic colonocyte physiology may play an important role in the process.

  19. Cloud point extraction of copper, lead, cadmium, and iron using 2,6-diamino-4-phenyl-1,3,5-triazine and nonionic surfactant, and their flame atomic absorption spectrometric determination in water and canned food samples.

    PubMed

    Citak, Demirhan; Tuzen, Mustafa

    2012-01-01

    A cloud point extraction procedure was optimized for the separation and preconcentration of lead(II), cadmium(II), copper(II), and iron(III) ions in various water and canned food samples. The metal ions formed complexes with 2,6-diamino-4-phenyl-1,3,5-triazine that were extracted by surfactant-rich phases in the nonionic surfactant Triton X-114. The surfactant-rich phase was diluted with 1 M HNO3 in methanol prior to its analysis by flame atomic absorption spectrometry. The parameters affecting the extraction efficiency of the proposed method, such as sample pH, complexing agent concentration, surfactant concentration, temperature, and incubation time, were optimized. LOD values based on three times the SD of the blank (3Sb) were 0.38, 0.48, 1.33, and 1.85 microg/L for cadmium(II), copper(II), lead(II), and iron(III) ions, respectively. The precision (RSD) of the method was in the 1.86-3.06% range (n=7). Validation of the procedure was carried out by analysis of National Institute of Standards and Technology Standard Reference Material (NIST-SRM) 1568a Rice Flour and GBW 07605 Tea. The method was applied to water and canned food samples for determination of metal ions.

  20. Beneficial effects of L-arginine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuronal degeneration in substantia nigra of Balb/c mice

    PubMed Central

    Hami, Javad; Hosseini, Mehran; Nezhad, Saeed Vafaei; Shahi, Sekineh; Lotfi, Nassim; Ehsani, Hossein; Sadeghi, Akram

    2016-01-01

    Background: L-arginine has been recently investigated and proposed to reduce neurological damage after various experimental models of neuronal cellular damage. In this study, we aim to evaluate the beneficial effects of L-arginine administration on the numerical density of dark neurons (DNs) in the substantia nigra pars compacta (SNc) of Balb/c mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Materials and Methods: Male Balb/c mice were randomly divided into 4 groups (n = 7 each): MPTP only; saline only (control); MPTP + L-arginine; and L-arginine only. The animals were infused intranasally with a single intranasal administration of the proneurotoxin MPTP (1 mg/nostril). L-arginine (300 mg/kg) was administrated intraperitoneally once daily for 1-week starting from 3 days after MPTP administration. Cavalieri principle method was used to estimate the numerical density of DNs in the SNc of different studied groups. Results: Twenty days following MPTP administration, the number of DNs was significantly increased when compared to sham-control and L-arginine-control groups (P < 0.05). Nevertheless, our results showed that L-arginine administration significantly decreased the numerical density of DNs in SNc of mice. Conclusion: This investigation provides new insights in experimental models of Parkinson’s disease, indicating that L-arginine represents a potential treatment agent for dopaminergic neuron degeneration in SNc observed in Parkinson’s disease patients. PMID:27656609

  1. 2-Amino-4-phenyl-5,6-dihydro-benzo[h]quinoline-3-carbonitrile-3-amino-1-phenyl-9,10-dihydro-phenanthrene-2,4-dicarbonitrile (5/3).

    PubMed

    Asiri, Abdullah M; Al-Youbi, Abdulrahman O; Faidallah, Hassan M; Ng, Seik Weng

    2011-11-01

    The asymmetric unit of the 5:3 title co-crystal of 2-amino-4-phenyl-5,6-dihydro-benzo[h]quinoline-3-carbonitrile and 3-amino-1-phenyl-9,10-dihydro-phenanthrene-2,4-dicarbonitrile, 0.625C(20)H(15)N(3).0.375C(22)H(15)N(3), has the atoms of the fused-ring system and those of the amino, cyano and phenyl substitutents overlapped. The fused-ring system is buckled owing to the ethyl-ene linkage in the central ring, the two flanking aromatic rings being twisted by 20.1 (1)°. This ethyl-ene portion is disordered over two positions in a 1:1 ratio. The phenyl ring is twisted by 69.5 (1)° relative to the amino- and cyano-bearing aromatic ring. In the crystal, two mol-ecules are linked by an N-H⋯N hydrogen bond, generating a a helical chain along [010]. PMID:22219912

  2. Beneficial effects of L-arginine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuronal degeneration in substantia nigra of Balb/c mice

    PubMed Central

    Hami, Javad; Hosseini, Mehran; Nezhad, Saeed Vafaei; Shahi, Sekineh; Lotfi, Nassim; Ehsani, Hossein; Sadeghi, Akram

    2016-01-01

    Background: L-arginine has been recently investigated and proposed to reduce neurological damage after various experimental models of neuronal cellular damage. In this study, we aim to evaluate the beneficial effects of L-arginine administration on the numerical density of dark neurons (DNs) in the substantia nigra pars compacta (SNc) of Balb/c mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Materials and Methods: Male Balb/c mice were randomly divided into 4 groups (n = 7 each): MPTP only; saline only (control); MPTP + L-arginine; and L-arginine only. The animals were infused intranasally with a single intranasal administration of the proneurotoxin MPTP (1 mg/nostril). L-arginine (300 mg/kg) was administrated intraperitoneally once daily for 1-week starting from 3 days after MPTP administration. Cavalieri principle method was used to estimate the numerical density of DNs in the SNc of different studied groups. Results: Twenty days following MPTP administration, the number of DNs was significantly increased when compared to sham-control and L-arginine-control groups (P < 0.05). Nevertheless, our results showed that L-arginine administration significantly decreased the numerical density of DNs in SNc of mice. Conclusion: This investigation provides new insights in experimental models of Parkinson’s disease, indicating that L-arginine represents a potential treatment agent for dopaminergic neuron degeneration in SNc observed in Parkinson’s disease patients.

  3. Bacopa monnieri Phytochemicals Mediated Synthesis of Platinum Nanoparticles and Its Neurorescue Effect on 1-Methyl 4-Phenyl 1,2,3,6 Tetrahydropyridine-Induced Experimental Parkinsonism in Zebrafish

    PubMed Central

    Nellore, Jayshree; Pauline, Cynthia; Amarnath, Kanchana

    2013-01-01

    Current discovery demonstrates the rapid formation of platinum nanoparticles using leaf extract of a neurobeneficial plant, Bacopa monnieri (BmE). The nanoparticles (BmE-PtNPs) were stabilized and then coated with varied phytochemicals present within the leaf extract. These nanoparticles demonstrated the same activity of Complex I, as that of oxidizing NADH to NAD+ using a spectrophotometric method. This suggests that BmE-PtNPs are a potential medicinal substance for oxidative stress mediated disease with suppressed mitochondrial complex I, namely, Parkinson's disease (PD). Hence, the neuroprotective potentials of the phytochemical coated nanoparticle were explored in 1-methyl 4-phenyl 1,2,3,6 tetrahydropyridine- (MPTP-)induced experimental Parkinsonism in zebrafish model. BmE-PtNPs pretreatment significantly reversed toxic effects of MPTP by increasing the levels of dopamine, its metabolites, GSH and activities of GPx, catalase, SOD and complex I, and reducing levels of MDA along with enhanced locomotor activity. Taken together, these findings suggest that BmE-PtNPs have protective effect in MPTP-induced neurotoxicity in this model of Parkinson's disease via their dual functions as mitochondrial complex I and antioxidant activity. PMID:26317003

  4. Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development.

    PubMed

    Uchiyama, Kazuhiko; Sakiyama, Toshio; Hasebe, Takumu; Musch, Mark W; Miyoshi, Hiroyuki; Nakagawa, Yasushi; He, Tong-Chuan; Lichtenstein, Lev; Naito, Yuji; Itoh, Yoshito; Yoshikawa, Toshikazu; Jabri, Bana; Stappenbeck, Thaddeus; Chang, Eugene B

    2016-01-01

    Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation. PMID:27561676

  5. Molecular basis of sodium butyrate-dependent proapoptotic activity in cancer cells.

    PubMed

    Pajak, B; Orzechowski, A; Gajkowska, B

    2007-01-01

    This review outlines the molecular events that accompany the antitumor action of sodium butyrate (NaBt). Butyrate, a low-molecular weight four-carbon chain volatile fatty acid (VFA) has been previously shown to withdraw cells from cell cycle or to promote cell differentiation, and finally to induce programmed cell death. Recent advances in molecular biology indicate, that this product of large bowel microbial fermentation of dietary fiber, might evoke the above-mentioned effects by indirect action on genes. NaBt was shown to inhibit histone deacetylase activity, allowing DNA binding of several transcription factors. Higher genomic activity leads to the higher expression of proapoptotic genes, higher level of their protein products and elevated sensitivity to death ligand-induced apoptosis. Cancer cells might be arrested in G1 phase of cell cycle in a p21-dependent manner. Proapoptotic activity of NaBt includes higher expression of membrane death receptors (DR4/5), higher level and activation of Smad3 protein in TGF-beta-dependent apoptotic pathway, lower level of antiapoptotic proteins (cFLIP, XIAP) and activation ofproapoptotic tBid protein. Thus, both intrinsic and extrinsic apoptotic pathways are stimulated to ampify the apoptotic signals. These effects are specific for tumor but not for regular cells. Unique properties of NaBt make this agent a promising metabolic inhibitor to retard tumorigenesis to suppress tumor growth.

  6. Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development

    PubMed Central

    Uchiyama, Kazuhiko; Sakiyama, Toshio; Hasebe, Takumu; Musch, Mark W.; Miyoshi, Hiroyuki; Nakagawa, Yasushi; He, Tong-Chuan; Lichtenstein, Lev; Naito, Yuji; Itoh, Yoshito; Yoshikawa, Toshikazu; Jabri, Bana; Stappenbeck, Thaddeus; Chang, Eugene B.

    2016-01-01

    Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation. PMID:27561676

  7. Isolation of butyrate-utilizing bacteria from thermophilic and mesophilic methane-producing ecosystems

    SciTech Connect

    Henson, J.M.

    1983-01-01

    The ability of various ecosystems to convert butyrate to methane was studied in order to isolate the bacteria responsible for the conversion. When thermophilic digester sludge was enriched with butyrate, methane was produced without a lag period. Marine sediments enriched with butyrate required a 2-week incubation period before methanogenesis began. A thermophilic digester was studied in more detail and found by most-probable-number enumeration to have ca. 5 x 10/sup 6/ butyrate-utilizing bactera/ml of sludge. A thermophilic butyrate-utilizing bacterium was isolated in coculture with Methanobacterium thermoautotrophicum and a Methanosarcina sp. This bacterium was a gram-negative, slightly curved rod that occurred singly, was nonmotile, and did not appear to produce spores. The thermophilic digester was infused with butyrate at the rate of 10 ..mu..moles/ml of sludge per day. Biogas production increased by 150%, with the percentage of methane increasing from 58% to 68%. Acetate, propionate, and butyrate did not accumulate. Butyrate-utilizing enrichments from mesophilic ecosystems were used in obtaining cocultures of butyrate-utilizing bacteria. These cocultures served as inocula for attempts to isolate pure cultures of butyrate-utilizing bacteria by use of hydrogenase-containing membrane fragments of Escherichia coli. After a 3-week incubation period, colonies appeared only in inoculated tubes that contained membrane fragments and butyrate.

  8. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

    SciTech Connect

    Chiaro, Christopher; Lazarova, Darina L.; Bordonaro, Michael

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer We investigate mechanisms responsible for butyrate resistance in colon cancer cells. Black-Right-Pointing-Pointer Tcf3 modulates butyrate's effects on Wnt activity and cell growth in resistant cells. Black-Right-Pointing-Pointer Tcf3 modulation of butyrate's effects differ by cell context. Black-Right-Pointing-Pointer Cell cycle factors are overexpressed in the resistant cells. Black-Right-Pointing-Pointer Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G{sub 1} to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that prevent or

  9. Effects of Na-butyrate supplementation in milk formula on plasma concentrations of GH and insulin, and on rumen papilla development in calves.

    PubMed

    Kato, Shin-Ichi; Sato, Katsuyoshi; Chida, Haruka; Roh, Sang-Gun; Ohwada, Shyuichi; Sato, Shusuke; Guilloteau, Paul; Katoh, Kazuo

    2011-12-01

    Although the growth-promoting action of sodium-butyrate (Na-butyrate) used as a feed additive has been observed in calves and pigs, the precise mechanisms involved remain to be clarified. In this study, pre-weaning calves were given milk formula (MF) supplemented with butyrate for 6 weeks to investigate its effects on postprandial changes in the plasma concentrations of metabolic hormones, and, simultaneously, on growth performance, the weight of the digestive organs and rumen papilla development. Ingestion of MF increased (P<0.05) the plasma concentrations of GH and insulin as well as the glucose level, but decreased the non-esterified fatty acid concentration. Na-butyrate supplementation in MF or in lactose solution (with the same quantity of lactose contained in the MF, 5%) suppressed the increase in plasma insulin and GH concentrations, and the plasma IGF1 level was not changed. The length of the rumen papilla and the weight of the perirenal fat tended to increase in the calves fed with Na-butyrate-supplemented MF, but the weight of the liver, spleen, and stomach were not changed. In addition, there was no difference in the expression of mRNA for sodium-dependent glucose transporter-1 in the small intestinal epithelial tissues. We conclude that the accelerated growth performance related to the intake of Na-butyrate used as a feed additive reported previously in several species is partly due to improved insulin sensitivity and a better digestive functional development. These data could be applicable to animal and human nutrition.

  10. Experimental and Pathalogical study of Pistacia atlantica, butyrate, Lactobacillus casei and their combination on rat ulcerative colitis model.

    PubMed

    Gholami, Mahdi; Ghasemi-Niri, Seyedeh Farnaz; Maqbool, Faheem; Baeeri, Maryam; Memariani, Zahra; Pousti, Iraj; Abdollahi, Mohammad

    2016-06-01

    This study evaluated the effects of Pistacia atlantica (P. atlantica), butyrate, Lactobacillus casei (L. casei) and especially their combination therapy on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced rat colitis model. Rats were divided into seven groups. Four groups received oral P. atlantica, butyrate, L. casei and the combination of three agents for 10 consecutive days. The remaining groups were negative and positive controls and a sham group. Macroscopic and histopathological examinations were carried out along with determination of the specific biomarker of colonic oxidative stress, the myeloperoxidase (MPO). Compared with controls, the combination therapy exhibited a significant alleviation of colitis in terms of pathological scores and reduction of MPO activity (55%, p=0.0009). Meanwhile, the macroscopic appearance such as stool consistency, tissue and histopathological scores (edema, necrosis and neutrophil infiltration) were improved. Although single therapy by each P. atlantica, butyrate, and L. casei was partially beneficial in reduction of colon oxidative stress markers, the combination therapy was much more effective. In conclusion, the combination therapy was able to reduce the severity of colitis that is clear from biochemical markers. Future studies have to focus on clinical effects of this combination in management of human ulcerative colitis. Further molecular and signaling pathway studies will help to understand the mechanisms involved in the treatment of colitis and inflammatory diseases. PMID:26972417

  11. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells.

    PubMed

    Chiaro, Christopher; Lazarova, Darina L; Bordonaro, Michael

    2012-11-01

    Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G(1) to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that prevent or reverse butyrate resistance.

  12. Clostridium butyricum reduce lipogenesis through bacterial wall components and butyrate.

    PubMed

    Zhao, Xu; Guo, Yuming; Liu, Hongbin; Gao, Jing; Nie, Wei

    2014-09-01

    Intervention strategies for obesity are global issues that require immediate attention. The objective of this study was to assess the possibility that Clostridium butyricum and its potential components could reduce lipogenesis. Co-culture experiments of Caco-2 cells and 1 × 10(6), 1 × 10(7), and 1 × 10(8) CFU/ml of C. butyricum were set up to monitor the cytotoxicity of C. butyricum and the changes of angiopoietin-like protein 4 (ANGPTL4) mRNA expression. It was found that cell viability was not affected by C. butyricum, and ANGPTL4 mRNA expression in Caco-2 cells was highly induced by 1 × 10(7) CFU/ml of C. butyricum. Co-culture experiment of Caco-2 cells and potential components of C. butyricum were set up to monitor any ensuing alteration in ANGPTL4. It was observed that bacterial wall components and potentially secreted factors from C. butyricum could induce ANGPTL4 mRNA expression and protein secretion. To determine whether butyrate could affect the ANGPTL4 production in Caco-2 cells, the role of monocarboxylate transporter 1 (MCT1) in mediating potentially secreted factors from C. butyricum-induced ANGPTL4 production in Caco-2 cells and the effect of 0.1 mM of butyrate on ANGPTL4 production in Caco-2 cells were investigated. It is confirmed that butyrate was the factor secreted by C. butyricum to stimulate ANGPTL4 production. Besides, the soluble factors secreted by live C. butyricum-Caco-2 cells interaction, bacterial wall components-Caco-2 cells interaction, and the main metabolites butyrate-Caco-2 cells interaction reduced lipogenic gene expression in HepG2 cells. In conclusion, 1 × 10(7) CFU/ml of C. butyricum could reduce lipogenesis through the bacterial wall components and the metabolites such as butyrate.

  13. Increasing butanol/acetone ratio and solvent productivity in ABE fermentation by consecutively feeding butyrate to weaken metabolic strength of butyrate loop.

    PubMed

    Li, Xin; Shi, Zhongping; Li, Zhigang

    2014-08-01

    In this study, we attempted to increase butanol/acetone ratio and total solvent productivity in ABE fermentations with corn- and cassava-based media, by consecutively feeding a small amount of butyrate/acetate during solventogenic phase to weaken the metabolic strengths in butyrate/acetate closed-loops. Consecutively feeding a small amount of butyrate (a total of 3.0 g/L-broth) is most effective in improving performance of corn-based ABE fermentations, as it simultaneously increased average butanol/acetone ratio by 23 % (1.92-2.36) and total solvent productivity by 16 % (0.355-0.410 g/L/h) as compared with those of control. However, the butyrate feeding strategy could not improve butanol/acetone ratio and total solvent productivity in cassava-based ABE fermentations, where the metabolic strength of butyrate closed-loop had already been very low.

  14. In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin

    PubMed Central

    Santoro, Matteo; Maetzler, Walter; Stathakos, Petros; Martin, Heather L.; Hobert, Markus A.; Rattay, Tim W.; Gasser, Thomas; Forrester, John V.; Berg, Daniela; Tracey, Kevin J.; Riedel, Gernot; Teismann, Peter

    2016-01-01

    High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells — including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression. Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner. These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD. PMID:26921471

  15. Response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) differs in mouse strains and reveals a divergence in JNK signaling and COX-2 induction prior to loss of neurons in the substantia nigra pars compacta.

    PubMed

    Boyd, Justin D; Jang, Haeman; Shepherd, Kennie R; Faherty, Ciaran; Slack, Sally; Jiao, Yun; Smeyne, Richard J

    2007-10-17

    Parkinson's disease (PD) is a neurodegenerative disease whose hallmark pathological features include a selective loss of dopaminergic neurons in the midbrain. Recent studies have described the activation of a stress-induced signal cascade, c-Jun N-terminal kinase (JNK)-mediated activation of c-Jun, and an increase in the expression of a downstream effector, cyclooxygenase 2 (COX-2), in postmortem PD brains. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces selective neuronal loss in the midbrain similar to that seen in PD, also induces JNK-mediated activation of c-Jun and generates a COX-2 response in C57BL/6J mice. However, mice exhibit a strain-dependent susceptibility to MPTP. Identifying the point(s) of molecular divergence in the MPTP-induced response may provide insight into the cause of PD or a means to identify susceptibility to PD in humans. Here we examined JNK signaling and COX-2 induction in two strains of mice, the MPTP-sensitive C57BL/6J and the MPTP-resistant Swiss Webster (SW). We show that C57BL/6J and SW strains differ in JNK and c-Jun activation in response to MPTP. In addition, the MPTP-induced COX-2 response occurs exclusively in C57BL/6J mice. Furthermore, strain-specific responses to MPTP are not due to differences in MPP(+) levels and are not secondary to cell death. These results provide evidence toward a mechanism of strain-dependent sensitivity to MPTP.

  16. Lithium and valproate prevent olfactory discrimination and short-term memory impairments in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rat model of Parkinson's disease.

    PubMed

    Castro, Adalberto A; Ghisoni, Karina; Latini, Alexandra; Quevedo, João; Tasca, Carla I; Prediger, Rui D S

    2012-04-01

    We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) display time-dependent impairments in olfactory, emotional, cognitive and motor functions associated with disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). On the other hand, lithium (Li) and valproate (VPA) are two primary drugs used to treat bipolar mood disorder that have recently emerged as promising neuroprotective agents. The present data indicates that the pretreatment with Li (47.5 mg/kg) or VPA (200 mg/kg) by intraperitoneal route during 7 consecutive days was able to prevent olfactory discrimination and short-term memory impairments evaluated in the social recognition and step-down inhibitory avoidance tasks in rats infused with a single intranasal (i.n.) administration of MPTP (0.1 mg/nostril). Despite the absence of clear depressive-like responses following the current MPTP dose, Li and VPA treatment presented an antidepressant profile reducing the immobility time in the forced swimming test. Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover, Li and VPA prevented dopamine depletion in the olfactory bulb and striatum of MPTP-infused rats. These results provide new insights in experimental models of PD, indicating that Li and VPA may represent new therapeutic tools for the management of olfactory and cognitive symptoms associated to early preclinical phases of PD, together with their neuroprotective potential demonstrated in previous research.

  17. Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

    PubMed

    Laćan, Goran; Dang, Hoa; Middleton, Blake; Horwitz, Marcus A; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2013-10-01

    We previously showed that, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), vaccination with bacillus Calmette-Guerin (BCG) prior to MPTP exposure limited the loss of striatal dopamine (DA) and dopamine transporter (DAT) and prevented the activation of nigral microglia. Here, we conducted BCG dose studies and investigated the mechanisms underlying BCG vaccination's neuroprotective effects in this model. We found that a dose of 1 × 10(6) cfu BCG led to higher levels of striatal DA and DAT ligand binding (28% and 42%, respectively) in BCG-vaccinated vs. unvaccinated MPTP-treated mice, but without a significant increase in substantia nigra tyrosine hydroxylase-staining neurons. Previous studies showed that BCG can induce regulatory T cells (Tregs) and that Tregs are neuroprotective in models of neurodegenerative diseases. However, MPTP is lymphotoxic, so it was unclear whether Tregs were maintained after MPTP treatment and whether a relationship existed between Tregs and the preservation of striatal DA system integrity. We found that, 21 days post-MPTP treatment, Treg levels in mice that had received BCG prior to MPTP were threefold greater than those in MPTP-only-treated mice and elevated above those in saline-only-treated mice, suggesting that the persistent BCG infection continually promoted Treg responses. Notably, the magnitude of the Treg response correlated positively with both striatal DA levels and DAT ligand binding. Therefore, BCG vaccine-mediated neuroprotection is associated with Treg levels in this mouse model. Our results suggest that BCG-induced Tregs could provide a new adjunctive therapeutic approach to ameliorating pathology associated with PD and other neurodegenerative diseases.

  18. Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine vervet model of parkinsonism.

    PubMed

    Raz, A; Vaadia, E; Bergman, H

    2000-11-15

    To investigate the role of the basal ganglia in parkinsonian tremor, we recorded hand tremor and simultaneous activity of several neurons in the external and internal segments of the globus pallidus (GPe and GPi) in two vervet monkeys, before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and development of parkinsonism with tremor of 5 and 11 Hz. In healthy monkeys, only 11% (20/174) of the GPe cells and 3% (1/29) of the GPi cells displayed significant 3-19 Hz oscillations. After MPTP treatment, 39% (107/271) of the GPe cells and 43% (26/61) of the GPi cells developed significant oscillations. Oscillation frequencies of single cells after MPTP treatment were bimodally distributed around 7 and 13 Hz. For 10% of the oscillatory cells that were recorded during tremor periods, there was a significant tendency for the tremor and neuronal oscillations to appear simultaneously. Cross-correlation analysis revealed a very low level of correlated activity between pallidal neurons in the normal state; 95.6% (477/499) of the pairs were not correlated, and oscillatory cross-correlograms were found in only 1% (5/499) of the pairs. After MPTP treatment, the correlations increased dramatically, and 40% (432/1080) of the cross-correlograms had significant oscillations, centered around 13-14 Hz. Phase shifts of the cross-correlograms of GPe pairs, but not of GPi, were clustered around 0 degrees. The results illustrate that MPTP treatment changes the pattern of activity and synchronization in the GPe and GPi. These changes are related to the symptoms of Parkinson's disease and especially to the parkinsonian tremor.

  19. Sparing of orexin-A and orexin-B neurons in the hypothalamus and of orexin fibers in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques.

    PubMed

    Bensaid, Manale; Tandé, Dominique; Fabre, Véronique; Michel, Patrick P; Hirsch, Etienne C; François, Chantal

    2015-01-01

    Several studies conducted in patients with Parkinson's disease have reported that the degeneration of substantia nigra dopaminergic neurons, which are essential for motor control, is associated with the loss of hypothalamic orexin neurons, which are involved in sleep regulation. In order to better explore the mutual interactions between these two systems, we wished to determine in macaques: (i) if the two orexin peptides, orexin-A and orexin-B, are distributed in the same hypothalamic cells and if they are localized in nerve terminals that project onto nigral dopaminergic neurons, and (ii) if there is a loss of orexin neurons in the hypothalamus and of orexin fibers innervating nigral dopaminergic neurons in macaques rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. We showed that virtually all cells stained for orexin-A in the hypothalamus co-expressed orexin-B. Numerous terminals stained for both orexin-A and orexin-B immunoreactivity that innervated the whole extent of the ventral tegmental area and substantia nigra pars compacta were found in close proximity to tyrosine hydroxylase-immunoreactive dendrites. These data indicate that orexin-A and orexin-B peptides are in a position to play a role in controlling the activity of nigral dopaminergic neurons. However, no loss of orexin-A or orexin-B neurons in the hypothalamus and no loss of orexin fibers in the substantia nigra pars compacta was found in MPTP-treated macaques when compared with control macaques. We conclude that a relatively selective dopaminergic lesion, such as that performed in MPTP-treated macaques, is not sufficient to induce a loss of hypothalamic orexin neurons.

  20. Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism.

    PubMed

    Annese, V; Herrero, María-Trinidad; Di Pentima, M; Gomez, A; Lombardi, L; Ros, C M; De Pablos, V; Fernandez-Villalba, E; De Stefano, Maria Egle

    2015-03-01

    Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson's disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9(+) glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism.

  1. The sigma-1 receptor agonist 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects against newborn excitotoxic brain injury by stabilizing the mitochondrial membrane potential in vitro and inhibiting microglial activation in vivo.

    PubMed

    Wegleiter, Karina; Hermann, Martin; Posod, Anna; Wechselberger, Karina; Stanika, Ruslan I; Obermair, Gerald J; Kiechl-Kohlendorfer, Ursula; Urbanek, Martina; Griesmaier, Elke

    2014-11-01

    Premature birth represents a clinical situation of risk for brain injury. The diversity of pathophysiological processes complicates efforts to find effective therapeutic strategies. Excitotoxicity is one important factor in the pathogenesis of preterm brain injury. The observation that sigma-1 receptor agonists possess neuroprotective potential, at least partly mediated by a variety of anti-excitotoxic mechanisms, has generated great interest in targeting those receptors to counteract brain injury. The objective of this study was to evaluate the effect of the highly specific sigma-1 receptor agonist, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) to protect against excitotoxic developmental brain injury in vivo and in vitro. Primary hippocampal neurons were pre-treated with PPBP before glutamate was applied and subsequently analyzed for cell death (PI/calcein AM), mitochondrial activity (TMRM) and morphology of the neuronal network (WGA) using confocal microscopy. Using an established neonatal mouse model we also determined whether systemic injection of PPBP significantly attenuates excitotoxic brain injury. PPBP significantly reduced neuronal cell death in primary hippocampal neurons exposed to glutamate. Neurons treated with PPBP showed a less pronounced loss of mitochondrial membrane potential and fewer morphological changes after glutamate exposure. A single intraperitoneal injection of PPBP given one hour after the excitotoxic insult significantly reduced microglial cell activation and lesion size in cortical gray and white matter. The present study provides strong support for the consideration of sigma-1 receptor agonists as a candidate therapy for the reduction of neonatal excitotoxic brain lesions and might offer a novel target to counteract developmental brain injury.

  2. Reactive astrocytes and Wnt/β-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease

    PubMed Central

    L’Episcopo, F.; Tirolo, C.; Testa, N.; Caniglia, S.; Morale, M.C.; Cossetti, C.; D’Adamo, P.; Zardini, E.; Andreoni, L.; Ihekwaba, A.E.C.; Serra, P.A.; Franciotta, D.; Martino, G.; Pluchino, S.; Marchetti, B.

    2013-01-01

    Emerging evidence points to reactive glia as a pivotal factor in Parkinson’s disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of basal ganglia injury, but whether astrocytes and microglia activation may exacerbate dopaminergic (DAergic) neuron demise and/or contribute to DAergic repair is presently the subject of much debate. Here, we have correlated the loss and recovery of the nigrostriatal DAergic functionality upon acute MPTP exposure with extensive gene expression analysis at the level of the ventral midbrain (VM) and striata (Str) and found a major upregulation of pro-inflammatory chemokines and wingless-type MMTV integration site1 (Wnt1), a key transcript involved in midbrain DAergic neurodevelopment. Wnt signaling components (including Frizzled-1 [Fzd-1] and β-catenin) were dynamically regulated during MPTP-induced DAergic degeneration and reactive glial activation. Activated astrocytes of the ventral midbrain were identified as candidate source of Wnt1 by in situ hybridization and real-time PCR in vitro. Blocking Wnt/Fzd signaling with Dickkopf-1 (Dkk1) counteracted astrocyte-induced neuroprotection against MPP+ toxicity in primary mesencephalic astrocyte–neuron cultures, in vitro. Moreover, astroglial-derived factors, including Wnt1, promoted neurogenesis and DAergic neurogenesis from adult midbrain stem/neuroprogenitor cells, in vitro. Conversely, lack of Wnt1 transcription in response to MPTP in middleaged mice and failure of DAergic neurons to recover were reversed by pharmacological activation of Wnt/β-catenin signaling, in vivo, thus suggesting MPTP-reactive astrocytes in situ and Wnt1 as candidate components of neuroprotective/neurorescue pathways in MPTP-induced nigrostriatal DAergic plasticity. PMID:21056667

  3. Kinetics and species of flash pyrolysis of cellulose acetate butyrate: The binder of LOVA

    SciTech Connect

    Gongwer, P.E.; Arisawa, H.; Brill, T.B.

    1996-07-01

    The principal binder of many LOVA propellants is cellulose acetate butyrate (CAB). By the use of T-Jump/FTIR spectroscopy, CAB was flash-pyrolyzed to set temperatures in the 465--600 C range, while rapid-scan IR spectra were used to identify the main decomposition products and to measure the rate of formation of each product as a function of temperature. Eleven specific products, which include oligomers of CAB, acids, aldehydes, ketenes, esters, CO{sub 2} and CO, were quantified by chemometric procedures. The ketenes are the most novel products. The Arrhenius parameters reveal that below 510 {+-} 20 C, the rate of product evolution is controlled mainly by condensed phase reactions. Above 510 {+-} 20 C, the rate of product evolution is controlled by desorption/evaporation of the volatile products.

  4. Down-regulation of protein kinase CKII activity by sodium butyrate.

    PubMed

    Russo, G L; Della Pietra, V; Mercurio, C; Della Ragione, F; Marshak, D R; Oliva, A; Zappia, V

    1997-04-28

    Butyrate, a dietary fiber derivative, is a well-known differentiating agent in cultured cell lines. In addition, its antineoplastic activity toward colon-rectum cancers has been documented both in vivo and in vitro. Despite the large amount of information on the potential clinical efficacy of butyrate, its mechanism of action at the molecular level has only been partially investigated. Here, we show that serine/threonine protein kinase CKII is a target of butyrate activity. In the human adenocarcinoma cell line, HT29, treated with 2 mM sodium butyrate, CKII activity decreases 50% at 24 and 48 hours after drug addition. The enzyme down-regulation is not due to changes in protein amount since the levels of the different CKII subunits remain constant during butyrate treatment. The data reported provide the first evidence that CKII down-regulation is involved in the signal transduction pathway started by butyrate.

  5. Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age.

    PubMed

    Hippe, Berit; Zwielehner, Jutta; Liszt, Kathrin; Lassl, Cornelia; Unger, Frank; Haslberger, Alexander G

    2011-03-01

    The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function.

  6. Inflammation-Induced Downregulation of Butyrate Uptake and Oxidation Is Not Caused by a Reduced Gene Expression.

    PubMed

    Boesmans, Leen; Ramakers, Meine; Arijs, Ingrid; Windey, Karen; Vanhove, Wiebe; Schuit, Frans; Rutgeerts, Paul; Verbeke, Kristin; De Preter, Vicky

    2015-02-01

    In ulcerative colitis (UC) the butyrate metabolism is impaired, leading to energy-deficiency in the colonic cells. The effect of inflammation on the butyrate metabolism was investigated. HT-29 cells were incubated with pro-inflammatory cytokines (TNF-α and/or IFN-γ) for 1 and 24 h. Cells were additionally stimulated with butyrate to investigate its anti-inflammatory potential. Butyrate uptake and oxidation were measured using (14)C-labeled butyrate. Gene expression of the butyrate metabolism enzymes, interleukin 8 (IL-8; inflammatory marker) and villin-1 (VIL-1; epithelial cell damage marker) was measured via quantitative RT-PCR. Significantly increased IL-8 expression and decreased VIL-1 expression after 24 h incubation with TNF-α and/or IFN-γ confirmed the presence of inflammation. These conditions induced a decrease of both butyrate uptake and oxidation, whereas the gene expression was not reduced. Simultaneous incubation with butyrate counteracted the reduced butyrate oxidation. In contrast, 1 h incubation with TNF-α induced a significant increased IL-8 expression and decreased butyrate uptake. Incubation with TNF-α and/or IFN-γ for 1 h did not induce cell damage nor influence butyrate oxidation. The inflammation-induced downregulation of the butyrate metabolism was not caused by a reduced gene expression, but appeared consequential to a decreased butyrate uptake. Increasing the luminal butyrate levels might have therapeutic potential in UC.

  7. Butyrate-induced changes in nuclease sensitivity of chromatin cannot be correlated with transcriptional activation

    SciTech Connect

    Birren, B.W.; Taplitz, S.J.; Herschman, H.R.

    1987-11-01

    The authors examined in the H4IIE rat heptoma cell line the relationship between butyrate-induced changes in the nuclease sensitivity of chromatin and changes in transcriptional activity of specific genes. The butyrate-inducible metallothionein I (MT-I) gene underwent a dramatic increase in DNase I sensitivity after 3 h of butyrate treatment. However, genes not transcribed in H4IIE cells underwent the same changes in DNase I sensitivity. Thus, butyrate-induced increases in DNase I sensitivity are not sufficient for the transcriptional activation of a gene. Butyrate treatment has also been reported to alter the sensitivity of sequence to micrococcal nuclease (MNase) in a manner reflecting their tissue-specific expression. Butyrate exposure caused increased digestion of the MT-I gene by MNase. However, butyrate-induced MNase sensitivity also occurred for genes which are neither transcribed in untreated cells nor butyrate inducible. Moreover, cadmium, a potent transcriptional activator of the MT-I gene, does not alter the sensitivity of the MT-I gene to MNase. Thus, the butyrate-induced alterations in MNase sensitivity are neither sufficient for, necessary for, nor indicative of transcriptional activation.

  8. Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate-Induced Histone Modification.

    PubMed

    Li, Cong-Jun; Li, Robert W; Baldwin, Ransom L; Blomberg, Le Ann; Wu, Sitao; Li, Weizhong

    2016-01-01

    Butyrate is a nutritional element with strong epigenetic regulatory activity as a histone deacetylase inhibitor. Based on the analysis of differentially expressed genes in the bovine epithelial cells using RNA sequencing technology, a set of unique genes that are activated only after butyrate treatment were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network, using Ingenuity Pathways Analysis, indicated that these genes activated by butyrate treatment are related to major cellular functions, including cell morphological changes, cell cycle arrest, and apoptosis. Our results offered insight into the butyrate-induced transcriptomic changes and will accelerate our discerning of the molecular fundamentals of epigenomic regulation. PMID:26819550

  9. Butyrate promotes the recovering of intestinal wound healing through its positive effect on the tight junctions.

    PubMed

    Ma, X; Fan, P X; Li, L S; Qiao, S Y; Zhang, G L; Li, D F

    2012-12-01

    Postweaning diarrhea is one of the most common causes of morbidity and mortality in weanling piglets. Feeding sodium butyrate to weanling piglets decreased the incidence of diarrhea, but the mechanism has not been fully elucidated. The present study was to evaluate the effect of sodium butyrate on diarrhea in relation to wound healing of intestinal barrier using IPEC-J2 cell model. Cultured cells were scratched to induce wound and then were treated with 4 mM sodium butyrate. The results showed that supplementation of the cells with sodium butyrate significantly promoted the process of wound healing, indicating the protective effects of butyrate on the intestinal mucosa. Butyrate treatment enhanced mRNA expression of the intestinal mucosal tight junction proteins occludin and zonula occluden protein-1 (P < 0.05), which suggested that the promotion of wound healing by butyrate is related to the maintenance of the function of the intestinal barrier. In addition, in the butyrate-treated group, intestinal total superoxide dismutase and glutathione peroxidase (P < 0.05), two of the main antioxidant enzymes, as well as glutathione (P < 0.05), one of the nonenzymatic antioxidant components, were enhanced whereas the malondialdehyde level, a marker of free radical mediated lipid peroxidation injury, was decreased (P < 0.05) compared with the control group. Collectively, these results indicate that dietary sodium butyrate might, at least partly, play an important role in recovering the intestinal tight junctions having a positive effect on maintaining the gut integrity.

  10. Sodium butyrate activates ERK to regulate differentiation of mesenchymal stem cells.

    PubMed

    Chen, Tain-Hsiung; Chen, Wei-Ming; Hsu, Ke-Hsun; Kuo, Cheng-Deng; Hung, Shih-Chieh

    2007-04-20

    Histone deacetylase inhibitors such as sodium butyrate are known to regulate the differentiation of a variety of cells. Mesenchymal stem cells (MSCs) differentiate into osteoblasts and adipocytes under transcriptional control of Runx2 and PPARgamma2, respectively. How these two transcription factors are regulated by sodium butyrate in order to specify the alternate cell fates remains a pivotal question. Sodium butyrate stimulated osteogenic differentiation and increased expression of Runx2 and genes regulated by Runx2 when cells were induced to undergo osteogenic differentiation. Sodium butyrate suppressed the adipogenic differentiation and decreased the expression of PPARgamma2 and LPL when MSCs were treated under conditions that promote adipogenic differentiation. Sodium butyrate also decreased the ratio of RANKL/OPG gene expression by MSCs. Analysis of MSCs induced in the presence of sodium butyrate revealed an immediate increase in ERK phosphorylation by sodium butyrate. The MEK-specific inhibitor, PD98059 but not p38- or JNK-specific inhibitor and the transfection with dominant negative ERK expressing plasmids blocked the sodium butyrate-induced regulation of MSC differentiation and increase in the RANKL/OPG ratio. Our results suggest that sodium butyrate modulates MSC differentiation and the RANKL/OPG ratio via activating ERK, and could be applied for in vivo bone growth using MSCs.

  11. Sodium butyrate stimulates monoclonal antibody over-expression in CHO cells by improving gene accessibility.

    PubMed

    Jiang, Zhou; Sharfstein, Susan T

    2008-05-01

    Sodium butyrate treatment can increase the specific productivity of recombinant proteins in mammalian cells; however, it dramatically decreases cell growth and frequently leads to apoptosis. We have studied the responses of several Chinese hamster ovary (CHO) cells lines with different specific productivities (qP) to sodium butyrate treatment. Cell clones with lower productivities exhibited greater enhancement from butyrate treatment than cells with higher productivities. As we observed previously in cell clone characterization (Jiang et al., 2006. Biotechnol Prog 22: 313-318), heavy chain (HC) mRNA levels correlate very well with specific productivity and are amplified by butyrate treatment, indicating that sodium butyrate regulates the HC transcription. Sodium butyrate is an inhibitor of histone deacetylation, and possibly, increases gene transcription by enhancing gene accessibility to transcription factors. In this study, we applied DNase I footprinting to probe the HC and LC gene accessibility. We determined that more HC and LC gene copies are accessible by DNase I in sodium butyrate-treated CHO cells than in untreated controls, demonstrating that sodium butyrate regulates gene transcription by improving gene accessibility. However, the increase in accessibility did not correlate with the increase in transcript abundance, suggesting that butyrate enhances transcription by other mechanisms as well.

  12. Sodium butyrate stimulates NHE8 expression via its role on activating NHE8 basal promoter activity.

    PubMed

    Xu, Hua; McCoy, Anthony; Li, Jing; Zhao, Yang; Ghishan, Fayez K

    2015-09-15

    Butyrate is a major metabolite in colonic lumen. It is produced from bacterial fermentation of dietary fiber. Butyrate has been shown to stimulate electroneutral sodium absorption through its regulation on sodium/hydrogen exchanger 3 (NHE3). Although NHE8, the newest addition of intestinal NHE family, is involved in sodium absorption in the intestinal tract, whether butyrate modulates NHE8 expression in the intestinal epithelial cells is not known. In the current study, we showed that butyrate treatment strongly induced NHE8 protein and NHE8 mRNA expression in human intestinal epithelial cells. Transfection with the human NHE8 promoter reporter constructs showed that butyrate treatment stimulated reporter gene expression at an amount comparable with its stimulation of NHE8 mRNA expression. Interestingly, a similar result was also observed in human NHE8 promoter transfected cells after trichostatin (TSA) treatment. Gel mobility shift assay identified an enhanced Sp3 protein binding on the human NHE8 basal promoter region upon butyrate stimulation. Furthermore, Sp3 acetylation modification is involved in butyrate-mediated NHE8 activation in Caco-2 cells. Our findings suggest that the mechanism of butyrate action on NHE8 expression involves enhanced Sp3 interaction at the basal promoter region of the human NHE8 gene promoter to activate NHE8 gene transcription. Thus butyrate is involved in intestinal regulation of NHE8 resulting enhanced sodium absorption.

  13. Sodium butyrate-induced DAPK-mediated apoptosis in human gastric cancer cells.

    PubMed

    Shin, Hyunsoo; Lee, Yeo Song; Lee, Yong Chan

    2012-04-01

    Epigenetic mechanisms of histone acetylation/deacetylation play an important role in the regulation of gene expression associated with the cell cycle and apoptosis. Recently, sodium butyrate, a histone deacetylase (HDAC) inhibitor, has been shown to exhibit anticancer effects via differentiation and apoptosis of cancer cells. Sodium butyrate may be a potential anticancer chemotherapeutic drug; however, the precise mechanism underlying the anticancer effects of sodium butyrate has not been clearly elucidated. In the present study, we investigated the role of death-associated protein kinase (DAPK) on the apoptosis of human gastric cancer cells induced by sodium butyrate. We observed that sodium butyrate induced apoptosis in human gastric cancer cells. Treatment with the HDAC inhibitor sodium butyrate increased the expression of caspase-3 and DAPK1/2 genes but decreased the expression of Bcl-2 in human gastric cancer cells. The expression of DAPK3, p53 and p21 were not altered by sodium butyrate treatment. Analysis of the general expression patterns revealed that sodium butyrate increased the expression of DAPK1/2 but decreased the expression of FAK and induced changes in the proliferation of apoptosis-related genes in human gastric cancer cells. These data suggest that DAPK expression prompts apoptosis by reducing the FAK protein level in sodium butyrate-induced apoptosis of human gastric cancer cells.

  14. Sodium butyrate inhibits the enhancing effect of high fat diet on mammary tumorigenesis.

    PubMed

    Yanagi, S; Yamashita, M; Imai, S

    1993-01-01

    We have studied the effect of butyrate on mammary tumorigenesis by 7,12-dimethylbenz(a)anthracene. As reported previously, a high incidence of mammary tumors was observed in rats fed a basal diet containing 20% margarine. However, the enhancing effect of margarine was inhibited when sodium butyrate was supplemented in the high margarine diet. Sodium butyrate did not cause any effect when it was supplemented in the basal diet. The result suggests a possibility that a part of the inhibitory effect of butter on mammary tumorigenesis, which we had previously reported, was caused by butyrate milk lipids.

  15. Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate-Induced Histone Modification

    PubMed Central

    Li, Cong-Jun; Li, Robert W.; Baldwin, Ransom L.; Blomberg, Le Ann; Wu, Sitao; Li, Weizhong

    2016-01-01

    Butyrate is a nutritional element with strong epigenetic regulatory activity as a histone deacetylase inhibitor. Based on the analysis of differentially expressed genes in the bovine epithelial cells using RNA sequencing technology, a set of unique genes that are activated only after butyrate treatment were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network, using Ingenuity Pathways Analysis, indicated that these genes activated by butyrate treatment are related to major cellular functions, including cell morphological changes, cell cycle arrest, and apoptosis. Our results offered insight into the butyrate-induced transcriptomic changes and will accelerate our discerning of the molecular fundamentals of epigenomic regulation. PMID:26819550

  16. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.

    PubMed

    Sikiric, P; Marovic, A; Matoz, W; Anic, T; Buljat, G; Mikus, D; Stancic-Rokotov, D; Separovic, J; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Zoricic, I; Turkovic, B; Aralica, G; Perovic, D; Duplancic, B; Lovric-Bencic, M; Rotkvic, I; Mise, S; Jagic, V; Hahn, V

    1999-12-01

    The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP. PMID:10672997

  17. MiR-144-3p and Its Target Gene β-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction

    PubMed Central

    Li, Kuo; Zhang, Junling; Ji, Chunxue; Wang, Lixuan

    2016-01-01

    MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neurodegenerative diseases, Parkinson’s disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, β-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process. PMID:27329039

  18. MiR-144-3p and Its Target Gene β-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction.

    PubMed

    Li, Kuo; Zhang, Junling; Ji, Chunxue; Wang, Lixuan

    2016-07-01

    MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neurodegenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, β-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process. PMID:27329039

  19. Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

    PubMed Central

    2010-01-01

    Background Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs) mitigate DAergic neurotoxicity in rodent models of PD. Consistent with these findings, epidemiological analysis indicated that certain NSAIDs may prevent or delay the progression of PD. However, a serious impediment of chronic NSAID therapy, particularly in the elderly, is gastric, renal and cardiac toxicity. Nitric oxide (NO)-donating NSAIDs, have a safer profile while maintaining anti-inflammatory activity of parent compounds. We have investigated the oral activity of the NO-donating derivative of flurbiprofen, [2-fluoro-α-methyl (1,1'-biphenyl)-4-acetic-4-(nitrooxy)butyl ester], HCT1026 (30 mg kg-1 daily in rodent chow) in mice exposed to the parkinsonian neurotoxin MPTP. Methods Ageing mice were fed with a control, flurbiprofen, or HCT1026 diet starting ten days before MPTP administration and continuing for all the experimental period. Striatal high affinity synaptosomial dopamine up-take, motor coordination assessed with the rotarod, tyrosine hydroxylase (TH)- and dopamine transporter (DAT) fiber staining, stereological cell counts, immunoblotting and gene expression analyses were used to assess MPTP-induced nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP. Results HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026 efficiently counteracted motor impairment and reversed MPTP-induced decreased synaptosomal [3H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH+ neuron loss in subtantia nigra pars compacta (SNpc), as opposed to age-matched mice fed with a control diet. These effects were associated to a significant decrease in reactive macrophage antigen-1 (Mac-1

  20. The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD.

    PubMed

    Rane, Pallavi; Shields, Jessica; Heffernan, Meghan; Guo, Yin; Akbarian, Schahram; King, Jean A

    2012-06-01

    Parkinson's disease (PD) patients often times experience impairment in their cognitive abilities early on in the progression of the disease. The reported deficits appear to mainly involve functions that are associated with frontal lobe and frontal-striatal pathways subserving attentional set-shifting, working memory and executive function. The current study explored executive function deficits in a rat model of PD in the pre-motor deficit stage. The rats were lesioned with 12 μg of 6-hydroxydonpamine (6-OHDA) in the striatum in a two step process (10 μg/μl followed by 2 μg/μl) 48 hours apart. Executive function was tested at 3 weeks post-surgery using a rat analogue of Wisconsin card sorting test called the Extra Dimensional/Intra Dimensional (ED/ID) set-shifting task. The results demonstrated that performance by the pre-motor rat model of PD was equivalent to that of the control groups in the simple and the compound discriminations as well as the intra-dimensional set-shifting. However the PD group exhibited attentional set-shifting deficits similar to those observed in PD patients. Additionally, sodium butyrate, a short chain fatty acid derivative and inhibitor of class I and II histone deacetylase (HDACi), was tested as a potential therapeutic agent to mitigate the pre-motor cognitive deficits in PD. The results indicated that the sodium butyrate treatment not only effectively alleviated the set-shifting deficits, but also improved the attentional set formation in the treated rats.

  1. Effects of dietary sodium butyrate on hepatic biotransformation and pharmacokinetics of erythromycin in chickens.

    PubMed

    Csikó, G; Nagy, G; Mátis, G; Neogrády, Z; Kulcsár, Á; Jerzsele, A; Szekér, K; Gálfi, P

    2014-08-01

    Butyrate, a commonly applied feed additive in poultry nutrition, can modify the expression of certain genes, including those encoding cytochrome P450 (CYP) enzymes. In comparative in vitro and in vivo experiments, the effect of butyrate on hepatic CYP genes was examined in primary cultures of chicken hepatocytes and in liver samples of chickens collected from animals that had been given butyrate as a feed additive. Moreover, the effect of butyrate on the biotransformation of erythromycin, a marker substance for the activity of enzymes of the CYP3A family, was investigated in vitro and in vivo. Butyrate increased the expression of the avian-specific CYP2H1 both in vitro and in vivo. In contrast, the avian CYP3A37 expression was decreased in hepatocytes following butyrate exposure, but not in the in vivo model. CYP1A was suppressed by butyrate in the in vitro experiments, and overexpressed in vivo in butyrate-fed animals. The concomitant incubation of hepatocytes with butyrate and erythromycin led to an increased CYP2H1 expression and a less pronounced inhibition of CYP3A37. In in vivo pharmacokinetic experiments, butyrate-fed animals given a single i.m. injection of erythromycin, a slower absorption phase (longer T(half-abs) and delayed T(max)) but a rapid elimination phase of this marker substrate was observed. Although these measurable differences were detected in the pharmacokinetics of erythromycin, it is unlikely that a concomitant application of sodium butyrate with erythromycin or other CYP substrates will cause clinically significant feed-drug interaction in chickens.

  2. Kinetics of syntrophic cultures: a theoretical treatise on butyrate fermentation.

    PubMed

    Kleerebezem, R; Stams, A J

    2000-03-01

    Numerous microbial conversions in methanogenic environments proceed at (Gibbs) free energy changes close to thermodynamic equilibrium. In this paper we attempt to describe the consequences of this thermodynamic boundary condition on the kinetics of anaerobic conversions in methanogenic environments. The anaerobic fermentation of butyrate is used as an example. Based on a simple metabolic network stoichiometry, the free energy change based balances in the cell, and the flux of substrates and products in the catabolic and anabolic reactions are coupled. In butyrate oxidation, a mechanism of ATP-dependent reversed electron transfer has been proposed to drive the unfavorable oxidation of butyryl-CoA to crotonyl-CoA. A major assumption in our model is that ATP-consumption and electron translocation across the cytoplasmic membrane do not proceed according to a fixed stoichiometry, but depend on the cellular concentration ratio of ATP and ADP. The energetic and kinetic impact of product inhibition by acetate and hydrogen are described. A major consequence of the derived model is that Monod-based kinetic description of this type of conversions is not feasible, because substrate conversion and biomass growth are proposed to be uncoupled. It furthermore suggests that the specific substrate conversion rate cannot be described as a single function of the driving force of the catabolic reaction but depends on the actual substrate and product concentrations. By using nonfixed stoichiometries for the membrane associated processes, the required flexibility of anaerobic bacteria to adapt to varying environmental conditions can be described.

  3. The efficacy of Na-butyrate encapsulated in palm fat on performance of broilers infected with necrotic enteritis with gene expression analysis

    PubMed Central

    Eshak, M. G.; Elmenawey, M. A.; Atta, A.; Gharib, H. B.; Shalaby, B.; Awaad, M. H. H.

    2016-01-01

    Aim: To study the efficacy of Na-butyrate encapsulated in palm fat on performance of broiler chickens experimentally infected with necrotic enteritis (NE) with the determination of its protective effect against the changes in the gene expression profiles and deoxyribonucleic acid (DNA) fragmentation. Materials and Methods: A total of 800 one-day-old male Arbor Acres Plus broiler chickens were randomly allocated into four groups for 5 weeks. Na-butyrate was supplemented at dosages of 1 kg/ton for starter diet, 0.5 kg/ton for grower diet, and 0.25 kg/ton for finisher diet (presence or absence). Birds of groups 1 and 2 were inoculated by crop gavages with 4×108 CFU/ml/bird of Clostridium perfringens in phosphate buffered saline for 4 successive days, from 14 to 17 days of age to produce NE. Results: Addition of Na-butyrate, encapsulated in palm fat, to ration of experimentally infected broilers with NE resulted in increased final body weight, at 35 days of age, reduced total feed consumption, improved feed conversion ratio, reduced cumulative mortality, and increased production number. There were increased intestinal diameter, intestinal length, and significantly increased the weight of bursa of Fabricius(BF) with higher hemagglutination inhibition titers against Newcastle disease (ND) vaccination versus untreated infected and untreated negative control birds. The results showed increased expression levels of alpha-toxin and glyceraldehyde-3-phosphate dehydrogenase in the bursa tissues of broilers infected with C. perfringens. However, the expression levels of these genes in broilers treated with Na-butyrate were similar to the non-infected control group. Supplementation of broilers with Na-butyrate increased the expression level of insulin-like growth factor-1 (IGF-1) and decreased the DNA fragmentation induced by C. perfringens. Conclusion: Na-butyrate significantly improved chicken broiler body weights, increased relative weights of BF, increased antibody titers

  4. Identification of potential target genes of butyrate in dimethylhydrazine-induced colorectal cancer in mice.

    PubMed

    Chen, Hui-Min; Lin, Yan-Wei; Wang, Ji-Lin; Kong, Xuan; Hong, Jie; Fang, Jing-Yuan

    2013-01-01

    The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression.

  5. Transcriptomic sequencing reveals a set of unique genes activated by butyrate-induced histone modification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate is a nutritional element with strong epigenetic regulatory activity as an inhibitor of histone deacetylases (HDACs). Based on the analysis of differentially expressed genes induced by butyrate in the bovine epithelial cell using deep RNA-sequencing technology (RNA-seq), a set of unique gen...

  6. Bioinformatic dissecting of TP53 regulation pathway underlying butyrate-induced histone modification in epigenetic regulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate affects cell proliferation, differentiation and motility. Butyrate inhibits histone deacetylase (HDAC) activities and induces cell cycle arrest and apoptosis. TP53 is one of the most active upstream regulators discovered by IPA in our RNA sequencing data set. The TP53 signaling pathway pl...

  7. Targeting cyclooxygenase-2 with sodium butyrate and NSAIDs on colorectal adenoma/carcinoma cells

    PubMed Central

    Zhang, Zhi-Hong; Ouyang, Qin; Gan, Hua-Tian

    2004-01-01

    AIM: The protective effects of sodium butyrate and NSAIDs (especially the highly selective COX-2 inhibitors) have attracted considerable interest recently. In this study, primary adenoma cells and HT-29 were used to investigate whether the above drugs would be effective for reducing proliferation and inducing apoptosis. Additionally, it was investigated whether NSAIDs would strengthen the effects of sodium butyrate and its possible mechanisms. METHODS: In vitro primary cell culture of colorectal adenomas and HT-29 were used for this investigation. PGE2 isolated from HT-29 cell culture supernatants was investigated by ELISA. MTT was employed to detect the anti-proliferative effects on both adenoma and HT-29 culture cells. FCM was used for apoptosis rate and cell cycle analysis. The morphology of apoptotic cells was investigated by means of electromicroscopy. RESULTS: Sodium butyrate could stimulate the secretion of PGE2, while NSAIDs inhibited it to below 30 pg/106 cells. Both butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis. The effects were time- and dose-dependent (P < 0.05). Aspirin and NS-398 could enhance the effects of sodium butyrate. The effects were stronger while sodium butyrate was used in combination with NS-398 than it was used in combination with Aspirin. CONCLUSION: Butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis respectively. NSAIDs could enhance the effects of sodium butyrate by down-regulating COX-2 expression. Selective COX-2 inhibitor is better than traditional NSAIDs. PMID:15378772

  8. Sodium butyrate regulates androgen receptor expression and cell cycle arrest in human prostate cancer cells.

    PubMed

    Kim, Jeonga; Park, Hyeyoung; Im, Ji Young; Choi, Wahn Soo; Kim, Hyung Sik

    2007-01-01

    Histone deacetylase (HDAC) inhibitors have been shown to modify the expression of a variety of genes related to cell cycle regulation and apoptosis in several cancer cells. However, the precise mode of action of HDAC inhibitors in prostate cancer cells is not completely understood. This study examined whether an HDAC inhibitor affects cell death in human prostate cancer cells through the epigenetic regulation of androgen receptor (AR) expression. The molecular mechanism of the HDAC inhibitor, sodium butyrate, on the epigenetic alterations of cell cycle regulators was evaluated in androgen-dependent human prostate cancer LNCaP cells. The expression levels of acetylated histone H3 and H4 increased significantly after 48 h treatment with sodium butyrate. Sodium butyrate induced the expression of AR after 48 h treatment. In addition, immunofluorescence assay revealed the nuclear localization of the AR after sodium butyrate treatment. Sodium butyrate also significantly decreased the expression of the cell cycle regulatory proteins (cyclin D1/cyclin dependent kinase (CDK)4, CDK6, and cyclin E/CDK2) in the LNCaP cells after 48 h treatment. Furthermore, p21Waf1/Cip1 and p27Kip1 were upregulated as a result of the sodium butyrate treatment. These results suggest that sodium butyrate effectively inhibited cell proliferation and induced apoptosis of human prostate cancer cells by altering the expression of cell cycle regulators and AR. This study indicated that sodium butyrate may be a potential agent in prostate cancer treatment.

  9. Effect of Sodium Butyrate on Growth Performance and Response to Lipopolysaccharide in Weanling Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two experiments were conducted to determine the effects of dietary sodium butyrate on growth performance and response to E. coli. lipopolysaccharide (LPS) in weanling pigs. In the first 28 d experiment, 180 pigs (initial BW 6.3 kg) were fed 0, 0.05, 0.1, 0.2, and 0.4% sodium butyrate, or 110 mg/kg d...

  10. Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro

    PubMed Central

    Dostal, Alexandra; Bircher, Lea; Pham, Van Thanh; Follador, Rainer; Zimmermann, Michael Bruce; Chassard, Christophe

    2015-01-01

    ABSTRACT The aim of this study was to investigate the effect of iron (Fe) availability on butyrate production in the complex bacterial ecosystem of the human gut. Hence, different Fe availabilities were mimicked in an in vitro colonic fermentation model (the polyfermenter intestinal model called PolyFermS) inoculated with immobilized gut microbiota from a child and in batch cultures of the butyrate producer Roseburia intestinalis. Shifts in the microbial community (16S rRNA sequencing and quantitative PCR), metabolic activity (high-performance liquid chromatography), and expression of genes involved in butyrate production were assessed. In the PolyFermS, moderate Fe deficiency resulted in a 1.4-fold increase in butyrate production and a 5-fold increase in butyryl-coenzyme A (CoA):acetate CoA-transferase gene expression, while very strong Fe deficiency significantly decreased butyrate concentrations and butyrate-producing bacteria compared with the results under normal Fe conditions. Batch cultures of R. intestinalis grown in a low-Fe environment preferentially produced lactate and had reduced butyrate and hydrogen production, in parallel with upregulation of the lactate dehydrogenase gene and downregulation of the pyruvate:ferredoxin-oxidoreductase gene. In contrast, under high-Fe conditions, R. intestinalis cultures showed enhanced butyrate and hydrogen production, along with increased expression of the corresponding genes, compared with the results under normal-Fe conditions. Our data reveal the strong regulatory effect of Fe on gut microbiota butyrate producers and on the concentrations of butyrate, which contributes to the maintenance of host gut health. PMID:26578675

  11. Carboplatin and sodium butyrate, separate--yes, but combined--never.

    PubMed

    Gurtowska, Natalia; Kloskowski, Tomasz; Olkowska, Joanna; Bajek, Anna; Debski, Robert; Zielaskowska, Jowita; Drewa, Tomasz

    2013-01-01

    With the object of improving the effectiveness of a malignant melanoma's treatment and a patients' quality of life, there is a serious need to identify new anticancer compounds, for example, among naturally derived compounds such as sodium butyrate. The aim of this study was to assess the combined impact of carboplatin (C) and sodium butyrate on the B16 melanoma viability by in vitro. B16 cell line was exposed to various concentrations of carboplatin (0.001-10 micromol/L) and sodium butyrate (1 to 100 mmol/L) for 24 h. LC10, LC50 and LC90 values were calculated. The influence of carboplatin and sodium butyrate on the cell cycle and apoptosis was assessed. Additionally, magnetic stem cell sorting was performed, positive melanoma CD133 cells were isolated and the effects of carboplatin and sodium butyrate on cell viability with heterogeneous population of melanoma cells (CD133+/CD133-) was compared. For carboplatin LC50 and LC90 were 1.2 micromol/L and 4.58 pmol/L, respectively. For sodium butyrate LC50 and LC90 were 65.73 mmol/L and 275.06 mmol/L. The value for LC10 could not be determined. Sodium butyrate at the highest concentration (100.0 mmol/L) resulted in only 57.36% mortality of cells. A synergistic effect of both compounds was observed in low concentrations of sodium butyrate and carboplatin. That synergism disappeared at concentrations corresponding to LC50. At the concentration corresponding to LC50 C and high concentration of sodium butyrate, a decrease of cell numbers in phase G2/M was observed (r = -0.97). Cells were arrested in phase G1/G0 and S. The presented results exclude the possibility of the combined application of sodium butyrate and carboplatin in cancer therapy.

  12. Consumption of partially hydrolysed guar gum stimulates Bifidobacteria and butyrate-producing bacteria in the human large intestine.

    PubMed

    Ohashi, Y; Sumitani, K; Tokunaga, M; Ishihara, N; Okubo, T; Fujisawa, T

    2015-01-01

    Partially hydrolysed guar gum (PHGG) is a water-soluble dietary fibre that is non-digestible in the upper gastrointestinal tract. It is believed that PHGG benefits the health of hosts by altering the colonic microbiota and stimulating short-chain fatty acid (SCFA) production. However, it remains unclear which bacteria ferment PHGG in the human large intestine. In this study, the effect of PHGG on faecal bacteria was analysed to specify the bacteria that contribute to the fermentation of PHGG in the human large intestine. Ten healthy volunteers consumed PHGG (6 g/day) for 2 weeks. Faeces were collected at 2 weeks prior to consumption, at the end of 2 weeks of consumption, and 2 weeks after consumption of PHGG. Bacterial DNA was extracted from these collected faeces and subjected to real-time PCR using bacterial group- or species-specific primers. The copy number of the butyryl-CoA CoA-transferase gene and the 16S rRNA gene copy numbers of Bifidobacterium, the Clostridium coccoides group, the Roseburia/ Eubacterium rectale group, Eubacterium hallii, and butyrate-producing bacterium strain SS2/1 were significantly increased by the intake of PHGG. Other bacteria and bacterial groups were not significantly influenced by the intake of PHGG. It was believed that the Roseburia/E. rectale group bacteria, Bifidobacterium, the lactate-utilising, butyrate-producing bacteria, E. hallii and bacterium strain SS2/1, would contribute to the fermentation of PHGG in the human large intestine. PHGG may benefit health by stimulating Bifidobacterium and butyrate-producing bacteria in the human large intestine.

  13. Butyrate plays differential roles in cellular signaling in cancerous HCT116 and noncancerous NCM460 colon cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects in colon. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate plays differential roles in cancerous and non-cancerous cells through si...

  14. Supplemental sodium butyrate stimulates different gastric cells in weaned pigs.

    PubMed

    Mazzoni, Maurizio; Le Gall, Maud; De Filippi, Sara; Minieri, Laura; Trevisi, Paolo; Wolinski, Jaroslaw; Lalatta-Costerbosa, Giovanna; Lallès, Jean-Paul; Guilloteau, Paul; Bosi, Paolo

    2008-08-01

    Sodium butyrate (SB) is used as an acidifier in animal feed. We hypothesized that supplemental SB impacts gastric morphology and function, depending on the period of SB provision. The effect of SB on the oxyntic and pyloric mucosa was studied in 4 groups of 8 pigs, each supplemented with SB either during the suckling period (d 4-28 of age), after weaning (d 29 to 39-40 of age) or both, or never. We assessed the number of parietal cells immunostained for H+/K+-ATPase, gastric endocrine cells immunostained for chromogranin A and somatostatin (SST) in the oxyntic mucosa, and gastrin-secreting cells in the pyloric mucosa. Gastric muscularis and mucosa thickness were measured. Expressions of the H+/K+-ATPase and SST type 2 receptor (SSTR2) genes in the oxyntic mucosa and of the gastrin gene in the pyloric mucosa were evaluated by real-time RT-PCR. SB increased the number of parietal cells per gland regardless of the period of administration (P < 0.05). SB addition after, but not before, weaning increased the number of enteroendocrine and SST-positive cells (P < 0.01) and tended to increase gastrin mRNA (P = 0.09). There was an interaction between the 2 periods of SB treatment for the expression of H/K-ATPase and SSTR2 genes (P < 0.05). Butyrate intake after weaning increased gastric mucosa thickness (P < 0.05) but not muscularis. SB used orally at a low dose affected gastric morphology and function, presumably in relationship with its action on mucosal maturation and differentiation.

  15. Removal and recovery of inhibitory volatile fatty acids from mixed acid fermentations by conventional electrodialysis.

    PubMed

    Jones, Rhys Jon; Massanet-Nicolau, Jaime; Guwy, Alan; Premier, Giuliano C; Dinsdale, Richard M; Reilly, Matthew

    2015-08-01

    Hydrogen production during dark fermentation is inhibited by the co-production of volatile fatty acids (VFAs) such as acetic and n-butyric acid. In this study, the effectiveness of conventional electrodialysis (CED) in reducing VFA concentrations in model solutions and hydrogen fermentation broths is evaluated. This is the first time CED has been reported to remove VFAs from hydrogen fermentation broths. During 60 min of operation CED removed up to 99% of VFAs from model solutions, sucrose-fed and grass-fed hydrogen fermentation broths, containing up to 1200 mg l(-1) each of acetic acid, propionic acid, i-butyric acid, n-butyric acid, i-valeric acid, and n-valeric acid. CED's ability to remove VFAs from hydrogen fermentation broths suggests that this technology is capable of improving hydrogen yields from dark fermentation.

  16. Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs.

    PubMed

    Hofmanová, Jirina; Vaculová, Alena; Koubková, Zuzana; Hýzd'alová, Martina; Kozubík, Alois

    2009-05-01

    We verified the hypothesis suggesting modulation of the effects of sodium butyrate (NaBt) by omega-3 or omega-6 PUFAs. Comparing the response of human colon epithelial cell lines of fetal (FHC) and adenocarcinoma (HT-29, HCT-116) origin, we detected significant differences in proliferation, differentiation and apoptotic response to the treatment of NaBt, arachidonic or docosahexaenoic acids and their combination. While in FHC and HT-29 cells NaBt induced G0/G1 arrest, differentiation and low level of apoptosis, in HCT-116 cells G2/M arrest, no differentiation and high degree of apoptosis were detected. Moreover, in FHC cells significant potentiation of apoptosis accompanied by increased arrest in the cell cycle, cell detachment and decrease in differentiation were detected after combined treatment with NaBt and both PUFAs. Changes in cytokinetics induced by fatty acids were accompanied by membrane lipid unpacking, reactive oxygen species (ROS) production, and decrease in mitochondrial membrane potential (MMP). Detection of caspase-3 activation and dynamic modulation of Mcl-1 protein expression imply their possible role in both cell differentiation and apoptotic response. Our results support the concept of modulation of NaBt effects by PUFAs, especially of omega-3 type, in colonic cells in vitro with diverse impact in cell lines derived from normal or neoplastic epithelium.

  17. Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-13C]butyrate and [1-13C]pyruvate

    PubMed Central

    Bastiaansen, Jessica A. M.; Merritt, Matthew E.; Comment, Arnaud

    2016-01-01

    Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) 13C magnetic resonance spectroscopy (MRS) has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-13C]pyruvate and [1-13C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections. Pyruvate and butyrate competed for acetyl-CoA production, as evidenced by significant changes in [13C]bicarbonate (−48%), [1-13C]acetylcarnitine (+113%), and [5-13C]glutamate (−63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-13C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-13C]acetoacetate and [1-13C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-13C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (−82%). Combining HP 13C technology and co-administration of separate imaging agents enables noninvasive and simultaneous monitoring of both fatty acid and carbohydrate oxidation. This protocol illustrates a novel method for assessing metabolic flux through different enzymatic pathways simultaneously and enables mechanistic studies of the changing myocardial energetics often associated with disease. PMID:27150735

  18. Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-(13)C]butyrate and [1-(13)C]pyruvate.

    PubMed

    Bastiaansen, Jessica A M; Merritt, Matthew E; Comment, Arnaud

    2016-01-01

    Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) (13)C magnetic resonance spectroscopy (MRS) has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-(13)C]pyruvate and [1-(13)C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections. Pyruvate and butyrate competed for acetyl-CoA production, as evidenced by significant changes in [(13)C]bicarbonate (-48%), [1-(13)C]acetylcarnitine (+113%), and [5-(13)C]glutamate (-63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-(13)C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-(13)C]acetoacetate and [1-(13)C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-(13)C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (-82%). Combining HP (13)C technology and co-administration of separate imaging agents enables noninvasive and simultaneous monitoring of both fatty acid and carbohydrate oxidation. This protocol illustrates a novel method for assessing metabolic flux through different enzymatic pathways simultaneously and enables mechanistic studies of the changing myocardial energetics often associated with disease. PMID:27150735

  19. Unexpected ring-closure products derived from 3-(2-allylanilino)-3-phenylacrylate esters: crystal and molecular structures of 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate and (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6-one.

    PubMed

    Luque, Adriana L; Sanabria, Carlos M; Palma, Alirio; Cobo, Justo; Glidewell, Christopher

    2016-08-01

    The reactions of two 3-(2-allylanilino)-3-phenylacrylate esters with acetic anhydride and with strong acids has revealed a richly diverse reactivity providing a number of unexpected products. Thus, acetylation of ethyl 3-(2-allylanilino)-3-phenylacrylate, (Ia), or ethyl 3-(2-allyl-4-methylanilino)-3-phenylacrylate, (Ib), with acetic anhydride yields not only the expected acetylated esters, (II), as the major products but also the unexpected polysubstituted quinolines 3-acetyl-8-allyl-2-phenylquinolin-4-yl acetate, (IIIa), and 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate, (IIIb), as minor products. Subsequent reaction of the major product ethyl 2-[(2-allyl-4-methylanilino)(phenyl)methylidene]-3-oxobutanoate, (IIb), with concentrated sulfuric acid did not provide the expected 3-acetylquinoline derivative, but instead two unexpected products, namely ethyl 4-ethyl-2-phenyl-1,4-dihydroquinoline-3-carboxylate, (IV), and ethyl 3-acetyl-4-ethyl-2-phenyl-3,4-dihydroquinoline-3-carboxylate, (V), in yields of 39 and 22%, respectively. The reaction of (Ib) with Eaton's reagent gave both the quinoline (Z)-6-methyl-2-phenyl-8-(prop-1-en-1-yl)quinolin-4(1H)-one, (VI), and the unexpected tricyclic product (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6-one, (VII), in yields of 71 and 12%, respectively. The products (II)-(VII) have all been fully characterized spectroscopically and the crystal structures of two of the unexpected products, i.e. (IIIb) (C23H21NO3) and (VII) (C19H17NO), are reported here. The formation of compounds (IV), (V) and (VII) all require an isomerization of the initial allyl substituent, with migration of the C=C double bond from the terminal site to the internal site. In (IIIb), the two acetyl substituents are oriented such that the intramolecular distance between the two carbonyl O atoms is only 3.243 (2) Å, and in (VII), the five-membered ring adopts a twisted half-chair conformation. The molecules of compound (IIIb

  20. Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice.

    PubMed

    Russo, Roberto; De Caro, Carmen; Avagliano, Carmen; Cristiano, Claudia; La Rana, Giovanna; Mattace Raso, Giuseppina; Berni Canani, Roberto; Meli, Rosaria; Calignano, Antonio

    2016-01-01

    In the present study we investigated the role of sodium butyrate (butyrate), and its more palatable derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), in animal models of acute and chronic pain. We found that oral administrations of butyrate (10-200mg/Kg) or equimolecular FBA (21.2-424mg/Kg) reduced visceral pain in a dose- and time-dependent manner. Both drugs were also effective in the formalin test, showing an antinociceptive effect. This analgesic effect was blocked by glibenclamide, suggesting the involvement of ATP-dependent K(+) channels. Moreover, following repeated administration butyrate (100-200mg/Kg) and FBA (212-424mg/Kg) retained their analgesic properties in a model of neuropathic pain, reducing mechanical and thermal hyperalgesia in the chronic constriction injury (CCI) model. The involvement of peroxisome proliferator-activated receptor (PPAR) -α and -γ for the analgesic effect of butyrate was also investigated by using PPAR-α null mice or the PPAR-γ antagonist GW9662. Western blot analysis, confirmed the role of peroxisome receptors in butyrate effects, evidencing the increase of PPAR-α and -γ expression, associated to the reduction of inflammatory markers (COX-2, iNOS, TNF-α and cFOS). In conclusion, we describe the role of butyrate-based drugs in pain, identifying different and converging non-genomic and genomic mechanisms of action, which cooperate in nociception maintenance.

  1. Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition

    PubMed Central

    Xiong, Haitao; Guo, Bingxiu; Gan, Zhenshun; Song, Deguang; Lu, Zeqing; Yi, Hongbo; Wu, Yueming; Wang, Yizhen; Du, Huahua

    2016-01-01

    Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days before E. coli O157:H7 challenge was designed to investigate porcine HDP expression, inflammation and E. coli O157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cells in vitro were examined. Butyrate treatment (i) alleviated the clinical symptoms of E. coli O157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced the E. coli O157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPs in vitro and in vivo via histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance of E. coli O157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition. PMID:27230284

  2. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut.

    PubMed

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

  3. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut

    PubMed Central

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

  4. Intestinimonas butyriciproducens gen. nov., sp. nov., a butyrate-producing bacterium from the mouse intestine.

    PubMed

    Kläring, Karoline; Hanske, Laura; Bui, Nam; Charrier, Cédric; Blaut, Michael; Haller, Dirk; Plugge, Caroline M; Clavel, Thomas

    2013-12-01

    A Gram-positive, spore-forming, non-motile, strictly anaerobic rod-shaped bacterium was isolated from the caecal content of a TNF(deltaARE) mouse. The isolate, referred to as strain SRB-521-5-I(T), was originally cultured on a reduced agar medium containing yeast extract, rumen fluid and lactic acid as main energy and carbon sources. Phylogenetic analysis of partial 16S rRNA genes revealed that the species most closely related to strain SRB-521-5-I(T) were Flavonifractor plautii and Pseudoflavonifractor capillosus (<95 % sequence similarity; 1436 bp). In contrast to F. plautii and P. capillosus, strain SRB-521-5-I(T) contained a substantial amount of C18 : 0 dimethylacetal. Additional major fatty acids were C14 : 0 methyl ester, C16 : 0 dimethylacetal and C18 : 0 aldehyde. Strain SRB-521-5-I(T) differed in its enzyme profile from F. plautii and P. capillosus by being positive for dextrin, maltotriose, turanose, dl-lactic acid and d-lactic acid methyl ester but negative for d-fructose. In reduced Wilkins-Chalgren-Anaerobe broth, strain SRB-521-5-I(T) produced approximately 8 mM butyrate and 4 mM acetate. In contrast to F. plautii, the strain did not metabolize flavonoids. It showed intermediate resistance towards the antibiotics ciprofloxacin, colistin and tetracycline. Based on genotypic and phenotypic characteristics, we propose the name Intestinimonas butyriciproducens gen. nov., sp. nov. to accommodate strain SRB-521-5-I(T) ( = DSM 26588(T) = CCUG 63529(T)) as the type strain. PMID:23918795

  5. Transcriptome Analysis Reveals Regulation of Gene Expression for Lipid Catabolism in Young Broilers by Butyrate Glycerides

    PubMed Central

    Yin, Fugui; Yu, Hai; Lepp, Dion; Shi, Xuejiang; Yang, Xiaojian; Hu, Jielun; Leeson, Steve; Yang, Chengbo; Nie, Shaoping; Hou, Yongqing; Gong, Joshua

    2016-01-01

    Background & Aims Butyrate has been shown to potently regulate energy expenditure and lipid metabolism in animals, yet the underlying mechanisms remain to be fully understood. The aim of this study was to investigate the molecular mechanisms of butyrate (in the form of butyrate glycerides, BG)-induced lipid metabolism at the level of gene expression in the jejunum and liver of broilers. Methodology/Principal Findings Two animal experiments were included in this study. In Experiment 1, two hundred and forty male broiler chickens were equally allocated into two groups: 1) basal diet (BD), 2) BG diets (BD + BG). Growth performance was compared between treatments for the 41-day trial. In Experiment 2, forty male broiler chickens were equally allocated into two groups. The general experimental design, group and management were the same as described in Experiment 1 except for reduced bird numbers and 21-day duration of the trial. Growth performance, abdominal fat deposition, serum lipid profiles as well as serum and tissue concentrations of key enzymes involved in lipid metabolism were compared between treatments. RNA-seq was employed to identify both differentially expressed genes (DEGs) and treatment specifically expressed genes (TSEGs). Functional clustering of DEGs and TSEGs and signaling pathways associated with lipid metabolism were identified using Ingenuity Pathways Analysis (IPA) and DAVID Bioinformatics Resources 6.7 (DAVID-BR). Quantitative PCR (qPCR) assays were subsequently conducted to further examine the expression of genes in the peroxisome proliferator-activated receptors (PPAR) signaling pathway identified by DAVID-BR. Dietary BG intervention significantly reduced abdominal fat ratio (abdominal fat weight/final body weight) in broilers. The decreased fat deposition in BG-fed chickens was in accordance with serum lipid profiles as well as the level of lipid metabolism-related enzymes in the serum, abdominal adipose, jejunum and liver. RNA-seq analysis

  6. Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require activation of CAD and downregulation of VEGF

    SciTech Connect

    Belakavadi, Madesh . E-mail: belakama@umdnj.edu; Prabhakar, B.T.; Salimath, Bharathi P.

    2005-10-07

    Butyrate, a short-chain fatty acid produced in the colon, induces cell cycle arrest, differentiation, and apoptosis in transformed cell lines. In this report, we study the effects of butyrate (BuA) on the growth of Ehrlich ascites tumor (EAT) cells in vivo. BuA, when injected intraperitoneally (i.p) into mice, inhibited proliferation of EAT cells. Further, induction of apoptosis in EAT cells was monitored by nuclear condensation, annexin-V staining, DNA fragmentation, and translocation of caspase-activated DNase into nucleus upon BuA-treatment. Ac-DEVD-CHO, a caspase-3 inhibitor, completely inhibited BuA-induced apoptosis, indicating that activation of caspase-3 mediates the apoptotic pathway in EAT cells. The proapoptotic effect of BuA also reflects on the antiangiogenic pathway in EAT cells. The antiangiogenic effect of BuA in vivo was demonstrated by the downregulation of the secretion of VEGF in EAT cells. CD31 immunohistochemical staining of peritoneum sections clearly indicated a potential angioinhibitory effect of BuA in EAT cells. These results suggest that BuA, besides regulating other fundamental cellular processes, is able to modulate the expression/secretion of the key angiogenic growth factor VEGF in EAT cells.

  7. Kinetic analysis of butyrate transport in human colon adenocarcinoma cells reveals two different carrier-mediated mechanisms.

    PubMed

    Lecona, Emilio; Olmo, Nieves; Turnay, Javier; Santiago-Gómez, Angélica; López de Silanes, Isabel; Gorospe, Myriam; Lizarbe, M Antonia

    2008-01-01

    Butyrate has antitumorigenic effects on colon cancer cells, inhibits cell growth and promotes differentiation and apoptosis. These effects depend on its intracellular concentration, which is regulated by its transport. We have analysed butyrate uptake kinetics in human colon adenocarcinoma cells sensitive to the apoptotic effects of butyrate (BCS-TC2, Caco-2 and HT-29), in butyrate-resistant cells (BCS-TC2.BR2) and in normal colonic cells (FHC). The properties of transport were analysed with structural analogues, specific inhibitors and different bicarbonate and sodium concentrations. Two carrier-mediated mechanisms were detected: a low-affinity/high-capacity (K(m)=109+/-16 mM in BCS-TC2 cells) anion exchanger and a high-affinity/low-capacity (K(m)=17.9+/-4.0 microM in BCS-TC2 cells) proton-monocarboxylate co-transporter that was energy-dependent and activated via PKCdelta (protein kinase Cdelta). All adenocarcinoma cells analysed express MCT (monocarboxylate transporter) 1, MCT4, ancillary protein CD147 and AE2 (anion exchanger 2). Silencing experiments show that MCT1, whose expression increases with butyrate treatment in butyrate-sensitive cells, plays a key role in high-affinity transport. Low-affinity uptake was mediated by a butyrate/bicarbonate antiporter along with a possible contribution of AE2 and MCT4. Butyrate treatment increased uptake in a time- and dose-dependent manner in butyrate-sensitive but not in butyrate-resistant cells. The two butyrate-uptake activities in human colon adenocarcinoma cells enable butyrate transport at different physiological conditions to maintain cell functionality. The high-affinity/low-capacity transport functions under low butyrate concentrations and may be relevant for the survival of carcinoma cells in tumour regions with low glucose and butyrate availability as well as for the normal physiology of colonocytes.

  8. Effects of sodium butyrate and salinomycin upon intestinal microbiota, mucosal morphology and performance of broiler chickens.

    PubMed

    Czerwiński, Jan; Højberg, Ole; Smulikowska, Stefania; Engberg, Ricarda M; Mieczkowska, Anna

    2012-04-01

    The effect of dietary sodium butyrate (SB) or salinomycin (SAL) or both additives on performance, small intestinal morphology and microbial ecology of broiler chickens was studied. A growth trial was conducted with 96 Ross 308 female broilers from 1 to 30 days of age. Four treatment groups were fed with a non-supplemented control diet or three experimental diets supplemented with i) 300 mg SB (Adimix 30 coated) per kg, ii) 60 mg SAL (Sacox) per kg or iii) both additives in combination. Feed intake and body-weight gain decreased and gain-to-feed ratio increased due to SAL supplementation, while addition of SB did not affect performance in comparison with the control diet but positively affected feed intake and body-weight gain in comparison with birds fed the SAL-supplemented diet. Villus height in jejunum decreased, while crypt depth increased due to SAL supplementation. Addition of SB increased crypt depth in jejunum. No significant effect of either additive was observed in ileum morphology. Total short-chain organic acids concentration in ileal digesta decreased with SAL supplementation, mainly due to lower lactic acid concentration, but no effects were observed in the caeca. The SAL supplementation was accompanied by a pH increase in ileum and a pH decrease in caecum. No significant effect of SB addition was observed for these parameters. Total bacterial numbers and Lactobacillus [lactic acid bacteria (LAB)] counts in ileal and caecal contents were lower in birds fed with SAL-supplemented diet in comparison with birds fed with control or SB diet. DNA fingerprints revealed SAL supplementation to affect the microbial population by suppressing dominating LAB, potentially L. aviarius. The presented results show that dietary SAL, supplemented alone or in combination with SB, suppressed the microbial activity and altered the microbial community structure mainly in ileum. SAL alone negatively affected feed intake and body-weight gain; however, the effect was

  9. Combining microbial cultures for efficient production of electricity from butyrate in a microbial electrochemical cell.

    PubMed

    Miceli, Joseph F; Garcia-Peña, Ines; Parameswaran, Prathap; Torres, César I; Krajmalnik-Brown, Rosa

    2014-10-01

    Butyrate is an important product of anaerobic fermentation; however, it is not directly used by characterized strains of the highly efficient anode respiring bacteria (ARB) Geobacter sulfurreducens in microbial electrochemical cells. By combining a butyrate-oxidizing community with a Geobacter rich culture, we generated a microbial community which outperformed many naturally derived communities found in the literature for current production from butyrate and rivaled the highest performing natural cultures in terms of current density (∼ 11A/m(2)) and Coulombic efficiency (∼ 70%). Microbial community analyses support the shift in the microbial community from one lacking efficient ARB in the marine hydrothermal vent community to a community consisting of ∼ 80% Geobacter in the anode biofilm. This demonstrates the successful production and adaptation of a novel microbial culture for generating electrical current from butyrate with high current density and high Coulombic efficiency, by combining two mixed microbial cultures containing complementing biochemical pathways.

  10. Combining microbial cultures for efficient production of electricity from butyrate in a microbial electrochemical cell

    PubMed Central

    Miceli, Joseph F.; Garcia-Peña, Ines; Parameswaran, Prathap; Torres, César I.; Krajmalnik-Brown, Rosa

    2014-01-01

    Butyrate is an important product of anaerobic fermentation; however, it is not directly used by characterized strains of the highly efficient anode respiring bacteria (ARB) Geobacter sulfurreducens in microbial electrochemical cells. By combining a butyrate-oxidizing community with a Geobacter rich culture, we generated a microbial community which outperformed many naturally derived communities found in the literature for current production from butyrate and rivaled the highest performing natural cultures in terms of current density (~11 A/m2) and Coulombic efficiency (~70%). Microbial community analyses support the shift in the microbial community from one lacking efficient ARB in the marine hydrothermal vent community to a community consisting of ~80% Geobacter in the anode biofilm. This demonstrates the successful production and adaptation of a novel microbial culture for generating electrical current from butyrate with high current density and high Coulombic efficiency, by combining two mixed micro bial cultures containing complementing biochemical pathways. PMID:25048958

  11. Statistical design for formulation optimization of hydrocortisone butyrate-loaded PLGA nanoparticles.

    PubMed

    Yang, Xiaoyan; Patel, Sulabh; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

    2014-06-01

    The aim of this investigation was to develop hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) with ideal encapsulation efficiency (EE), particle size, and drug loading (DL) under emulsion solvent evaporation technique utilizing various experimental statistical design modules. Experimental designs were used to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. Plackett-Burman design for independent variables was first conducted to prescreen various formulation and process variables during the development of NP. Selected primary variables were further optimized by central composite design. This process leads to an optimum formulation with desired EE, particle size, and DL. Contour plots and response surface curves display visual diagrammatic relationships between the experimental responses and input variables. The concentration of PLGA, drug, and polyvinyl alcohol and sonication time were the critical factors influencing the responses analyzed. Optimized formulation showed EE of 90.6%, particle size of 164.3 nm, and DL of 64.35%. This study demonstrates that statistical experimental design methodology can optimize the formulation and process variables to achieve favorable responses for HB-loaded NP.

  12. Chitin butyrate coated electrospun nylon-6 fibers for biomedical applications

    NASA Astrophysics Data System (ADS)

    Pant, Hem Raj; Kim, Han Joo; Bhatt, Lok Ranjan; Joshi, Mahesh Kumar; Kim, Eun Kyo; Kim, Jeong In; Abdal-hay, Abdalla; Hui, K. S.; Kim, Cheol Sang

    2013-11-01

    In this study, we describe the preparation and characterizations of chitin butyrate (CB) coated nylon-6 nanofibers using single-spinneret electrospinning of blends solution. The physicochemical properties of nylon-6 composite fibers with different proportions of CB to nylon-6 were determined using FE-SEM, TEM, FT-IR spectroscopy, and water contact angle measurement. FE-SEM and TEM images revealed that the nylon-6 and CB were immiscible in the as-spun nanofibers, and phase separated nanofiber morphology becomes more pronounced with increasing amounts of CB. The bone formation ability of composite fibers was evaluated by incubating in biomimetic simulated body fluid. In order to assay the cytocompatibility and cell behavior on the composite scaffolds, osteoblast cells were seeded on the matrix. Results suggest that the deposition of CB layer on the surface of nylon-6 could increase its cell compatibility and bone formation ability. Therefore, as-synthesized nanocomposite fibrous mat has great potentiality in hard tissue engineering.

  13. Comparative pharmaceutical evaluation of brand and generic clobetasone butyrate ointments.

    PubMed

    Yamamoto, Yoshihisa; Fukami, Toshiro; Koide, Tatsuo; Onuki, Yoshinori; Suzuki, Toyofumi; Metori, Koichi; Katori, Noriko; Hiyama, Yukio; Tomono, Kazuo

    2014-03-10

    In the present study, we performed comprehensive pharmaceutical evaluation among an original clobetasone butyrate (CLB) ointment product and three generic products. Although spherocrystal images were observed under a polarizing microscope for only Kindavate®, the original product, distribution of active and inactive ingredients was chemically equivalent between the original and generic medicine by the attenuated total reflection infrared spectroscopy. These results suggest that the spherocrystals observed in Kindavate® are composed of hydrocarbon. On GC/MS, it was revealed that linear alkanes having 25-27 carbon atoms are densely present in Sun White®, the base used in Kindavate®. On the other hand, linear alkanes having 22-31 carbon atoms were broadly distributed in most other white petrolatums. In the CLB ointment products, the distribution equivalent of linear alkane to Sun White® was observed only in Kindavate®. Thus, the GC/MS method is extremely useful for identification of white petrolatum used in the ointment. A similar amount of CLB among the pharmaceutical products was detected in the skin tissue by skin accumulation test, although there were the differences in rheological properties and the quality of white petrolatum. The present results will be very useful for pharmacists in selecting medicine products that match the needs of the patient. Such pharmaceutical information will help spread objective knowledge about products in the future, and will contribute to the appropriate selection of medication.

  14. Sodium butyrate protects the intestinal barrier function in peritonitic mice

    PubMed Central

    Han, Xiaofeng; Song, Huimin; Wang, Yunlei; Sheng, Yingmo; Chen, Jie

    2015-01-01

    Objective: Peritonitis is a commonly seen disease with high morbidity and mortality. It is prevalently considered that the impaired intestinal barrier during peritonitis is the access point of gut microbes into the blood system, and acts as the engine of the following systemic infection. In our previous study, we found that Sodium Butyrate (NaB) was protective on intestinal barrier function. In this study, we aim to evaluate the effects of NaB on overwhelming infection animal models of peritonitis. Methods: Mouse cecal ligation and puncture (CLP) model was used to study the effects of NaB on the intestinal barrier. Experimental animals were fed of NaB by gavage. Post-CLP mortality, gut permeability and intestinal histological alterations were studied. Results: Gastrointestinal NaB pharmacodynamics profiles after medication were studied. Measurements of NaB concentration in chyme showed significantly higher intestinal concentration of NaB in the NaB treated group than that of the control group. CLP-induced mortality was significantly decreased by oral NaB treatments. Gut permeability was largely increased after CLP, which was partially prevented by NaB feeding. Histological study showed that intestinal, especially ileal injury following peritonitis was substantially alleviated by NaB treatments. Moreover, tissue regeneration was also prompted by NaB. Conclusion: NaB has a potential protective effect on intestinal barrier function in peritonitis. PMID:26064302

  15. CREB-binding protein, p300, butyrate, and Wnt signaling in colorectal cancer.

    PubMed

    Bordonaro, Michael; Lazarova, Darina L

    2015-07-21

    This paper reviews the distinctive roles played by the transcriptional coactivators CREB-binding protein (CBP) and p300 in Wnt/β-catenin signaling and cell physiology in colorectal cancer (CRC). Specifically, we focus on the effects of CBP- and p300-mediated Wnt activity on (1) neoplastic progression; (2) the activities of butyrate, a breakdown product of dietary fiber, on cell signaling and colonic cell physiology; (3) the development of resistance to histone deacetylase inhibitors (HDACis), including butyrate and synthetic HDACis, in colonic cells; and (4) the physiology and number of cancer stem cells. Mutations of the Wnt/β-catenin signaling pathway initiate the majority of CRC cases, and we have shown that hyperactivation of this pathway by butyrate and other HDACis promotes CRC cell apoptosis. This activity by butyrate may in part explain the preventive action of fiber against CRC. However, individuals with a high-fiber diet may still develop neoplasia; therefore, resistance to the chemopreventive action of butyrate likely contributes to CRC. CBP or p300 may modify the ability of butyrate to influence colonic cell physiology since the two transcriptional coactivators affect Wnt signaling, and likely, its hyperactivation by butyrate. Also, CBP and p300 likely affect colonic tumorigenesis, as well as stem cell pluripotency. Improvement of CRC prevention and therapy requires a better understanding of the alterations in Wnt signaling and gene expression that underlie neoplastic progression, stem cell fate, and the development of resistance to butyrate and clinically relevant HDACis. Detailed knowledge of how CBP- and p300 modulate colonic cell physiology may lead to new approaches for anti-CRC prevention and therapeutics, particularly with respect to combinatorial therapy of CBP/p300 inhibitors with HDACis.

  16. Cyclic AMP synergizes with butyrate in promoting β-defensin 9 expression in chickens.

    PubMed

    Sunkara, Lakshmi T; Zeng, Xiangfang; Curtis, Amanda R; Zhang, Guolong

    2014-02-01

    Host defense peptides (HDP) have both microbicidal and immunomodulatory properties. Specific induction of endogenous HDP synthesis has emerged as a novel approach to antimicrobial therapy. Cyclic adenosine monophosphate (cAMP) and butyrate have been implicated in HDP induction in humans. However, the role of cAMP signaling and the possible interactions between cAMP and butyrate in regulating HDP expression in other species remain unknown. Here we report that activation of cAMP signaling induces HDP gene expression in chickens as exemplified by β-defensin 9 (AvBD9). We further showed that, albeit being weak inducers, cAMP agonists synergize strongly with butyrate or butyrate analogs in AvBD9 induction in macrophages and primary jejunal explants. Additionally, oral supplementation of forskolin, an adenylyl cyclase agonist in the form of a Coleus forskohlii extract, was found to induce AvBD9 expression in the crop of chickens. Furthermore, feeding with both forskolin and butyrate showed an obvious synergy in triggering AvBD9 expression in the crop and jejunum of chickens. Surprisingly, inhibition of the MEK-ERK mitogen-activated protein kinase (MAPK) pathway augmented the butyrate-FSK synergy, whereas blocking JNK or p38 MAPK pathway significantly diminished AvBD9 induction in chicken macrophages and jejunal explants in response to butyrate and FSK individually or in combination. Collectively, these results suggest the potential for concomitant use of butyrate and cAMP signaling activators in enhancing HDP expression, innate immunity, and disease resistance in both animals and humans.

  17. Sodium-butyrate as a growth promoter in milk replacer formula for young calves.

    PubMed

    Guilloteau, P; Zabielski, R; David, J C; Blum, J W; Morisset, J A; Biernat, M; Wolinski, J; Laubitz, D; Hamon, Y

    2009-03-01

    In milk-fed calves, the effects of sodium-butyrate (Na-butyrate) to replace flavomycin on growth performance and some mechanisms involved were studied. Pancreatic and intestinal morphology, digestive enzyme activities, plasma gut regulatory peptide concentrations, and expression of their receptors in the gastrointestinal tract were measured. Gastrointestinal tract defense systems were examined by measuring protein levels of 2 heat-shock proteins (HSP27 and HSP70). The calves were randomly allocated into 2 groups fed the same basic diet with flavomycin as an antimicrobial growth promoter or with Na-butyrate (3 g/kg of dry matter). Sodium-butyrate disappeared quickly in the upper gut and was not found in circulating blood. Supplementation with Na-butyrate enhanced growth rate and improved feed conversion into body weight gain compared with the flavomycin group. Supplementation with Na-butyrate was likely associated with an improvement in efficacy of the gastrointestinal tract digestive capacities expressed by enhanced production of digestive enzymes and increased absorptive capacities in the upper small intestine. The effects could have been controlled by insulin-like growth factor-1 but probably not by any of the cholecystokinin/gastrin peptide family. Concentrations of HSP27 and HSP70 were increased in stomach and colon of calves receiving Na-butyrate, thereby assuring protection of cells with intensive metabolism (chaperone function). In conclusion, beneficial effects of Na-butyrate on maturation of gastrointestinal functions were shown in milk-fed calves and may be applied to young mammals of other species.

  18. Kinetic and thermodynamic control of butyrate conversion in non-defined methanogenic communities.

    PubMed

    Junicke, H; van Loosdrecht, M C M; Kleerebezem, R

    2016-01-01

    Many anaerobic conversions proceed close to thermodynamic equilibrium and the microbial groups involved need to share their low energy budget to survive at the thermodynamic boundary of life. This study aimed to investigate the kinetic and thermodynamic control mechanisms of the electron transfer during syntrophic butyrate conversion in non-defined methanogenic communities. Despite the rather low energy content of butyrate, results demonstrate unequal energy sharing between the butyrate-utilizing species (17 %), the hydrogenotrophic methanogens (9-10 %), and the acetoclastic methanogens (73-74 %). As a key finding, the energy disproportion resulted in different growth strategies of the syntrophic partners. Compared to the butyrate-utilizing partner, the hydrogenotrophic methanogens compensated their lower biomass yield per mole of electrons transferred with a 2-fold higher biomass-specific electron transfer rate. Apart from these thermodynamic control mechanisms, experiments revealed a ten times lower hydrogen inhibition constant on butyrate conversion than proposed by the Anaerobic Digestion Model No. 1, suggesting a much stronger inhibitory effect of hydrogen on anaerobic butyrate conversion. At hydrogen partial pressures exceeding 40 Pa and at bicarbonate limited conditions, a shift from methanogenesis to reduced product formation was observed which indicates an important role of the hydrogen partial pressure in redirecting electron fluxes towards reduced products such as butanol. The findings of this study demonstrate that a careful consideration of thermodynamics and kinetics is required to advance our current understanding of flux regulation in energy-limited syntrophic ecosystems.

  19. Activation of PPAR{gamma} is not involved in butyrate-induced epithelial cell differentiation

    SciTech Connect

    Ulrich, S.; Waechtershaeuser, A.; Loitsch, S.; Knethen, A. von; Bruene, B.; Stein, J. . E-mail: j.stein@em.uni-frankfurt.de

    2005-10-15

    Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPAR{gamma} in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPAR{gamma} in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPAR{gamma} ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPAR{gamma} ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPAR{gamma} mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPAR{gamma} is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation.

  20. Antagonistic effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide on prostate cancer.

    PubMed

    Kuefer, Rainer; Genze, Felicitas; Zugmaier, Waltraud; Hautmann, Richard E; Rinnab, Ludwig; Gschwend, Juergen E; Angelmeier, Marina; Estrada, Aidee; Buechele, Berthold

    2007-03-01

    Butyrates and retinoids are promising antineoplastic agents. Here we analyzed effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide (4-HPR) on prostate cancer cells as monotherapy or in combination in vitro and in vivo. Sodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered together antagonize effects of each other. For the in vivo studies, a water-soluble complex (4-HPR with a cyclodextrin) was created. A single dose of sodium butyrate and 4-HPR showed a peak level in chicken plasma within 30 minutes. Both compounds induced inhibition of proliferation and apoptosis in xenografts of the chicken chorioallantoic membrane. Analysis of the cytotoxic effects of the drugs used in combination demonstrated an antagonistic effect on inhibition of proliferation and on induction of apoptosis. Prolonged jun N-terminal kinase phosphorylation induced by sodium butyrate and 4-HPR was strongly attenuated when both compounds were used in combination. Both compounds induced inhibition of NF-kappaB. This effect was strongly antagonized in LNCaP cells when the compounds were used in combination. These results indicate that combinational therapies have to be carefully investigated due to potential antagonistic effects in the clinical setting despite promising results of a monotherapy.

  1. Cellulose acetate butyrate/poly(caprolactonetriol) blends: Miscibility, mechanical properties, and in vivo inflammatory response.

    PubMed

    Kanis, Luiz A; Marques, Ellen L; Zepon, Karine M; Pereira, Jefferson R; Pamato, Saulo; de Oliveira, Marcelo T; Danielski, Lucinéia G; Petronilho, Fabricia C

    2014-11-01

    This study reports the results of the characterization of cellulose acetate butyrate and polycaprolactone-triol blends in terms of miscibility, swelling capacity, mechanical properties, and inflammatory response in vivo. The cellulose acetate butyrate film was opaque and rigid, with glass transition (T g ) at 134℃ and melting temperature of 156℃. The cellulose acetate butyrate/polycaprolactone-triol films were transparent up to a polycaprolactone-triol content of 60%. T g of the cellulose acetate butyrate films decreased monotonically as polycaprolactone-triol was added to the blend, thus indicating miscibility. FTIR spectroscopy revealed a decrease in intramolecular hydrogen bonding in polycaprolactone-triol, whereas no hydrogen bonding was observed between cellulose acetate butyrate and -OH from polycaprolactone-triol. The increase in polycaprolactone-triol content in the blend decreased the water uptake. An increase in polycaprolactone-triol content decreased the modulus of elasticity and increased the elongation at break. A cellulose acetate butyrate/polycaprolactone-triol 70/30 blend implanted in rats showed only an acute inflammatory response 7 days after surgery. No change in inflammation mediators was observed.

  2. Effects of sodium butyrate on methamphetamine-sensitized locomotor activity.

    PubMed

    Harkness, John H; Hitzemann, Robert J; Edmunds, Stephanie; Phillips, Tamara J

    2013-02-15

    Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, mice were treated repeatedly with MA (10 days of 2mg/kg MA) or saline (10 days), and then vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge and locomotor response was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, increased striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior.

  3. Butyrate modulates antioxidant enzyme expression in malignant and non-malignant human colon tissues.

    PubMed

    Jahns, Franziska; Wilhelm, Anne; Jablonowski, Nadja; Mothes, Henning; Greulich, Karl Otto; Glei, Michael

    2015-04-01

    The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth.

  4. Butyrate suppresses murine mast cell proliferation and cytokine production through inhibiting histone deacetylase.

    PubMed

    Zhang, Hanying; Du, Min; Yang, Qiyuan; Zhu, Mei-Jun

    2016-01-01

    Beyond their nutritional impact to colonic epithelial cells, the intestinal microbiota metabolite butyrate has pleotropic effects to host cells and is known for its beneficial effects on intestinal homeostasis and metabolism. However, it remains unclear how it modulates mast cell function. Here, we demonstrate that butyrate profoundly inhibited proliferation of mouse mastocytoma P815 cells through inducing cell cycle arrest and apoptosis, as well as decreasing c-Kit activation. In addition, butyrate increased early- and late-stage apoptotic P815 cells. In murine bone marrow-derived mast cells (BMMC), butyrate-suppressed FcεRI-dependent tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) release without affecting β-Hexosaminidase, but that was associated with decreased mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinases activation. Butyrate treatment substantially enhanced histone 3 acetylation in both P815 and BMMC and decreased FcεRI-dependent mRNA expression of tnf-α and il-6 in BMMC, mimicking the effect of Trichostatin A, a known histone deacetylase inhibitor. Chromatin immunoprecipitation revealed that butyrate enhanced acetylation of the tnf-α and il-6 promoter regions but blocked RNA polymerase II binding to the promoters of tnf-α and il-6 genes, indicating suppressed transcription initiation. These phenotypes mimicked those of Trichostatin A treatment. In conclusion, butyrate inhibits cell proliferation and increases cell apoptosis in mastocytoma P815 cells and suppresses FcεRI-dependent cytokine production in murine primary BMMC, which are likely mediated by HDAC inhibition.

  5. Propolis augments apoptosis induced by butyrate via targeting cell survival pathways.

    PubMed

    Drago, Eric; Bordonaro, Michael; Lee, Seon; Atamna, Wafa; Lazarova, Darina L

    2013-01-01

    Diet is one of the major lifestyle factors affecting incidence of colorectal cancer (CC), and despite accumulating evidence that numerous diet-derived compounds modulate CC incidence, definitive dietary recommendations are not available. We propose a strategy that could facilitate the design of dietary supplements with CC-preventive properties. Thus, nutrient combinations that are a source of apoptosis-inducers and inhibitors of compensatory cell proliferation pathways (e.g., AKT signaling) may produce high levels of programmed death in CC cells. Here we report the combined effect of butyrate, an apoptosis inducer that is produced through fermentation of fiber in the colon, and propolis, a honeybee product, on CC cells. We established that propolis increases the apoptosis of CC cells exposed to butyrate through suppression of cell survival pathways such as the AKT signaling. The programmed death of CC cells by combined exposure to butyrate and propolis is further augmented by inhibition of the JNK signaling pathway. Analyses on the contribution of the downstream targets of JNK signaling, c-JUN and JAK/STAT, to the apoptosis of butyrate/propolis-treated CC cells ascertained that JAK/STAT signaling has an anti-apoptotic role; whereas, the role of cJUN might be dependent upon regulatory cell factors. Thus, our studies ascertained that propolis augments apoptosis of butyrate-sensitive CC cells and re-sensitizes butyrate-resistant CC cells to apoptosis by suppressing AKT signaling and downregulating the JAK/STAT pathway. Future in vivo studies should evaluate the CC-preventive potential of a dietary supplement that produces high levels of colonic butyrate, propolis, and diet-derived JAK/STAT inhibitors.

  6. In vitro dissolution and in vivo absorption of calcium [1-(14)c]butyrate in free or protected forms.

    PubMed

    Smith, David J; Barri, Adriana; Herges, Grant; Hahn, Joe; Yersin, Andrew G; Jourdan, Alissa

    2012-03-28

    Butyrate is a byproduct of microbial carbohydrate fermentation that occurs primarily in the large intestine. When added to feed, butyrate quickly disappears in the upper digestive tract. Because butyrate is important for epithelial cell development, mucosal integrity, and animal growth, an encapsulation technique has been developed that allows for the slow release of butyrate into the small and large intestines. The purpose of this study was to describe the in vitro release of calcium [1-(14)C]butyrate, formulated into a slow-release (protected) bead, into water and simulated intestinal fluids and to compare the in vivo absorption and disposition of unprotected versus protected calcium [1-(14)C]butyrate in broiler chicks. Formulation of calcium [1-(14)C]butyrate into protected beads allowed release of 5.8 ± 0.2 and 3.4 ± 0.2% of the formulated radiocarbon into water and gastric fluid, respectively, after 2 h of incubation. Beads incubated in gastric fluid for 2 h and subsequently incubated in simulated intestinal fluid released a total of 17.4 ± 0.8% of the formulated radioactivity. Release of respiratory [(14)C]CO(2) after oral dosing of aqueous calcium [1-(14)C]butyrate in broiler chicks peaked at 15.2 ± 5.2% per hour 1.5 h after dosing; in contrast, maximal rates of release in chicks dosed with protected calcium [1-(14)C]butyrate occurred 4 h after dosing at 9.0 ± 3.1% per hour. The data suggested an improved efficacy of protected butyrate delivery to intestinal tissues over nonprotected butyrate. This study confirmed that encapsulation strategies designed to enhance delivery of ingredients to improve intestinal health are effective at prolonging intestinal exposure to butyrate. Encapsulation of such ingredients might benefit the food and feed industries.

  7. Toxic and metabolic effect of sodium butyrate on SAS tongue cancer cells: role of cell cycle deregulation and redox changes.

    PubMed

    Jeng, Jiiang-Huei; Kuo, Mark Yen-Ping; Lee, Po-Hsuen; Wang, Ying-Jan; Lee, Mon-Ying; Lee, Jang-Jaer; Lin, Bor-Ru; Tai, Tseng-Fang; Chang, Mei-Chi

    2006-06-15

    Butyrate is a metabolite produced by oral and colonic microorganism. Butyrate has been shown to reduce colon cancer, whereas its role in oral carcinogenesis is not clear. Butyrate concentration in dental plaque and saliva ranged from 0.2 to 16 mM. In this study, we found that sodium butyrate inhibited the growth of SAS tongue cancer cells by 32% and 53% at concentrations of 1 and 2mM, respectively. Low concentrations of sodium butyrate (1-8mM) induced G0/G1 cell cycle arrest of SAS cells, whereas concentrations of 4-16 mM elicited G2/M arrest and a slight increase in apoptotic cell populations. These events were concomitant with induction of intracellular reactive oxygen species (ROS) production. An elevation in p21 mRNA and protein level was noted in SAS cells by sodium butyrate. On the contrary, a decline of cyclin Bl, cdc2 and cdc25C mRNA and protein expression in SAS cells was found after exposure to sodium butyrate. In addition, no evident increase in cdc2 inhibitory phosphorylation was found in sodium butyrate-treated SAS cancer cells. Inclusion of N-acetyl-l-cysteine (NAC) (3mM), catalase (1000 U/ml) and dimethylthiourea (DMT, 5mM), and also SOD (500 U/ml) attenuated the sodium butyrate-induced ROS production in SAS cells. However, they were not able to prevent the cell cycle arrest, apoptosis and growth inhibition in SAS cells induced by 1, 2 and 16 mM of sodium butyrate. These results indicate that sodium butyrate is toxic and inhibits the tongue cancer cell growth via induction of cell cycle arrest and apoptosis. Sodium butyrate mediates these events by mechanisms additional to ROS production.

  8. Isolation of a Butyrate-Utilizing Bacterium in Coculture with Methanobacterium thermoautotrophicum from a Thermophilic Digester †

    PubMed Central

    Henson, J. Michael; Smith, P. H.

    1985-01-01

    Sludge from a thermophilic, 55°C digester produced methane without a lag period when enriched with butyrate. The sludge was found by most-probable-number enumeration to have ca. 5 × 106 butyrate-utilizing bacteria per ml. A thermophilic butyrate-utilizing bacterium was isolated in coculture with Methanobacterium thermoautotrophicum. This bacterium was a gram-negative, slightly curved rod, occurred singly, was nonmotile, and did not appear to produce spores. When this coculture was incubated with Methanospirillum hungatei at 37°C, the quantity of methane produced was less than 5% of the methane produced when the coculture was incubated at 55°C, the routine incubation temperature. The coculture required clarified digester fluid. The addition of yeast extract to medium containing 5% clarified digester fluid stimulated methane production when a Methanosarcina sp. was present. Hydrogen in the gas phase prevented butyrate utilization. However, when the hydrogen was removed, butyrate utilization began. Penicillin G and d-cycloserine caused the complete inhibition of butyrate utilization by the coculture. The ability of various ecosystems to convert butyrate to methane was studied. Marine sediments enriched with butyrate required a 2-week incubation period before methanogenesis began. Hypersaline sediments did not produce methane after 3 months when enriched with butyrate. Images PMID:16346813

  9. Apoptosis of U937 human leukemic cells by sodium butyrate is associated with inhibition of telomerase activity.

    PubMed

    Choi, Yung Hyun

    2006-11-01

    Sodium butyrate as a histone deacetylase inhibitor is known to exhibit anti-cancer effects via the differentiation and apoptosis of various carcinoma cells. However, the mechanism by which sodium butyrate induces apoptosis and the involvement of telomerase activity during apoptosis is not completely understood. To investigate the underlying pathways, sodium butyrate's potential to induce apoptosis in human leukemic U937 cells and its effects on telomerase activity were investigated. Exposure of U937 cells to sodium butyrate resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. The increase in apoptosis was associated with the up-regulation in pro-apoptotic Bax expression, and down-regulation of anti-apoptotic Bcl-2 and Bcl-XL. Sodium butyrate treatment also inhibited the levels of cIAP family members and induced the activation of caspase-3. Furthermore, sodium butyrate markedly inhibited the activity of telomerase and the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by sodium butyrate. Taken together, it is suggested that sodium butyrate can be a promising chemopreventive agent for leukemic cells and changes in Bcl-2 family expressions, as well as telomerase activity may, play critical roles in sodium butyrate-induced apoptosis in U937 cells.

  10. Inhibition of histone deacetylase by butyrate protects rat liver from ischemic reperfusion injury.

    PubMed

    Sun, Jie; Wu, Qiujv; Sun, Huiling; Qiao, Yingli

    2014-11-14

    We showed previously that pretreatment of butyrate, which is an endogenous histone deacetylase (HDAC) inhibitor normally fermented from undigested fiber by intestinal microflora, seriously alleviated ischemia reperfusion (I/R)-induced liver injury by inhibiting the nuclear factor κB (NF-κB) pathway. The goal of this study was to investigate the effect of butyrate administrated at the onset of ischemia for HDAC inhibition in hepatic I/R injury. Sprague Dawley rats were subjected to warm ischemia for 60 min followed by 6 and 24 h of reperfusion. Butyrate was administrated at the onset of ischemia. Liver injury was evaluated by serum levels of aminotransferase, inflammatory factors, and histopathology. The levels of acetylated histone H3 and expression of heat shock protein (Hsp) 70 were measured by Western blot. After reperfusion, the levels of acetylated histone H3 significantly decreased. Butyrate treatment markedly prevented the reduction of acetylated histone H3 and upregulated the expression of Hsp70, thereby reducing liver injury. Our study demonstrated that I/R resulted in marked reduction of histone acetylation; butyrate exerted a great hepatoprotective effect through HDAC inhibition and Hsp70 induction.

  11. The induction of vimentin gene expression by sodium butyrate in human promonocytic leukemia U937 cells

    SciTech Connect

    Rius, C.; Aller, P. ); Cabanas, C. Universidad Complutense, Madrid )

    1990-05-01

    The administration of 1 mM sodium butyrate induced the phenotypic differentiation of human promonocytic leukemia U937 cells, as judged by the expression of cD11b and cD11c antigens, two differentiation-specific surface markers. At the same time, butyrate greatly induced the expression at the mRNA level of the vimentin gene. The increase in the level of this RNA started at 6 hours of treatment and reached the maximum at Hour 24. Such an increase was caused at least in part by a stimulation in the rate of gene transcription, as suggested by transcription assays in isolated nuclei. Experiments in the presence of cycloheximide suggested that vimentin induction is probably a direct response to the action of butyrate, not mediated by the prior induction of other gene products. Unlike the case the vimentin, the levels of other RNAs, namely {beta}-actin ornithine decarboxylase, and c-myc, were not enhanced, but they decreased at different times of treatment with butyrate. Finally, the authors observed that butyrate induced also the differentiation of HL60 cells, another human myeloid cell type. Nevertheless, the drug failed to stimulate the expression of vimentin in this cell line.

  12. Butyrate production in phylogenetically diverse Firmicutes isolated from the chicken caecum

    PubMed Central

    Eeckhaut, Venessa; Van Immerseel, Filip; Croubels, Siska; De Baere, Siegrid; Haesebrouck, Freddy; Ducatelle, Richard; Louis, Petra; Vandamme, Peter

    2011-01-01

    Summary Sixteen butyrate‐producing bacteria were isolated from the caecal content of chickens and analysed phylogenetically. They did not represent a coherent phylogenetic group, but were allied to four different lineages in the Firmicutes phylum. Fourteen strains appeared to represent novel species, based on a level of ≤ 98.5% 16S rRNA gene sequence similarity towards their nearest validly named neighbours. The highest butyrate concentrations were produced by the strains belonging to clostridial clusters IV and XIVa, clusters which are predominant in the chicken caecal microbiota. In only one of the 16 strains tested, the butyrate kinase operon could be amplified, while the butyryl‐CoA : acetate CoA‐transferase gene was detected in eight strains belonging to clostridial clusters IV, XIVa and XIVb. None of the clostridial cluster XVI isolates carried this gene based on degenerate PCR analyses. However, another CoA‐transferase gene more similar to propionate CoA‐transferase was detected in the majority of the clostridial cluster XVI isolates. Since this gene is located directly downstream of the remaining butyrate pathway genes in several human cluster XVI bacteria, it may be involved in butyrate formation in these bacteria. The present study indicates that butyrate producers related to cluster XVI may play a more important role in the chicken gut than in the human gut. PMID:21375722

  13. Epigenetic effects of dietary butyrate on hepatic histone acetylation and enzymes of biotransformation in chicken.

    PubMed

    Mátis, Gábor; Neogrády, Zsuzsanna; Csikó, György; Gálfi, Péter; Fébel, Hedvig; Jemnitz, Katalin; Veres, Zsuzsanna; Kulcsár, Anna; Kenéz, Akos; Huber, Korinna

    2013-12-01

    The aim of the study was to investigate the in vivo epigenetic influences of dietary butyrate supplementation on the acetylation state of core histones and the activity of drug-metabolising microsomal cytochrome P450 (CYP) enzymes in the liver of broiler chickens in the starter period. One-day-old Ross 308 broilers were fed a starter diet without or with sodium butyrate (1.5 g/kg feed) for 21 days. After slaughtering, nucleus and microsome fractions were isolated from the exsanguinated liver by multi-step differential centrifugation. Histone acetylation level was detected from hepatocyte nuclei by Western blotting, while microsomal CYP activity was examined by specific enzyme assays. Hyperacetylation of hepatic histone H2A at lysine 5 was observed after butyrate supplementation, providing modifications in the epigenetic regulation of cell function. No significant changes could be found in the acetylation state of the other core histones at the acetylation sites examined. Furthermore, butyrate did not cause any changes in the drugmetabolising activity of hepatic microsomal CYP2H and CYP3A37 enzymes, which are mainly involved in the biotransformation of most xenobiotics in chicken. These data indicate that supplementation of the diet with butyrate probably does not have any pharmacokinetic interactions with simultaneously applied xenobiotics.

  14. Upregulation of activin A gene by butyrate in human colon cancer cell lines.

    PubMed

    Sonoyama, Kei; Pholnukulkit, Pimara; Toyoda, Masahiko; Rutatip, Suriya; Kasai, Takanori

    2003-06-01

    Activin A has been reported to play a role in the progression of colorectal cancer. Because dietary fiber protects against colorectal cancer, we hypothesized that butyrate, a fermentation product of dietary fiber, may affect the expression of activin A in colon cancer cells. Semiquantitative RT-PCR demonstrated that the activin A gene was upregulated by sodium butyrate in the human colon cancer cell lines HT-29 and Caco-2 in a concentration- and time-dependent manner. However, the activin A gene did not respond to sodium butyrate in the human normal colonic cell line FHC, rat normal intestinal epithelial cell (IEC) line IEC-6, and the explant of rat colon. Flow cytometry and agarose gel electrophoresis of genomic DNA revealed that cell cycle arrest and apoptosis were induced by sodium butyrate but not exogenous activin A in HT-29 cells, indicating that activin A could not act as an autocrine factor in colon cancer cells. By assuming that activin A promotes colorectal cancer spread as a paracrine factor, our findings suggest that butyrate could act as a tumor promoter in some circumstances.

  15. catena-Poly[(diaqua­cadmium)-μ-4,4′-[sulfonyl­bis­(1,4-phenyl­ene­oxy)]­di­acet­ato-κ4 O,O′:O′′,O′′′

    PubMed Central

    Ma, Zhan-Ling

    2012-01-01

    In the title coordination polymer, [Cd(C16H12O8S)(H2O)2]n, the CdII ion is situated on a crystallographic twofold rotation axis, being coordinated by four O atoms from two bidentate 4,4′-[sulfonyl­bis­(1,4-phenyl­ene­oxy)]diacetate (L) ligands and two water mol­ecules in a highly distorted CdO6 octa­hedral geometry. Each complete ligand L, which is also generated by twofold symmetry with the S atom lying on the rotation axis, bridges two CdII atoms to form a polymeric zigzag chain propagating in the [10-1] direction. O—H⋯O hydrogen bonds between the coordinated water mol­ecules and carboxyl­ate O atoms are involved in the packing. PMID:22412419

  16. Nonprotein Amino Acids from Spark Discharges and Their Comparison with the Murchison Meteorite Amino Acids

    PubMed Central

    Wolman, Yecheskel; Haverland, William J.; Miller, Stanley L.

    1972-01-01

    All the nonprotein amino acids found in the Murchison meteorite are products of the action of electric discharge on a mixture of methane, nitrogen, and water with traces of ammonia. These amino acids include α-amino-n-butyric acid, α-aminoisobutyric acid, norvaline, isovaline, pipecolic acid, β-alanine, β-amino-n-butyric acid, β-aminoisobutyric acid, γ-aminobutyric acid, sarcosine, N-ethylglycine, and N-methylalanine. In addition, norleucine, alloisoleucine, N-propylglycine, N-isopropylglycine, N-methyl-β-alanine, N-ethyl-β-alanine α,β-diaminopropionic acid, isoserine, α,γ-diaminobutyric acid, and α-hydroxy-γ-aminobutyric acid are produced by the electric discharge, but have not been found in the meteorite. PMID:16591973

  17. Effects of Sodium Butyrate Treatment on Histone Modifications and the Expression of Genes Related to Epigenetic Regulatory Mechanisms and Immune Response in European Sea Bass (Dicentrarchus Labrax) Fed a Plant-Based Diet.

    PubMed

    Terova, Genciana; Díaz, Noelia; Rimoldi, Simona; Ceccotti, Chiara; Gliozheni, Emi; Piferrer, Francesc

    2016-01-01

    Bacteria that inhabit the epithelium of the animals' digestive tract provide the essential biochemical pathways for fermenting otherwise indigestible dietary fibers, leading to the production of short-chain fatty acids (SCFAs). Of the major SCFAs, butyrate has received particular attention due to its numerous positive effects on the health of the intestinal tract and peripheral tissues. The mechanisms of action of this four-carbon chain organic acid are different; many of these are related to its potent regulatory effect on gene expression since butyrate is a histone deacetylase inhibitor that play a predominant role in the epigenetic regulation of gene expression and cell function. In the present work, we investigated in the European sea bass (Dicentrarchus labrax) the effects of butyrate used as a feed additive on fish epigenetics as well as its regulatory role in mucosal protection and immune homeostasis through impact on gene expression. Seven target genes related to inflammatory response and reinforcement of the epithelial defense barrier [tnfα (tumor necrosis factor alpha) il1β, (interleukin 1beta), il-6, il-8, il-10, and muc2 (mucin 2)] and five target genes related to epigenetic modifications [dicer1(double-stranded RNA-specific endoribonuclease), ehmt2 (euchromatic histone-lysine-N-methyltransferase 2), pcgf2 (polycomb group ring finger 2), hdac11 (histone deacetylase-11), and jarid2a (jumonji)] were analyzed in fish intestine and liver. We also investigated the effect of dietary butyrate supplementation on histone acetylation, by performing an immunoblotting analysis on liver core histone extracts. Results of the eight-week-long feeding trial showed no significant differences in weight gain or SGR (specific growth rate) of sea bass that received 0.2% sodium butyrate supplementation in the diet in comparison to control fish that received a diet without Na-butyrate. Dietary butyrate led to a twofold increase in the acetylation level of histone H4 at

  18. Effects of Sodium Butyrate Treatment on Histone Modifications and the Expression of Genes Related to Epigenetic Regulatory Mechanisms and Immune Response in European Sea Bass (Dicentrarchus Labrax) Fed a Plant-Based Diet.

    PubMed

    Terova, Genciana; Díaz, Noelia; Rimoldi, Simona; Ceccotti, Chiara; Gliozheni, Emi; Piferrer, Francesc

    2016-01-01

    Bacteria that inhabit the epithelium of the animals' digestive tract provide the essential biochemical pathways for fermenting otherwise indigestible dietary fibers, leading to the production of short-chain fatty acids (SCFAs). Of the major SCFAs, butyrate has received particular attention due to its numerous positive effects on the health of the intestinal tract and peripheral tissues. The mechanisms of action of this four-carbon chain organic acid are different; many of these are related to its potent regulatory effect on gene expression since butyrate is a histone deacetylase inhibitor that play a predominant role in the epigenetic regulation of gene expression and cell function. In the present work, we investigated in the European sea bass (Dicentrarchus labrax) the effects of butyrate used as a feed additive on fish epigenetics as well as its regulatory role in mucosal protection and immune homeostasis through impact on gene expression. Seven target genes related to inflammatory response and reinforcement of the epithelial defense barrier [tnfα (tumor necrosis factor alpha) il1β, (interleukin 1beta), il-6, il-8, il-10, and muc2 (mucin 2)] and five target genes related to epigenetic modifications [dicer1(double-stranded RNA-specific endoribonuclease), ehmt2 (euchromatic histone-lysine-N-methyltransferase 2), pcgf2 (polycomb group ring finger 2), hdac11 (histone deacetylase-11), and jarid2a (jumonji)] were analyzed in fish intestine and liver. We also investigated the effect of dietary butyrate supplementation on histone acetylation, by performing an immunoblotting analysis on liver core histone extracts. Results of the eight-week-long feeding trial showed no significant differences in weight gain or SGR (specific growth rate) of sea bass that received 0.2% sodium butyrate supplementation in the diet in comparison to control fish that received a diet without Na-butyrate. Dietary butyrate led to a twofold increase in the acetylation level of histone H4 at

  19. Effects of Sodium Butyrate Treatment on Histone Modifications and the Expression of Genes Related to Epigenetic Regulatory Mechanisms and Immune Response in European Sea Bass (Dicentrarchus Labrax) Fed a Plant-Based Diet

    PubMed Central

    Díaz, Noelia; Rimoldi, Simona; Ceccotti, Chiara; Gliozheni, Emi; Piferrer, Francesc

    2016-01-01

    Bacteria that inhabit the epithelium of the animals’ digestive tract provide the essential biochemical pathways for fermenting otherwise indigestible dietary fibers, leading to the production of short-chain fatty acids (SCFAs). Of the major SCFAs, butyrate has received particular attention due to its numerous positive effects on the health of the intestinal tract and peripheral tissues. The mechanisms of action of this four-carbon chain organic acid are different; many of these are related to its potent regulatory effect on gene expression since butyrate is a histone deacetylase inhibitor that play a predominant role in the epigenetic regulation of gene expression and cell function. In the present work, we investigated in the European sea bass (Dicentrarchus labrax) the effects of butyrate used as a feed additive on fish epigenetics as well as its regulatory role in mucosal protection and immune homeostasis through impact on gene expression. Seven target genes related to inflammatory response and reinforcement of the epithelial defense barrier [tnfα (tumor necrosis factor alpha) il1β, (interleukin 1beta), il-6, il-8, il-10, and muc2 (mucin 2)] and five target genes related to epigenetic modifications [dicer1(double-stranded RNA-specific endoribonuclease), ehmt2 (euchromatic histone-lysine-N-methyltransferase 2), pcgf2 (polycomb group ring finger 2), hdac11 (histone deacetylase-11), and jarid2a (jumonji)] were analyzed in fish intestine and liver. We also investigated the effect of dietary butyrate supplementation on histone acetylation, by performing an immunoblotting analysis on liver core histone extracts. Results of the eight-week-long feeding trial showed no significant differences in weight gain or SGR (specific growth rate) of sea bass that received 0.2% sodium butyrate supplementation in the diet in comparison to control fish that received a diet without Na-butyrate. Dietary butyrate led to a twofold increase in the acetylation level of histone H4 at

  20. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data.

    PubMed

    Vital, Marius; Howe, Adina Chuang; Tiedje, James M

    2014-04-22

    Butyrate-producing bacteria have recently gained attention, since they are important for a healthy colon and when altered contribute to emerging diseases, such as ulcerative colitis and type II diabetes. This guild is polyphyletic and cannot be accurately detected by 16S rRNA gene sequencing. Consequently, approaches targeting the terminal genes of the main butyrate-producing pathway have been developed. However, since additional pathways exist and alternative, newly recognized enzymes catalyzing the terminal reaction have been described, previous investigations are often incomplete. We undertook a broad analysis of butyrate-producing pathways and individual genes by screening 3,184 sequenced bacterial genomes from the Integrated Microbial Genome database. Genomes of 225 bacteria with a potential to produce butyrate were identified, including many previously unknown candidates. The majority of candidates belong to distinct families within the Firmicutes, but members of nine other phyla, especially from Actinobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Thermotogae, were also identified as potential butyrate producers. The established gene catalogue (3,055 entries) was used to screen for butyrate synthesis pathways in 15 metagenomes derived from stool samples of healthy individuals provided by the HMP (Human Microbiome Project) consortium. A high percentage of total genomes exhibited a butyrate-producing pathway (mean, 19.1%; range, 3.2% to 39.4%), where the acetyl-coenzyme A (CoA) pathway was the most prevalent (mean, 79.7% of all pathways), followed by the lysine pathway (mean, 11.2%). Diversity analysis for the acetyl-CoA pathway showed that the same few firmicute groups associated with several Lachnospiraceae and Ruminococcaceae were dominating in most individuals, whereas the other pathways were associated primarily with Bacteroidetes. IMPORTANCE Microbiome research has revealed new, important roles of our gut microbiota for

  1. Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon.

    PubMed

    Suply, Etienne; de Vries, Philine; Soret, Rodolphe; Cossais, François; Neunlist, Michel

    2012-06-15

    Postnatal changes in the enteric nervous system (ENS) are involved in the establishment of colonic motility. In adult rats, butyrate induced neuroplastic changes in the ENS, leading to enhanced colonic motility. Whether butyrate can induce similar changes during the postnatal period remains unknown. Enemas (Na-butyrate) were performed daily in rat pups between postnatal day (PND) 7 and PND 17. Effects of butyrate were evaluated on morphological and histological parameters in the distal colon at PND 21. The neurochemical phenotype of colonic submucosal and myenteric neurons was analyzed using antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS). Colonic motility and neuromuscular transmission was assessed in vivo and ex vivo. Butyrate (2.5 mM) enemas had no impact on pup growth and histological parameters compared with control. Butyrate did not modify the number of Hu-immunoreactive (IR) neurons per ganglia. A significant increase in the proportion (per Hu-IR neurons) of nNOS-IR myenteric and submucosal neurons and ChAT-IR myenteric neurons was observed in the distal colon after butyrate enemas compared with control. In addition, butyrate induced a significant increase in both nitrergic and cholinergic components of the neuromuscular transmission compared with control. Finally, butyrate increased distal colonic transit time compared with control. We concluded that butyrate enemas induced neuroplastic changes in myenteric and submucosal neurons, leading to changes in gastrointestinal functions. Our results support exploration of butyrate as potential therapy for motility disorders in preterm infants with delayed maturation of the ENS.

  2. Evaluation of recycling the effluent of hydrogen fermentation for biobutanol production: kinetic study with butyrate and sucrose concentrations.

    PubMed

    Chen, Wen-Hsing; Jian, Zih-Ce

    2013-10-01

    Butyrate in the effluent of hydrogen-producing bioreactor is a potential feed for biobutanol production. For recycling butyrate, this study investigated the kinetics of biobutanol production by Clostridium beijerinckii NRRL B592 from different paired concentrations of butyrate and sucrose in a series of batch reactors. Results show that the lag time of butanol production increased with higher concentration of either sucrose or butyrate. In regression analyses, the maximum specific butanol production potential of 6.49 g g(-1) of dry cell was projected for 31.9 g L(-1) sucrose and 1.3 g L(-1) butyrate, and the maximum specific butanol production rate of 0.87 g d(-1) g(-1) of dry cell was predicted for 25.0 g L(-1) sucrose and 2.6 g L(-1) butyrate. The specific butanol production potential will decrease if more butyrate is added to the reactor. However, both sucrose and butyrate concentrations are weighted equally on the specific butanol production rate. This observation also is true on butanol yield. The maximum butanol yield of 0.49 mol mol(-1) was projected for 25.0 g L(-1) sucrose and 2.3 g L(-1) butyrate. In addition, a confirmation study found butanol yield increased from 0.2 to 0.3 mol mol(-1) when butyrate addition increased from 0 to 1 g L(-1) under low sugar concentration (3.8 g L(-1) sucrose). The existence of butyrate increases the activity of biobutanol production and reduces the fermentable sugar concentration needed for acetone-butanol-ethanol fermentation.

  3. High-Fat Diet Reduces the Formation of Butyrate, but Increases Succinate, Inflammation, Liver Fat and Cholesterol in Rats, while Dietary Fibre Counteracts These Effects

    PubMed Central

    Jakobsdottir, Greta; Xu, Jie; Molin, Göran; Ahrné, Siv; Nyman, Margareta

    2013-01-01

    Introduction Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. Objective To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. Material and Methods Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. Results and Discussion Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet. PMID:24236183

  4. Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

    PubMed Central

    Van den Abbeele, Pieter; Belzer, Clara; Goossens, Margot; Kleerebezem, Michiel; De Vos, Willem M; Thas, Olivier; De Weirdt, Rosemarie; Kerckhof, Frederiek-Maarten; Van de Wiele, Tom

    2013-01-01

    The human gut is colonized by a complex microbiota with multiple benefits. Although the surface-attached, mucosal microbiota has a unique composition and potential to influence human health, it remains difficult to study in vivo. Therefore, we performed an in-depth microbial characterization (human intestinal tract chip (HITChip)) of a recently developed dynamic in vitro gut model, which simulates both luminal and mucosal gut microbes (mucosal-simulator of human intestinal microbial ecosystem (M-SHIME)). Inter-individual differences among human subjects were confirmed and microbial patterns unique for each individual were preserved in vitro. Furthermore, in correspondence with in vivo studies, Bacteroidetes and Proteobacteria were enriched in the luminal content while Firmicutes rather colonized the mucin layer, with Clostridium cluster XIVa accounting for almost 60% of the mucin-adhered microbiota. Of the many acetate and/or lactate-converting butyrate producers within this cluster, Roseburia intestinalis and Eubacterium rectale most specifically colonized mucins. These 16S rRNA gene-based results were confirmed at a functional level as butyryl-CoA:acetate-CoA transferase gene sequences belonged to different species in the luminal as opposed to the mucin-adhered microbiota, with Roseburia species governing the mucosal butyrate production. Correspondingly, the simulated mucosal environment induced a shift from acetate towards butyrate. As not only inter-individual differences were preserved but also because compared with conventional models, washout of relevant mucin-adhered microbes was avoided, simulating the mucosal gut microbiota represents a breakthrough in modeling and mechanistically studying the human intestinal microbiome in health and disease. Finally, as mucosal butyrate producers produce butyrate close to the epithelium, they may enhance butyrate bioavailability, which could be useful in treating diseases, such as inflammatory bowel disease. PMID

  5. Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells.

    PubMed

    Schwartz, B; Avivi-Green, C; Polak-Charcon, S

    1998-11-01

    Sodium butyrate causes alteration of colon cancer cell morphology and biology towards that of a more differentiated phenotype. The retinoblastoma gene encodes a nuclear phosphoprotein (pRb) present in a wide range of human cancer cell lines including colon cancer cell lines. pRB is synthesized throughout the cell cycle and phosphorylated in a phase specific manner: the predominant proteins in G0/G1 are the unphosphorylated species (110 kD) whereas phosphorylated pRb (112-114 kD) are in S and G2. 110 kD pRb binds transcription factors and prevents transcription of responsive genes such as the gene for thymidine kinase, which are expressed in late G1. The precise mechanisms controlling cell arrest are unknown, but recent data suggest that cyclin-dependent kinase inhibitors such as p16 may play a role. The aim of the present study was to assess the effect of sodium butyrate on cell cycle staging, thymidine kinase activity, phosphorylation of the pRb protein and expression of p16. We show that sodium butyrate treatment induces differentiation of LS174T colon cancer cells, inhibits thymidine kinase activity concomitantly with induction of pRb dephosphorylation, p16 transcription and cell cycle arrest at G0/G1. Initial dephosphorylation was observed 24 h after treatment of LS174T cells with sodium butyrate, whereas complete shift to the dephosphorylated form was observed 3 days after treatment. Induction of pRb dephosphorylation by sodium butyrate preceded inhibition of growth and the specific cell cycle arrest. RNase protection assay with a p16 specific riboprobe showed undetectable levels in proliferating cells to several fold increase in differentiated colonocytes. In conclusion, the results provide evidence for a specific cellular mechanism of butyrate induced growth arrest and differentiation of a colon cancer cell line.

  6. Short-chain fatty acid modulation of apoptosis in the Kato III human gastric carcinoma cell line.

    PubMed

    Matthews, Geoffrey M; Howarth, Gordon S; Butler, Ross N

    2007-07-01

    The short-chain fatty acid (SCFA) butyrate is known to induce apoptosis in colon cancer cells in vitro and in vivo, however, its mode of action is poorly defined, whilst less is known regarding the effects of the SCFA propionate. This study investigated the potential for butyrate and propionate to alter cell viability, cell cycle regulation and intracellular protective mechanisms in a human gastric cancer cell line (Kato III). Kato III cells were incubated with butyrate or propionate for 24, 48 and 72 hr. At each time point, cells were assessed for the induction of apoptosis and cell cycle alterations using flow cytometry. Oxidative pentose pathway (OPP) activity and glutathione (GSH) availability were also measured as an index of intracellular protection. Butyrate and propionate differentially induced apoptosis and necrosis in Kato III cells and arrested cells in the G2-M phase. OPP activity was significantly increased by both SCFAs although butyrate induced a 10-fold greater increase than propionate. GSH availability was significantly decreased in Kato III cells by butyrate and propionate. These findings demonstrate that butyrate and propionate induce apoptosis and cell cycle alterations in Kato III gastric cancer cells. Moreover, the effects of butyrate were significantly greater than propionate. We propose that alterations to intracellular redox state and GSH availability play an important role in SCFA-mediated cell death in this cell type. The inclusion of butyrate and propionate as adjunctive cancer therapies has the potential to enhance the efficacy of current chemotherapeutics in the treatment of gastric cancer. PMID:17611404

  7. Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells

    PubMed Central

    Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

    2016-01-01

    The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

  8. Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells.

    PubMed

    Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

    2016-01-01

    The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

  9. Sodium butyrate inhibits Staphylococcus aureus internalization in bovine mammary epithelial cells and induces the expression of antimicrobial peptide genes.

    PubMed

    Ochoa-Zarzosa, Alejandra; Villarreal-Fernández, Edith; Cano-Camacho, Horacio; López-Meza, Joel E

    2009-07-01

    A distinctive feature of bovine milk fat is the presence of butyrate, molecule with recognized antimicrobial and antiinflammatory properties. Bovine mastitis is a pathology characterized by inflammatory and infectious processes; however, the role of sodium butyrate on Staphylococcus aureus infection in mammary epithelium has not been studied. In this work we assess the role of sodium butyrate on the invasion of bovine mammary epithelial cells (bMEC) by S. aureus responsible of mastitis and on the expression of antimicrobial peptide genes. Our data show that sodium butyrate (0.25-0.5mM) reduces approximately 50% the internalization of S. aureus (ATCC 27543) into bMEC. By RT-PCR analysis, we showed that sodium butyrate is able to up-regulate the expression of tracheal antimicrobial peptide (TAP), beta-defensin and inducible nitric oxide synthase (iNOS) mRNAs, as well as nitric oxide production. Also, sodium butyrate and infection increased acetylation of histone H3 in bMEC. These results indicate that sodium butyrate</