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Sample records for 4-phenyl butyric acid

  1. Butyric acid in irritable bowel syndrome.

    PubMed

    Załęski, Andrzej; Banaszkiewicz, Aleksandra; Walkowiak, Jarosław

    2013-01-01

    Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS. PMID:24868283

  2. Butyric acid in irritable bowel syndrome

    PubMed Central

    Załęski, Andrzej; Walkowiak, Jarosław

    2013-01-01

    Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS. PMID:24868283

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Impact of butyric acid on butanol formation by Clostridium pasteurianum.

    PubMed

    Regestein, Lars; Doerr, Eric Will; Staaden, Antje; Rehmann, Lars

    2015-11-01

    The butanol yield of the classic fermentative acetone-butanol-ethanol (ABE) process has been enhanced in the past decades through the development of better strains and advanced process design. Nevertheless, by-product formation and the incomplete conversion of intermediates still decrease the butanol yield. This study demonstrates the potential of increasing the butanol yield from glycerol though the addition of small amounts of butyric acid. The impact of butyric acid was investigated in a 7L stirred tank reactor. The results of this study show the positive impact of butyric acid on butanol yield under pH controlled conditions and the metabolic stages were monitored via online measurement of carbon dioxide formation, pH value and redox potential. Butyric acid could significantly increase the butanol yield at low pH values if sufficient quantities of primary carbon source (glycerol) were present. PMID:26233327

  8. Amidation inhibitors 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester are novel HDAC inhibitors with anti-tumorigenic properties.

    PubMed

    Ali, Amna; Burns, Timothy J; Lucrezi, Jacob D; May, Sheldon W; Green, George R; Matesic, Diane F

    2015-08-01

    4-Phenyl-3-butenoic acid (PBA) is an inhibitor of peptidylglycine alpha-amidating monooxygenase with anti-inflammatory properties that has been shown to inhibit the growth of ras-mutated epithelial and human lung carcinoma cells. In this report, we show that PBA also increases the acetylation levels of selected histone subtypes in a dose and time dependent manner, an effect that is attributable to the inhibition of histone deacetylase (HDAC) enzymes. Comparison studies with the known HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) using high resolution two-dimensional polyacrylamide gels and Western analysis provide evidence that PBA acts as an HDAC inhibitor within cells. PBA and a more potent amidation inhibitor, 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me), inhibit HDAC enzymes in vitro at micromolar concentrations, with IC50 values approximately 30 fold lower for AOPHA-Me than PBA for selected HDAC isoforms. Overall, these results indicate that PBA and AOPHA-Me are novel anti-tumorigenic HDAC inhibitors. PMID:26065689

  9. EFFECT OF LEAD ON GAMMA AMINO BUTYRIC ACID SYNTHESIS

    EPA Science Inventory

    The project studies the inhibitory effect of lead on the enzymatic activity of brain glutamic amino acid decarboxylase (GADC). The enzyme is responsible for the catalytic formation of gamma amino butyric acid (GABA) inhibitory neurons which is believed to be involved with the tra...

  10. 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

  11. 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

  12. Redetermined structure of 4,4′-bi­pyridine–1,4-phenyl­enedi­acetic acid (1/1) co-crystal

    PubMed Central

    Paul, Rima; Bora, Sanchay Jyoti

    2015-01-01

    The asymmetric unit of the title 1:1 co-crystal, C10H8N2·C10H10O4, consists of one half-mol­ecule each of 4,4′-bi­pyridine and 1,4-phenyl­enedi­acetic acid: the complete mol­ecules 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 carb­oxy­lic acid mol­ecules. The chains are cross-linked by C—H⋯O inter­actions. This structure was previously incorrectly described as a (C10H10N2)2+·(C10H8O4)2− mol­ecular salt [Jia et al. (2009 ▸). Acta Cryst. E65, o2490–o2490]. PMID:26594486

  13. 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

  14. Butyric acid stimulates bovine neutrophil functions and potentiates the effect of platelet activating factor.

    PubMed

    Carretta, M D; Hidalgo, A I; Burgos, J; Opazo, L; Castro, L; Hidalgo, M A; Figueroa, C D; Taubert, A; Hermosilla, C; Burgos, R A

    2016-08-01

    Increased short-chain fatty acid (SCFA) production is associated with subacute ruminal acidosis (SARA) and activation of inflammatory processes. In humans and rodents, SCFAs modulate inflammatory responses in the gut via free fatty acid receptor 2 (FFA2). In bovines, butyric acid is one of the most potent FFA2 agonists. Its expression in bovine neutrophils has recently been demonstrated, suggesting a role in innate immune response in cattle. This study aimed to evaluate if butyric acid modulates oxidative and non-oxidative functions or if it can potentiate other inflammatory mediators in bovine neutrophils. Our results showed that butyric acid can activate bovine neutrophils, inducing calcium (Ca(2+)) influx and mitogen-activated protein kinase (MAPK) phosphorylation, two second messengers involved in FFA2 activation. Ca(2+) influx induced by butyric acid was dependent on the extracellular and intracellular Ca(2+) source and phospholipase C (PLC) activation. Butyric acid alone had no significant effect on reactive oxygen species (ROS) production and chemotaxis; however, a priming effect on platelet-activating factor (PAF), a potent inflammatory mediator, was observed. Butyric acid increased CD63 expression and induced the release of neutrophil granule markers matrix metalloproteinase-9 (MMP-9) and lactoferrin. Finally, we observed that butyric acid induced neutrophil extracellular trap (NET) formation without affecting cellular viability. These findings suggest that butyric acid, a component of the ruminal fermentative process, can modulate the innate immune response of ruminants. PMID:27288853

  15. 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

  16. 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...

  17. 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...

  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. 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

  20. 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...

  1. 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

  2. Short-chain fatty acids and colon cancer cells: the vitamin D receptor--butyrate connection.

    PubMed

    Gaschott, Tanja; Stein, Jürgen

    2003-01-01

    Butyrate and its prodrug tributyrin, as well as 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), have important physiological effects on proliferation and differentiation in a variety of malignant cells. The aim of this study was to elucidate the role of the vitamin D receptor (VDR) in butyrate-induced cell differentiation and cell cycle arrest in Caco-2 cells, a human colon cancer cell line. Cell differentiation was evaluated by analyzing the activity of alkaline phosphatase (AP). Protein of VDR, cyclins, cyclin-dependent kinases (cdks) and of cdk inhibitors was quantified by Western blot analysis, VDR-mRNA by PCR. Pre- and postconfluent cells were assessed for VDR binding activity. Cell cycle was analyzed by flow cytometry. Tributyrin significantly increased VDR-mRNA level (250% vs. control) and VDR binding activity. Butyrate also enhanced VDR protein content in the nucleus in a time- and dose-dependent manner and more potently than other short-chain fatty acids of a related structure. Both butyrate (640% vs. control) and 1,25-(OH)2D3 (350% vs. control) significantly stimulated differentiation, whereas combined treatment with butyrate and 1,25-(OH)2D3 resulted in a synergistic amplification of AP activity (1400% vs. control). In the presence of the VDR antagonist ZK 191732, butyrate-induced differentiation was completely abolished (150% vs. control). While butyrate alone increased p21Waf1/Cip1 expression and down-regulated cdk 6 and cyclin A, and combined exposure with 1,25-(OH)2D3 resulted in a synergistic enhancement of butyrate-induced changes, expressions did not change from control level after treatment with butyrate and ZK 191732. G1 cell cycle arrest induced by butyrate was also abolished after combined treatment with butyrate and ZK 191732. In conclusion, differentiation and cell cycle arrest of Caco-2 cells induced by butyrate are mediated by up-regulation of VDR, followed by a stimulation of the negative cell cycle regulator p21Waf1/Cip1 and by a down

  3. Efficient production of butyric acid from Jerusalem artichoke by immobilized Clostridium tyrobutyricum in a fibrous-bed bioreactor.

    PubMed

    Huang, Jin; Cai, Jin; Wang, Jin; Zhu, Xiangcheng; Huang, Lei; Yang, Shang-Tian; Xu, Zhinan

    2011-02-01

    Butyric acid is an important specialty chemical with wide industrial applications. The feasible large-scale fermentation for the economical production of butyric acid requires low-cost substrate and efficient process. In the present study, butyric acid production by immobilized Clostridium tyrobutyricum was successfully performed in a fibrous-bed bioreactor using Jerusalem artichoke as the substrate. Repeated-batch fermentation was carried out to produce butyric acid with a high butyrate yield (0.44 g/g), high productivity (2.75 g/L/h) and a butyrate concentration of 27.5 g/L. Furthermore, fed-batch fermentation using sulfuric acid pretreated Jerusalem artichoke hydrolysate resulted in a high butyric acid concentration of 60.4 g/L, with the yield of 0.38 g/g and the selectivity of ∼ 85.1 (85.1g butyric acid/g acetic acid). Thus, the production of butyric acid from Jerusalem artichoke on a commercial scale could be achieved based on the system developed in this work. PMID:21169015

  4. 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...

  5. 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...

  6. 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. PMID:26779817

  7. 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

  8. 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). PMID:19297150

  9. Oncogenic ras alters sensitivity of mouse colonocytes to butyrate and fatty acid mediated growth arrest and apoptosis.

    PubMed

    Turner, Nancy D; Zhang, Jianhu; Davidson, Laurie A; Lupton, Joanne R; Chapkin, Robert S

    2002-12-01

    Docosahexaenoic acid (DHA) and butyrate favorably modulate colonocyte proliferation and apoptosis. In order to elucidate how oncogenic Ras modulates responses to these chemopreventive nutrients, we incubated isogenic non-transformed and Ras malignant transformed mouse colon cells with butyrate and DHA or linoleic acid (LA). Combining DHA with 1mM butyrate decreased proliferation relative to LA or no PUFA treatment in both cell lines. At a higher butyrate dose (5mM), caspase 3 activity was elevated to a greater extent in Ras transformed cells. Only non-transformed cells were sensitive to the apoptogenic effects of DHA, indicating that Ras transformation alters sensitivity to dietary chemopreventive agents. PMID:12183072

  10. Investigations on the synthesis and pharmacological properties of amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4- dioxo-1,2,3,4-tetrahydropyrido[2,3-d]-pyrimidine-5-carboxylic acid.

    PubMed

    Sladowska, H; Sieklucka-Dziuba, M; Rajtar, G; Sadowski, M; Kleinrok, Z

    1999-01-01

    Synthesis of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (6-10) and their 1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl] derivatives (11-15) are described. Some of them displayed strong analgesic activity. PMID:10668178

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

    2014-01-01

    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

  16. 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

  17. 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

  18. Co-culturing a novel Bacillus strain with Clostridium tyrobutyricum ATCC 25755 to produce butyric acid from sucrose

    PubMed Central

    2013-01-01

    Background Currently, the most promising microorganism used for the bio-production of butyric acid is Clostridium tyrobutyricum ATCC 25755T; however, it is unable to use sucrose as a sole carbon source. Consequently, a newly isolated strain, Bacillus sp. SGP1, that was found to produce a levansucrase enzyme, which hydrolyzes sucrose into fructose and glucose, was used in a co-culture with this strain, permitting C. tyrobutyricum ATCC 25755T to ferment sucrose to butyric acid. Results B. sp. SGP1 alone did not show any butyric acid production and the main metabolite produced was lactic acid. This allowed C. tyrobutyricum ATCC 25755T to utilize the monosaccharides resulting from the activity of levansucrase together with the lactic acid produced by B. sp. SGP1 to generate butyric acid, which was the main fermentative product within the co-culture. Furthermore, the final acetic acid concentration in the co-culture was significantly lower when compared with pure C. tyrobutyricum ATCC 25755T cultures grown on glucose. In fed-batch fermentations, the optimum conditions for the production of butyric acid were around pH 5.50 and a temperature of 37°C. Under these conditions, the final butyrate concentration was 34.2±1.8 g/L with yields of 0.35±0.03 g butyrate/g sucrose and maximum productivity of 0.3±0.04 g/L/h. Conclusions Using this co-culture, sucrose can be utilized as a carbon source for butyric acid production at a relatively high yield. In addition, this co-culture offers also the benefit of a greater selectivity, with butyric acid constituting 92.8% of the acids when the fermentation was terminated. PMID:23452443

  19. 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.

  20. 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

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

    PubMed

    Goddard, Andrew W

    2016-03-22

    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

  2. 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. PMID:20879917

  3. 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

  4. 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

  5. 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

  6. 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...

  7. Butyric acid production from sugarcane bagasse hydrolysate by Clostridium tyrobutyricum immobilized in a fibrous-bed bioreactor.

    PubMed

    Wei, Dong; Liu, Xiaoguang; Yang, Shang-Tian

    2013-02-01

    A fermentation process using Clostridium tyrobutyricum immobilized in a fibrous-bed bioreactor (FBB) was developed for butyric acid production from sugarcane bagasse (SCB) hydrolysate. SCB was first treated with dilute acid and then hydrolyzed with cellulases. The hydrolysate containing glucose and xylose was used as carbon source for the fermentation without detoxification. The bacterium was able to grow at a specific growth rate of ∼0.06 h(-1) in media containing 15-20% (w/v) SCB in serum bottles. In batch cultures in the FBB, both glucose and xylose in the SCB hydrolysate were simultaneously converted to butyrate with a high yield (0.45-0.54 g/gsugar) and productivity (0.48-0.60 g/Lh). A final butyrate concentration of 20.9 g/L was obtained in a fed-batch culture, with an overall productivity of 0.51 g/Lh and butyrate yield of 0.48 g/g sugar consumed. This work demonstrated the feasibility of using SCB as a low-cost feedstock to produce butyric acid. PMID:23270719

  8. [Susceptibility of spore-forming butyric acid bacteria to antimicrobial agents].

    PubMed

    Kaneko, Naofumi; Nakayama, Tomohiro; Ichikawa, Nobuhiro

    2012-01-01

    Antimicrobial agents occasionally cause certain adverse effects, such as diarrhea and loose stool, by altering the composition of the intestinal flora. Antibiotic-resistant lactic acid bacteria are used to prevent these adverse effects. Although these bacteria are not resistant to several recently introduced antimicrobial agents, bacterial preparations are still sometimes prescribed concomitantly with these antimicrobial agents. In this study, we investigated whether the administration of the spore-forming butyric acid bacteria Clostridium butyricum improves the adverse clinical effects by preventing diarrhea. Inhibition of C. butyricum growth was observed with 17 of the 20 antimicrobial agents used. However, dilution of 11 of these 17 agents resulted in the regrowth of C. butyricum. These results suggest that C. butyricum may survive exposure to several antibiotic agents by forming spores. Further, a decrease in the antimicrobial agent concentration in the gastrointestinal tract permits the vegetative growth of C. butyricum, which functions as a probiotic. PMID:22790032

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

    PubMed

    Wróbel-Kwiatkowska, Magdalena; Zuk, Magdalena; Szopa, Jan; Dymińska, Lucyna; Maczka, Mirosław; Hanuza, Jerzy

    2009-07-15

    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. PMID:19328737

  10. 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.

  11. 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

  12. 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

  13. β-Amino-n-butyric Acid Regulates Seedling Growth and Disease Resistance of Kimchi Cabbage

    PubMed Central

    Kim, Yeong Chae; Kim, Yeon Hwa; Lee, Young Hee; Lee, Sang Woo; Chae, Yun-Soek; Kang, Hyun-Kyung; Yun, Byung-Wook; Hong, Jeum Kyu

    2013-01-01

    Non-protein amino acid, β-amino-n-butyric acid (BABA), has been involved in diverse physiological processes including seedling growth, stress tolerance and disease resistance of many plant species. In the current study, treatment of kimchi cabbage seedlings with BABA significantly reduced primary root elongation and cotyledon development in a dose-dependent manner, which adverse effects were similar to the plant response to exogenous abscisic acid (ABA) application. BABA was synergistically contributing ABA-induced growth arrest during the early seedling development. Kimchi cabbage leaves were highly damaged and seedling growth was delayed by foliar spraying with high concentrations of BABA (10 to 20 mM). BABA played roles differentially in in vitro fungal conidial germination, mycelial growth and conidation of necrotroph Alternaria brassicicola causing black spot disease and hemibiotroph Colletotrichum higginsianum causing anthracnose. Pretreatment with BABA conferred induced resistance of the kimchi cabbage against challenges by the two different classes of fungal pathogens in a dose-dependent manner. These results suggest that BABA is involved in plant development, fungal development as well as induced fungal disease resistance of kimchi cabbage plant. PMID:25288957

  14. Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa.

    PubMed

    Inagaki, Akiko; Sakata, Takashi

    2005-06-01

    Large bowel bacteria convert various carbohydrates into short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the large intestine in vivo and inhibit that of various cells in vitro. Supposing that too high concentration of SCFA on the serosal side is responsible for their inhibitory effect in vitro, we studied effects of luminal and serosal n-butyric acid (0, 0.1, 1, or 10 mmol/L, adjusted to neutral pH) on the epithelial cell proliferation rate of pig colonic mucosa in organ culture taking crypt cell production rate (CCPR) as the measure of proliferative activity. With 0 or 0.1 mmol/L n-butyric acid on the serosal side, luminal n-butyric acid increased CCPR at 1.0 mmol/L, and decreased CCPR at 10 mmol/L when compared to the luminal 0 mmol/L control. With 1.0 or 10 mmol/L serosal n-butyric acid, luminal n-butyric acid depressed CCPR dose-dependently. The above results indicated that n-butyric acid stimulated colonic epithelial cell proliferation at low concentration and inhibit it at high concentration with interaction effect to enhance the inhibitory action. The stimulatory effect of a low dose of serosal n-butyric acid may be responsible for the distant trophic effect of SCFA. PMID:16161765

  15. 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

  16. 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

  17. Synthesis and pharmacological properties of N,N-dialkyl(dialkenyl)amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid.

    PubMed

    Sladowska, Helena; Sabiniarz, Aleksandra; Filipek, Barbara; Kardasz, Małgorzata; Maciag, Dorota

    2003-01-01

    Synthesis of N,N-dialkyl(dialkenyl)amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (5-9) and their 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl] derivatives (10-14) is described. Compounds 10-14 were tested for analgesic and sedative activities as well as for mu-opioid receptors binding affinities. All the amides, being the object of investigation, displayed an interesting analgesic action, which in case of the compounds 10-12 and 14 was superior to that of acetylsalicylic acid in two different tests. Furthermore all the amides (10-14) significantly suppressed the spontaneous locomotor activity, prolonged barbiturate sleep in mice and showed a weak affinity to mu-opioid receptors. PMID:12595034

  18. 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). PMID:25525616

  19. 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

  20. Structural alterations of adhesion mediating components in cells cultured on poly-beta-hydroxy butyric acid.

    PubMed

    Nebe, B; Forster, C; Pommerenke, H; Fulda, G; Behrend, D; Bernewski, U; Schmitz, K P; Rychly, J

    2001-09-01

    Polymers may serve as a biodegradable material in tissue engineering. To assess the biocompatibility of poly-beta-hydroxy butyric acid (PHB), we studied the structural organization of cellular molecules involved in adhesion using osteoblastic and epithelial cell lines. On PHB, both cell lines revealed a rounded cell shape due to reduced spreading. The filamentous organization of the actin cytoskeleton was impaired. In double immunofluorescence analyses we demostrated that the colocalization of the fibronectin fibrils with the actin filaments was lost in cultures on PHB. Similarly, collagen II distribution was altered, whereas the organization of collagen I was not obviously affected. Further evidence for impaired structural organization was obtained for the beta1-integrin receptor and vinculin which mediate the interaction of the cytoskeleton with the extracellular matrix. In confluent epithelial cells, the tight junction protein ZO-1 showed a larger lateral extension in the cell-cell contacts when cells were grown on PHB. Because structural organization of components which mediate cell-matrix and cell-cell adhesion controls cell physiology these parameters could be a sensitive indicator for the biocompatibility of implant materials. PMID:11511040

  1. 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.

  2. Negative polarity of phenyl-C61 butyric acid methyl ester adjacent to donor macromolecule domains

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    Interfacial fields within organic photovoltaics influence the movement of free charge carriers, including exciton dissociation and recombination. Open circuit voltage (Voc) 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 Voc, 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-C61 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 Voc, 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.

  3. The effect of butyric acid with autogenous omental graft on healing of experimental Achilles tendon injury in rabbits

    PubMed Central

    Jahani, S; Moslemi, H. R.; Dehghan, M. M.; Sedaghat, R; Mazaheri Nezhad, R; Rezaee Moghaddam, D

    2015-01-01

    In this study, the role of local injection of butyric acid (BA) with autogenous omental graft was evaluated in healing of experimental Achilles tendon injury in rabbits. Nine adult male New Zealand rabbits were anesthetized and a partial thickness tenotomy was created on both hindlimbs. In treated group, omental graft was secured in place using BA soaked polygalactin 910 suture. In control group, the graft was sutured without BA. Butyric acid and normal saline were injected daily to treatment and control groups for three days, respectively. Based on the findings, on day 15 after injury, the tendon sections showed that healing rate in BA treated group was higher than that in control group. Furthermore, at days 28 and 45, comparison between BA treated and control groups demonstrated that BA increased the healing rate but with no significance. In summary, results of this study show that application of BA with autogenous omental graft can improve healing process of damaged Achilles tendon. PMID:27175160

  4. A comparison of three pH control methods for revealing effects of undissociated butyric acid on specific butanol production rate in batch fermentation of Clostridium acetobutylicum

    PubMed Central

    2013-01-01

    pH control has been essential for butanol production with Clostridium acetobutylicum. However, it is not very clear at what pH level the acid crash will occur, at what pH level butanol production will be dominant, and at what pH level butyric acid production will be prevailing. Furthermore, contradictory results have been reported about required acidic conditions for initiation of solventogenesis. In this study, with the aim of further understanding the role of undissociated butyric acid in butanol production, we investigated the correlation between undissociated butyric acid concentration and specific butanol production rate in batch fermentation of Clostridium acetobutylicum by comparing three pH control approaches: NaOH neutralization (at 12, 24 or 36 h), CaCO3 supplementation (2, 5, or 8 g/l) and NaOAc buffering (pH 4.6, 5.0 or 5.6). By neutralizing the fermentation pH to ~5.0 at different time, we observed that neutralization should take place at the beginning of exponential phase (12 h), and otherwise resulting in lower concentrations of undissociated butyric acid, cell biomass and final butanol. CaCO3 supplementation extended cell growth to 36 h and resulted in higher butyrate yield under 8 g/L of CaCO3. In the NaOAc buffering, the highest specific butanol rate (0.58 h−1) was associated with the highest undissociated butyric acid (1.92 g/L). The linear correlation of the undissociated butyric acid with the specific butanol production rates suggested the undissociated butyric acid could be the major driving force for butanol production. PMID:23294525

  5. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): modifying serotonin's downstream effects on glutamate and GABA (gamma amino butyric acid) release.

    PubMed

    Stahl, Stephen M

    2015-08-01

    Vortioxetine is an antidepressant with multiple pharmacologic modes of action at targets where serotonin neurons connect with other neurons. These actions modify the release of both glutamate and GABA (gamma amino butyric acid) within various brain circuits. PMID:26062900

  6. 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

  7. 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.

  8. The Long and Winding Road to Gamma-Amino-Butyric Acid as Neurotransmitter.

    PubMed

    Avoli, Massimo; Krnjević, Krešimir

    2016-03-01

    This review centers on the discoveries made during more than six decades of neuroscience research on the role of gamma-amino-butyric acid (GABA) as neurotransmitter. In doing so, special emphasis is directed to the significant involvement of Canadian scientists in these advances. Starting with the early studies that established GABA as an inhibitory neurotransmitter at central synapses, we summarize the results pointing at the GABA receptor as a drug target as well as more recent evidence showing that GABAA receptor signaling plays a surprisingly active role in neuronal network synchronization, both during development and in the adult brain. Finally, we briefly address the involvement of GABA in neurological conditions that encompass epileptic disorders and mental retardation. RESUMÉ: Le chemin long et sinueux pour que le GABA soit reconnu comme un neurotransmetteur. Cette revue est axée sur les découvertes réalisées durant plus de six décennies de recherche en neurosciences sur l'acide gamma-aminobutyrique (GABA) comme neurotransmetteur. À cet effet, nous mettons une emphase particulière sur le rôle significatif de chercheurs canadiens dans ce domaine de recherche. En prenant comme point de départ les premières études qui ont établi que le GABA était un neurotransmetteur au niveau de synapses centrales, nous faisons le sommaire des résultats identifiant le récepteur GABA comme étant une cible thérapeutique ainsi que des données plus récentes montrant que la signalisation du récepteur GABAA joue, de façon surprenante, un rôle actif dans la synchronisation du réseau neuronal, tant au cours du développement que dans le cerveau adulte. Finalement, nous traitons brièvement du rôle de GABA dans les maladies neurologiques incluant les troubles épileptiques et l'arriération mentale. PMID:26763167

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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. PMID:26086956

  16. 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. PMID:22036982

  17. 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. PMID:25384192

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Cholesteryl butyrate solid lipid nanoparticles as a butyric acid pro-drug: effects on cell proliferation, cell-cycle distribution and c-myc expression in human leukemic cells.

    PubMed

    Serpe, Loredana; Laurora, Stefano; Pizzimenti, Stefania; Ugazio, Elena; Ponti, Renata; Canaparo, Roberto; Briatore, Federica; Barrera, Giuseppina; Gasco, Maria Rosa; Bernengo, Maria Grazia; Eandi, Mario; Zara, Gian Paolo

    2004-06-01

    Cholesteryl butyrate solid lipid nanoparticles (chol-but SLN) have been proposed as a pro-drug to deliver butyric acid. We compared the effects on cell growth, cell-cycle distribution and c-myc expression of chol-but SLN and sodium butyrate (Na-but) in the human leukemic cell lines Jurkat, U937 and HL-60. In all the cell lines 0.5 and 1.0 mM chol-but SLN provoked a complete block of cell growth. Cell-cycle analysis demonstrated in Jurkat cells that 0.25 mM chol-but SLN caused a pronounced increase of G2/M cells and a decrease of G0/G1 cells, whereas in U937 and HL-60 cells chol-but SLN led to a dose-dependent increase of G0/G1 cells, with a decrease of G2/M cells. In Jurkat and HL-60 cells 0.5 mM chol-but SLN induced a significant increase of sub-G0/G1 apoptotic cells. Cell growth and cell-cycle distribution were unaffected by the same concentrations of Na-but. A concentration of 0.25 mM chol-but SLN was able to cause a rapid and transient down-regulation of c-myc expression in all the cell lines, whereas 1 mM Na-but caused a slight reduction of c-myc expression only in U937 cells. The results show how chol-but SLN affects the proliferation pattern of both myeloid and lymphoid cells to an extent greater than the natural butyrate. PMID:15166628

  3. Bioprotective carnitinoids: lipoic acid, butyrate, and mitochondria-targeting to treat radiation injury: mitochondrial drugs come of age.

    PubMed

    Steliou, Kosta; Faller, Douglas V; Pinkert, Carl A; Irwin, Michael H; Moos, Walter H

    2015-06-01

    Preclinical Research Given nuclear-power-plant incidents such as the 2011 Japanese Fukushima-Daiichi disaster, an urgent need for effective medicines to protect against and treat the harmful biological effects of radiation is evident. To address such a challenge, we describe potential strategies herein including mitochondrial and epigenetic-driven methods using lipoic and butyric acid ester conjugates of carnitine. The antioxidant and other therapeutically beneficial properties of this class of agents may protect against ionizing radiation and resultant mitochondrial dysfunction. Recent studies of the compounds described herein reveal the potential-although further research and development is required to prove the effectiveness of this approach-to provide field-ready radiation-protective drugs. PMID:26109467

  4. 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...

  5. 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...

  6. The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer.

    PubMed

    Hu, Shien; Dong, Tien Sy; Dalal, Sushila R; Wu, Feng; Bissonnette, Marc; Kwon, John H; Chang, Eugene B

    2011-01-01

    Colonic microbiota ferment non-absorbed dietary fiber to produce prodigious amounts of short chain fatty acids (SCFAs) that benefit the host through a myriad of metabolic, trophic, and chemopreventative effects. The chemopreventative effects of the SCFA butyrate are, in part, mediated through induction of p21 gene expression. In this study, we assessed the role of microRNA(miRNA) in butyrate's induction of p21 expression. The expression profiles of miRNAs in HCT-116 cells and in human sporadic colon cancers were assessed by microarray and quantitative PCR. Regulation of p21 gene expression by miR-106b was assessed by 3' UTR luciferase reporter assays and transfection of specific miRNA mimics. Butyrate changed the expression of 44 miRNAs in HCT-116 cells, many of which were aberrantly expressed in colon cancer tissues. Members of the miR-106b family were decreased in the former and increased in the latter. Butyrate-induced p21 protein expression was dampened by treatment with a miR-106b mimic. Mutated p21 3'UTR-reporter constructs expressed in HCT-116 cells confirmed direct miR-106b targeting. Butyrate decreased HCT-116 proliferation, an effect reversed with the addition of the miR-106b mimic. We conclude that microbe-derived SCFAs regulate host gene expression involved in intestinal homeostasis as well as carcinogenesis through modulation of miRNAs. PMID:21283757

  7. Demonstration of in situ product recovery of butyric acid via CO2 -facilitated pH swings and medium development in two-phase partitioning bioreactors.

    PubMed

    Peterson, Eric C; Daugulis, Andrew J

    2014-03-01

    Production of organic acids in solid-liquid two-phase partitioning bioreactors (TPPBs) is challenging, and highly pH-dependent, as cell growth occurs near neutral pH, while acid sorption occurs only at low pH conditions. CO2 sparging was used to achieve acidic pH swings, facilitating undissociated organic acid uptake without generating osmotic stress inherent in traditional acid/base pH control. A modified cultivation medium was formulated to permit greater pH reduction by CO2 sparging (pH 4.8) compared to typical media (pH 5.3), while still possessing adequate nutrients for extensive cell growth. In situ product recovery (ISPR) of butyric acid (pKa = 4.8) produced by Clostridium tyrobutyricum was achieved through intermittent CO2 sparging while recycling reactor contents through a column packed with absorptive polymer Hytrel® 3078. This polymer was selected on the basis of its composition as a polyether copolymer, and the use of solubility parameters for predicting solute polymer affinity, and was found to have a partition coefficient for butyric acid of 3. Total polymeric extraction of 3.2 g butyric acid with no CO2 mediated pH swings was increased to 4.5 g via CO2 -facilitated pH shifting, despite the buffering capacity of butyric acid, which resists pH shifting. This work shows that CO2 -mediated pH swings have an observable positive effect on organic acid extraction, with improvements well over 150% under optimal conditions in early stage fermentation compared to CO2 -free controls, and this technique can be applied other organic acid fermentations to achieve or improve ISPR. PMID:23996152

  8. 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

  9. 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

  10. 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

  11. 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

  12. 40 CFR 180.318 - 4-(2-Methyl-4-chlorophenoxy) butyric acid; tolerance for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... established for the combined residues, free and conjugated, of the herbicide MCPB, 4-(4-chloro-2-methylphenoxy)butanoic acid, and its metabolite MCPA, (4-chloro-2-methylphenoxy)acetic acid, in or on the following...

  13. The effect of short-chain fatty acids butyrate, propionate, and acetate on urothelial cell kinetics in vitro: potential therapy in augmentation cystoplasty.

    PubMed

    Dyer, J P; Featherstone, J M; Solomon, L Z; Crook, T J; Cooper, A J; Malone, P S

    2005-07-01

    The intestinal element of enterocystoplasty is affected by chronic inflammatory changes, which lead to excess mucus production, urinary tract infections, and stone formation. There is also an increased risk of malignancy. These inflammatory changes may be due to diversion colitis, which affects colonic segments excluded from the faecal stream and likewise may respond to intraluminal short-chain fatty acid (SCFA) therapy. The SCFAs have interesting antiproliferative, differentiating, and pro-apoptotic effects, which are protective against colorectal cancer and may influence the risk of malignancy in enterocystoplasty. Before intravesical therapy can be considered, the effect on normal urothelium must be investigated. Primary urothelial cells cultured from biopsy specimens and transformed urothelial (RT112 and MGH-U1) and intestinal cell lines (HT29 and CaCo-2) were incubated with SCFAs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the residual viable biomass to assess cell proliferation. Proliferation of primary and transformed urothelial cells in culture was inhibited by all SCFAs in a similar time- and dose-dependent manner. The concentration of SCFA required to inhibit growth of primary cells by 50% (IC50) was 20 mM of butyrate, 120 mM of propionate, and 240 mM of acetate after incubation for 1 h. After 72 h the IC50 was 2 mM of butyrate, 4 mM of propionate, and 20 mM of acetate. Transformed urothelial and colon cancer cell lines demonstrated similar growth inhibition. Butyrate was the most potent inhibitor of cell proliferation, followed by propionate and then acetate. Growth inhibition is not an immediate cytotoxic effect, and urothelial cells show a degree of adaptation to butyrate and growth recovery after incubation with butyrate. In conclusion, butyrate- and propionate-induced growth inhibition is potentially clinically significant and may have therapeutically beneficial implications in vivo. PMID:15864601

  14. 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

  15. The rib1 Mutant of Arabidopsis Has Alterations in Indole-3-Butyric Acid Transport, Hypocotyl Elongation, and Root Architecture1

    PubMed Central

    Poupart, Julie; Rashotte, Aaron M.; Muday, Gloria K.; Waddell, Candace S.

    2005-01-01

    Polar transport of the auxin indole-3-butyric acid (IBA) has recently been shown to occur in Arabidopsis (Arabidopis thaliana) seedlings, yet the physiological importance of this process has yet to be fully resolved. Here we describe the first demonstration of altered IBA transport in an Arabidopsis mutant, and show that the resistant to IBA (rib1) mutation results in alterations in growth, development, and response to exogenous auxin consistent with an important physiological role for IBA transport. Both hypocotyl and root IBA basipetal transport are decreased in rib1 and root acropetal IBA transport is increased. While indole-3-acetic acid (IAA) transport levels are not different in rib1 compared to wild type, root acropetal IAA transport is insensitive to the IAA efflux inhibitor naphthylphthalamic acid in rib1, as is the dependent physiological process of lateral root formation. These observed changes in IBA transport are accompanied by altered rib1 phenotypes. Previously, rib1 roots were shown to be less sensitive to growth inhibition by IBA, but to have a wild-type response to IAA in root elongation. rib1 is also less sensitive to IBA in stimulation of lateral root formation and in hypocotyl elongation under most, but not all, light and sucrose conditions. rib1 has wild-type responses to IAA, except under one set of conditions, low light and 1.5% sucrose, in which both hypocotyl elongation and lateral root formation show altered IAA response. Taken together, our results support a model in which endogenous IBA influences wild-type seedling morphology. Modifications in IBA distribution in seedlings affect hypocotyl and root elongation, as well as lateral root formation. PMID:16258013

  16. Dorso-lateral prefrontal γ-amino butyric acid in men predicts individual differences in rash impulsivity

    PubMed Central

    Boy, Frederic; Evans, C. John; Edden, Richard A. E.; Lawrence, Andrew D.; Singh, Krish D.; Husain, Masud; Sumner, Petroc

    2011-01-01

    Background Impulsivity is a multifaceted personality construct associated with numerous psychiatric disorders. Recent research has characterized four facets of impulsivity: ‘urgency’ (the tendency to act rashly especially in the context of distress or cravings); ‘lack of premeditation’ (not envisaging the consequences of actions); ‘lack of perseverance’ (not staying focused on a task); ‘sensation seeking’ (engaging in exciting activities). Urgency is particularly associated with clinical populations and problematic disinhibited behaviour. Methods We used magnetic resonance spectroscopy (MRS) to measure concentration of the inhibitory neurotransmitter γ-amino butyric acid (GABA) in the dorso-lateral prefrontal cortex (dlPFC) in two cohorts of 12 and 13 participants. Results We find that variation in trait urgency in healthy men correlates with GABA concentration in the dlPFC. The result was replicated in an independent cohort. More GABA predicted lower urgency scores, consistent with a role in self-control for GABA-mediated inhibitory mechanisms in dlPFC. Conclusions These findings help account for individual differences in self-control, and thus clarify the relationship between GABA and a wide range of psychiatric disorders associated with impaired self-control. PMID:21757187

  17. Surface-directed spinodal decomposition in poly[3-hexylthiophene] and C₆₁-butyric acid methyl ester blends.

    PubMed

    Vaynzof, Yana; Kabra, Dinesh; Zhao, Lihong; Chua, Lay Lay; Steiner, Ullrich; Friend, Richard H

    2011-01-25

    Demixed blends of poly[3-hexylthiophene] (P3HT) and C₆₁-butyric acid methyl ester (PCBM) are widely used in photovoltaic diodes (PV) and show excellent quantum efficiency and charge collection properties. We find the empirically optimized literature process conditions give rise to demixing during solvent (chlorobenzene) evaporation by spinodal decomposition. Ultraviolet photoemission spectroscopy (UPS) and X-ray photoemission spectroscopy (XPS) results are consistent with the formation of 1-2 nm thick surface layers on both interfaces, which trigger the formation of surface-directed waves emanating from both film surfaces. This observation is evidence that spinodal demixing (leading to a bicontinuous phase morphology) precedes the crystallization of the two components. We propose a model for the interplay of demixing and crystallization which explains the broadly similar PV performance for devices made with the bottom electrodes either as hole or electron collector. The process regime of temporal separation of demixing and crystallization is attractive because it provides a way to control the morphology and thereby the efficiency of PV devices. PMID:21189029

  18. 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

  19. 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

  20. 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

  1. 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

  2. Elevated spectroscopic glutamate/gamma-amino butyric acid in rats bred for learned helplessness.

    PubMed

    Sartorius, Alexander; Mahlstedt, Magdalena M; Vollmayr, Barbara; Henn, Fritz A; Ende, Gabriele

    2007-09-17

    The theory of depression is dominated by the monoamine hypothesis but there is increasing evidence that beyond monoamines, glutamate (Glu) and gamma-aminobutyric acid (GABA) play an essential role in the pathogenesis of depression. In this study, the effect of alterations of GABA and Glu were investigated in the congenital learned helplessness paradigm. Proton magnetic resonance spectroscopy is an important monitoring tool to bridge the findings in clinical and preclinical studies. We found increased Glu/GABA ratios in the hippocampus and prefrontal cortex of placebo-treated (saline intraperitoneally) congenital learned helplessness rats versus wild-type rats, and a treatment-induced (desipramine 10 mg/kg intraperitoneally or electroconvulsive shock) decrease of this monoamine ratio in both brain regions. Our results corroborate previous findings of an amino-acid influence on the pathomechanisms of mood disorders. PMID:17712276

  3. 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

  4. 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.

  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. Effect of γ-amino butyric acid on limpet populations: towards the future management and conservation of endangered patellid species.

    PubMed

    Rivera-Ingraham, G A; Espinosa, F; García-Gómez, J C

    2011-01-01

    Many neurotransmitters, such as γ-amino butyric acid (GABA), can act as chemical cues influencing settlement and metamorphosis in benthic marine invertebrates. This effect has been described especially in mollusks, such as mussels, clams, or haliotids. This study describes the first record of the effect of GABA on patellogastropod populations. Special attention was paid to the effect of the compound on recruitment processes. The experiment was carried out using 10 × 10 cm artificial limestone plates that were drilled into intertidal rocks at different inclinations, and periodically treated with a 1 mM GABA solution. A total of five limpet species was considered (four patellid limpet species and the pulmonate Siphonaria pectinata). Each individual recorded on the plates as well as within a 20 × 20 cm quadrant was measured, identified to species level, and its straight-line distance to the application point was registered. Treated surfaces were the first to possess both adults and recruits. Individuals also were found in a higher number around GABA-treated plates than around controls. The results indicated that the compound may not only enhance recruitment, but also might accelerate it. Recruits were located at higher distances from GABA treated plates than from control surfaces. This supports the hypothesis that this is the life history stage most sensitive to the compound. The behavior shown by the individuals belonging to the two endangered patellid species present in the study area (Patella ferruginea and Cymbula nigra) also were analyzed. For the former, the results indicated that the use of GABA may have similar effects on recruitment similar to the presence of adult conspecifics. This is the first report of the effect of GABA on patellid limpet recruitment and population dynamics. Conservational implications of the results are discussed. PMID:21107997

  8. Photophysics and morphology of poly (3-dodecylthienylenevinylene)-[6,6]-phenyl-C{sub 61}-butyric acid methyl ester composite

    SciTech Connect

    Lafalce, E.; Toglia, P.; Jiang, X.; Zhang, C.

    2012-05-21

    A series of low band gap poly(3-dodecylthienylenevinylene) (PTV) with controlled morphological order have been synthesized and blended with the electron acceptor [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) for organic photovoltaic devices. Two polymers with the most and least side chain regioregularity were chosen in this work, namely the PTV010 and PTV55, respectively. Using photoluminescence, photo-induced absorption spectroscopy, and atomic force microscopy, we find no direct evidence of photoinduced charge transfer between the two constituents, independent of the bulk-heterojunction morphology of the film, although the possibility of formation of P{sup +}/C{sub 60}{sup -} charge transfer complex was not completely ruled out. The large exciton binding energy (E{sub b} = 0.6 eV) in PTV inhibits the photoinduced electron transfer from PTV to PCBM. In addition, excitons formed on polymer chains suffer ultrafast (

  9. Indole-3-butyric acid synthesis in ecotypes and mutants of Arabidopsis thaliana under different growth conditions.

    PubMed

    Ludwig-Müller, Jutta

    2007-01-01

    Although IBA is a naturally occurring auxin, its role in plant development is still under debate. In this study a set of Arabidopsis mutants was used to analyze the biosynthesis of IBA in vitro. The mutants chosen for this study can be classified as: (1) involvement in auxin metabolism, transport or synthesis (amt1, aux1, ilr1, nit1, rib1, sur1, trp1-100); (2) other hormones possibly involved in the regulation of IBA synthesis (aba1, aba3, eto2, fae1, hls1, jar1); (3) photomorphogenesis (det1, det2, det3); and (4) root architecture (cob1, cob2, scr1). In addition, two transgenic lines overexpressing the IAA glucose synthase (iaglu) gene from maize were analyzed. The ecotypes No-0 and Wassilewskija showed the highest IBA synthetase activity under control conditions, followed by Columbia, Enkheim and Landsberg erecta. In the mutant lines IBA synthetase activity differed in most cases from the wild type, however no particular pattern of up- or down-regulation, which could be correlated to their possible function, was found. For rib1 mutant seedlings it was tested whether reduced IBA synthetase activity correlates with the endogenous IBA levels. Free IBA differed only depending on the culture conditions, but gave no clear correlation with IBA synthetase activity compared to the wild type. Since drought and osmotic stress as well as abscisic acid (ABA) application enhanced IBA synthesis in maize, it was tested whether IBA synthetase from Arabidopsis is also inducible by drought stress conditions. This was confirmed for the two ecotypes Col and Ler which showed different IBA synthetase activity when cultivated with various degrees of drought stress. IBA synthetase was also determined in photomorphogenic mutants under different light regimes. Induction of IBA synthetase in det1 and det3 plants was found under short day plus a red light pulse or in the dark, respectively. The results are discussed with respect to the functions of the mutated genes. PMID:16325963

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

    PubMed

    Weber, T E; van Sambeek, D M; Gabler, N K; Kerr, B J; Moreland, S; Johal, S; Edmonds, M S

    2014-09-01

    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 inflammation in young pigs. An experiment was conducted using 448 crossbred weanling pigs, which were stratified by gender and BW and were randomly assigned to 1 of 4 dietary treatments in a 2 × 2 factorial arrangement consisting of control and MFG with or without BA. The pigs were housed at a density of 8 pigs/pen and with 14 pens/dietary treatment. Growth performance and feed intake were assessed for 35 d. To assess the inflammation-related properties of MFG and BA, on d 36 a subset of 48 pigs from each treatment was intramuscular injected with either sterile saline or Escherichia coli LPS (20 μg/kg BW; E. coli serotype O55:B5) for 4 h in a 2 × 2 × 2 factorial arrangement (± LPS, ± MFG and ± BA; n = 6 pigs/treatment group) to assess their febrile response as well as serum, liver, and muscle cytokine responses. Results from this study showed that neither BA nor MFG alone or in combination altered pig ADG, ADFI, and G:F. Moreover, in the presence of LPS, the combination of MFG and BA resulted in a 62% decrease (P = 0.08) in serum cortisol compared to when neither compound was added to the diet. In contrast, serum IGF-I was increased (P < 0.01) by 59% from the use of both MFG and BA, as opposed to when neither was added, with pigs subjected to LPS. However, both MFG and BA inclusion appear to have a complex role in modulating different aspects of the immune response to LPS, particularly when both are fed in combination. Humic acid also appeared to play a role in decreasing oxidative stress. PMID:25023805

  11. 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

  12. Indolyl-3-butyric acid-induced Arabidopsis stomatal opening mediated by 3',5'-cyclic guanosine-monophosphate.

    PubMed

    Cousson, A

    2010-12-01

    It has been pharmacologically suggested that 3',5'-cyclic guanosine-monophosphate (cGMP) mediates indolyl-3-butyric acid (IBA)-induced stomatal opening. In Arabidopsis thaliana (L.) Heynh., such investigations compared the wild type (Columbia and Ws ecotypes) to mutants knockout for either GTP-binding protein (G protein) α subunit 1 (gpa1-4), putative G protein-coupled receptor 1 (gcr1-5), calcineurin B-like isoform 1 (cbl1) or 9 (cbl9), or the NADPH oxidases AtrbohD and AtrbohF (atrbohD/F). Stomatal opening to IBA or the permeant cGMP analogue, 8-bromo-cGMP (8-Br-cGMP) was abolished in the atrbohD/F mutant. The IBA response was fully or partially suppressed, respectively, in the gcr1-5 mutant, or the gpa1-4 and cbl1 mutants. In the cbl9 mutant, the response to IBA or 8-Br-cGMP, respectively, was partially or fully suppressed. Phenylarsine oxide (PAO) affected the IBA response, which the cbl1 mutant overlapped or the gpa1-4 and cbl9 mutants increased up to 100% inhibition. 6-anilino-5,8-quinolinedione, mas17, the (Rp)-diastereomer of 8-bromo-3',5'-cyclic guanosine monophosphorothioate (Rp-8-Br-cGMPS), nicotinamide, ruthenium red (RRed), 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), cyclosporine A (CsA) and FK506 converged to affect the IBA response, which the gpa1-4 and cbl9 mutants overlapped or the cbl1 mutant and PAO increased up to 100% inhibition. Rp-8-Br-cGMPS, nicotinamide, RRed, BAPTA, CsA or FK506 paralled the cbl9 and atrbohD/F mutants to abolish the 8-Br-cGMP response. Based on so far revealed features of these mutants and pharmacological compounds, these results confirmed cGMP as a Ca(2+)-mobilizing second messenger for apoplastic auxin whose perception and transduction would implicate a seven-transmembrane receptor - G protein - guanylyl cyclase unit at the guard cell plasma membrane. PMID:20951600

  13. 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

  14. Relationship between Indole-3-Acetic Acid Levels in Apple (Malus pumila Mill) Rootstocks Cultured in Vitro and Adventitious Root Formation in the Presence of Indole-3-Butyric Acid.

    PubMed

    Alvarez, R; Nissen, S J; Sutter, E G

    1989-02-01

    In vitro rooting response and indole-3-acetic acid (IAA) levels were examined in two genetically related dwarfing apple (Malus pumila Mill) rootstocks. M.26 and M.9 were cultured in vitro using Linsmaier-Skoog medium supplemented with benzyladenine (BA), indole-3-butyric acid (IBA), and 1,3,5-trihydroxybenzoic acid (PG). Rooting response was tested in Lepoivre medium supplemented with IBA and PG. IBA concentrations of 12.0 and 4.0 micromolar induced the maximum rooting percentages for M.9 and M.26, respectively. At these concentrations rooting response was 100% for M.26 and 80% for M.9. Free and conjugated IAA levels were determined in M.26 and M.9 shoots prior to root inducing treatment by high performance liquid chromatography with fluorescence detection and validated by gas chromatography-mass spectrometry using (13)[C(6)]IAA as internal standard. Basal sections of M.26 shoots contained 2.8 times more free IAA than similar tissue in M.9 (477.1 +/- 6.5 versus 166.6 +/- 6.7 nanograms per gram fresh weight), while free IAA levels in apical sections of M.26 and M.9 shoots were comparable (298.0 +/- 4.4 versus 263.7 +/- 9.3 nanograms per gram fresh weight). Conjugated IAA levels were significantly higher in M.9 than in M.26 indicating that a greater proportion of total IAA was present as a conjugate in M.9. These data suggest that differences between M.26 and M.9 rooting responses may be related to differences in free IAA levels in the shoot base. PMID:16666562

  15. Simultaneous detection and quantification of indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) produced by rhizobacteria from l-tryptophan (Trp) using HPTLC.

    PubMed

    Goswami, Dweipayan; Thakker, Janki N; Dhandhukia, Pinakin C

    2015-03-01

    A simple, quick and reliable method is proposed for the detection and quantitation of indole-3-acetate (IAA) and indole-3-butyrate (IBA), an auxin phytohormone produced by rhizobacteria from l-tryptophan (Trp) metabolism using high performance thin-layer chromatography (HPTLC). Microbial auxin biosynthesis routes involve Trp as a precursor where other than IAA and IBA, products such as indole-3-pyruvate (IPA), indole-3-acetamide (IAM), tryptamine, indole-3-acetonitrile (IAN), indole-3-lactic acid (ILA) and indole-3-acetaldehyde (IAAld) are also produced. In traditional spectrophotometric method, Salkowski reagent develops color by reacting with indolic compounds. The color development is non-specific contributed by several Trp derivatives produced by rhizobacteria rather than IAA only. To overcome this limitation, HPTLC based protocol is developed to precisely detect and quantify IAA and IBA in the range of 100 to 1000ng per spot. This protocol is applicable to detect and quantify IAA and IBA from microbial samples ignoring other Trp derivatives. For microbial samples, the spectrophotometric method gives larger values as compared to HPTLC derived values which may be attributed by total indolic compounds reacting with Salkowski reagent rather than only IAA and/or IBA. PMID:25573587

  16. Vibrational and quantum chemical investigation of cyclization of thiosemicarbazide group in 1-benzoyl-4-phenyl-3-thiosemicarbazide

    NASA Astrophysics Data System (ADS)

    Gautam, Priyanka; Prakash, Om; Dani, R. K.; Singh, N. K.; Singh, Ranjan K.

    2014-11-01

    1-Benzoyl-4-phenyl-3-thiosemicarbazide (H3bpt) was treated with acid - base in one sequence and base - acid in other sequence, both of which lead to ring formation of thiosemicarbazide group, giving N-phenyl-5-phenyl-1,3,4-thiadiazol-2-amine (Hppta) in the first case and 4,5-diphenyl-2,4-dihydro-1,2,4-triazole-3-thione (Hdptt) in the second case. The primary (H3bpt) as well as the resulting compounds (Hppta & Hdptt) has been characterized by elemental analyses, NMR, FTIR and Raman spectroscopic techniques. The quantum chemical calculations of the compounds are performed using DFT/B3LYP/6311G(d,p) method for geometry optimizations and also for prediction of the molecular properties. The cyclization is confirmed by disappearance of many bands belonging to the open chain subgroups of H3bpt such as; Nsbnd H stretching, Nsbnd H bending, Csbnd N stretching, Nsbnd H puckering, Cdbnd O stretching etc. The ring formation of 1-benzoyl-4-phenyl-3-thiosemicarbazide (H3bpt) has been further confirmed by the appearance of many bands belonging to the closed ring of thiosemicarbazide in the resulting compounds Hppta and Hdptt.

  17. Cytokine responses of intestinal epithelial-like Caco-2 cells to non-pathogenic and opportunistic pathogenic yeasts in the presence of butyric acid.

    PubMed

    Saegusa, Shizue; Totsuka, Mamoru; Kaminogawa, Shuichi; Hosoi, Tomohiro

    2007-10-01

    Candida albicans, Saccharomyces cerevisiae and their cell wall components, zymosan and glucan, have been shown to stimulate interleukin-8 (IL-8/CXCL-8) production by intestinal epithelial cell-like Caco-2 cells pre-cultured with 10 mM butyric acid. We examined in this study whether these yeasts also altered the production of other cytokines and cyclooxygenases (COXs) by Caco-2 cells. Culturing Caco-2 cells with 10 mM butyric acid and 15% FBS for 4 days enhanced the basal levels of mRNA encoding IL-6, IL-8, IL-18, monocyte chemoattractant protein (MCP)-1, stem cell factor, transforming growth factor (TGF)-beta1, TGF-beta3, tumor necrosis factor (TNF)-alpha, COX-1, and COX-2, but not of granulocyte-macrophage colony-stimulating factor (GM-CSF) and TGF-beta2. The inclusion of live S. cerevisiae or C. albicans further enhanced the production of IL-8, but not of the other cytokines and COXs. The non-pathogenic yeasts, C. kefyr, C. utilis, C. versatilis, Kluyveromyces lactis, K. marxianus, Schizosaccharomyces pombe and Zygosaccharomyces rouxii, used for the production of fermented foods and probiotics, and the opportunistic pathogens, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis, isolated from human tissue samples also enhanced IL-8 secretion by Caco-2 cells. PMID:17928716

  18. 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 ...

  19. Bi-functional prodrugs of 5-aminolevulinic acid and butyric acid increase erythropoiesis in anemic mice in an erythropoietin-independent manner.

    PubMed

    Rephaeli, Ada; Tarasenko, Nataly; Fibach, Eitan; Rozic, Gabriela; Lubin, Ido; Lipovetsky, Julia; Furman, Svetlana; Malik, Zvi; Nudelman, Abraham

    2016-08-25

    Anemia is a major cause of morbidity and mortality worldwide resulting from a wide variety of pathological conditions. In severe cases it is treated by blood transfusions or injection of erythroid stimulating agents, e.g., erythropoietin (Epo), which can be associated with serious adverse effects. Therefore, there is a need to develop new treatment modalities. We recently reported that treatment of erythroleukemic cells with the novel the bi-functional prodrugs of 5-aminolevulinic acid (ALA) and butyric acid (BA), AN233 and AN908, enhanced hemoglobin (Hb) synthesis to a substantially higher level than did ALA and BA individually or their mixture. Herein, we describe that these prodrugs when given orally to mice induced histone deacetylase inhibition in the kidneys, bone marrow and spleen, thus, indicating good penetrability to the tissues. In mice where anemia was chemically induced, treatment with the prodrugs increased the Hb, the number of red blood cells (RBCs) and the percentage of reticulocytes to normal levels. The prodrugs had no adverse effects even after repeated treatment at 100-200mg/kg for 50days. The lack of increased levels of Epo in the blood of mice that were treated with the prodrugs suggests that AN233 and AN908 affected the Hb and RBC levels in an Epo-independent manner. Taken together with our previous studies, we propose that the prodrugs increase globin expression by BA inhibition of histone deacetylase and elevation heme synthesis by ALA. These results support an Epo-independent approach for treating anemia with these prodrugs. PMID:27283485

  20. Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

    PubMed

    Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

    2016-05-01

    Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

  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. Modeling of Open-Circuit Voltage of Phenyl-C61-Butyric Acid Methyl Ester-Like Based Bulk-Heterojunction Solar Cells.

    PubMed

    Ferreira, Rodrigo M; Batagin-Neto, Augusto; Lavarda, Francisco C

    2015-12-01

    New materials are currently being sought for use in active layers of bulk-heterojunction organic solar cells, and computational modeling plays an important role in this search. Although open circuit voltage (V(oc)) is one of the fundamental quantities that determine the efficiency of a solar cell, there is no consensus on the best way to estimate this magnitude for new materials from calculations of the electronic structure. In this paper, we compare ways of predicting V(oc) values employing a diverse group of blends and conclude that it is possible to have a good prediction tool for organic solar cells based on phenyl-C61-butyric acid methyl ester (PCBM) acceptor molecules. PMID:26682440

  3. Dependence of protein binding capacity of dimethylamino-γ-butyric-acid (DMGABA)-immobilized porous membrane on composition of solvent used for DMGABA immobilization

    NASA Astrophysics Data System (ADS)

    Iwanade, Akio; Umeno, Daisuke; Saito, Kyoichi; Sugo, Takanobu

    2013-06-01

    Dimethylamino-γ-butyric acid (DMGABA) as an ampholite was reacted with the epoxy group of the poly-glycidyl methacrylate chain grafted onto the pore surface of a porous hollow-fiber polyethylene membrane by radiation-induced graft polymerization. DMGABA was dissolved in a mixture of dioxane and water at various dioxane volume fractions, defined by dividing the dioxane volume by the total volume. The equilibrium binding capacity (EBC) of the DMGABA-immobilized porous hollow-fiber membrane for lysozyme was evaluated in the permeation mode. The EBC was varied from a 1/50-fold monolayer binding capacity to a 10-fold monolayer binding capacity by controlling the composition of the solvent used for DMGABA immobilization and the molar conversion of the epoxy group into the DMGABA group.

  4. On the Inapplicability of Electron-Hopping Models for the Organic Semiconductor Phenyl-C61-butyric Acid Methyl Ester (PCBM).

    PubMed

    Gajdos, Fruzsina; Oberhofer, Harald; Dupuis, Michel; Blumberger, Jochen

    2013-03-21

    Phenyl-C61-butyric acid methyl ester (PCBM) is one of the most popular semiconductors in organic photovoltaic cells, but the electron-transport mechanism in the microcrystalline domains of this material as well as its preferred packing structure remain unclear. Here we use density functional theory to calculate electronic-coupling matrix elements, reorganization energies, and activation energies for available experimental and model crystal structures. We find that the picture of an excess electron hopping from one fullerene to another does not apply for any of the crystalline phases, rendering traditional rate equations inappropriate. We also find that the cohesive energy increases in the order body-centered-cubic < hexagonal < simple cubic < monoclinic < triclinic, independently of the type of dispersion correction used. Our results indicate that the coupled electron-ion dynamics needs to be solved explicitly to obtain a realistic description of charge transfer in this material. PMID:26291369

  5. Determination of 4-(methylnitrosamino)-4-(3-pyridyl)-butyric acid in tobacco, tobacco smoke and the urine of rats and smokers.

    PubMed

    Pachinger, A; Begutter, H; Ultsch, I; Klus, H

    1993-10-22

    The potential endogenous nitrosation of nicotine and/or nicotine metabolites has led to speculation on the possible formation of 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid (iso-NNAC) in smokers. A gas chromatographic method with thermal energy analytical detection is described for the determination of iso-NNAC in tobacco, tobacco smoke and urine. Sample pre-concentration is performed using C18 extraction cartridges prior to esterification of iso-NNAC using ethereal diazomethane solution. Sample clean-up includes chromatography on aluminum and silica, and fractionation using high-performance liquid chromatography. The detection limits for iso-NNAC in tobacco, tobacco smoke and urine are 2 ng/g tobacco, 0.1 ng/cigarette and 20 ng/l urine, respectively. PMID:8106592

  6. 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.

  7. 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

  8. The Arabidopsis PLEIOTROPIC DRUG RESISTANCE8/ABCG36 ATP Binding Cassette Transporter Modulates Sensitivity to the Auxin Precursor Indole-3-Butyric Acid[C][W

    PubMed Central

    Strader, Lucia C.; Bartel, Bonnie

    2009-01-01

    Plants have developed numerous mechanisms to store hormones in inactive but readily available states, enabling rapid responses to environmental changes. The phytohormone auxin has a number of storage precursors, including indole-3-butyric acid (IBA), which is apparently shortened to active indole-3-acetic acid (IAA) in peroxisomes by a process similar to fatty acid β-oxidation. Whereas metabolism of auxin precursors is beginning to be understood, the biological significance of the various precursors is virtually unknown. We identified an Arabidopsis thaliana mutant that specifically restores IBA, but not IAA, responsiveness to auxin signaling mutants. This mutant is defective in PLEIOTROPIC DRUG RESISTANCE8 (PDR8)/PENETRATION3/ABCG36, a plasma membrane–localized ATP binding cassette transporter that has established roles in pathogen responses and cadmium transport. We found that pdr8 mutants display defects in efflux of the auxin precursor IBA and developmental defects in root hair and cotyledon expansion that reveal previously unknown roles for IBA-derived IAA in plant growth and development. Our results are consistent with the possibility that limiting accumulation of the IAA precursor IBA via PDR8-promoted efflux contributes to auxin homeostasis. PMID:19648296

  9. Selective oxidation of trimethylolpropane to 2,2-bis(hydroxymethyl)butyric acid using growing cells of Corynebacterium sp. ATCC 21245.

    PubMed

    Sayed, Mahmoud; Dishisha, Tarek; Sayed, Waiel F; Salem, Wesam M; Temerk, Hanan A; Pyo, Sang-Hyun

    2016-03-10

    Multifunctional chemicals including hydroxycarboxylic acids are gaining increasing interest due to their growing applications in the polymer industry. One approach for their production is a biological selective oxidation of polyols, which is difficult to achieve by conventional chemical catalysis. In the present study, trimethylolpropane (TMP), a trihydric alcohol, was subjected to selective oxidation using growing cells of Corynebacterium sp. ATCC 21245 as a biocatalyst and yielding the dihydroxy-monocarboxylic acid, 2,2-bis(hydroxymethyl)butyric acid (BHMB). The study revealed that co-substrates are crucial for this reaction. Among the different evaluated co-substrates, a mixture of glucose, xylose and acetate at a ratio of 5:5:2 was found optimum. The optimal conditions for biotransformation were pH 8, 1v/v/m airflow and 500rpm stirring speed. In batch mode of operation, 70.6% of 5g/l TMP was converted to BHMB in 10 days. For recovery of the product the adsorption pattern of BHMB to the anion exchange resin, Ambersep(®) 900 (OH(-)), was investigated in batch and column experiments giving maximum static and dynamic binding capacities of 135 and 144mg/g resin, respectively. BHMB was separated with 89.7% of recovery yield from the fermentation broth. The approach is applicable for selective oxidation of other highly branched polyols by biotransformation. PMID:26804932

  10. Gas chromatographic detection of D-(-)-2,3-butanediol and butyric acid produced by sporeformers in cream-style corn and canned beef noodle soup: collaborative study.

    PubMed

    Schafer, M L; Peeler, J T; Bradshaw, J G; Hamilton, C H; Carver, R B

    1985-01-01

    A gas chromatographic method that identifies sporeformers as the cause of spoilage in swollen cans of low-acid foods was collaboratively studied in 2 stages. Two organic compounds produced by sporeformers, D-(-)-2,3-butanediol and butyric acid, are measured in the upper phase after centrifugation of the liquid portion of the can contents. Each sample is assayed on 2 packed columns designed for the assay of aqueous solutions of volatile fatty acids, using flame ionization detectors. For study 1, 16 duplicate inoculated cans of cream-style corn and beef noodle soup were sent to 9 collaborators. For study 2, 7 collaborators received 11 duplicate inoculated cans of the 2 foods. Duplicate uninoculated cans of each food served as negative controls. The inocula were 6 sporeforming organisms (4 Clostridium and 2 gas-forming Bacillus species) and 2 nonsporeformers. After the deletion of marginal samples, the percentages of correctly identified sporeformers and nonsporeformers in beef noodle soup were 83 (110/132) and 90 (54/60), respectively; corresponding percentages for cream-style corn were 80 (98/123) and 100 (35/35). The method has been adopted official first action. PMID:4030630

  11. Different control mechanisms of growth hormone (GH) secretion between gamma-amino- and gamma-hydroxy-butyric acid: neuroendocrine evidence in Parkinson's disease.

    PubMed

    Volpi, R; Chiodera, P; Caffarra, P; Scaglioni, A; Saccani, A; Coiro, V

    1997-10-01

    The observation that baclofen stimulates growth hormone (GH) secretion in normal men, but not in parkinsonian patients led us to test the GH releasing effect of other gamma-amino-butyric acid (GABA)ergic agents with different mechanisms of action in Parkinson's disease. For this purpose 10 normal men and 10 de novo parkinsonian patients were tested with sodium valproate (800 mg PO), gamma-hydroxybutyric acid (GHB) (25 mg/kg body weight PO) and baclofen (10 mg PO). All drugs induced a significant increment in serum GH levels in the normal controls. On the other hand, GH secretion in parkinsonian patients did not change after baclofen or sodium valproate administration, whereas it showed normal responsiveness to GHB. These data suggest that the mechanism underlying the GH response to GHB is different from that (or those) mediating sodium valproate and/or baclofen action. In addition, the former, but not the latter mechanism appears to be preserved in the parkinsonian brain. PMID:9373886

  12. 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.

  13. 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

  14. Ultraviolet photoelectron spectroscopy and inverse photoemission spectroscopy of [6,6]-phenyl-C{sub 61}-butyric acid methyl ester in gas and solid phases

    SciTech Connect

    Akaike, Kouki; Nishi, Toshio; Ouchi, Yukio; Seki, Kazuhiko; Kanai, Kaname; Yoshida, Hiroyuki; Tsutsumi, Jun'ya; Sato, Naoki

    2008-07-15

    The electronic structure of [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) was studied using ultraviolet photoelectron spectroscopy of vapor and thin film and inverse photoemission spectroscopy of thin film. The threshold ionization energy of PCBM was found to be 7.17{+-}0.04 eV in gas phase and 5.96{+-}0.02 eV in solid phase. The threshold electron affinity was 3.9{+-}0.1 eV in solid phase. These values are 0.4-0.6 eV smaller than C{sub 60}. The density functional theory calculations gave consistent results with these trends and suggested that the electron donation from the side chain to C{sub 60} backbone raised the C{sub 60}-backbone-derived {pi} orbitals of PCBM. The polarization energy of PCBM is 1.21 eV, which is almost the same as C{sub 60} but is about 0.5 eV smaller than the value of typical aromatic hydrocarbons.

  15. 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

  16. On the inapplicability of electron-hopping models for the organic semiconductor Phenyl-C61-butyric Acid Methyl Ester (PCBM)

    SciTech Connect

    Gajdos, Fruzsina; Oberhofer, Harald; Dupuis, Michel; Blumberger, Jochen

    2013-03-21

    Phenyl-C61-butyric Acid Methyl Ester (PCBM) is one of the most popular semiconductors in organic photovoltaic cells, but the electron transport mechanism in the microcrystalline domains of this material as well as its preferred packing structure remains unclear. Here we use density functional theory to calculate electronic coupling matrix elements, reorganization energies and activation energies for available experimental and model crystal structures. We find that the picture of an excess electron hopping from one fullerene to another does not apply for any of the crystalline phases, rendering traditional rate equations inappropriate. We also find that the cohesive energy increases in the order body-centred-cubic < hexagonal < simple cubic < monoclinic < triclinic, independently on the type of dispersion correction used. Our results indicate that the electron-ion dynamics needs to be solved explicitly in order to obtain a realistic description of charge transfer in this material. M.D. was supported by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences (BES), Division of Chemical Sciences, Geosciences and Biosciences. PNNL is a multiprogram national laboratory operated for DOE by Battelle.

  17. Investigation of TiO2 Surface Modification with [6,6]-Phenyl-C61-butyric Acid for Titania/Polymer Hybrid Solar Cells

    NASA Astrophysics Data System (ADS)

    Ma, Teng; Zhang, Jinyu; Kojima, Ryota; Tadaki, Daisuke; Kimura, Yasuo; Niwano, Michio

    2013-11-01

    We have investigated modification of TiO2 surfaces with [6,6]-phenyl-C61-butyric acid (PCBA) used for fabrication of TiO2/poly(3-hexylthiophene-2,5-diyl) (P3HT) hybrid solar cells. The surface modification process was monitored using in-situ infrared absorption spectroscopy in the multiple-internal reflection geometry (MIR-IRAS). IR data showed that longer exposure of TiO2 surfaces to an organic solution of PCBA leads to undesirable formation of a physisorbed PCBA overlayer that cannot be removed by rinsing the surface in pure solvent. We found that ultrasonic cleaning of the TiO2 surface removed most of the physisorbed PCBA molecules. Modification of TiO2 surfaces with PCBA molecules drastically increased the short circuit current of TiO2/P3HT-based hybrid solar cells, which is ascribed to improved charge separation efficiency at the TiO2/P3HT interface. The physisorbed PCBA molecules decreased the open circuit voltage and the fill factor. We demonstrated that the power conversion efficiency is improved by ultrasonic cleaning following PCBA deposition.

  18. 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

  19. Osteogenesis from Dental Pulp Derived Stem Cells: A Novel Conditioned Medium Including Melatonin within a Mixture of Hyaluronic, Butyric, and Retinoic Acids

    PubMed Central

    Maioli, Margherita; Basoli, Valentina; Santaniello, Sara; Cruciani, Sara; Delitala, Alessandro Palmerio; Pinna, Roberto; Milia, Egle; Grillari-Voglauer, Regina; Fontani, Vania; Rinaldi, Salvatore; Muggironi, Roberta; Pigliaru, Gianfranco; Ventura, Carlo

    2016-01-01

    Human dental pulp stem cells (hDPSCs) have shown relevant potential for cell therapy in the orthopedic and odontoiatric fields. The optimization of their osteogenic potential is currently a major challenge. Vascular endothelial growth factor A (VEGF A) has been recently reported to act as a major conductor of osteogenesis in vitro and in vivo. Here, we attempted to prime endogenous VEGF A expression without the need for viral vector mediated gene transfer technologies. We show that hDPSCs exposure to a mixture of hyaluronic, butyric, and retinoic acids (HA + BU + RA) induced the transcription of a gene program of osteogenesis and the acquirement of an osteogenic lineage. Such response was also elicited by cell exposure to melatonin, a pleiotropic agent that recently emerged as a remarkable osteogenic inducer. Interestingly, the commitment to the osteogenic fate was synergistically enhanced by the combinatorial exposure to a conditioned medium containing both melatonin and HA + BU + RA. These in vitro results suggest that in vivo osteogenesis might be improved and further studies are needed. PMID:26880937

  20. Evaluation of 4-(N-methylnitrosamino)-4-(3-pyridyl)butyric acid as a potential monitor of endogenous nitrosation of nicotine and its metabolites.

    PubMed

    Tricker, A R; Scherer, G; Conze, C; Adlkofer, F; Pachinger, A; Klus, H

    1993-07-01

    The potential endogenous nitrosation of nicotine and cotinine to yield 4-(N-methylnitrosamino)-4-(3-pyridyl)butyric acid (Iso-NNAC) has been studied in smokers and non-smokers. Following i.v. administration of 100 micrograms Iso-NNAC to rats, excretion in urine (67.4 +/- 25.4%) and feces (6.1 +/- 1.6%) occurred within 24 h. The urinary excretion of nitrate, nicotine, cotinine and Iso-NNAC were determined in 24 h urine samples from 19 smokers and 10 non-smokers. Iso-NNAC excretion was found on four occasions (44, 65, 74 and 163 ng/day) in smokers; non-smokers did not excrete Iso-NNAC. Oral administration of nicotine (n = 8; 12-40 mg) and cotinine (n = 3; 40-60 mg) to abstinent smokers did not result in Iso-NNAC excretion, even after oral nitrate (150 mg) supplementation. However, Iso-NNAC was found in cigarette tobacco (10-330 ng/g) and mainstream cigarette smoke (1.1-5.5 ng/cig.). Our studies suggest that the occasional presence of Iso-NNAC in smokers' urine results from exogenous exposure to the preformed compound in mainstream cigarette smoke and not from endogenous nitrosation of nicotine and its metabolites. PMID:8330358

  1. Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice.

    PubMed

    Kapuvári, Bence; Hegedüs, Rózsa; Schulcz, Ákos; Manea, Marilena; Tóvári, József; Gacs, Alexandra; Vincze, Borbála; Mező, Gábor

    2016-08-01

    Compared to classical chemotherapy, peptide-based drug targeting is a promising therapeutic approach for cancer, which can provide increased selectivity and decreased side effects to anticancer drugs. Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety, in particular in the treatment of hormone independent tumors that highly express GnRH receptors (e.g. colon carcinoma). We have previously shown that GnRH-III[(4)Lys(Ac),(8)Lys(Dau = Aoa)] bioconjugate, in which daunorubicin was attached via oxime linkage to the (8)Lys of a GnRH-III derivative, exerted significant in vivo antitumor effect on subcutaneously developed HT-29 colon tumor. In contrast, results of the study reported here indicated that this compound was not active on an orthotopically developed tumor. However, if Lys in position 4 was acylated with butyric acid instead of acetic acid, the resulting bioconjugate GnRH-III[(4)Lys(Bu),(8)Lys(Dau = Aoa)] had significant tumor growth inhibitory effect. Furthermore, it prevented tumor neovascularization, without detectable side effects. Nevertheless, the development of metastases could not be inhibited by the bioconjugate; therefore, its application in combination with a metastasis preventive agent might be necessary in order to achieve complete tumor remission. In spite of this result, the treatment with GnRH-III[(4)Lys(Bu),(8)Lys(Dau = Aoa)] bioconjugate proved to have significant benefits over the administration of free daunorubicin, which was used at the maximum tolerated dose. PMID:27146514

  2. Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice.

    PubMed

    Subramanian, Umadevi; Kumar, Prerna; Mani, Indra; Chen, David; Kessler, Isaac; Periyasamy, Ramu; Raghavaraju, Giri; Pandey, Kailash N

    2016-07-01

    The objective of the present study was to examine the genetically determined differences in the natriuretic peptide receptor-A (NPRA) gene (Npr1) copies affecting the expression of cardiac hypertrophic markers, proinflammatory mediators, and matrix metalloproteinases (MMPs) in a gene-dose-dependent manner. We determined whether stimulation of Npr1 by all-trans retinoic acid (RA) and histone deacetylase (HDAC) inhibitor sodium butyric acid (SB) suppress the expression of cardiac disease markers. In the present study, we utilized Npr1 gene-disrupted heterozygous (Npr1(+/-), 1-copy), wild-type (Npr1(+/+), 2-copy), gene-duplicated (Npr1(++/+), 3-copy) mice, which were treated intraperitoneally with RA, SB, and a combination of RA/SB, a hybrid drug (HB) for 2 wk. Untreated 1-copy mice showed significantly increased heart weight-body weight (HW/BW) ratio, blood pressure, hypertrophic markers, including beta-myosin heavy chain (β-MHC) and proto-oncogenes (c-fos and c-jun), proinflammatory mediator nuclear factor kappa B (NF-κB), and MMPs (MMP-2, MMP-9) compared with 2-copy and 3-copy mice. The heterozygous (haplotype) 1-copy mice treated with RA, SB, or HB, exhibited significant reduction in the expression of β-MHC, c-fos, c-jun, NF-κB, MMP-2, and MMP-9. In drug-treated animals, the activity and expression levels of HDAC were significantly reduced and histone acetyltransferase activity and expression levels were increased. The drug treatments significantly increased the fractional shortening and reduced the systolic and diastolic parameters of the Npr1(+/-) mice hearts. Together, the present results demonstrate that a decreased Npr1 copy number enhanced the expression of hypertrophic markers, proinflammatory mediators, and MMPs, whereas an increased Npr1 repressed the cardiac disease markers in a gene-dose-dependent manner. PMID:27199456

  3. 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

  4. [Effect of cultivation conditions on the accumulation of poly-beta-hydroxy-butyric acid in Rhizobium lupini].

    PubMed

    Yushkova, L A; Fedulova, N G; Romanov, V I; Kretovich, W L

    1975-01-01

    The influence of the age of the culture and nitrogen source on the accumulation of poly-beta-hydroxybutyric acid by different strains of Rhizobium lupini was studied. The accumulation depended on the age of the culture and reached maximum at the end of the logarithmic and at the beginning of the stationary phase of the bacterial growth (about 50-60% dry weight). The accumulation varied in relation to the nitrogen source used: it was the highest in the glutamate medium and the lowest on nitrate nitrogen; the culture grown on ammonium phosphate was intermediate. PMID:1208373

  5. 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...

  6. Quantum confinement-tunable ultrafast charge transfer at the PbS quantum dot and phenyl-C₆₁-butyric acid methyl ester interface.

    PubMed

    El-Ballouli, Ala'a O; Alarousu, Erkki; Bernardi, Marco; Aly, Shawkat M; Lagrow, Alec P; Bakr, Osman M; Mohammed, Omar F

    2014-05-14

    Quantum dot (QD) solar cells have emerged as promising low-cost alternatives to existing photovoltaic technologies. Here, we investigate charge transfer and separation at PbS QDs and phenyl-C61-butyric acid methyl ester (PCBM) interfaces using a combination of femtosecond broadband transient absorption (TA) spectroscopy and steady-state photoluminescence quenching measurements. We analyzed ultrafast electron injection and charge separation at PbS QD/PCBM interfaces for four different QD sizes and as a function of PCBM concentration. The results reveal that the energy band alignment, tuned by the quantum size effect, is the key element for efficient electron injection and charge separation processes. More specifically, the steady-state and time-resolved data demonstrate that only small-sized PbS QDs with a bandgap larger than 1 eV can transfer electrons to PCBM upon light absorption. We show that these trends result from the formation of a type-II interface band alignment, as a consequence of the size distribution of the QDs. Transient absorption data indicate that electron injection from photoexcited PbS QDs to PCBM occurs within our temporal resolution of 120 fs for QDs with bandgaps that achieve type-II alignment, while virtually all signals observed in smaller bandgap QD samples result from large bandgap outliers in the size distribution. Taken together, our results clearly demonstrate that charge transfer rates at QD interfaces can be tuned by several orders of magnitude by engineering the QD size distribution. The work presented here will advance both the design and the understanding of QD interfaces for solar energy conversion. PMID:24521255

  7. 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

  8. 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. PMID:25837010

  9. 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

  10. 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. PMID:24446756

  11. γ-Amino-butyric acid (GABA) receptor subunit and transporter expression in the gonad and liver of the fathead minnow (Pimephales promelas).

    PubMed

    Biggs, Katie; Seidel, Jason S; Wilson, Alex; Martyniuk, Christopher J

    2013-09-01

    γ-Amino-butyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate central nervous system. GABA receptors and synthesizing enzymes have also been localized to peripheral tissues including the liver, oviduct, uterus and ovary of mammals but the distribution and role of GABA in peripheral tissues of fish has not been fully investigated. The objectives of this study were to (1) determine if mRNA encoding GABA synthesizing enzymes (glutamic acid decarboxylase 65 and 67; gad65 and gad67), GABA transporters, and GABAA receptor subunits are localized to liver and gonad of fathead minnow (Pimephales promelas) (FHM) (2) investigate the effects of GABA on ovarian 17β-estradiol (E2) production, and (3) measure transcript responses in the ovary after in vitro incubation to GABA. Real-time PCR assays were developed for gad65, gad67, vesicular GABA transporter (vgat) and GABA transporter 1 (gat1), and select GABAA receptor subunits (gabra1, gabra5, gabrb1, gabrb2, gabrg1, gabrg2). All transcripts were localized to the brain as expected; however transcripts were also detected in the liver, ovary, and testis of FHMs. In the female liver, gad65 mRNA was significantly higher in expression compared to the male liver. Transcripts for gad67 were the highest in the brain>gonad>liver and in the gonads, gad67 was significantly higher in expression than gad65 mRNA. In the liver and gonad, the relative abundance of the subunits followed a general trend of gabrb1>gabrb2=gabrg1=gabrg2>gabra1=gabra5. To explore the effects of GABA in the ovary, tissue explants from reproductive female FHMs were treated with GABA (10(-10), 10(-8) and 10(-6)M) for 12h. GABA had no significant effect on 17β-estradiol production or on mRNA abundance for genes involved in ovarian steroidogenesis (e.g., 11βhsd, cyp17, cyp19a). There was a significant decrease in estrogen receptor 2a (esr2a) mRNA with 10(-10)M GABA. This study begins to investigate the GABA system in non-neural tissues of

  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. Preparation of chitin butyrate by using phosphoryl mixed anhydride system.

    PubMed

    Bhatt, Lok Ranjan; Kim, Bo Mi; Hyun, Kim; Kang, Kyung Hee; Lu, Chichong; Chai, Kyu Yun

    2011-04-01

    Acylation of chitin with butyric acid was performed in the presence of trifluoroacetic anhydride/phosphoric acid mediated system. The products were characterized by (1)H NMR and FT-IR spectroscopy and their solubility was tested in different organic solvents. Inclusion of butyric acid moieties into the parent molecule was confirmed from the (1)H NMR and FT-IR spectra. FT-IR analysis revealed that the degree of acid substitution (DS) of the products was in a range of 1.9-2.38, which increased with increasing the amounts of butyric acid added to the reaction system. Degree of N-deacetylation (DD) of the products, as determined by (1)H NMR was between 54.2% and 65.6%. The products with DS >2.0 were soluble in dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, methanol, acetone, chloroform, and acetic acid. PMID:21353204

  14. Strategies for production of butanol and butyl-butyrate through lipase-catalyzed esterification.

    PubMed

    Xin, Fengxue; Basu, Anindya; Yang, Kun-Lin; He, Jianzhong

    2016-02-01

    In this study, a fermentation process for production of butanol and butyl-butyrate by using Clostridium sp. strain BOH3 is developed. This strain is able to produce butyric acid and butanol when it ferments 60 g/L xylose. Meanwhile, it also excreted indigenous lipases (induced by olive oil) which naturally convert butyric acid and butanol into 1.2 g/L of butyl-butyrate. When Bio-OSR was used as both an inducer for lipase and extractant for butyl-butyrate, the butyl-butyrate concentration can reach 6.3 g/L. To further increase the yield, additional lipases and butyric acid are added to the fermentation system. Moreover, kerosene was used as an extractant to remove butyl-butyrate in situ. When all strategies are combined, 22.4 g/L butyl-butyrate can be produced in a fed-batch reactor spiked with 70 g/L xylose and 7.9 g/L butyric acid, which is 4.5-fold of that in a similar system (5 g/L) with hexadecane as the extractant. PMID:26710347

  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. 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. PMID:24860384

  17. 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.

  18. Mitochondria Targeted Peptides Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity

    PubMed Central

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y.; Luo, Guoxiong; Szeto, Hazel H.

    2009-01-01

    Abstract A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD. Antioxid. Redox Signal. 11, 2095–2104. PMID:19203217

  19. Rationale for the luminal provision of butyrate in intestinal diseases.

    PubMed

    Wächtershäuser, A; Stein, J

    2000-08-01

    Short chain fatty acids (SCFA), especially butyrate, play central metabolic roles in maintaining the mucosal barrier in the gut. A lack of SCFA, leading to endogenous starvation of enterocytes, may be the cause of ulcerative colitis and other inflammatory conditions. The main source of SCFA is dietary fibre, but they can also be derived from structured lipids, e. g. tributyrin. Once absorbed by non-ionic diffusion or carrier-mediated anion exchanges, SCFA are either used locally as fuel for the enterocytes or enter the portal bloodstream. Butyrate has been shown to increase wound healing and to reduce inflammation in the small intestine. In the colon, butyrate is the dominant energy source for epithelial cells and affects cellular proliferation and differentiation by yet unknown mechanisms. Recent data suggest that the luminal provision of butyrate may be an appropriate means to improve wound healing in intestinal surgery and to ameliorate symptoms of inflammatory bowel diseases. PMID:11079736

  20. 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...

  1. Regioselective synthesis of novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole and 2,2‧-(1,3-phenylene)bis(3-substituted-2-imino-4-phenyl-3H-thiazole) derivatives as antibacterial agents

    NASA Astrophysics Data System (ADS)

    Abbasi Shiran, Jafar; Yahyazadeh, Asieh; Mamaghani, Manouchehr; Rassa, Mehdi

    2013-05-01

    Several novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole derivatives were synthesized by the reaction of allyl-thioureas and 2-bromoacetophenone. We also report the synthesis of bis-allyl-3H thiazoles using the reaction of various isothiocyanates and 1,3-phenylenediamine. The structures of all compounds were characterized by spectral and elemental analysis. Most of the synthesized compounds exhibited efficient antibacterial activities against Salmonella enterica, Micrococcus luteus, Bacillus subtilis and Pseudomonas aeruginosa.

  2. 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.

  3. The Tinkerbell (Tink) Mutation Identifies the Dual-Specificity MAPK Phosphatase INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5) as a Novel Regulator of Organ Size in Arabidopsis.

    PubMed

    Johnson, Kim L; Ramm, Sascha; Kappel, Christian; Ward, Sally; Leyser, Ottoline; Sakamoto, Tomoaki; Kurata, Tetsuya; Bevan, Michael W; Lenhard, Michael

    2015-01-01

    Mitogen-activated dual-specificity MAPK phosphatases are important negative regulators in the MAPK signalling pathways responsible for many essential processes in plants. In a screen for mutants with reduced organ size we have identified a mutation in the active site of the dual-specificity MAPK phosphatase indole-3-butyric acid-response5 (IBR5) that we named tinkerbell (tink) due to its small size. Analysis of the tink mutant indicates that IBR5 acts as a novel regulator of organ size that changes the rate of growth in petals and leaves. Organ size and shape regulation by IBR5 acts independently of the KLU growth-regulatory pathway. Microarray analysis of tink/ibr5-6 mutants identified a likely role for this phosphatase in male gametophyte development. We show that IBR5 may influence the size and shape of petals through auxin and TCP growth regulatory pathways. PMID:26147117

  4. 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.

  5. Metabolic Activity of Fatty Acid-Oxidizing Bacteria and the Contribution of Acetate, Propionate, Butyrate, and CO2 to Methanogenesis in Cattle Waste at 40 and 60°C

    PubMed Central

    Mackie, Roderick I.; Bryant, Marvin P.

    1981-01-01

    The quantitative contribution of fatty acids and CO2 to methanogenesis was studied by using stirred, 3-liter bench-top digestors fed on a semicontinuous basis with cattle waste. The fermentations were carried out at 40 and 60°C under identical loading conditions (6 g of volatile solids per liter of reactor volume per day, 10-day retention time). In the thermophilic digestor, acetate turnover increased from a prefeeding level of 16 μM/min to a peak (49 μM/min) 1 h after feeding and then gradually decreased. Acetate turnover in the mesophilic digestor increased from 15 to 40 μM/min. Propionate turnover ranged from 2 to 5.2 and 1.5 to 4.5 μM/min in the thermophilic and mesophilic digestors, respectively. Butyrate turnover (0.7 to 1.2 μM/min) was similar in both digestors. The proportion of CH4 produced via the methyl group of acetate varied with time after feeding and ranged from 72 to 75% in the mesophilic digestor and 75 to 86% in the thermophilic digestor. The contribution from CO2 reduction was 24 to 29% and 19 to 27%, respectively. Propionate and butyrate turnover accounted for 20% of the total CH4 produced. Acetate synthesis from CO2 was greatest shortly after feeding and was higher in the thermophilic digestor (0.5 to 2.4 μM/min) than the mesophilic digestor (0.3 to 0.5 μM/min). Counts of fatty acid-degrading bacteria were related to their turnover activity. PMID:16345789

  6. 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

    2016-03-15

    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) (), [Cu(OCOPh)2L] (), [Cu(o-OCOC6H4OH)2L] (), [Cu(m-OCOC6H4OH)2L]·MeOH (·MeOH) and [Cu(p-OCOC6H4OH)2L]·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 , are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular ππ stacking interactions could also be found in (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 and ) and to an infinite 2D network (in ). Compounds and show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 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 , 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. PMID:26905013

  7. Amelioration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced behavioural dysfunction and oxidative stress by Pycnogenol in mouse model of Parkinson's disease.

    PubMed

    Khan, Mohammad Moshahid; Hoda, Md Nasrul; Ishrat, Tauheed; Ahmad, Ajmal; Khan, Mohammad Badruzzaman; Khuwaja, Gulrana; Raza, Syed Shadab; Safhi, Mohammed M; Islam, Fakhrul

    2010-09-01

    Increased oxidative stress is implicated in the pathogenesis of Parkinson's disease in which dopaminergic neurons are intrinsically susceptible to oxidative damage. Swiss albino mice were pretreated with Pycnogenol (PYC), an extract of Pinus maritime bark [20 mg/kg body weight, intraperitoneally (i.p.)] once daily for 15 days. Thereafter, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (20 mg/kg body weight, intraperitoneally) was given four times at 2-hour intervals on 1 day only. Behaviours were altered in the MPTP group as compared with the vehicle-treated group and were restored in the PYC-pretreated MPTP group. The activity of antioxidant enzymes and the content of glutathione were significantly depleted in the MPTP-induced Parkinsonian group. The MPTP group pretreated with PYC showed significant protection of the activity of antioxidant enzymes and glutathione content when compared with the vehicle-treated MPTP group. A significantly elevated level of thiobarbituric acid reactive substances in the MPTP group was decreased significantly in the animals pretreated with PYC. An increase in the number of dopaminergic D2 receptors and decrease in the level of dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid in the striatum were observed after MPTP injection, and restored significantly after PYC pretreatment. Thus, PYC may be used to prevent or reduce the deterioration caused by free radicals, thereby preventing subsequent behavioural and biochemical changes that occur in Parkinsonian mice. PMID:20657266

  8. Prevention of the nigrostriatal toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibitors of 3,4-dihydroxyphenylethylamine transport.

    PubMed

    Mayer, R A; Kindt, M V; Heikkila, R E

    1986-10-01

    The 3,4-dihydroxyphenylethylamine (DA, dopamine) uptake inhibitors GBR 13,069, amfonelic acid, WIN-35,065-2, WIN-35,428, nomifensine, mazindol, cocaine, McN-5908, McN-5847, and McN-5292 were effective in preventing [3H]DA and [3H]1-methyl-4-phenylpyridinium (MPP+) uptake in rat and mouse neostriatal tissue slices. These DA uptake inhibitors also were effective in attenuating the MPP+-induced release of [3H]DA in vitro. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to mice (6 X 25 mg/kg i.p.) resulted in a large (70-80%) decrement in neostriatal DA. WIN-35,428 (5 mg/kg), GBR 13,069 (10 mg/kg), McN-5292 (5 mg/kg), McN-5908 (2 mg/kg), and amfonelic acid (2 mg/kg), when administered intraperitoneally 30 min prior to each MPTP injection, fully protected against MPTP-induced neostriatal damage. Other DA uptake inhibitors showed partial protection in vivo at the doses selected. Desmethylimipramine did not prevent [3H]MPP+ uptake or MPP+-induced release of [3H]DA in vitro, and did not protect against MPTP neurotoxicity in vivo. These results support the hypothesis put forth previously by others that the active uptake of MPP+ by dopaminergic neurons is necessary for toxicity. PMID:3489072

  9. 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. PMID:25599616

  10. 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.

  11. Microbial electrosynthesis of butyrate from carbon dioxide.

    PubMed

    Ganigué, R; Puig, S; Batlle-Vilanova, P; Balaguer, M D; Colprim, J

    2015-02-21

    This work proves for the first time the bioelectrochemical production of butyrate from CO2 as a sole carbon source. The highest concentration of butyrate achieved was 20.2 mMC, with a maximum butyrate production rate of 1.82 mMC d(-1). The electrochemical characterisation demonstrated that the CO2 reduction to butyrate was hydrogen driven. Production of ethanol and butanol was also observed opening up the potential for biofuel production. PMID:25608945

  12. 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.

  13. Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat.

    PubMed Central

    Butzner, J D; Parmar, R; Bell, C J; Dalal, V

    1996-01-01

    BACKGROUND--The short chain fatty acid (SCFA) butyrate provides energy for colonocytes, stimulates colonic fluid and electrolyte absorption and is recognised as an effective treatment for multiple types of colitis. AIM--To examine the impact of butyrate enema therapy on the clinical course, severity of inflammation, and SCFA stimulated Na+ absorption in a chronic experimental colitis. METHODS--Distal colitis was induced in rats with a trinitrobenzenesulphonic acid (TNBS) enema. Five days after induction, rats were divided into groups to receive: no treatment, saline enemas, or 100 mM Na-butyrate enemas daily. On day 24, colonic damage score and tissue myeloperoxidase (MPO) activity were evaluated. Colon was mounted in Ussing chambers and Na+ transport and electrical activities were measured during a basal period and after stimulation with 25 mM butyrate. RESULTS--In the untreated and the saline enema treated TNBS groups, diarrhoea and extensive colonic damage were seen, associated with increased tissue MPO activities and absent butyrate stimulated Na+ absorption. In contrast, in the butyrate enema treated TNBS group, diarrhoea ceased, colonic damage score improved, and tissue MPO activity as well as butyrate stimulated Na+ absorption recovered to control values. CONCLUSION--Butyrate enema therapy stimulated colonic repair, as evidenced by clinical recovery, decreased inflammation, and restoration of SCFA stimulated electrolyte absorption. PMID:8707089

  14. 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. PMID:26510314

  15. Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors.

    PubMed

    Matsuda, T; Seong, Y H; Aono, H; Kanda, T; Baba, A; Saito, K; Tobe, A; Iwata, H

    1989-10-24

    We used an in vitro radioligand receptor binding assay with rat cerebral cortex, hippocampus and striatum membrane preparations to show that 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554) had much higher affinity for 5-HT1A recognition sites than for 5-HT1-non-A, 5-HT2, benzodiazepine, dopamine D-2 and alpha 2-adrenergic recognition sites. The compound inhibited the activity of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Intraperitoneal injection of BP-554 to mice decreased the concentration of only 5-hydroxy-indoleacetic acid of the amines and their metabolites in the brain and decreased the accumulation of 5-hydroxytryptophan in the brain after decarboxylase inhibition by 3-hydroxybenzylhydrazine. Furthermore, the administration of BP-554 caused hypothermia and increased serum corticosterone levels in mice. The observed effects of BP-554 were similar to those of 8-hydroxy-2-(di-n-propylamino)tetralin. These results suggest that BP-554 acts as a selective 5-HT1A receptor agonist in vivo. PMID:2533078

  16. (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

  17. Destructive effects of butyrate on the cell envelope of Helicobacter pylori.

    PubMed

    Yonezawa, Hideo; Osaki, Takako; Hanawa, Tomoko; Kurata, Satoshi; Zaman, Cynthia; Woo, Timothy Derk Hoong; Takahashi, Motomichi; Matsubara, Sachie; Kawakami, Hayato; Ochiai, Kuniyasu; Kamiya, Shigeru

    2012-04-01

    Helicobacter pylori can be found in the oral cavity and is mostly detected by the use of PCR techniques. Growth of H. pylori is influenced by various factors in the mouth, such as the oral microflora, saliva and other antimicrobial substances, all of which make colonization of the oral cavity by H. pylori difficult. In the present study, we analysed the effect of the cell supernatant of a representative periodontal bacterium Porphyromonas gingivalis on H. pylori and found that the cell supernatant destroyed the H. pylori cell envelope. As P. gingivalis produces butyric acid, we focused our research on the effects of butyrate and found that it significantly inhibited the growth of H. pylori. H. pylori cytoplasmic proteins and DNA were detected in the extracellular environment after treatment with butyrate, suggesting that the integrity of the cell envelope was compromised and indicating that butyrate has a bactericidal effect on H. pylori. In addition, levels of extracellular H. pylori DNA increased following treatment with the cell supernatant of butyric acid-producing bacteria, indicating that the cell supernatant also has a bactericidal effect and that this may be due to its butyric acid content. In conclusion, butyric acid-producing bacteria may play a role in affecting H. pylori colonization of the oral cavity. PMID:22194341

  18. 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. PMID:25659146

  19. Butyrate-rich colonic microenvironment is a relevant selection factor for metabolically adapted tumor cells.

    PubMed

    Serpa, Jacinta; Caiado, Francisco; Carvalho, Tânia; Torre, Cheila; Gonçalves, Luís G; Casalou, Cristina; Lamosa, Pedro; Rodrigues, Margarida; Zhu, Zhenping; Lam, Eric W F; Dias, Sérgio

    2010-12-10

    The short chain fatty acid (SCFA) butyrate is a product of colonic fermentation of dietary fibers. It is the main source of energy for normal colonocytes, but cannot be metabolized by most tumor cells. Butyrate also functions as a histone deacetylase (HDAC) inhibitor to control cell proliferation and apoptosis. In consequence, butyrate and its derived drugs are used in cancer therapy. Here we show that aggressive tumor cells that retain the capacity of metabolizing butyrate are positively selected in their microenvironment. In the mouse xenograft model, butyrate-preselected human colon cancer cells gave rise to subcutaneous tumors that grew faster and were more angiogenic than those derived from untreated cells. Similarly, butyrate-preselected cells demonstrated a significant increase in rates of homing to the lung after intravenous injection. Our data showed that butyrate regulates the expression of VEGF and its receptor KDR at the transcriptional level potentially through FoxM1, resulting in the generation of a functional VEGF:KDR autocrine growth loop. Cells selected by chronic exposure to butyrate express higher levels of MMP2, MMP9, α2 and α3 integrins, and lower levels of E-cadherin, a marker for epithelial to mesenchymal transition. The orthotopic model of colon cancer showed that cells preselected by butyrate are able to colonize the animals locally and at distant organs, whereas control cells can only generate a local tumor in the cecum. Together our data shows that a butyrate-rich microenvironment may select for tumor cells that are able to metabolize butyrate, which are also phenotypically more aggressive. PMID:20926374

  20. 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. PMID:26043725

  1. 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. PMID:27012776

  2. Butyrate inhibits inflammatory responses through NFκB inhibition: implications for Crohn's disease

    PubMed Central

    Segain, J; de la Bletiere, D R.; Bourreille, A; Leray, V; Gervois, N; Rosales, C; Ferrier, L; Bonnet, C; Blottiere, H; Galmiche, J

    2000-01-01

    BACKGROUND/AIM—Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFκB), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression.
METHODS—Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFκB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFκB inhibitory protein (IκBα) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis.
RESULTS—Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFκB from the cytoplasm to the nucleus. LPS induced NFκB transcriptional activity was decreased by butyrate while IκBα levels were stable. Butyrate treatment also improved TNBS induced colitis.
CONCLUSIONS—Butyrate decreases proinflammatory cytokine expression via inhibition of NFκB activation and IκBα degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.


Keywords: inflammation; butyrate; Crohn's disease; nuclear factor kappa B; cytokines PMID:10940278

  3. 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. PMID:26661480

  4. 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.

  5. The Dependence of Donor:Acceptor Ratio on the Photovoltaic Performances of Blended poly (3-octylthiophene-2,5-diyl) and (6,6)-phenyl C71 butyric acid methyl ester Bulk Heterojunction Organic Solar Cells

    NASA Astrophysics Data System (ADS)

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

    2010-10-01

    Bulk heterojunction organic solar cells using blended poly (3-octylthiophene-2,5-diyl)(P3OT) and (6,6)-phenyl C71 butyric acid methyl ester (PC71BM) have been fabricated. P3OT and PC71BM 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.

  6. 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

  7. Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells.

    PubMed

    Yan, Hui; Ajuwon, Kolapo M

    2015-01-01

    Short chain fatty acids (SCFA), products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity. PMID:26713737

  8. 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

  9. Structural and spectral perspectives of a novel thiosemicarbazone synthesized from di-2-pyridyl ketone and 4-phenyl-3-thiosemicarbazide

    NASA Astrophysics Data System (ADS)

    Suni, V.; Prathapachandra Kurup, M. R.; Nethaji, Munirathinam

    2006-01-01

    A new thiosemicarbazone, HL is synthesized from di-2-pyridyl ketone and 4-phenyl-3-thiosemicarbazide and structurally and spectrochemically characterized. 1H NMR, 13C NMR, COSY, HMQC and IR spectra of the compound are studied and the proton magnetic resonance spectrum reveals some unprecedented observations. The thione form is predominant in the solid state, as supported by the crystal structure and IR data, while a thiol-thione equilibrium is proposed in the solution state by NMR studies. The compound crystallizes into a monoclinic lattice with space group C2/c and the ZE conformation is exhibited by the thiosemicarbazone. Intra- and intermolecular hydrogen-bonding interactions give rise to a two-dimensional packing in the crystal lattice.

  10. Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP(+)).

    PubMed

    Kempuraj, Duraisamy; Thangavel, Ramasamy; Fattal, Ranan; Pattani, Sagar; Yang, Evert; Zaheer, Smita; Santillan, Donna A; Santillan, Mark K; Zaheer, Asgar

    2016-05-01

    Microglial activation and release of inflammatory cytokines and chemokines are crucial events in neuroinflammation. Microglial cells interact and respond to other inflammatory cells such as T cells and mast cells as well as inflammatory mediators secreted from these cells. Recent studies have shown that neuroinflammation causes and accelerates neurodegenerative disease such as Parkinson's disease (PD) pathogenesis. 1-methyl-4-phenyl-pyridinium ion (MPP(+)), the active metabolite of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine activates glial cells and mediate neurodegeneration through release of inflammatory mediators. We have shown that glia maturation factor (GMF) activates glia and induces neuroinflammation and neurodegeneration and that MPP(+) activates mast cells and release proinflammatory cytokines and chemokines. The chemokine (C-C motif) ligand 2 (CCL2) levels have been shown to be elevated and play a role in PD pathogenesis. In the present study, we analyzed if MPP(+) activates mouse and human mast cells to release chemokine CCL2. Mouse bone marrow-derived mast cells (BMMCs) and human umbilical cord blood-derived cultured mast cells (hCBMCs) were incubated with MPP(+) (10 µM) for 24 h and CCL2 levels were measured in the supernatant media by ELISA. MPP(+)-significantly induced CCL2 release from BMMCs and hCBMCs. Additionally, GMF overexpression in BMMCs obtained from wild-type mice released significantly more CCL2, while BMMCs obtained from GMF-deficient mice showed less CCL2 release. Further, we show that MPP(+)-induced CCL2 release was greater in BMMCs-astrocyte co-culture conditions. Uncoupling protein 4 (UCP4) which is implicated in neurodegenerative diseases including PD was detected in BMMCs by immunocytochemistry. Our results suggest that mast cells may play role in PD pathogenesis. PMID:26646004

  11. (E)-2-benzylidene-4-phenyl-1,3-diselenole has antioxidant and hepatoprotective properties against oxidative damage induced by 2-nitropropane in rats.

    PubMed

    Wilhelm, Ethel A; Jesse, Cristiano R; Bortolatto, Cristiani F; Nogueira, Cristina W

    2011-02-01

    The in vitro effect of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) was evaluated through iron/EDTA-induced thiobarbituric acid reactive species (TBARS) and reactive species (RS) determinations as well as of the scavenging 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical quantification. BPD at the concentrations of 10 and 50 μΜ decreased RS and TBARS levels, respectively. The antioxidant activity was not related to the scavenging DPPH radical mechanism. A second objective of this study was to investigate the hepatoprotective action of BPD, administered by oral route, against oxidative damage induced by 2-nitropropane (2-NP) (100 mg/kg of body weight) in liver of rats. At the dose of 50 mg/kg, BPD protected against the increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities induced by 2-NP. BPD (10 and 50 mg/kg) protected against the increase in TBARS levels and alkaline phosphatase (ALP) activity. Sections of liver from 2-NP-exposed rats presented intense infiltration of inflammatory cells and loss of cellular architecture. BPD (10 and 50 mg/kg) attenuated 2-NP-induced hepatic histological alterations. The inhibition of δ-aminolevulinic dehydratase (δ-ALA-D), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities and the decreased GSH levels caused by 2-NP were protected by BPD (50 mg/kg). Catalase activity and ascorbic acid levels were not altered by 2-NP. These results demonstrated the antioxidant and hepatoprotective effects of BPD in liver of rats. PMID:20141535

  12. Butyrate regulates the expression of inflammatory and chemotactic cytokines in human acute leukemic cells during apoptosis.

    PubMed

    Pulliam, Stephanie R; Pellom, Samuel T; Shanker, Anil; Adunyah, Samuel E

    2016-08-01

    Butyrate is a histone deacetylase inhibitor implicated in many studies as a potential therapy for various forms of cancer. High concentrations of butyrate (>1.5mM) have been shown to activate apoptosis in several cancer cell lines including prostate, breast, and leukemia. Butyrate is also known to influence multiple signaling pathways that are mediators of cytokine production. The purpose of this study was to evaluate the impact of high concentrations of butyrate on the cancer microenvironment vis-à-vis apoptosis, cellular migration, and capacity to modulate cytokine expression in cancer cells. The results indicate that high concentrations of butyrate induced a 2-fold activation of caspase-3 and reduced cell viability by 60% in U937 leukemia cells. Within 24h, butyrate significantly decreased the levels of chemokines CCL2 and CCL5 in HL-60 and U937 cells, and decreased CCL5 in THP-1 leukemia cells. Differential effects were observed in treatments with valproic acid for CCL2 and CCL5 indicating butyrate-specificity. Many of the biological effects examined in this study are linked to activation of the AKT and MAPK signaling pathways; therefore, we investigated whether butyrate alters the levels of phosphorylated forms of these signaling proteins and how it correlated with the expression of chemokines. The results show that butyrate may partially regulate CCL5 production via p38 MAPK. The decrease in p-ERK1/2 and p-AKT levels correlated with the decrease in CCL2 production. These data suggest that while promoting apoptosis, butyrate has the potential to influence the cancer microenvironment by inducing differential expression of cytokines. PMID:27253488

  13. Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis

    PubMed Central

    Zhang, Jintao; Yi, Man; Zha, Longying; Chen, Siqiang; Li, Zhijia; Li, Cheng; Gong, Mingxing; Deng, Hong; Chu, Xinwei; Chen, Jiehua; Zhang, Zheqing; Mao, Limei; Sun, Suxia

    2016-01-01

    Purpose Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells. Methods Human colorectal cancer cell lines (HCT-116 and HT-29) were treated with sodium butyrate at concentrations ranging from 0.5–5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining), and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot. Results Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagy-associated proteins, including microtubule-associated protein II light chain 3 (LC3-II), beclin-1, and autophagocytosis-associated protein (Atg)3. The autophagy inhibitors 3-methyladenine (3-MA) and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin

  14. Proliferative effects of gamma-amino butyric acid on oral squamous cell carcinoma cells are associated with mitogen-activated protein kinase signaling pathways.

    PubMed

    Ma, Jing; Zhang, Yan; Wang, Jun; Zhao, Tianyu; Ji, Ping; Song, Jinlin; Zhang, Hongmei; Luo, Wenping

    2016-07-01

    Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult mammalian central nervous system, has been reported to play an important physiological role in peripheral non-neuronal tissues, such as tumors. However, whether deregulated GABA is associated with oral squamous cell carcinoma (OSCC) is currently unknown. In this study, we investigated the effects of GABA on the proliferation of the OSCC cell line, Tca8113. Immunohistochemical analyses were performed to examine the expression of GABA A type receptor pi subunit (GABRP) in human OSCC tissues, and reverse transcription polymerase chain reaction, immunofluorescence staining and western blot analysis were performed to examine the expression of GABRP in Tca8113 cells. The proliferative effects of GABA on Tca8113 cells were analyzed by CCK-8 assay and flow cytometry. The activation status of mitogen-activated protein kinases (MAPKs) was examined by western blot analysis. GABRP expression was observed in the cytoplasm with a higher level in poorly differentiated OSCC tissues. The mRNA and protein expression levels of GABRP were detected in the Tca8113 cells. The addition of GABA and the GABA A type receptor agonist, Muscimol, promoted cell proliferation and inhibited cell apoptosis through the activation of the p38 MAPK and the inhibition of the JNK MAPK signaling pathways. These results imply a novel role of GABA in OSCC. PMID:27222045

  15. A novel approach for the characterization of a bilayer of phenyl-c71-butyric-acid-methyl ester and pentacene using ultraviolet photoemission spectroscopy and argon gas cluster ion beam sputtering process

    SciTech Connect

    Yun, Dong-Jin; Chung, JaeGwan; Jung, Changhoon; Chung, Yeonji; Kim, SeongHeon; Lee, Seunghyup; Kim, Ki-Hong; Han, Hyouksoo; Park, Gyeong-Su; Park, SungHoon

    2013-09-07

    The material arrangement and energy level alignment of an organic bilayer comprising of phenyl-c71-butyric-acid-methyl ester (PCBM-71) and pentacene were studied using ultraviolet photoelectron spectroscopy (UPS) and the argon gas cluster ion beam (GCIB) sputtering process. Although there is a small difference in the full width at half maximum of the carbon C 1s core level peaks and differences in the oxygen O 1s core levels of an X-ray photoemission spectroscopy spectra, these differences are insufficient to clearly distinguish between PCBM-71 and pentacene layers and to classify the interface and bulk regions. On the other hand, the valence band structures in the UPS spectra contain completely distinct configurations for the PCBM-71 and pentacene layers, even when they have similar atomic compositions. According to the valence band structures of the PCBM-71/pentacene/electrodes, the highest unoccupied molecular orbital (HOMO) region of pentacene is at least 0.8 eV closer to the Fermi level than that of PCBM-71 and it does not overlap with any of the chemical states in the valence band structure of PCBM-71. Therefore, by just following the variations in the area of the HOMO region of pentacene, the interface/bulk regions of the PCBM/pentacene layers were distinctly categorized. Besides, the variation of valence band structures as a function of the Ar GCIB sputtering time fully corroborated with the surface morphologies observed in the atomic force microscope images. In summary, we believe that the novel approach, which involves UPS analysis in conjunction with Ar GCIB sputtering, can be one of the best methods to characterize the material distribution and energy level alignments of stacks of organic layers.

  16. Ondansetron reverses anti-hypersensitivity from clonidine in rats following peripheral nerve injury: Role of γ-amino butyric acid in α2-adrenoceptor and 5-HT3 serotonin receptor analgesia

    PubMed Central

    Hayashida, Ken-ichiro; Kimura, Masafumi; Yoshizumi, Masaru; Hobo, Shotaro; Obata, Hideaki; Eisenach, James C.

    2012-01-01

    Introduction Monoaminergic pathways, impinging an α2-adrenoceptors and 5-HT3 serotonin receptors, modulate nociceptive transmission, but their mechanisms and interactions after neuropathic injury are unknown. Here we examine these interactions in rodents after nerve injury. Methods Male Sprague-Dawley rats following L5-L6 spinal nerve ligation (SNL) were used for either behavioral testing, in vivo microdialysis for γ-amino butyric acid (GABA) and acetylcholine release, or synaptosome preparation for GABA release. Results Intrathecal administration of the α2-adrenoceptor agonist (clonidine) and 5-HT3 receptor agonist (chlorophenylbiguanide) reduced hypersensitivity in SNL rats via GABA receptor-mediated mechanisms. Clonidine increased GABA and acetylcholine release in vivo in the spinal cord of SNL rats but not in normal rats. Clonidine-induced spinal GABA release in SNL rats was blocked by α2-adrenergic and nicotinic cholinergic antagonists. The 5-HT3 receptor antagonist ondansetron decreased and chlorophenylbiguanide increased spinal GABA release in both normal and SNL rats. In synaptosomes from the spinal dorsal horn of SNL rats, pre-synaptic GABA release was increased by nicotinic agonists and decreased by muscarinic and α2-adrenergic agonists. Spinally administered ondansetron significantly reduced clonidine-induced anti-hypersensitivity and spinal GABA release in SNL rats. Conclusion These results suggest that spinal GABA contributes to anti-hypersensitivity from intrathecal α2-adrenergic and 5-HT3 receptor agonists in the neuropathic pain state, that cholinergic neuroplasticity after nerve injury is critical for α2-adrenoceptor-mediated GABA release, and that blockade of spinal 5-HT3 receptors reduces α2-adrenoceptor-mediated anti-hypersensitivity via reducing total GABA release. PMID:22722575

  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. PMID:26655363

  18. INDUCTION OF APOPTOSIS BY BUTYRATE CORRELATES WITH INCREASING LEVEL OF PROTEIN UBIQUITINATION IN BOVINE KIDNEY EPITHELIAL CELLS (MDBK)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While butyrate (BT) is largely regarded as the minor short-chain fatty acid ([butyrate]< [acetate] or [proiponate]) formed during microbial fermatation in ruminants, an increasing body of evidence has clearly shown effects beyond those attributable to its function in nutrition. BT modulates cell d...

  19. 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

  20. 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

  1. 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

  2. 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-INDUCED DAMAGE OF STRIATAL DOPAMINERGIC FIBERS ATTENUATES SUBSEQUENT ASTROCYTE RESPONSE TO MPTP

    EPA Science Inventory

    Acute administration of the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the C57B1/6 mouse caused a rapid decrease in the amount of striatal tyrosine hydroxylase (TH), a marker of dopaminergic neurons, followed by a large increase in the astr...

  3. 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…

  4. NEUROTOXICANT 1-METHYL-4-PHENYL-1,2,36-TETRAHYDROPYRIDINE (MPTP) ALTERS IMMUNE FUNCTION WHEN GIVEN IN COMBINATION WITH DIETHYLDITHIOCARBAMATE (DDC)

    EPA Science Inventory

    The T-cell suppression induced by the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be reversed if treatment is proceeded by low dosages of diethyldithocarbamate (DDC). owever, if the dosage of DDC is high enough to potentiate the neurotoxici...

  5. Facile N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the flavin-containing monooxygenase. A convenient synthesis of tritiated (methyl-/sup 3/H)-4-phenyl-2,3-dihydropyridinium species

    SciTech Connect

    Cashman, J.R.

    1988-06-01

    A rapid, efficient procedure useful for the radiosynthesis of (Me-/sup 3/H)-MPDP+ ((methyl-/sup 3/H)-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms (Me-/sup 3/H)-MPTP to its corresponding radiolabeled N-oxide. For the small-scale synthesis required for radiolabeling procedures, this enzymatic process is superior to H/sub 2/O/sub 2/-mediated N-oxygenation of MPTP. In the presence of 0.5 mM NADPH, 4.5 mM n-octylamine, and 2 microCi (Me-/sup 3/H)-MPTP, the only product detected in extracts from incubations performed with hog liver microsomes or purified hog liver flavin-containing monooxygenase is (Me-/sup 3/H)-MPTP N-oxide. (Me-/sup 3/H)-MPTP N-oxide is almost completely converted to (Me-/sup 3/H)-MPDP+ by the action of trifluoroacetic anhydride. This procedure has the advantage of using a commercially available tritiated starting material, efficient transformations, and easily accomplished purification to afford a rapid synthesis of (Me-/sup 3/H)-MPDP+.

  6. 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. PMID:25171217

  7. 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

  8. Upregulation of genes related to bone formation by γ-amino butyric acid and γ-oryzanol in germinated brown rice is via the activation of GABAB-receptors and reduction of serum IL-6 in rats

    PubMed Central

    Muhammad, Sani Ismaila; Maznah, Ismail; Mahmud, Rozi; Zuki, Abu Bakar Zakaria; Imam, Mustapha Umar

    2013-01-01

    Background Osteoporosis and other bone degenerative diseases are among the most challenging non-communicable diseases to treat. Previous works relate bone loss due to osteoporosis with oxidative stress generated by free radicals and inflammatory cytokines. Alternative therapy to hormone replacement has been an area of interest to researchers for almost three decades due to hormone therapy-associated side effects. Methods In this study, we investigated the effects of gamma-amino butyric acid (GABA), gamma-oryzanol (ORZ), acylated steryl glucosides (ASG), and phenolic extracts from germinated brown rice (GBR) on the expression of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2), secreted protein acidic and rich in cysteine (SPARC), runt-related transcription factor 2 (RUNX-2), osteoblast-specific transcription factor osterix (Osx), periostin, osteoblast specific factor (Postn), collagen 1&2 (Col1&2), calcitonin receptor gene (CGRP); body weight measurement and also serum interleukin-6 (IL-6) and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and ASG at (100 and 200 mg/kg); estrogen (0.2 mg/kg), or remifemin (10 and 20 mg/kg), compared to ovariectomized non-treated group as well as non-ovariectomized non-treated (sham) group. Enzyme-linked immunosorbent assay was used to measure the IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the bone tissue was determined using the Genetic Analysis System (Beckman Coulter Inc., Brea, CA, USA). Results The results indicate that groups treated with GABA (100 and 200 mg/kg) showed significant upregulation of SPARC, calcitonin receptor, and BMP-2 genes (P < 0.05), while the ORZ-treated group (100 and 200 mg/kg) revealed significant (P < 0.05) upregulation of Osx, Postn, RUNX-2, and Col1&2. Similarly, IL-6 concentration decreased, while osteocalcin levels increased significantly (P < 0.05) in the treated groups as compared to ovariectomized non

  9. Synthesis, Fungicidal Activity and Mode of Action of 4-Phenyl-6-trifluoromethyl-2-aminopyrimidines against Botrytis cinerea.

    PubMed

    Liu, Chunhui; Cui, Zining; Yan, Xiaojing; Qi, Zhiqiu; Ji, Mingshan; Li, Xinghai

    2016-01-01

    Anilinopyrimidines are the main chemical agents for management of Botrytis cinerea. However, the drug resistance in fungi against this kind of compounds is very serious. To explore new potential fungicides against B. cinerea, a series of 4-phenyl-6-trifluoromethyl-2-amino-pyrimidine compounds (compounds III-1 to III-22) were synthesized, and their structures were confirmed by ¹H-NMR, IR and MS. Most of these compounds possessed excellent fungicidal activity. The compounds III-3 and III-13 showed higher fungicidal activity than the positive control pyrimethanil on fructose gelatin agar (FGA), and compound III-3 on potato dextrose agar (PDA) indicated high activity compared to the positive control cyprodinil. In vivo greenhouse results indicated that the activity of compounds III-3, III-8, and III-11 was significantly higher than that of the fungicide pyrimethanil. Scanning electron micrography (SEM) and transmission electron micrography (TEM) were applied to illustrate the mechanism of title compounds against B. cinerea. The title compounds, especially those containing a fluorine atom at the ortho-position on the benzene ring, could maintain the antifungal activity against B. cinerea, but their mechanism of action is different from that of cyprodinil. The present study lays a good foundation for us to find more efficient reagents against B. cinerea. PMID:27347910

  10. 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

  11. 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

  12. 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

  13. e-Cadherin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson Disease

    PubMed Central

    Cataldi, Samuela; Codini, Michela; Hunot, Stéphane; Légeron, François-Pierre; Ferri, Ivana; Siccu, Paola; Sidoni, Angelo; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Curcio, Francesco; Albi, Elisabetta

    2016-01-01

    Today a large number of studies are focused on clarifying the complexity and diversity of the pathogenetic mechanisms inducing Parkinson disease. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that induces Parkinson disease, to evaluate the change of midbrain structure and the behavior of the anti-inflammatory factor e-cadherin, interleukin-6, tyrosine hydroxylase, phosphatase and tensin homolog, and caveolin-1. The results showed a strong expression of e-cadherin, variation of length and thickness of the heavy neurofilaments, increase of interleukin-6, and reduction of tyrosine hydroxylase known to be expression of dopamine cell loss, reduction of phosphatase and tensin homolog described to impair responses to dopamine, and reduction of caveolin-1 known to be expression of epithelial-mesenchymal transition and fibrosis. The possibility that the overexpression of the e-cadherin might be implicated in the anti-inflammatory reaction to MPTP treatment by influencing the behavior of the other analyzed molecules is discussed. PMID:27194825

  14. Restricted Distribution of the Butyrate Kinase Pathway among Butyrate-Producing Bacteria from the Human Colon

    PubMed Central

    Louis, Petra; Duncan, Sylvia H.; McCrae, Sheila I.; Millar, Jacqueline; Jackson, Michelle S.; Flint, Harry J.

    2004-01-01

    The final steps in butyrate synthesis by anaerobic bacteria can occur via butyrate kinase and phosphotransbutyrylase or via butyryl-coenzyme A (CoA):acetate CoA-transferase. Degenerate PCR and enzymatic assays were used to assess the presence of butyrate kinase among 38 anaerobic butyrate-producing bacterial isolates from human feces that represent three different clostridial clusters (IV, XIVa, and XVI). Only four strains were found to possess detectable butyrate kinase activity. These were also the only strains to give PCR products (verifiable by sequencing) with degenerate primer pairs designed within the butyrate kinase gene or between the linked butyrate kinase/phosphotransbutyrylase genes. Further analysis of the butyrate kinase/phosphotransbutyrylase genes of one isolate, L2-50, revealed similar organization to that described previously from different groups of clostridia, along with differences in flanking sequences and phylogenetic relationships. Butyryl-CoA:acetate CoA-transferase activity was detected in all 38 strains examined, suggesting that it, rather than butyrate kinase, provides the dominant route for butyrate formation in the human colonic ecosystem that contains a constantly high concentration of acetate. PMID:15028695

  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. 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.

  19. Synthesis and enantioselectivity of optically active 1- and 3-substituted 4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols and related compounds as norepinephrine potentiators.

    PubMed

    Kihara, M; Ikeuchi, M; Adachi, S; Nagao, Y; Moritoki, H; Yamaguchi, M; Taira, Z

    1995-09-01

    Optically active 1,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (1R,4R-3a and 1S,4S-3b, 1S,4R-4a, and 1R,4S-4b) and 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines (4S-5a and 4R-5b) were prepared in order to examine the effects of the 1-, 3-, and 4-substituents of 2-methyl-4-phenyl- 1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) on the enantioselectivity for norepinephrine (NE) potentiating activity. The conformations and absolute configurations of 3-5 were determined from their 1H-NMR and circular dichroism (CD) spectra and by single-crystal X-ray diffractometric analysis. The NE potentiating activity of the optically active 3-5 and previously prepared 3-methyl derivatives (3R,4R-6a and 3S,4S-6b) of PI-OH were tested. The results show that compounds 3, 4, and 6 had high enantioselectivity for NE potentiation: the 4R series of the enantiomers exhibited activity but not the 4S-enantiomers. The activity of the 4-desoxy compound 5 also resided exclusively in the 4S-enantiomer. These findings suggest the presence of a specific receptor for NE uptake, and the enantiomers 3a, 4a, 5a, and 6a may be antagonistic at this NE uptake receptor. PMID:7586079

  20. 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...

  1. Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretion and MAPK signaling pathway

    PubMed Central

    Jung, Tae-Hwan; Park, Jeong Hyeon; Han, Kyoung-Sik

    2015-01-01

    BACKGROUND/OBJECTIVES Fermentation of dietary fiber results in production of various short chain fatty acids in the colon. In particular, butyrate is reported to regulate the physical and functional integrity of the normal colonic mucosa by altering mucin gene expression or the number of goblet cells. The objective of this study was to investigate whether butyrate modulates mucin secretion in LS174T human colorectal cells, thereby influencing the adhesion of probiotics such as Lactobacillus and Bifidobacterium strains and subsequently inhibiting pathogenic bacteria such as E. coli. In addition, possible signaling pathways involved in mucin gene regulation induced by butyrate treatment were also investigated. MATERIALS/METHODS Mucin protein content assay and periodic acid-Schiff (PAS) staining were performed in LS174T cells treated with butyrate at various concentrations. Effects of butyrate on the ability of probiotics to adhere to LS174T cells and their competition with E. coli strains were examined. Real time polymerase chain reaction for mucin gene expression and Taqman array 96-well fast plate-based pathway analysis were performed on butyrate-treated LS174T cells. RESULTS Treatment with butyrate resulted in a dose-dependent increase in mucin protein contents in LS174T cells with peak effects at 6 or 9 mM, which was further confirmed by PAS staining. Increase in mucin protein contents resulted in elevated adherence of probiotics, which subsequently reduced the adherent ability of E. coli. Treatment with butyrate also increased transcriptional levels of MUC3, MUC4, and MUC12, which was accompanied by higher gene expressions of signaling kinases and transcription factors involved in mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS Based on our results, butyrate is an effective regulator of modulation of mucin protein production at the transcriptional and translational levels, resulting in changes in the adherence of gut microflora. Butyrate

  2. 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

  3. 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. PMID:25172888

  4. Butyrate and glucose metabolism by colonocytes in experimental colitis in mice

    PubMed Central

    Ahmad, M; Krishnan, S; Ramakrishna, B; Mathan, M; Pulimood, A; Murthy, S

    2000-01-01

    oxidation.


Keywords: butyrate; colonocytes; dextran sulphate sodium; cell metabolism; short chain fatty acids; ulcerative colitis PMID:10716678

  5. Direct block of the cystic fibrosis transmembrane conductance regulator Cl(-) channel by butyrate and phenylbutyrate.

    PubMed

    Linsdell, P

    2001-01-12

    Chloride permeation through the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is inhibited by a broad range of intracellular organic anions. Here it is shown, using patch clamp recording from CFTR-transfected mammalian cell lines, that the fatty acids butyrate and 4-phenylbutyrate cause a voltage-dependent block of CFTR Cl(-) currents when applied to the cytoplasmic face of membrane patches, with apparent K(d)s (at 0 mV) of 29.6 mM for butyrate and 6.6 mM for 4-phenylbutyrate. At the single channel level, both these fatty acids caused an apparent reduction in CFTR current amplitude, suggesting a kinetically fast blocking mechanism. The concentration-dependence of block suggests that CFTR-mediated Cl(-) currents in vivo may be affected by both 4-phenylbutyrate used in the treatment of various diseases, including cystic fibrosis, and by butyrate produced endogenously within the colonic lumen. PMID:11164382

  6. 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. PMID:22080572

  7. Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

    PubMed

    Mitchell, I J; Clarke, C E; Boyce, S; Robertson, R G; Peggs, D; Sambrook, M A; Crossman, A R

    1989-01-01

    The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was either (a) administered intravenously to induce generalized Parkinsonism, or (b) infused into one carotid artery to induce unilateral Parkinsonism. Post-mortem examination revealed profound cell loss from the substantia nigra, pars compacta either bilaterally or unilaterally in the two groups, respectively. In addition, there was pathological involvement of the ventral tegmental area and locus coeruleus in animals receiving intravenous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2-Deoxyglucose autoradiography revealed widespread changes in 2-deoxyglucose uptake in the brains of parkinsonian animals when compared to controls. Most of these changes were in basal ganglia and related structures and were qualitatively similar in the two groups of experimental animals. Prominent increases in 2-deoxyglucose uptake were observed in the lateral segment of the globus pallidus (24-27%), the ventral anterior and ventral lateral nuclei of the thalamus (14-22%) and the nucleus tegmenti pedunculopontinus of the caudal midbrain (17-69%). A profound decrease (17-26%) in 2-deoxyglucose uptake was observed in the subthalamic nucleus. We propose these data to indicate that in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism there is the following pattern of abnormal neuronal activity in basal ganglia circuitry: (i) increased activity in the projection from the putamen to the lateral segment of the globus pallidus; (ii) decreased activity in the projection from the putamen to the medial segment of the globus pallidus; (iii) decreased activity in the projection from the lateral segment of the globus pallidus to the subthalamic nucleus; (iv) increased activity in the

  8. Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

    PubMed

    Aguilar, Edenil C; Santos, Lana Claudinez Dos; Leonel, Alda J; de Oliveira, Jamil Silvano; Santos, Elândia Aparecida; Navia-Pelaez, Juliana M; da Silva, Josiane Fernandes; Mendes, Bárbara Pinheiro; Capettini, Luciano S A; Teixeira, Lilian G; Lemos, Virginia S; Alvarez-Leite, Jacqueline I

    2016-08-01

    Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. PMID:27261536

  9. 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 ...

  10. 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...

  11. Conformational polymorphs of isobutyl-6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate: spectroscopic, structural and DFT approach.

    PubMed

    Prasad, A Aditya; Kumar, C Udhaya; Prakasam, B Arul; Meenakshisundaram, S P

    2016-06-01

    The crystal structure of a new crystalline phase, polymorph (II) of isobutyl-6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate, was accurately determined by single-crystal X-ray diffraction analysis providing a clean identification of polymorphic forms. Comparison with a known phase, referred to as polymorph (I), reveals the type of supramolecular assembly. Inter- and intramolecular hydrogen-bonding interactions exhibit various supramolecular architectures in crystal packing and these variations confirm well the polymorphism in isobutyl-6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate (IAPC) crystal structure. Crystal cohesion is achieved by N-H...N, N-H...O and C-H...H-C interactions, responsible for the formation and strengthening of the supramolecular assembly. The objective of this investigation is to study crystalline forms which can offer enhanced physicochemical properties, and also to recognize the molecular orientations between such forms. The conformational polymorphs of IAPC were compared spectroscopically by FT-IR and FT-Raman. The bulk phases were studied by X-ray powder diffraction patterns. External morphology was investigated using scanning electron microscopic images. The molecular interactions were quantified using Hirshfeld surface and fingerprint analysis. Density functional theory (DFT) computations were used to optimize the structure. The optimized structure is further subjected to an analysis of Mulliken population, natural population and electrostatic potential. PMID:27240761

  12. Synthesis, infrared spectral studies and theoretical calculations of 4-phenyl-4,5-dihydrobenzo[ f][1,4]oxazepin-3(2 H)-one (thione)

    NASA Astrophysics Data System (ADS)

    Agirbas, Hikmet; Sagdinc, Seda; Kandemirli, Fatma; Kemal, Berat

    2008-12-01

    Salicylaldehyde (1) was reacted with aniline to afford 2-[( E)-(phenylimino)methyl]phenol (2). The reduction of (2) by NaBH 4 gave 2-((phenylamino)methyl)phenol ( 3) which was reacted with chloroacetyl chloride to give 2-chloro- N-(2-hydroxybenzyl)- N-phenylacetamide ( 4). Compound ( 4) was cyclized to 4-phenyl-4,5-dihydrobenzo[ f][1,4]oxazepin-3( 2H)-one (5) by NaOH in ethanol solution. The treatment of compound (5) with P 2S 5 gave corresponding 4-phenyl-4,5-dihydrobenzo[ f][1,4]oxazepin-3( 2H)-thione (6). The structures of (5) and (6) were determined by 1H NMR and IR spectra. The optimized structural parameters and vibrational frequencies of (5) and (6) were calculated by DFT with 6-31G(d,p) basis set. The mechanism of the cyclization reaction was studied by RHF with the standard 3-21G basis set.

  13. Ampelopsis Radix Protects Dopaminergic Neurons against 1-Methyl-4-phenylpyridinium/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Toxicity in Parkinson's Disease Models In Vitro and In Vivo

    PubMed Central

    Shim, Jin Sup; Lee, Hyejung; Oh, Myung Sook

    2013-01-01

    Ampelopsis Radix, the root of Ampelopsis japonica (Thunb.) Makino (Vitaceae), is a herbal medicine which has been widely used in East Asia. The present study was done to explore whether the standardized extract of Ampelopsis Radix (AJW) protects dopaminergic neurons via antioxidant mechanisms in Parkinson's disease (PD) models. The effects of AJW on primary mesencephalic cultures stressed with 1-methyl-4-phenylpyridinium were investigated using tyrosine hydroxylase (TH) immunohistochemistry and reactive oxygen species measurement. The eliminative effects of AJW on the 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radicals were explored using colorimetric methods. The effects of AJW on the mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were determined by pole test as well as TH and 8-hydroxydeoxyguanosine immunohistochemistry. AJW protected dopaminergic neurons by inhibiting reactive oxygen species generation in vitro. Moreover, AJW showed potent radical scavenging activities in vitro. In the mouse PD model, AJW protected the dopaminergic neurons in the brain, leading to motor improvements. AJW inhibited the MPTP-evoked accumulation of 8-hydroxydeoxyguanosine in the brain. These data suggest that AJW has neuroprotective effects with antioxidant mechanisms in PD models. PMID:24204389

  14. 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

  15. Concentration of clobetasone butyrate in aqueous humour.

    PubMed Central

    Debnath, S C; Richards, A B

    1983-01-01

    The concentrations of clobetasone butyrate and betamethasone were measured in aqueous humour of patients undergoing cataract extraction 12.5 to 18.5 hours after application into the lower conjunctival sac of an ointment containing 0.1% of the steroid. Samples were assayed from 10 patients receiving clobetasone butyrate and 13 patients receiving betamethasone phosphate. There were measurable concentrations in only 2 samples in the former group, and both were 0.1 ng/ml. In the betamethasone group measurable concentrations were found in 11 samples, and the concentrations ranged from 0.5 to 20.3 ng/ml, with the highest concentrations between 12.5 and 13.5 hours after application. The concentration of betamethasone in the aqueous humour decreased by about 90% in the 6 hours from 12.5 to 18.5 hours after application. It is speculative as to whether it is these differences in pharmacokinetic behaviour, or other differences in biological or physicochemical properties, which are responsible for the minimal effect on intraocular pressure induced by clobetasone butyrate compared with betamethasone. PMID:6824626

  16. 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.

  17. Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

    PubMed Central

    Vila, Miquel; Jackson-Lewis, Vernice; Vukosavic, Slobodanka; Djaldetti, Ruth; Liberatore, Gabriel; Offen, Daniel; Korsmeyer, Stanley J.; Przedborski, Serge

    2001-01-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis. In adult mice, there is an up-regulation of Bax in the SNpc after MPTP administration and a decrease in Bcl-2. These changes parallel MPTP-induced dopaminergic neurodegeneration. We also show that mutant mice lacking Bax are significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that Bax plays a critical role in the MPTP neurotoxic process and suggests that targeting Bax may provide protective benefit in the treatment of Parkinson's disease. PMID:11226327

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    2-Amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[3,2- c]pyran-3-carbonitrile, C16H12N2O3 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. P21/ 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.

  19. Synthesis, characterization, and crystal structure of 2-amino-5-oxo-4-phenyl-4,5-dihydropyrano[3,2- c]chromene-3-carbonitrile

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    The title compound, 2-amino-5-oxo-4-phenyl-4,5-dihydropyrano[3,2- c]chromene-3-carbonitrile was synthesized in excellent yield by one-pot multicomponent reaction and its crystal structure is determined by X-ray structure analysis. The crystals are monoclinic, sp. gr. P21/ c, a = 9.0750(6), b = 13.2729(8), c = 12.6892(9) Å, β = 96.975(6)°, Z = 4; R = 0.0466 for 1771 observed reflections. The crystal structure is stabilized by N-H···N, N-H···O and C-H···O hydrogen bonds. In addition, C-H···π and π···π interactions are observed in the crystal structure.

  20. Altered nitric oxide production in mouse brain after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin or methamphetamine.

    PubMed

    Halász, A S; Pálfi, M; Tábi, T; Magyar, K; Szöko, E

    2004-06-01

    Several studies have demonstrated the involvement of reactive nitrogen and oxygen species (RNOS) in the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin (MPTP) and methamphetamine (METH), so the contribution of altered nitric oxide synthase (NOS) enzyme function can be suspected. In this study, about 50% increase in nitric oxide (NO) production in the mouse striatum was found between 4 and 12 h after a single MPTP injection, allowing an increased peroxynitrite (ONOO-) formation in the target brain region. However, METH injection induced a rapid decrease of NO formation both in mouse striatum and hippocampus, reaching its minimum level at 2 h, and restored to the control value after 6 h in the striatum and 12 h in the hippocampus. The uncoupled function of NOS with increased superoxide (O2*-) production after METH injection is suggested. PMID:15016479

  1. Synthesis of 2-amino-8-chloro-4-phenyl-5,11-dihydro-6H-pyrido[2,3-a]carbazole-3-carbonitrile: Structural and biological evaluation

    NASA Astrophysics Data System (ADS)

    Indumathi, Thangavel; Fronczek, Frank R.; Rajendra Prasad, K. J.

    2012-05-01

    The title compound 2-amino-8-chloro-4-phenyl-5,11-dihydro-6H-pyrido[2,3-a]carbazole-3-carbonitrile was prepared in good yield by multicomponent reaction under L-proline as promoter structure of the prepared compound was studied and characterized using IR, 1H and 13C NMR spectroscopic techniques. The crystal structure of the compound was determined by X-ray diffraction on single crystals. The spectroscopic experimental evidences strongly suggested that the compound could interact with calf thymus DNA (CT-DNA) through intercalation. The cytotoxicity was evaluated by Sulforhodamine B assay against A-549, B16F10, HCT-15, SKMel2 and SKOV3 cell lines and compared with standard drug cisplatin. The title compound bearing the chloro group depicted better and selective cytotoxicity against SKMel2 cell line. The compound showed moderate capacity for scavenging DPPH.

  2. 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. PMID:24270685

  3. Increased growth of Bifidobacterium and Eubacterium by germinated barley foodstuff, accompanied by enhanced butyrate production in healthy volunteers.

    PubMed

    Kanauchi, O; Fujiyama, Y; Mitsuyama, K; Araki, Y; Ishii, T; Nakamura, T; Hitomi, Y; Agata, K; Saiki, T; Andoh, A; Toyonaga, A; Bamba, T

    1999-02-01

    Germinated barley foodstuff (GBF) derived from the aleurone and scutellum fractions of germinated barley mainly consists of low-lignified hemicellulose and glutamine-rich protein. GBF improves the proliferation of intestinal epithelial cells and defecation, through the bacterial production of short chain fatty acids (SCFA), especially butyrate. In this study we investigated the mechanism of production of butyrate by microflora in humans and in vitro. Daily administration of 9 g GBF for 14 successive days significantly increased fecal butyrate content. Fecal Bifidobacterium and Eubacterium were also significantly increased by GBF administration in healthy volunteers. Ten anaerobic micro-organisms selected from intestinal microflora were cultured in vitro in the medium containing GBF as a sole carbon source (GBF medium). After a 3-day incubation, 7 strains (Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei subsp. casei, Bacteroides ovatus, Clostridium butyricum, and Eubacterium limosum) lowered the medium pH producing SCFA. Eubacterium grown together with Bifidobacterium in GBF medium efficiently produced butyrate. On the other hand, GBF changed the intestinal microflora and increased probiotics such as Bifidobacterium in the intestinal tract. As a result, butyrate was produced by the mutual action of Eubacterium and Bifidobacterium. This butyrate is considered to enhance the proliferation of colonic epithelial cells. PMID:9917526

  4. 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. PMID:23300800

  5. 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

  6. 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

  7. 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. PMID:26420851

  8. Fed-batch strategies using butyrate for high cell density cultivation of Pseudomonas putida and its use as a biocatalyst.

    PubMed

    Cerrone, Federico; Duane, Gearoid; Casey, Eoin; Davis, Reeta; Belton, Ian; Kenny, Shane T; Guzik, Maciej W; Woods, Trevor; Babu, Ramesh P; O'Connor, Kevin

    2014-11-01

    A mathematically based fed-batch bioprocess demonstrated the suitability of using a relatively cheap and renewable substrate (butyric acid) for Pseudomonas putida CA-3 high cell density cultivation. Butyric acid fine-tuned addition is critical to extend the fermentation run and avoid oxygen consumption while maximising the biomass volumetric productivity. A conservative submaximal growth rate (μ of 0.25 h(-1)) achieved 71.3 g L(-1) of biomass after 42 h of fed-batch growth. When a more ambitious feed rate was supplied in order to match a μ of 0.35 h(-1), the volumetric productivity was increased to 2.0 g L(-1) h(-1), corresponding to a run of 25 h and 50 g L(-1) of biomass. Both results represent the highest biomass and the best biomass volumetric productivity with butyrate as a sole carbon source. However, medium chain length polyhydroxyalkanoate (mcl-PHA) accumulation with butyrate grown cells is low (4 %). To achieve a higher mcl-PHA volumetric productivity, decanoate was supplied to butyrate grown cells. This strategy resulted in a PHA volumetric productivity of 4.57 g L(-1) h(-1) in the PHA production phase and 1.63 g L(-1) h(-1)over the lifetime of the fermentation, with a maximum mcl-PHA accumulation of 65 % of the cell dry weight. PMID:25104034

  9. Age and Region-Specific Responses of Microglia, but not Astrocytes, Suggest a Role in Selective Vulnerability of Dopamine Neurons After 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Exposure in Monkeys

    PubMed Central

    KANAAN, NICHOLAS M.; KORDOWER, JEFFREY H.; COLLIER, TIMOTHY J.

    2012-01-01

    Little is known about the effects of aging, the strongest risk factor for Parkinson’s disease (PD), on glial responses to dopamine (DA) neuron degeneration in midbrain subregions that display selective vulnerability to degeneration. We evaluated the impact of aging on astrocytes and microglia in a regionally specific manner in a monkey model of PD. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was delivered unilaterally via the internal carotid artery of young, middle-aged, and old-aged rhesus monkeys. Astrocytes and microglia were identified using glial fibrillary acidic protein and human leukocyte antigen-DR (HLA-DR) immunolabeling, respectively. Glial reactivity was assessed using (1) stereological cell counting, (2) fluorescence intensity, and (3) a morphology rating scale. In the midbrain contralateral and ipsilateral to the MPTP injection, astrocyte number and intensity did not change with age. In both sides of the midbrain, cellular morphology suggested astrocyte hypertrophy in middle-age dissipated in old-age, irrespective of DA subregion and regional differences in vulnerability to degeneration. In the contralateral midbrain, microglia became mildly activated (increased cell number and intensity, and morphological changes) with advancing age. Inflammation was evident at 3 months postlesion by severe microglial activation in the ipsilateral midbrain. HLA-DR fluorescence intensity and an abundance of activated microglia (based on morphological criteria) were consistently exacerbated in the vtSN of both sides of the midbrain. These results suggest the glial responses accompanying aging and DA neuron degeneration following a toxic insult represent persistent alterations in the microenvironment of surviving DA neurons that are important factors in understanding regional differences in susceptibility to degeneration. PMID:18484101

  10. Genome-wide ChIP-seq mapping and analysis of butyrate-induced H3K9 and H3K27 acetylation and epigenomic landscapes alteration in bovine cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Volatile short-chain fatty acids (VFAs, acetate, propionate, and butyrate) are nutrients especially critical to ruminants. Beyond their nutritional impact, clear evidence is beginning to link modifications in chromatin structure induced by butyrate to cell cycle progression, DNA replication and over...

  11. 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. PMID:25825149

  12. Specific cell cycle synchronization with butyrate and cell cycle analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synchronized cells have been invaluable for many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in MDBK cells. To explore the possibility of using butyrate-blocked cells to obtain synchronized cells, we investigated the property of the cell cyc...

  13. Reductive Carboxylation of Propionate to Butyrate in Methanogenic Ecosystems

    PubMed Central

    Tholozan, J. L.; Samain, E.; Grivet, J. P.; Moletta, R.; Dubourguier, H. C.; Albagnac, G.

    1988-01-01

    During the batch degradation of sodium propionate by the anaerobic sludge from an industrial digestor, we observed a significant amount of butyrate formation. Varying the initial propionate concentrations did not alter the ratio of maximal butyrate accumulation to initial propionate concentration within a large range. By measuring the decrease in the radioactivity of [1-14C]butyrate during propionate degradation, we estimated that about 20% of the propionate was converted to butyrate. Labeled butyrate was formed from [1-14C]propionate with the same specific radioactivity, suggesting a possible direct pathway from propionate to butyrate. We confirmed this hypothesis by nuclear magnetic resonance studies with [13C]propionate. The results showed that [1-13C]-, [2-13C]-, and [3-13C]propionate were converted to [2-13C]-, [3-13C]-, and [4-13C]butyrate, respectively, demonstrating the direct carboxylation on the carboxyl group of propionate without randomization of the other two carbons. In addition, we observed an exchange reaction between C-2 and C-3 of the propionate, indicating that acetogensis may proceed through a randomizing pathway. The physiological significance and importance of various metabolic pathways involved in propionate degradation are discussed, and an unusual pathway of butyrate synthesis is proposed. PMID:16347557

  14. 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...

  15. Enhanced production of IL-18 in butyrate-treated intestinal epithelium by stimulation of the proximal promoter region.

    PubMed

    Kalina, Uwe; Koyama, Noriko; Hosoda, Tomoko; Nuernberger, Heike; Sato, Kazuto; Hoelzer, Dieter; Herweck, Frank; Manigold, Tobias; Singer, Manfred V; Rossol, Siegbert; Böcker, Ulrich

    2002-09-01

    Expression of IL-18 in intestinal epithelial cells (IEC) has been implicated in Th1 cell-mediated chronic intestinal inflammation and anti-tumor immunity. However, physiological regulatory factors have not been identified. Besides their effects on proliferation and restitution, immunomodulatory functions have been attributed to short chain fatty acids (SCFA). We investigated the effect of SCFA (butyrate, propionate, acetate) on expression of IL-18 in IEC in vitro and in vivo. Expression of IL-18 mRNA and protein in human carcinoma-derived HT-29 and Caco-2 cells was analyzed by reverse transcription-PCR and Western blot. Transcriptional regulation of IL-18 gene expression was determined by transient transfection of wild-type and mutated IL-18 promoter. Further, in vivo expression of IL-18 in the intestine from butyrate-treated and untreated mice was assessed by immunohistochemistry. IL-18 mRNA and the IL-18 protein were expressed in IEC, while IL-18 secretion was not observed. Butyrate and acetate increased intracellular IL-18 content in a time- and dose-dependent fashion. In contrast to proinflammatory stimuli butyrate potently activated the IL-18 promoter, indicating that IL-18 is regulated at the transcriptional level by SCFA. Furthermore, a 108-bp sequence in the proximal region was identified to be essential for IL-18 promoter activation by butyrate. As proof of principle butyrate effects were confirmed in vivo by demonstration of increased IL-18 protein expression in IEC from butyrate-treated mice. In conclusion, SCFA up-regulate IL-18 protein expression in IEC, suggesting a potential regulatory contribution of these luminal constituents to T cell mediated inflammatory and neoplastic intestinal conditions. PMID:12207348

  16. 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.

  17. 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. PMID:26332770

  18. 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

  19. 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

  20. Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Neurotoxicity with Blood-Brain Barrier Monoamine Oxidase Activity

    NASA Astrophysics Data System (ADS)

    Kalaria, Rajesh N.; Mitchell, Mary Jo; Harik, Sami 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, we 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. We tested this hypothesis by assessing monoamine oxidase in isolated cerebral microvessels of humans, rats, and mice by measuring the specific binding of [3H]pargyline, an irreversible monoamine oxidase inhibitor, and by estimating the rates of MPTP and benzylamine oxidation. [3H]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 disease.

  1. Synthesis, spectral characterization and biological activities of Mn(II) and Co(II) complexes with benzyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone

    NASA Astrophysics Data System (ADS)

    Prathima, B.; Subba Rao, Y.; Ramesh, G. N.; Jagadeesh, M.; Reddy, Y. P.; Chalapathi, P. V.; Varada Reddy, A.

    2011-06-01

    Mn(II) and Co(II) complexes of benzyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone have been synthesized and characterized by the investigations of electronic and EPR spectra and X-ray diffraction. Based on the spectral studies, an octahedral geometry is assigned for the Mn(II) and Co(II) complexes. X-ray powder diffraction studies reveal that Mn(II) and Co(II) complexes have triclinic crystal lattices. The unit cell parameters of the Mn(II) complex are a = 11.0469 Å, b = 6.2096 Å, c = 7.4145 Å, α = 90.646°, β = 95.127°, γ = 104.776°, V = 489.7 Å 3 and those of Co(II) complex are a = 9.3236 Å, b = 10.2410 Å, c = 7.8326 Å, α = 90.694°, β = 99.694°, γ = 100.476°, V = 724.2 Å 3. When the free ligand and its metal complexes are subjected to antibacterial activity, the metal complexes are proved to be more active than the ligand. However with regard to in vitro antioxidant activity, the ligand exhibits greater antioxidant activity than its metal(II) complexes.

  2. 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.

  3. Synthesis, spectroscopic and structural characterization of 5-benzoyl-4-phenyl-2-methylthio-1H-pyrimidine with theoretical calculations using density functional theory

    NASA Astrophysics Data System (ADS)

    İnkaya, Ersin; Dinçer, Muharrem; Şahan, Emine; Yıldırım, İsmail

    2013-10-01

    In this paper, we will report a combined experimental and theoretical investigation of the molecular structure and spectroscopic parameters (FT-IR, 1H NMR, 13C NMR) of 5-benzoyl-4-phenyl-2-methylthio-1H-pyrimidine. The compound crystallizes in the triclinic space group P-1 with Z = 2. The molecular geometry was also optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) and 6-311++G(d,p) basis sets in ground state and compared with the experimental data. All the assignments of the theoretical frequencies were performed by potential energy distributions using VEDA 4 program. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecules has been obtained by mapping electron density isosurface with electrostatic potential (ESP). Also, non-linear optical properties of the title compound were performed at B3LYP/6-311++G(d,p) level. The theoretical results showed an excellent agreement with the experimental values.

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

    PubMed

    Sampath, Krishnan; Sathiyaraj, Subbaiyan; Jayabalakrishnan, Chinnasamy

    2013-11-01

    Two 4-phenyl-3-thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-phenylhydrazinecarbothioamide (HL(1)) and (E)-2-(2-nitrobenzylidene)-N-phenylhydrazinecarbothioamide (HL(2)), 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 HL(1) and HL(2) 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. PMID:23845986

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

    PubMed

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

    1987-08-01

    The quantitative 2-deoxy[14C]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 (100 mg with 10 mg carbidopa) 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. PMID:3497401

  6. Dietary curcumin supplementation attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in C57BL mice

    PubMed Central

    He, Xi-Jun; Uchida, Kazuyuki; Megumi, Chiaki; Tsuge, Nobuaki; Nakayama, Hiroyuki

    2015-01-01

    Studies in vivo and in vitro suggest that curcumin is a neuroprotective agent. Experiments were conducted to determine whether dietary supplementation with curcumin has neuroprotective effects in a mouse model of Parkinson’s disease (PD). Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly induced the loss of dopaminergic cells in the substantia nigra and deletion of dopamine in the striatum, which was attenuated by long-term (7 weeks) dietary supplementation with curcumin at a concentration of 0.5% or 2.0% (w/w). Although curcumin did not prevent the MPTP-induced apoptosis of neuroblasts in the subventricular zone (SVZ), it promoted the regeneration of neuroblasts in the anterior part of the SVZ (SVZa) at 3 days after MPTP treatment. Furthermore, curcumin enhanced the MPTP-induced activation of microglia and astrocytes in the striatum and increased the expression of glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-β1 (TGFβ1) in the striatum and SVZ. GDNF and TGFβ1 are thought to play an important role in protecting neurons from injury in the central and peripheral nervous systems. These results suggest that long-term administration of curcumin blocks the neurotoxicity of MPTP in the nigrostriatal dopaminergic system of the mouse and that the neuroprotective effect might be correlated with the increased expression of GDNF and TGFβ1. Curcumin may be effective in preventing or slowing the progression of PD. PMID:26538809

  7. Influence of pH values on the self-assembly in three trinuclear nickel complexes with bridging ligand N-salicylyl 4-phenyl-thiosemicarbazide

    NASA Astrophysics Data System (ADS)

    Du, Kang-Kai; Liu, Shi-Xiong

    2008-02-01

    Three trinuclear nickel complexes containing N-salicylyl 4-phenyl-thiosemicarbazide(abbreviated as spt 3-) have been synthesized. They are complex [Ni 3(spt) 2(dpt) 2]·2C 3H 7NO ( 1) with 2,5-diphenylamiyl 1,3,4 thiodiazone ligand(dpt) and the other two complexes without dpt ligand ([Ni 3(spt) 2(H 2O) 4]·2C 3H 7NO ( 2) and [Ni 3(spt) 2(C 5H 5N) 2(H 2O) 2]·2C 3H 7NO ( 3)). Central Ni atom and two terminal Ni atoms in the three complexes are combined by two bridging deprotonated spt 3- ligands, forming a strictly linear trinuclear nickel structure unit with a Ni sbnd N sbnd N sbnd Ni sbnd N sbnd N sbnd Ni core. There is an extended 1D structure in 2 and 3 formed by intermolecular hydrogen bonds O sbnd H…O. The influence of pH of the reaction medium upon the composition of the final products is discussed.

  8. Fluorescent Sensing of both Fe(III) and pH Based on 4-Phenyl-2-(2-Pyridyl)Thiazole and Construction of OR Logic Function.

    PubMed

    Yang, Ming-Yang; Zhao, Xiao-Long; Zheng, Ming-Hua; Wang, Yue; Jin, Jing-Yi

    2016-09-01

    In the presented paper we investigated a 2-pyridylthiazole derivative, 4-phenyl-2-(2-pyridyl)thiazole (2-PTP), as the molecular fluorescent switches. It was firstly found that 2-PTP could perform a "turn-on" fluorescent sensing for Fe(III) with selectivity and reversibility. A 2:1 stoichiometry between 2-PTP and Fe(III) was determined according to the molar ratio method. The binding constant was evaluated as (1.90 ± 0.05) × 10(5) (L/mol)(2). The detection limit was found as 2.2 × 10(-7) M (S/N = 3). Secondly, 2-PTP also exhibited a pH-dependent dual-emission. The pK a(2-PTP-H(+)/2-PTP) value was then estimated as 2.0. To explain the identical emission at 479 nm of both the Fe(III) coordinated form and the protonated form of the ligand, we proposed a "locked" conformation. Finally, combining the two external stimuli as inputs, an OR logic gate was constructed using the fluorescent emission at 479 nm as the output channel. PMID:27465707

  9. Acute effects of a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mouse body temperature.

    PubMed

    Satoh, N; Yonezawa, A; Tadano, T; Kisara, K; Arai, Y; Kinemuchi, H

    1987-09-14

    The parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given in single systemic doses (i.p.) to mice produced marked hyperthermia, and subsequent long-lasting hypothermia. Administration of MPTP or its oxidized product, 1-methyl-4-phenylpyridinium ion, MPP+, via i.c.v. resulted in only hypothermia. In contrast, i.p. MPP+ administration resulted in only hyperthermia. The MPTP-induced hyperthermia (i.p.) was blocked by quaternary derivatives of anti-cholinergic agents, atropine and scopolamine, but not by the tertiary-derivative of atropine. Duration of this hyperthermic effect was potentiated by neostigmine. Pretreatment with 1-deprenyl did not prevent hypothermia, but nomifensine partially or clorgyline completely prevented the effect without preventing MPTP-induced hyperthermia. The thermic effects by MPTP, unlike its neurotoxicity for the nigrostriatal DA system, may not require metabolism to MPP+. These results indicate that peripheral cholinergic functions are responsible for the MPTP-induced hyperthermia, whereas its hypothermic effect may be centrally mediated via dysregulation of the various neuron systems. PMID:3498107

  10. Immunomodulatory and neuroprotective effects of ginsenoside Rg1 in the MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) -induced mouse model of Parkinson's disease.

    PubMed

    Zhou, Ting-ting; Zu, Guo; Wang, Xi; Zhang, Xiao-gang; Li, Shao; Liang, Zhan-hua; Zhao, Jie

    2015-12-01

    Ginsenoside Rg1, one of the biologically active ingredients of ginseng, has been considered to be a candidate neuroprotective drug. The objective of the study was to study the protective effects of Rg1 through the peripheral and central inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Rg1 treatment protected TH-positive cells in the SNpc region from MPTP toxicity measured with immunofluoresence. The protein expression levels of TH in the SNpc region of MPTP-induced mice following treatment with Rg1 were higher than MPTP-induced mice which were tested with Western blot. The ratio of CD3(+)CD4(+) to CD3(+)CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells in the blood increased in MPTP-induced mice following treatment with Rg1 which were detected by flow cytometry analysis. Moreover, Rg1 reduced the serum concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-1β and IL-6 which were tested with enzyme-linked immunosorbent assay (ELISA). In addition, Rg1 inhibited the activation of microglia and reduced the infiltration of CD3(+) T cells into the SNpc region which were measured by immunofluorescence. Our results indicated that Rg1 may represent a promising drug for the treatment of PD via the regulation of the peripheral and central inflammation. PMID:26548343

  11. 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.

  12. Hydrogen in Drinking Water Reduces Dopaminergic Neuronal Loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mouse Model of Parkinson's Disease

    PubMed Central

    Fujita, Kyota; Seike, Toshihiro; Yutsudo, Noriko; Ohno, Mizuki; Yamada, Hidetaka; Yamaguchi, Hiroo; Sakumi, Kunihiko; Yamakawa, Yukiko; Kido, Mizuho A.; Takaki, Atsushi; Katafuchi, Toshihiko; Tanaka, Yoshinori

    2009-01-01

    It has been shown that molecular hydrogen (H2) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). Here, we show that drinking H2-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration-dependency of H2 showed that H2 as low as 0.08 ppm had almost the same effect as saturated H2 water (1.5 ppm). MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H2-containing water, whereas production of superoxide (O2•−) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly. Our results indicated that low concentration of H2 in drinking water can reduce oxidative stress in the brain. Thus, drinking H2-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration. PMID:19789628

  13. Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

    PubMed

    Fujita, Kyota; Seike, Toshihiro; Yutsudo, Noriko; Ohno, Mizuki; Yamada, Hidetaka; Yamaguchi, Hiroo; Sakumi, Kunihiko; Yamakawa, Yukiko; Kido, Mizuho A; Takaki, Atsushi; Katafuchi, Toshihiko; Tanaka, Yoshinori; Nakabeppu, Yusaku; Noda, Mami

    2009-01-01

    It has been shown that molecular hydrogen (H(2)) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). Here, we show that drinking H(2)-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration-dependency of H(2) showed that H(2) as low as 0.08 ppm had almost the same effect as saturated H(2) water (1.5 ppm). MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H(2)-containing water, whereas production of superoxide (O(2)*(-)) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly. Our results indicated that low concentration of H(2) in drinking water can reduce oxidative stress in the brain. Thus, drinking H(2)-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration. PMID:19789628

  14. Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.

    PubMed

    Thiollier, Thibaud; Wu, Caisheng; Contamin, Hugues; Li, Qin; Zhang, Jinlan; Bezard, Erwan

    2016-06-01

    Brain bioavailability of drugs developed to address central nervous system diseases is classically documented through cerebrospinal fluid collected in normal animals, i.e., through an approximation as there are fundamental differences between cerebrospinal fluid and tissue contents. The fact that disease might affect brain availability of drugs is almost never considered at this stage although several conditions are associated with blood-brain barrier damage. Building upon our expertise in Parkinson's disease translational research, the present study addressed this gap comparing plasma and cerebrospinal fluid bioavailability of l-3,4-dihydroxyphenylalanine, carbamazepine, quinidine, lovastatin, and simvastatin, in healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques, the gold standard model of Parkinson's disease. The drugs were selected based upon their differential transport across the blood-brain barrier. Interestingly, brain bioavailability of quinidine was decreased while others were unaffected. Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson's disease might thus be performed in healthy animals unless the drugs are known to interact with the organic cation transporter. Synapse 70:231-239, 2016. © 2016 Wiley Periodicals, Inc. PMID:26799359

  15. 1-Benzyl-4-phenyl-1H-1,2,3-triazoles improve the transcriptional functions of estrogen-related receptor γ and promote the browning of white adipose.

    PubMed

    Xu, Shilin; Mao, Liufeng; Ding, Ping; Zhuang, Xiaoxi; Zhou, Yang; Yu, Lei; Liu, Yingxue; Nie, Tao; Xu, Tingting; Xu, Yong; Liu, Jinsong; Smaill, Jeff; Ren, Xiaomei; Wu, Donghai; Ding, Ke

    2015-07-01

    The estrogen-related receptor γ (ERRγ) is a potential molecular target for the development of small molecules to stimulate the adipose browning process, which may represent a novel attractive strategy to treat obesity related disorders. The receptor possesses a very small ligand binding cavity and therefore identification of small molecule ERRγ modulators is a considerable challenge. We have successfully designed and synthesized a series of 1-benzyl-4-phenyl-1H-1,2,3-triazoles and demonstrated that they improve the transcriptional functions of ERRγ, potently elevating both the mRNA levels and the protein levels of ERRγ downstream targets. One of the most promising compounds, 4-(1-(4-iso-propylbenzyl)-1H-1,2,3-triazol-4-yl)benzene-1,2-diol (2e) was further shown to directly bind with the ERRγ ligand binding domain (ERRγ-LBD) in an isothermal calorimetric (ITC) assay and to thermally stabilize ERRγ-LBD protein by increasing its melting temperature (Tm) as demonstrated by circular dichroism (CD) spectroscopy. Furthermore, 2e potently stimulates the adipocyte browning process and induces mitochondrial biogenesis both in vitro and in vivo, suggesting the considerable therapeutic potential of this compound for the treatment of obesity and related disorders. PMID:25910584

  16. 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

  17. Unexpected Lack of Hypersensitivity in LRRK2 Knock-out Mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

    PubMed Central

    Andres-Mateos, Eva; Mejias, Rebeca; Sasaki, Masayuki; Li, Xiaojie; Lin, Brian M; Biskup, Saskia; Zhang, Li; Banerjee, Rebecca; Thomas, Bobby; Yang, Lichuan; Liu, Guosheng; Beal, M Flint; Huso, David L; Dawson, Ted M; Dawson, Valina L

    2010-01-01

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known cause of Parkinson's disease (PD). Whether loss of LRRK2 function accounts for neurodegeneration of dopamine neurons in PD is not known, nor is it known whether LRRK2 kinase activity modulates the susceptibility of dopamine (DA) neurons to the selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). To better understand the role of LRRK2 in DA neuronal survival and its role in the susceptibility of DA neurons to MPTP, we generated LRRK2 knockout (KO) mice lacking the kinase domain of LRRK2. Here we show that LRRK2 KO mice are viable and have no major abnormalities and live to adulthood. The dopaminergic system is normal in LRRK2 KO mice as assessed via HPLC for DA and its metabolites and via stereologic assessment of DA neuron number in young and aged mice. Importantly, there is no significant difference in the susceptibility of LRRK2 KO and wild type (WT) mice to MPTP. These results suggest that LRRK2 plays little if any role in the development and survival of DA neurons under physiologic conditions. Thus, PD due to LRRK2 mutations are likely not due to a loss of function. Moreover, LRRK2 is not required for the susceptibility of DA neurons to MPTP. PMID:20016100

  18. The combined use of ultrasound and molecular sieves improves the synthesis of ethyl butyrate catalyzed by immobilized Thermomyces lanuginosus lipase.

    PubMed

    Paludo, Natalia; Alves, Joana S; Altmann, Cintia; Ayub, Marco A Z; Fernandez-Lafuente, Roberto; Rodrigues, Rafael C

    2015-01-01

    In this work, the combined use of ultrasound energy and molecular sieves was investigated for the synthesis of ethyl butyrate, ester with mango and banana notes, catalyzed by the immobilized lipase from Thermomyces lanuginosus (Lipozyme TL-IM). Initially, the best concentrations of biocatalysts (35%) and butyric acid (0.7M) were tested using ultrasound as an alternative to mechanical agitation. The amount of acid in the reaction could be increased by 2-fold when compared to previous works where mechanical agitation was used. In the next step, substrate molar ratio and reaction temperature were optimized and the best conditions were at their lowest levels: 1:1 (acid:alcohol), and 30°C, reaching 61% of conversion in 6h. Molecular sieves (3Å) were added to optimized reaction medium in order to remove the formed water and improve the maximum yield. The reaction yield increased 1.5 times, reaching 90% of conversion in 6h, when 60mg of molecular sieves per mmol of butyric acid was used. Finally, the reuse of Lipozyme TL-IM for the ultrasound-assisted synthesis of ethyl butyrate was verified for 10 batches, without any appreciable loss of activity, whereas in systems using mechanical agitation, the biocatalyst was completely inactivated after 5 batches. These results suggest that the combined use of ultrasound and molecular sieves greatly improve esterification reactions by stabilizing the enzyme and increasing yields. PMID:24844439

  19. Pathways analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VFA), acetate, propionate, and butyrate to fulfill up to 70% of their nutrient energy requirements. The inherent VFA dependence of ruminant cells was exploited in order to add a level of increased sensitivity to the s...

  20. Vancomycin treatment and butyrate supplementation modulate gut microbe composition and severity of neointimal hyperplasia after arterial injury.

    PubMed

    Ho, Karen J; Xiong, Liqun; Hubert, Nathaniel J; Nadimpalli, Anuradha; Wun, Kelly; Chang, Eugene B; Kibbe, Melina R

    2015-12-01

    Gut microbial metabolites are increasingly recognized as determinants of health and disease. However, whether host -: microbe crosstalk influences peripheral arteries is not understood. Neointimal hyperplasia, a proliferative and inflammatory response to arterial injury, frequently limits the long-term benefits of cardiovascular interventions such as angioplasty, stenting, and bypass surgery. Our goal is to assess the effect of butyrate, one of the principal short chain fatty acids produced by microbial fermentation of dietary fiber, on neointimal hyperplasia development after angioplasty. Treatment of male Lewis Inbred rats with oral vancomycin for 4 weeks changed the composition of gut microbes as assessed by 16S rRNA-based taxonomic profiling and decreased the concentration of circulating butyrate by 69%. In addition, rats treated with oral vancomycin had exacerbated neointimal hyperplasia development after carotid angioplasty. Oral supplementation of butyrate reversed these changes. Butyrate also inhibited vascular smooth muscle cell proliferation, migration, and cell cycle progression in a dose-dependent manner in vitro. Our results suggest for the first time that gut microbial composition is associated with the severity of arterial remodeling after injury, potentially through an inhibitory effect of butyrate on VSMC. PMID:26660548

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Aging-related 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurochemial and behavioral deficits and redox dysfunction: improvement by AK-7.

    PubMed

    Guan, Qiang; Wang, Meihua; Chen, Hanqing; Yang, Liu; Yan, Zhiqiang; Wang, Xijin

    2016-09-01

    Aging is a prominent risk factor for the occurrence and progression of Parkinson disease (PD). Aging animals are more significant for PD research than young ones. It is promising to develop effective treatments for PD through modulation of aging-related molecules. Sirtuin 2 (SIRT2), a strong deacetylase highly expressed in the brain, has been implicated in the aging process. In our present study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 12mg/kg once daily) was observed to bring about significant behavioral deficits and striatal dopamine depletion in aging male and female mice, while it did not do so in young animals. MPTP did not cause significant reduction in striatal 5-hydroxytryptamine content in aging male and female mice. Furthermore, we observed that MPTP treatment resulted in significant reduction in GSH content and significant increase in MDA content and SIRT2 expression in the substantia nigra (SN) of aging mice, while it did not do so in young animals. Importantly, we observed that AK-7 (a selective SIRT2 inhibitor) significantly improved behavior abnormality and neurochemical deficits in aging male and female mice treated with MPTP. Significant increase in GSH content and significant decrease in MDA content were also observed in the SN of aging male and female mice co-treated with MPTP and AK-7 compared with the MPTP-treated animals. Our results indicated that MPTP induce aging-related neurochemical and behavioural deficits and dysfunction of redox network in male and female mice and AK-7 may be neuroprotective in PD through modulating redox network. PMID:27235848

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

    PubMed

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

    2016-09-01

    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

  8. 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

  9. 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

  10. Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model.

    PubMed

    Yang, Wei; Chen, Yu-Hua; Liu, Hao; Qu, Hong-Dang

    2015-11-01

    Parkinson's disease (PD) is second only to Alzheimer's disease as the most common and debilitating age-associated neurodegenerative disorder. Currently, no therapy has been shown to unequivocally retard or arrest the progression of the disease. The aim of the present study was to investigate the protective effect of piperine on the 1-methyl-4-phenyl-1,2,3,6‑tetrahydropyridine (MPTP)-induced Parkinson's mouse model. For MPTP treatment, the animals received repeated intraperitoneal injections (i.p.) of MPTP (30 mg/kg) solution for 7 days. Piperine (10 mg/kg) was administered orally for 15 days including 8 days of pretreatment. Motor behavior analysis was conducted with the rotarod test. The Morris water maze (MWM) was used to assess the cognitive learning ability of the mice. A histological examination was subsequently conducted. The results ddemonstrate that piperine treatment attenuated MPTP-induced deficits in motor coordination and cognitive functioning. Piperine also prevented MPTP-induced decreases in the number of tyrosine hydroxylase-positive cells in the substantia nigra. Additionally, piperine reduced the number of activated microglia, expression of cytokine IL-1β, and oxidative stress following MPTP treatment. An anti-apoptotic property of piperine was identified by maintaining the balance of Bcl-2/Bax. In conclusion, the results show that piperine exerts a protective effect on dopaminergic neurons via antioxidant, anti-apoptotic, and anti-inflammatory mechanisms in an MPTP-induced mouse model of PD. Thus, piperine is a potential therapeutic treatment for PD. PMID:26648012

  11. Catecholamine uptake sites: characterization, localization, and a role in the production of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism

    SciTech Connect

    Javitch, J.A.

    1985-01-01

    Dopamine and norepinephrine are inactivated by specific high affinity transport systems which mediate the recapture of the amines into presynaptic nerve terminals. (/sup 3/H)Maxindol labels neuronal dopamine uptake sites in corpus striatum membranes and neuronal norepinephrine uptake sites in cerebral cortex and submaxillary/sublingual gland membranes. The potencies of various inhibitors of biogenic amine uptake in reducing (/sup 3/H)mazindol binding in striatal membranes correlate with their potencies for inhibition of neurona (/sup 3/H)dopamine accumulation, whereas their potencies in reducing (/sup 3/H)mazindol binding to cortical and salivary gland membranes correlate with their potencies for inhibition of neuronal (/sup 3/H)norepinephrine accumulation. The association of (/sup 3/H)mazindol binding sites with neuronal dopamine uptake sites in the corpus striatum is further supported by the reduction of (/sup 3/H)mazindol binding sites in striatal membranes following destruction of dopaminergic neurons by 6-hydroxydopamine. Similarly, destruction of noradrenergic neurons by N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine(DSP-4) decreases (/sup 3/H)mazindol binding to cortical membranes. Dopamine and norepinephrine uptake sites in rat brain have been differentially visualized using (/sup 3/H)mazindol autoradiography. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathologic and clinical abnormalities in humans and animals that closely resemble idiopathic Parkinson disease. (/sup 3/H)MPTP binds with high affinity to brain membranes. The chemical specificity of the binding sites corresponds to structure-activity requirements for neurotoxicity.

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    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 Ni2+ ion coordinates with two deprotonated ligands of L- and adopts a distorted square planar configuration with the Ni2+ 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.

  13. Primate adult brain cell autotransplantation produces behavioral and biological recovery in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian St. Kitts monkeys.

    PubMed

    Bloch, Jocelyne; Brunet, Jean-François; McEntire, Caleb R S; Redmond, D Eugene

    2014-08-15

    The potential for "replacement cells" to restore function in Parkinson's disease has been widely reported over the past 3 decades, rejuvenating the central nervous system rather than just relieving symptoms. Most such experiments have used fetal or embryonic sources that may induce immunological rejection and generate ethical concerns. Autologous sources, in which the cells to be implanted are derived from recipients' own cells after reprogramming to stem cells, direct genetic modifications, or epigenetic modifications in culture, could eliminate many of these problems. In a previous study on autologous brain cell transplantation, we demonstrated that adult monkey brain cells, obtained from cortical biopsies and kept in culture for 7 weeks, exhibited potential as a method of brain repair after low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused dopaminergic cell death. The present study exposed monkeys to higher MPTP doses to produce significant parkinsonism and behavioral impairments. Cerebral cortical cells were biopsied from the animals, held in culture for 7 weeks to create an autologous neural cell "ecosystem" and reimplanted bilaterally into the striatum of the same six donor monkeys. These cells expressed neuroectodermal and progenitor markers such as nestin, doublecortin, GFAP, neurofilament, and vimentin. Five to six months after reimplantation, histological analysis with the dye PKH67 and unbiased stereology showed that reimplanted cells survived, migrated bilaterally throughout the striatum, and seemed to exert a neurorestorative effect. More tyrosine hydroxylase-immunoreactive neurons and significant behavioral improvement followed reimplantation of cultured autologous neural cells as a result of unknown trophic factors released by the grafts. PMID:24610674

  14. Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

    PubMed

    Liu, W; Jalewa, J; Sharma, M; Li, G; Li, L; Hölscher, C

    2015-09-10

    Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer's disease. Here we demonstrate the neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20mg/kg i.p.) for 7 days, and drugs were injected once-daily for 14 days i.p. When comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD. PMID:26141845

  15. 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

  16. 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. PMID:22542874

  17. 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

  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. Clinical evaluation of clobetasone butyrate eye drops in episcleritis.

    PubMed Central

    Lloyd-Jones, D; Tokarewicz, A; Watson, P G

    1981-01-01

    Thirty-nine patients took part in a double-blind, between-patient clinical trial to compare clobetasone butyrate, betamethasone phosphate, and placebo eye drops in the treatment of episcleritis. Although from the symptom scores the patients given placebo appeared to do as well as the other patients in the first week of treatment, they did significantly less well after this time. Clobetasone butyrate and betamethasone phosphate eye drops seemed to be equally effective in the treatment of this disease. PMID:7028088

  20. Comparison of desoximetasone and hydrocortisone butyrate in psoriasis.

    PubMed

    Zachariae, H

    1976-01-01

    Thirty psoriatics were treated for 2 weeks on a double-blind controlled basis with desoximetasone (0.25%) and with hydrocortisone butyrate (0.1%). It was a randomised left-right comparative trial. Thirteen out of 27 patients preferred desoximetasone, 3 patients preferred hydrocortisone butyrate. There was also a significantly better effect of desoximetasone as judged by the observer after the second week of treatment. PMID:60029

  1. 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

  2. Microbial metabolite butyrate facilitates M2 macrophage polarization and function

    PubMed Central

    Ji, Jian; Shu, Dingming; Zheng, Mingzhu; Wang, Jie; Luo, Chenglong; Wang, Yan; Guo, Fuyou; Zou, Xian; Lv, Xiaohui; Li, Ying; Liu, Tianfei; Qu, Hao

    2016-01-01

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease. PMID:27094081

  3. Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

    PubMed

    Ji, Jian; Shu, Dingming; Zheng, Mingzhu; Wang, Jie; Luo, Chenglong; Wang, Yan; Guo, Fuyou; Zou, Xian; Lv, Xiaohui; Li, Ying; Liu, Tianfei; Qu, Hao

    2016-01-01

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease. PMID:27094081

  4. 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. PMID:22714808

  5. Distinct mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine resistance revealed by transcriptome mapping in mouse striatum

    PubMed Central

    Pattarini, Roberto; Rong, Yongqi; Qu, Chunxu; Morgan, James I.

    2008-01-01

    The etiology of idiopathic Parkinson’s disease is thought to involve interplay between environmental factors and predisposing genetic traits, although the identification of genetic risk factors remain elusive. The neurotoxicant, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrimidine (MPTP) produces parkinsonian-like symptoms and pathology in mice and humans. As sensitivity to MPTP is genetically determined in mice this provides an opportunity to identify genes and biological mechanisms that modify the response to an exogenous agent that produces a Parkinson’s disease-like condition. MPTP primarily targets dopaminergic nerve terminals in the striatum and elicits changes in striatal gene expression. Therefore, we used Affymetrix® and real-time PCR technology to characterize temporal mRNA changes in striatum in response to MPTP in genetically MPTP-sensitive, C57BL/6J, and MPTP-resistant Swiss Webster and Bax−/− mice. We identified three phases of mRNA expression changes composed of largely distinct gene sets. An early response (5 hours) occurred in all strains of mice and multiple brain regions. In contrast, intermediate (24 hours) and late (72 hours) phases were striatum specific and much reduced in Swiss Webster, indicating these genes contribute and/or are responsive to MPTP-induced pathology. However, Bax−/− mice have robust intermediate responses. We propose a model in which the acute entry of MPP+ into dopaminergic nerve terminals damages them but is insufficient per se to kill the neurons. Rather, we suggest that the compromised nerve terminals elicit longer lasting transcriptional responses in surrounding cells involving production of molecules that feedback on the terminals to cause additional damage that results in cell death. In Swiss Webster, resistance lies upstream in the cascade of events triggered by MPTP and uncouples the acute events elicited by MPTP from the damaging secondary responses. In contrast, in Bax−/− mice resistance lies

  6. 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

  7. 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

  8. 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. PMID:26095388

  9. 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. PMID:26216027

  10. 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.

  11. Liquid chromatographic determination of clobetasone-17-butyrate in ointments.

    PubMed

    Patel, A G; Patel, R B; Patel, M R

    1990-01-01

    A liquid chromatographic (LC) method has been developed for determination of clobetasone-17-butyrate in ointment using clobetasone propionate as an internal standard. Separation was carried out on a C18 reverse-phase column using water-methanol as a mobile phase. Methylparaben and propylparaben (both sodium salt) used as preservatives did not interfere with separation. Compounds are detected photometrically at 235 nm. Mean assay results for 0.05% commercial ointments were 100.36% (n = 5). Mean recovery of clobetasone-17-butyrate added to commercial ointment was 99.89%. PMID:2289922

  12. 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

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. BUTYRATE DIFFERENTIALLY REGULATES CYTOKINES AND PROLIFERATION IN PORCINE PERIPHERAL BLOOD MONONUCLEAR CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although butyrate modulates proliferation and cytokine production by PBMC in some species, the role of butyrate as a regulator of immunocyte function in the pig has not been studied. Therefore, the primary objective of this study was to determine whether butyrate influences peripheral blood mononuc...

  18. Swine Intestinal Tract Harbors a High Diversity of Butyrate-Producing Bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate is a preferred energy source of human colonic epithelial cells, and changes in the communities of butyrate-producing bacteria have been associated with adverse health. We hypothesize that in swine, like in humans, butyrate-producing bacteria contribute to a healthy intestinal ecosystem. T...

  19. 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...

  20. 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

  1. 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

  2. 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 ...

  3. Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?

    PubMed

    Bourassa, Megan W; Alim, Ishraq; Bultman, Scott J; Ratan, Rajiv R

    2016-06-20

    As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration. PMID:26868600

  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. 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

  6. 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-INDUCED ASTROGLIOSIS DOES NOT REQUIRE ACTIVATION OF ORNITHINE DECARBOXYLASE

    EPA Science Inventory

    Mechanical injury to the brain results in enhanced immunostaining for glial fibrillary acidic protein (GFAP) that is markedly inhibited by difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. n the current study, systemic exposure of mice to the d...

  7. 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

  8. 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. PMID:21911440

  9. 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

  10. DIETHYLDITHIOCARBAMATE POTENTIATES THE NEUROTOXICITY OF IN VIVO 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND OF IN VITRO 1-METHYL-4-PHENYLPYRIDINIUM

    EPA Science Inventory

    Diethyldithiocarbamic acid (DDC), a dithiocarbamate, potentiates the neurotoxicity of 1-methyl-r-pheny-1,2,3,6-tetrahydropyridine (MPTP) in vivo and of its major metabolite, 1,-methyl-4-phenylpyridinium (MPP+), in bovine adrenal medullary (BAM) cells maintained in culture. ale C5...

  11. CHARACTERIZATION OF THE ASTROCYTE RESPONSE TO INJURY USING THE DOPAMINERGIC NEUROTOXICANT, 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE

    EPA Science Inventory

    The amount of glial fibrillary acidic protein (GFAP), an astrocyte protein, increases following injury of the CNS. e used a radioimmunoassay of GFAP to characterize the astrocytic response to injury resulting from exposure to the dopaminergic neurotoxicant, 1-methyl-1,2,3,6-tetra...

  12. Loss of collapsin response mediator protein 4 suppresses dopaminergic neuron death in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease.

    PubMed

    Tonouchi, Aine; Nagai, Jun; Togashi, Kentaro; Goshima, Yoshio; Ohshima, Toshio

    2016-06-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several lines of evidence suggest that neurodegeneration in PD is accelerated by a vicious cycle in which apoptosis in dopaminergic neurons triggers the activation of microglia and harmful inflammatory processes that further amplify neuronal death. Recently, we demonstrated that the deletion of collapsin response mediator protein 4 (CRMP4) suppresses inflammatory responses and cell death in a mouse model of spinal cord injury, leading to improved functional recovery. We thus hypothesized that Crmp4-/- mice may have limited inflammatory responses and a decrease in the loss of SNc dopaminergic neurons in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. We observed CRMP4 expression in neurons, astrocytes, and microglia/macrophages following the injection of 25 mg/kg MPTP. We compared the number of dopaminergic neurons and the inflammatory response in SNc between Crmp4+/+ and Crmp4-/- mice after MPTP injection. Limited loss of SNc dopaminergic neurons and decreased activations of microglia and astrocytes were observed in Crmp4-/- mice. These results suggest that CRMP4 is a novel therapeutic target in the treatment of PD patients. We demonstrated that genetic CRMP4 deletion delays a vicious cycle of inflammation and neurodegeneration in a Parkinson's disease mouse model. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) injection to wild-type mice induces collapsin response mediator protein 4 (CRMP4) up-regulation in neurons, astrocytes, and microglia. CRMP4-deficient mice show reduced inflammation and suppressed dopaminergic neuronal death after MPTP injection. These findings suggest that CRMP4 deletion may be a new therapeutic strategy against Parkinson's diseases. PMID:26991935

  13. 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

  14. Effects of supplementary butyrate on butanol production and the metabolic switch in Clostridium beijerinckii NCIMB 8052: genome-wide transcriptional analysis with RNA-Seq

    PubMed Central

    2013-01-01

    Background Butanol (n-butanol) has high values as a promising fuel source and chemical feedstock. Biobutanol is usually produced by the solventogenic clostridia through a typical biphasic (acidogenesis and solventogenesis phases) acetone-butanol-ethanol (ABE) fermentation process. It is well known that the acids produced in the acidogenic phase are significant and play important roles in the switch to solventogenesis. However, the mechanism that triggers the metabolic switch is still not clear. Results Sodium butyrate (40 mM) was supplemented into the medium for the ABE fermentation with Clostridium beijerinckii NCIMB 8052. With butyrate addition (reactor R1), solvent production was triggered early in the mid-exponential phase and completed quickly in < 50 h, while in the control (reactor R2), solventogenesis was initiated during the late exponential phase and took > 90 h to complete. Butyrate supplementation led to 31% improvement in final butanol titer, 58% improvement in sugar-based yield, and 133% improvement in butanol productivity, respectively. The butanol/acetone ratio was 2.4 versus 1.8 in the control, indicating a metabolic shift towards butanol production due to butyrate addition. Genome-wide transcriptional dynamics was investigated with RNA-Seq analysis. In reactor R1, gene expression related to solventogenesis was induced about 10 hours earlier when compared to that in reactor R2. Although the early sporulation genes were induced after the onset of solventogenesis in reactor R1 (mid-exponential phase), the sporulation events were delayed and uncoupled from the solventogenesis. In contrast, in reactor R2, sporulation genes were induced at the onset of solventogenesis, and highly expressed through the solventogenesis phase. The motility genes were generally down-regulated to lower levels prior to stationary phase in both reactors. However, in reactor R2 this took much longer and gene expression was maintained at comparatively higher levels

  15. Regulation of T-type calcium channel expression by sodium butyrate in prostate cancer cells.

    PubMed

    Weaver, Erika M; Zamora, Francis J; Puplampu-Dove, Yvonne A; Kiessu, Ezechielle; Hearne, Jennifer L; Martin-Caraballo, Miguel

    2015-02-15

    Several cellular mechanisms contribute to the neuroendocrine differentiation of prostate cancer cells, including exposure to sodium butyrate (NaBu), a naturally occurring salt of the short chain fatty acid n-butyric acid. NaBu belongs to a class of histone deacetylase inhibitors with potential anticancer function. T-type calcium channel expression constitutes an important route for calcium influx in tumor cells that may trigger changes in cell proliferation and differentiation. In this work we investigated the role NaBu on the differentiation of lymph node carcinoma of the prostate (LNCaP) cells and its effect on T-type Ca(2+) channel expression. NaBu stimulates the morphological and molecular differentiation of LNCaP cells. Stimulation of LNCaP cells with NaBu evokes a significant increase in the expression of the Cav3.2 T-type channel subunits. Furthermore, the increased Cav3.2 expression promotes membrane insertion of T-type Ca(2+) channels capable of generating fast inactivating Ca(2+) currents, sensitive to 100μM Ni(2+) ions. Inhibition of T-type Ca(2+) channel function reduces the outgrowth of neurite-like processes in LNCaP cells. NaBu-evoked expression of T-type Ca(2+) channels is also involved in the regulation of cell viability. Inhibition of T-type Ca(2+) channels causes a significant reduction in the viability of LNCaP cells treated with 1mM NaBu, suggesting that Ca(2+) influx via T-type channels can promote cell proliferation. However, increased expression of T-type Ca(2+) channels enhanced the cytotoxic effect of thapsigargin and paclitaxel on cell proliferation. These findings demonstrate that NaBu stimulates T-type Ca(2+) channel expression, thereby regulating both the morphological differentiation and growth of prostate cancer cells. PMID:25557765

  16. 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

  17. 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

  18. 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.

  19. Zinc Sensing Receptor Signaling, Mediated by GPR39, Reduces Butyrate-Induced Cell Death in HT29 Colonocytes via Upregulation of Clusterin

    PubMed Central

    Cohen, Limor; Azriel-Tamir, Hagit; Arotsker, Natan; Sekler, Israel; Hershfinkel, Michal

    2012-01-01

    Zinc enhances epithelial proliferation, protects the digestive epithelial layer and has profound antiulcerative and antidiarrheal roles in the colon. Despite the clinical significance of this ion, the mechanisms linking zinc to these cellular processes are poorly understood. We have previously identified an extracellular Zn2+ sensing G-protein coupled receptor (ZnR) that activates Ca2+ signaling in colonocytes, but its molecular identity as well as its effects on colonocytes' survival remained elusive. Here, we show that Zn2+, by activation of the ZnR, protects HT29 colonocytes from butyrate induced cell death. Silencing of the G-protein coupled receptor GPR39 expression abolished ZnR-dependent Ca2+ release and Zn2+-dependent survival of butyrate-treated colonocytes. Importantly, GPR39 also mediated ZnR-dependent upregulation of Na+/H+ exchange activity as this activity was found in native colon tissue but not in tissue obtained from GPR39 knock-out mice. Although ZnR-dependent upregulation of Na+/H+ exchange reduced the cellular acid load induced by butyrate, it did not rescue HT29 cells from butyrate induced cell death. ZnR/GPR39 activation however, increased the expression of the anti-apoptotic protein clusterin in butyrate-treated cells. Furthermore, silencing of clusterin abolished the Zn2+-dependent survival of HT29 cells. Altogether, our results demonstrate that extracellular Zn2+, acting through ZnR, regulates intracellular pH and clusterin expression thereby enhancing survival of HT29 colonocytes. Moreover, we identify GPR39 as the molecular moiety of ZnR in HT29 and native colonocytes. PMID:22545109

  20. HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2.

    PubMed

    Wächtershäuser, A; Akoglu, B; Stein, J

    2001-07-01

    Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Butyrate, a short-chain fatty acid, reduces proliferation and induces differentiation of human colon cancer cells. The aim of our study was to determine the effect of mevastatin, alone or in combination with butyrate, on proliferation, the cell cycle and apoptosis in the human colorectal carcinoma cell line Caco-2. In this report we show that mevastatin combined with butyrate synergistically suppressed growth of Caco-2 cells in a dose- and time-dependent manner. In addition, incubation with mevastatin arrested cells in the G1 phase of the cell cycle after 24 h with a switch to the G2/M phase after 72 h. This was accompanied by a down-regulation of cyclin-dependent kinases (cdk) 4 and cdk 6 as well as cyclin D1, while cdk 2 and cyclin E protein levels remained unchanged during mevastatin treatment. Cell cycle inhibitors p21 and p27 were significantly upregulated by mevastatin. The proapoptotic properties of mevastatin were further enhanced by co-incubation with butyrate. Lastly, the effects of mevastatin could be reversed by addition of mevalonate, but not farnesyl- or geranylgeranylpyrophosphate, intermediate products of cholesterol synthesis, to the medium. These results suggest that HMG-CoA reductase inhibitors like mevastatin may enhance the antiproliferative effect of butyrate in colon cancer cells via induction of apoptosis together with a G0/G1 cell cycle arrest. PMID:11408350

  1. 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

  2. TRAPPING YELLOWJACKETS (HYMENOPTERA: VESPIDAE) WITH HEPTYL BUTYRATE EMITTED FROM CONTROLLED-RELEASE DISPENSERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numbers of workers of Vespula pensylvanica (Saussure) (western yellowjacket) and V. atropilosa (Sladen) trapped with heptyl butyrate in Washington increased with increased release of the attractant from vial dispensers, up to an estimated 2.3 milligrams heptyl butyrate per hour. Vespula germanica F...

  3. 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...

  4. FLOW CYTOMETRIC EVALUATION OF THE EFFECTS OF SODIUM BUTYRATE ON APOPTOSIS OF BOVINE NEUTROPHILS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine blood neutrophils(PMN) from four clinically healthy cows were suspended in Dulbecco's minimal essential medium and incubated at 37C for 0, 2 or 6 hours in medium alone, with 100ng/ml bacterial endotoxin, 160nM sodium butyrate, 16uM actinomycin D, mixture of sodium butyrate and bacterial endot...

  5. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model.

    PubMed Central

    McIntyre, A; Gibson, P R; Young, G P

    1993-01-01

    Butyrate slows the growth of cancer cells cultured in vitro. To determine the relevance of the fermentative production of butyrate in vivo, colonic butyrate concentrations were manipulated by feeding different dietary fibres and were related to tumour development in the rat dimethylhydrazine model of large bowel cancer. It has previously been shown that guar gum and oat bran, while highly fermentable, are associated with low butyrate levels in the distal colon, while wheat bran causes significantly higher concentrations. Diets containing these fibres (nominally 10% w:w) were administered for 3 weeks before, for 10 weeks during, and for 20 weeks after dimethylhydrazine administration, after which animals were killed and examined for tumours. Significantly fewer tumours were seen in the rats fed wheat bran compared with those fed guar or oat bran, and the total tumour mass was lowest in rats fed wheat bran. Rats on a 'no added fibre diet' had an intermediate tumour mass. Regression analysis, performed regardless of dietary group, showed that the concentration in stools of butyrate but not of acetate or stool volume, correlated significantly (and negatively) with tumour mass. These findings indicate that fibre which is associated with high butyrate concentrations in the distal large bowel is protective against large bowel cancer, while soluble fibres that do not raise distal butyrate concentrations, are not protective. Thus, butyrate production in vivo does bear a significant relationship to suppression of tumour formation. PMID:8386131

  6. Conversion of N-butyrate to N-butanol with Continuous Fermentation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of our study is to optimize n-butanol production from n-butyrate, using pure cultures of solventogenic Clostridia. In addition to butyrate as a substrate, glucose was used as a source of energy and to provide reducing equivalents to facilitate the conversion. To prevent product inhibition...

  7. 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...

  8. 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...

  9. Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors.

    PubMed

    Mahal, Katharina; Biersack, Bernhard; Schruefer, Sebastian; Resch, Marcus; Ficner, Ralf; Schobert, Rainer; Mueller, Thomas

    2016-08-01

    5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vbl cervix and MCF-7/Topo mamma carcinoma cells, and also against CA-4-resistant HT-29 colon carcinoma cells. While not interfering markedly with the polymerization of tubulin in vitro, indole 5c completely disrupted the microtubule cytoskeleton of cancer cells at low concentrations. It also destroyed real blood vessels, both in the chorioallantoic membrane (CAM) of fertilized chicken eggs and within tumor xenografts in mice, without harming embryo or mouse, respectively. Indole 5c was less toxic than CA-4 to endothelial cells, fibroblasts, and cardiomyocytes. In highly vascularized xenograft tumors 5c induced distinct discolorations and histological features typical of vascular-disrupting agents, such as disrupted vessel structures, hemorrhages, and extensive necrosis. In a first preliminary therapy trial, indole 5c retarded the growth of resistant xenograft tumors in mice. © 2016 Elsevier Science Ltd. All rights reserved. PMID:27116710

  10. Chloridodiphen­yl{[1-(1,3-thia­zol-2-yl-κN)ethyl­idene]-4-phenyl­thio­semicarbazidato-κ2 N 1,S}tin(IV) methanol monosolvate

    PubMed Central

    Arumugam, Sri Ranjini; Dasary, Samuel S. R.; Venkatraman, Ramaiyer; Yu, Hongtao; Fronczek, Frank R.

    2011-01-01

    The title compound, [Sn(C6H5)2(C12H11N4S2)Cl]·CH4O, is formed during the reaction between 2-acetyl­thia­zole 4-phenyl­thio­semicarbazone (Hacthptsc) and diphenyl­tin(IV) dichloride in methanol. In the crystal structure, the Sn atom exhibits an octa­hedral geometry with the [N2S] anionic tridentate thio­semicarbazone ligand having chloride trans to the central N and the two phenyl groups trans to each other. The Sn—Cl distance is 2.5929 (6), Sn—S is 2.4896 (6) and Sn—N to the central N is 2.3220 (16) Å. The MeOH mol­ecules link the Sn complexes into one-dimensional chains via N—H⋯O and O—H⋯Cl hydrogen bonds. PMID:22065366

  11. Effects of L-arginine pre-treatment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s diseases in Balb/c mice

    PubMed Central

    Hami, Javad; Hosseini, Mehran; Shahi, Sekineh; Lotfi, Nassim; Talebi, Abolfazl; Afshar, Mohammad

    2015-01-01

    Background: Parkinson’s disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage. This study aimed to evaluate the effects of L-arginine on the numerical density of dark neurons (DNs) in the SNc of Balb/c mice subjected to MPTP administration. Methods: In the present study, we demonstrated that repeated treatment with L-arginine (300 mg/kg, i.p.) during 7 consecutive days attenuated the production of DNs in SNc of adult male Balb/c mice infused with a single intranasal administration of MPTP (1 mg/nostril). Results: Pre-treatment with L-arginine significantly decreased the numerical density of DNs in SNc of mice 21 days after intranasal MPTP administration. Conclusion: This investigation provides new insights in experimental models of PD, indicating that L-arginine represents a potential neuroprotective agent for the prevention of DA neuron degeneration in SNc observed in PD patients. PMID:26885338

  12. Molecular structure and vibrational and chemical shift assignments of 3-(2-Hydroxyphenyl)-4-phenyl-1 H-1,2,4-triazole-5-(4 H)-thione by DFT and ab initio HF calculations

    NASA Astrophysics Data System (ADS)

    Avcı, Davut; Atalay, Yusuf; Şekerci, Mehmet; Dinçer, Muharrem

    2009-07-01

    The molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) 1H and 13C chemical shift values and several thermodynamic parameters of 3-(2-Hydroxyphenyl)-4-phenyl-1 H-1,2,4-triazole-5-(4 H)-thione in the ground state have been calculated by using the Hartree-Fock (HF) and density functional methods (BLYP and B3LYP) with 6-31G(d) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction. The molecule contains one O-H···N and one C-H···π (phenyl) intramolecular interactions. The computed vibrational frequencies are used to determine the types of molecular motions associated with each of the experimental bands observed. Data of the title compound display significant structure-correlation and provide the basis for future design of efficient materials having the derivatives of 1,2,4-triazole. Also, calculated 1H chemical shift values compared with the experimental ones.

  13. Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function.

    PubMed

    Kelly, Caleb J; Zheng, Leon; Campbell, Eric L; Saeedi, Bejan; Scholz, Carsten C; Bayless, Amanda J; Wilson, Kelly E; Glover, Louise E; Kominsky, Douglas J; Magnuson, Aaron; Weir, Tiffany L; Ehrentraut, Stefan F; Pickel, Christina; Kuhn, Kristine A; Lanis, Jordi M; Nguyen, Vu; Taylor, Cormac T; Colgan, Sean P

    2015-05-13

    Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide energy for the host epithelium through the production of the short-chain fatty acid butyrate. We sought to determine the role of epithelial butyrate metabolism in establishing the austere oxygenation profile of the distal gut. Bacteria-derived butyrate affects epithelial O2 consumption and results in stabilization of hypoxia-inducible factor (HIF), a transcription factor coordinating barrier protection. Antibiotic-mediated depletion of the microbiota reduces colonic butyrate and HIF expression, both of which are restored by butyrate supplementation. Additionally, germ-free mice exhibit diminished retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the influences of butyrate are lost in cells lacking HIF, thus linking butyrate metabolism to stabilized HIF and barrier function. This work highlights a mechanism where host-microbe interactions augment barrier function in the distal gut. PMID:25865369

  14. Chemostat Enrichments of Human Feces with Resistant Starch Are Selective for Adherent Butyrate-Producing Clostridia at High Dilution Rates

    PubMed Central

    Sharp, Richard; Macfarlane, George T.

    2000-01-01

    Resistant starch (RS) enrichments were made using chemostats inoculated with human feces from two individuals at two dilution rates (D = 0.03 h−1 and D = 0.30 h−1) to select for slow- and fast-growing amylolytic communities. The fermentations were studied by analysis of short-chain fatty acids, amylase and α-glucosidase activities, and viable counts of the predominant culturable populations and the use of 16S rRNA-targeted oligonucleotide probes. Considerable butyrate was produced at D = 0.30 h−1, which corresponded with reduced branched-chain fatty acid formation. At both dilution rates, high levels of extracellular amylase activity were produced, while α-glucosidase was predominantly cell associated. Bacteroides and bifidobacteria predominated at the low dilution rate, whereas saccharolytic clostridia became more important at D = 0.30 h−1. Microscopic examination showed that within 48 h of inoculation, one particular bacterial morphotype predominated in RS enrichments at D = 0.30 h−1. This organism attached apically to RS granules and formed rosette-like structures which, with glycocalyx formation, agglomerated to form biofilm networks in the planktonic phase. Attempts to isolate this bacterium in pure culture were repeatedly unsuccessful, although a single colony was eventually obtained. On the basis of its 16S rDNA sequence, this RS-degrading, butyrate-producing organism was identified as being a previously unidentified group I Clostridium sp. A 16S rRNA-targeted probe was designed using this sequence and used to assess the abundance of the population in the enrichments. At 240 h, its contributions to total rRNA in the chemostats were 5 and 23% at D = 0.03 and 0.30 h−1, respectively. This study indicates that bacterial populations with significant metabolic potential can be overlooked using culture-based methodologies. This may provide a paradigm for explaining the discrepancy between the low numbers of butyrate-producing bacteria that are

  15. Vimentin, colon cancer progression and resistance to butyrate and other HDACis.

    PubMed

    Lazarova, Darina L; Bordonaro, Michael

    2016-06-01

    Dietary fibre protects against colorectal cancer (CRC) most likely through the activity of its fermentation product, butyrate. Butyrate functions as a histone deacetylase inhibitor (HDACi) that hyperactivates Wnt signalling and induces apoptosis of CRC cells. However, individuals who consume a high-fibre diet may still develop CRC; therefore, butyrate resistance may develop over time. Furthermore, CRC cells that are resistant to butyrate are cross-resistant to clinically relevant therapeutic HDACis, suggesting that the development of butyrate resistance in vivo can result in HDACi-resistant CRCs. Butyrate/HDACi-resistant CRC cells differ from their butyrate/HDACi-sensitive counterparts in the expression of many genes, including the gene encoding vimentin (VIM) that is usually expressed in normal mesenchymal cells and is involved in cancer metastasis. Interestingly, vimentin is overexpressed in butyrate/HDACi-resistant CRC cells although Wnt signalling is suppressed in such cells and that VIM is a Wnt activity-targeted gene. The expression of vimentin in colonic neoplastic cells could be correlated with the stage of neoplastic progression. For example, comparative analyses of LT97 microadenoma cells and SW620 colon carcinoma cells revealed that although vimentin is not detectable in LT97 cells, it is highly expressed in SW620 cells. Based upon these observations, we propose that the differential expression of vimentin contributes to the phenotypic differences between butyrate-resistant and butyrate-sensitive CRC cells, as well as to the differences between early-stage and metastatic colorectal neoplastic cells. We discuss the hypothesis that vimentin is a key factor integrating epithelial to mesenchymal transition, colonic neoplastic progression and resistance to HDACis. PMID:27072512

  16. [Pharmacological study on hydrocortisone 17-butyrate 21-propionate (author's transl)].

    PubMed

    Otomo, S; Higuchi, S; Nakaike, S; Takeshita, K; Tanaka, M; Gotoh, Y; Osada, Y; Tsuchida, K; Inoue, K; Kyogoku, K; Tarumoto, Y; Sasajima, M; Ohzeki, M

    1981-12-01

    The topical and systemic anti-inflammatory activities of hydrocortisone 17-butyrate 21-propionate (HBP) were studied. The systemic anti-inflammatory activities of HBP and reference steroids were examined for their effects on dinitrochlorobenzene dermatitis, carrageenin edema, cotton pellet granuloma and adjuvant arthritis in rats and by the delayed allergic edema test in mice. The topical anti-inflammatory activities of these steroids were examined for their effects on croton oil dermatitis, croton oil ear edema, carrageenin edema and cotton pellet granuloma in rats. Furthermore, effects of these steroids on liver glycogen deposition in mice, thymolysis, and decrease of serum corticosterone level in rats were examined. Systemically administered HBP was less potent than betamethasone 17-valerate (BV), but was almost equal to hydrocortisone 17-butyrate (HB) in anti-inflammatory activity, and its effects on liver glycogen deposition, thymolysis, and the decrease of serum corticosterone level. However, the topical anti-inflammatory activity of HBP was more potent than that of BV and HB, although in the same experiment, thymolytic activity of HBP was less potent than that of BV, but was almost equal to HB. The inhibitory effect of HBP on hypotonic induced hemolysis was weaker than that of BV, but was stronger than that of HB in vitro. The affinity of HBP was higher than that of BV and HB to polymorphonuclear leucocytes used as the inflammatory cells in vitro. On the other hand no marked difference was observed in the affinity to erythrocytes used as the non-inflammatory cells in vitro. These results suggest that HBP is a useful drug which has superior topical anti-inflammatory activity, but has a weak systemic effect. PMID:7333567

  17. 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...

  18. In vitro dissolution and in vivo absorption of calcium [1-14C]butyrate in free or protected forms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butyrate is a by-product 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 the epithelial cell development and for mucosal integrity, and for animal grow...

  19. 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

  20. 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

  1. Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition.

    PubMed

    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. 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

  3. Genotype-dependency of butyrate efficacy in children with congenital chloride diarrhea

    PubMed Central

    2013-01-01

    Background Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by life-long, severe diarrhea with intestinal Cl- malabsorption. It results from a reduced activity of the down regulated in adenoma exchanger (DRA), due to mutations in the solute carrier family 26, member 3 (SLC26A3) gene. Currently available therapies are not able to limit the severity of diarrhea in CLD. Conflicting results have been reported on the therapeutic efficacy of oral butyrate. Methods We investigated the effect of oral butyrate (100 mg/kg/day) in seven CLD children with different SLC26A3 genotypes. Nasal epithelial cells were obtained to assess the effect of butyrate on the expression of the two main Cl- transporters: DRA and putative anion transporter-1 (PAT-1). Results A variable clinical response to butyrate was observed regarding the stool pattern and fecal ion loss. The best response was observed in subjects with missense and deletion mutations. Variable response to butyrate was also observed on SLC26A3 (DRA) and SLC26A6 (PAT1) gene expression in nasal epithelial cells of CLD patients. Conclusions We demonstrate a genotype-dependency for butyrate therapeutic efficacy in CLD. The effect of butyrate is related in part on a different modulation of the expression of the two main apical membrane Cl- exchangers of epithelial cells, members of the SLC26 anion family. Trial registration Australian New Zealand Clinical trial Registry ACTRN12613000450718. PMID:24350656

  4. Butyrate enemas upregulate Muc genes expression but decrease adherent mucus thickness in mice colon.

    PubMed

    Gaudier, E; Rival, M; Buisine, M-P; Robineau, I; Hoebler, C

    2009-01-01

    Colonic mucosal protection is provided by the mucus gel, mainly composed of mucins. Several factors can modulate the formation and the secretion of mucins, and among them butyrate, an end-product of carbohydrate fermentation. However, the specific effect of butyrate on the various colonic mucins, and the consequences in terms of the mucus layer thickness are not known. Our aim was to determine whether butyrate modulates colonic MUC genes expression in vivo and whether this results in changes in mucus synthesis and mucus layer thickness. Mice received daily for 7 days rectal enemas of butyrate (100 mM) versus saline. We demonstrated that butyrate stimulated the gene expression of both secreted (Muc2) and membrane-linked (Muc1, Muc3, Muc4) mucins. Butyrate especially induced a 6-fold increase in Muc2 gene expression in proximal colon. However, butyrate enemas did not modify the number of epithelial cells containing the protein Muc2, and caused a 2-fold decrease in the thickness of adherent mucus layer. Further studies should help understanding whether this last phenomenon, i.e. the decrease in adherent mucus gel thickness, results in a diminished protective function or not. PMID:18198997

  5. 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. PMID:25898090

  6. 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

  7. 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

  8. Atorvastatin improves cognitive, emotional and motor impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats, an experimental model of Parkinson's disease.

    PubMed

    Castro, Adalberto A; Wiemes, Bárbara P; Matheus, Filipe C; Lapa, Fernanda R; Viola, Giordano G; Santos, Adair R; Tasca, Carla I; Prediger, Rui D

    2013-06-01

    Affective disorders and memory impairments precede the classical motor symptoms seen in Parkinson's disease (PD) and the currently approved antiparkinsonian agents do not alleviate the non-motor symptoms as well as the underlying dopaminergic neuron degeneration. On the other hand, there is increasing evidence that inflammation plays a key role in the pathophysiology of PD and that the anti-inflammatory actions of statins are related to their neuroprotective properties against different insults in the CNS. The present data indicates that the oral treatment with atorvastatin (10mg/kg/day), once a day during 7 consecutive days, was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1mg/nostril). Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover, atorvastatin was found to protect against the long-lasting motor deficits evaluated in activity chambers and the loss of dopaminergic neurons in the substantia nigra pars compacta observed at 21 days after i.n. MPTP administration. At this time, despite the absence of spatial memory deficits in the water maze and in concentrations of the cytokines TNF-α, IL-1β and IL-10 in striatum and hippocampus following i.n. MPTP administration, atorvastatin treatment resulted in a significant increase in the striatal and hippocampal levels of nerve growth factor (NGF). These findings reinforce and extend the notion of the neuroprotective potential of atorvastatin and suggest that it may represent a new therapeutic tool for the management of motor and non-motor symptoms of PD. PMID:23548600

  9. Protection against 1-methyl-4-phenyl pyridinium-induced neurotoxicity in human neuroblastoma SH-SY5Y cells by Soyasaponin I by the activation of the phosphoinositide 3-kinase/AKT/GSK3β pathway.

    PubMed

    Guo, Zheng; Cao, Wei; Zhao, Shifeng; Han, Zengtai; Han, Boxiang

    2016-07-01

    Parkinson's disease (PD) can be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of Soyasaponin I (Soya-I), a naturally occurring triterpene extracted from a widely used ingredient in many foods, such as Glycine max (soybean), were evaluated in a widely used cellular PD model in which neurotoxicity was induced by 1-methyl-4-phenyl pyridinium (MPP) in cultured SH-SY5Y cells. We found that Soya-I at 10-40 μM considerably protected against MPP-induced neurotoxicity as evidenced by an increase in cell viability, a decrease in lactate dehydrogenase release, and a reduction in apoptotic nuclei. Moreover, Soya-I effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as the Bax/Bcl-2 ratio caused by MPP. Most importantly, Soya-I markedly reversed the inhibition of protein expression of phosphorylated AKT and phosphorylated GSK3β caused by MPP. LY294002, the specific inhibitor of phosphoinositide 3-kinase, significantly abrogated the upregulated phosphorylated AKT and phosphorylated GSK3β offered by Soya-I, suggesting that the neuroprotection of Soya-I was mainly dependent on the activation of the phosphoinositide 3-kinase/AKT/GSK3β signaling pathway. The results taken together indicate that Soya-I may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. PMID:27196724

  10. Comparative studies between 4-allyl-, 4-phenyl- and 4-ethyl-1-(2-hydroxybenzoyl) thiosemicarbazides and the synthesis, characterization and DFT calculations of binary and ternary complexes derived from 4-ethyl (L(1)) and 2,2'-dipyridyl.

    PubMed

    Azhari, Shaker J; Mlahi, Mosaad R; Mostafa, Mohsen M

    2015-11-01

    The metal complexes of 4-ethyl-1-(2-hydroxybenzoyl) thiosemicarbazide (L(1)) with MCl2 (M=Co(2+), Cu(2+) and Zn(2+)) and Zn(Ac)2 in EtOH were synthesized and characterized using spectral (IR, (1)H-NMR, mass, UV-Visible), magnetic moment and thermal measurements. Binary and ternary complexes with the general formulae, [Cu(L(1)-H)2]·EtOH, [Co(L(1)-H)2], [Zn3(L(1)-H)(L(1))(Ac)5], [Cu2(L(2))2(L(1)-2H)2(H2O)2]·4H2O, [Co(L(2))(L(1)-2H)]·3H2O and [Zn2(L(2))(OH)(L(1)-3H)(H2O)]·1/2EtOH where L(2) is 2,2'-dipyridyl, have been suggested and characterized. The bond lengths, bond angles, chemical reactivates, energy components, binding energies and dipole moments for the isolated complexes were evaluated by DFT method from DMOL(3). Also, the MEP for L(1) is illustrated. The existence of the OH group in the Zn(2+) ternary complexes is confirmed by IR, mass and (1)H-NMR spectra. Biological activity for the L(1) and some its complexes was tested against DNA. Comparative studies between the ligation behavior and reactivity of our previous work derived from 4-phenyl- and 4-allyl-1-(2-hydroxybenzoyl) thiosemicarbazides have been investigated. PMID:26123512

  11. 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

    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

    2016-07-01

    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

  12. 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. PMID:23907992

  13. 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

  14. 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. PMID:24558048

  15. 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

  16. 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.

  17. 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

  18. Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway.

    PubMed

    Wang, Xukai; He, Gang; Peng, Yan; Zhong, Weitian; Wang, Yan; Zhang, Bo

    2015-01-01

    Insulin resistance (IR) is a common feature of Type II diabetes, metabolic disorders, hypertension and other vascular diseases. Recent studies showed that obesity-induced inflammation may be critical for IR. To investigate the anti-inflammatory effect of sodium butyrate (NaB) on obesity-induced inflammation, the db/db mice were intraperitoneally injected with NaB for 6 weeks. Glucose control was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT). Adipose tissue was harvested for gene expression analysis. 3T3-L1 adipocytes were treated with Tnf-α to mimic the inflammatory state and gene expression was detected by realtime PCR and Western blotting. Our results showed that NaB treatment improved glucose control in db/db mice as determined by GTT and ITT tests. Gene expression analysis showed that NaB inhibited cytokines and immunological markers including CD68, Interferon-γ and Mcp in adipose tissues in db/db mice. Moreover, NaB inhibited cytokine releasing in 3T3-L1 adipocytes treated with TNF-α. Further analysis of inflammation pathway showed that NLRP3 was activated in db/db mice, which was efficiently inhibited by NaB treatment. Our data suggest that inhibition of obesity-induced inflammation alleviates IR, and NaB might be a potential anti-inflammatory agent for obesity. PMID:26234821

  19. Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway

    PubMed Central

    Wang, Xukai; He, Gang; Peng, Yan; Zhong, Weitian; Wang, Yan; Zhang, Bo

    2015-01-01

    Insulin resistance (IR) is a common feature of Type II diabetes, metabolic disorders, hypertension and other vascular diseases. Recent studies showed that obesity-induced inflammation may be critical for IR. To investigate the anti-inflammatory effect of sodium butyrate (NaB) on obesity-induced inflammation, the db/db mice were intraperitoneally injected with NaB for 6 weeks. Glucose control was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT). Adipose tissue was harvested for gene expression analysis. 3T3-L1 adipocytes were treated with Tnf-α to mimic the inflammatory state and gene expression was detected by realtime PCR and Western blotting. Our results showed that NaB treatment improved glucose control in db/db mice as determined by GTT and ITT tests. Gene expression analysis showed that NaB inhibited cytokines and immunological markers including CD68, Interferon-γ and Mcp in adipose tissues in db/db mice. Moreover, NaB inhibited cytokine releasing in 3T3-L1 adipocytes treated with TNF-α. Further analysis of inflammation pathway showed that NLRP3 was activated in db/db mice, which was efficiently inhibited by NaB treatment. Our data suggest that inhibition of obesity-induced inflammation alleviates IR, and NaB might be a potential anti-inflammatory agent for obesity. PMID:26234821

  20. 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. PMID:24406671

  1. 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.

  2. Stable molecular configuration in crystalline carboxylic acids

    NASA Astrophysics Data System (ADS)

    Hayashi, Soichi; Umemura, Junzo; Nakamura, Ryoko

    1980-12-01

    The stable (lower enthalpy) molecular configurations of propionic, butyric, Jeric and lauric acids in the crystalline state have been examined via their atom-atom potentials. It was found that the cis configuration is more stable than the trans configuration for propionic, butyric and valeric acids, and that the trans configuration is more stable than the cis configuration for lauric acid, in accord with a previous IR spectral analysis. The potential energy of benzoic acid was recalculated using the positions of atoms given by Speakman, and indicates that the A form is more stable than the B form, in agreement with the results of previous work.

  3. 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

  4. Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson’s disease

    PubMed Central

    Sikorska, Marianna; Lanthier, Patricia; Miller, Harvey; Beyers, Melissa; Sodja, Caroline; Zurakowski, Bogdan; Gangaraju, Sandhya; Pandey, Siyaram; Sandhu, Jagdeep K.

    2016-01-01

    Although the support for the use of antioxidants, such as coenzyme Q10 (CoQ10), to treat Parkinson’s disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ10 (Ubisol-Q10) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q10 was delivered in drinking water. Prophylactic application of Ubisol-Q10, started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q10 group by day 28). Therapeutic application of Ubisol-Q10, given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals’ motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ10/kg body weight/day, showing clearly that high doses of CoQ10 were not required to deliver these effects. Furthermore, the Ubisol-Q10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q10 was capable of halting the neurodegeneration already in progress

  5. Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease.

    PubMed

    Sikorska, Marianna; Lanthier, Patricia; Miller, Harvey; Beyers, Melissa; Sodja, Caroline; Zurakowski, Bogdan; Gangaraju, Sandhya; Pandey, Siyaram; Sandhu, Jagdeep K

    2014-10-01

    Although the support for the use of antioxidants, such as coenzyme Q(10) (CoQ(10)), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ(10) is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ(10) (Ubisol-Q(10)) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q(10) was delivered in drinking water. Prophylactic application of Ubisol-Q(10), started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q(10) group by day 28). Therapeutic application of Ubisol-Q(10), given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q(10) concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ(10)/kg body weight/day, showing clearly that high doses of CoQ(10) were not required to deliver these effects. Furthermore, the Ubisol-Q(10) treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q(10) was capable of halting the

  6. 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

  7. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\\ increased motor disability.

    PubMed

    Iravani, Mahmoud M; Tayarani-Binazir, Kayhan; Chu, Wing B; Jackson, Michael J; Jenner, Peter

    2006-12-01

    5-Hydroxytryptamine 1a (5-HT(1a)) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopa-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT(1a) receptors and also possess dopamine antagonist actions. We now report on the effects of (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-(+)-8-OHDPAT], a selective 5-HT(1a) agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(+)-8-OHDPAT (0.2, 0.6, and 2.0 mg/kg s.c), in conjunction with levodopa/carbidopa (12.5 mg/kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(+)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(+)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(+)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT(1a) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (WAY-100635) (1.0 mg/kg s.c.). Administration of (R)-(+)-8-OHDPAT (0.6 mg/kg s.c.) also reduced chorea produced by the administration of the D(2)/D(3) dopamine receptor agonist pramipexole (0.06 mg/kg p.o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT(1a) agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism. PMID:16959959

  8. Dual motor response to l-dopa and nociceptin/orphanin FQ receptor antagonists in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated mice: Paradoxical inhibition is relieved by D(2)/D(3) receptor blockade.

    PubMed

    Viaro, Riccardo; Marti, Matteo; Morari, Michele

    2010-06-01

    Motor activity of mice acutely treated with the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) was monitored for 6 days using behavioral tests which provide complementary information on motor function: the bar, reaction time, drag, stair climbing, grip, rotarod and footprinting tests. These tests consistently disclosed a prolonged motor impairment characterized by akinesia, bradykinesia, speed reduction, loss of coordination and gait patterns. This impairment was associated with approximately 60% loss of striatal dopamine terminals, as revealed by tyrosine hydroxylase immunohistochemistry, and was attenuated by dopaminergic drugs. Indeed, the dopamine precursor, l-dopa (1-10 mg/kg), and the D(3)/D(2) receptor agonist pramipexole (0.0001-0.001 mg/kg) promoted stepping activity in the drag test (a test for akinesia/bradykinesia). The novel nociceptin/orphanin FQ receptor (NOP) antagonist 1-[1-(cyclooctylmethyl)-1,2,3,6-tetrahydro-5-(hydroxymethyl)-4-pyridinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (Trap-101, 0.001-0.1 mg/kg), an analogue of 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397), also promoted stepping and synergistically or additively (depending on test) attenuated parkinsonism when combined to dopamine agonists. High doses of l-dopa (100 mg/kg), pramipexole (0.1 mg/kg), Trap-101 and J-113397 (1 mg/kg), however, failed to modulate stepping, worsening immobility time and/or rotarod performance. Low doses of amisulpride (0.1 mg/kg) reversed motor inhibition induced by l-dopa and J-113397, suggesting involvement of D(2)/D(3) receptors. This study brings further evidence for a dopamine-dependent motor phenotype in MPTP-treated mice reinforcing the view that this model can be predictive of symptomatic antiparkinsonian activity provided the appropriate test is used. Moreover, it offers mechanistic interpretation to clinical reports of paradoxical worsening of parkinsonism

  9. Effects of Sodium Butyrate on Methamphetamine-Sensitized Locomotor Activity

    PubMed Central

    Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.

    2012-01-01

    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, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge 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 2 mg/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, appeared to increase 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. PMID:23137698

  10. 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. PMID:24677319

  11. Anti-inflammatory effect of sodium butyrate preconditioning during myocardial ischemia/reperfusion

    PubMed Central

    HU, XIAORONG; ZHANG, KAI; XU, CHANGWU; CHEN, ZHIQAING; JIANG, HONG

    2014-01-01

    High mobility group box 1 protein (HMGB1) has an important role in myocardial ischemia/reperfusion (I/R) injury. Sodium butyrate, an inhibitor of histone deacetylase, has been shown to inhibit HMGB1 expression. In the present study, the effect of sodium butyrate on myocardial I/R injury in rats was investigated. Anesthetized male rats were intraperitoneally administered sodium butyrate (100 or 300 mg/kg) 30 min prior to the induction of ischemia. The rats were then subjected to ischemia for 30 min followed by reperfusion for 4 h. Infarct size, lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were then measured. The expression of HMGB1 was assessed using western blot analysis. The results demonstrated that pretreatment with sodium butyrate (300 mg/kg) significantly reduced the infarct size, as well as the levels of LDH and CK (P<0.05). In addition, sodium butyrate (300 mg/kg) was shown to significantly inhibit the I/R-induced increase in the level of MDA and reduction in the level of SOD (P<0.05). Furthermore, treatment with sodium butyrate (300 mg/kg) was found to significantly inhibit the expression of TNF-α, IL-6 and HMGB1 induced by I/R injury (P<0.05). In conclusion, the results from the present study suggest that preconditioning with sodium butyrate may attenuate myocardial I/R injury by inhibition of the expression of inflammatory mediators during myocardial I/R. PMID:24944626

  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. Production of Butyrate from Lactate by a Newly Isolated Clostridium sp. BPY5.

    PubMed

    Tao, Yong; Hu, Xiaohong; Zhu, Xiaoyu; Jin, Hong; Xu, Zhancheng; Tang, Qinglan; Li, Xiangzhen

    2016-06-01

    Lactate-utilizing bacteria play important roles in the production of Chinese strong-flavored liquor (CSFL). However, the identity of these bacteria and their lactate-utilizing properties are largely unknown. Here, a lactate-utilizing, butyrate-producing bacterium BPY5 was isolated from an old fermentation pit for CSFL production. The isolate represented a novel species belonging to Clostridium cluster XIVa of family Lachnospiraceae based on phylogenetic analysis using 16S rRNA gene sequences. Strain BPY5 could ferment lactate into butyrate as the major metabolic product. Butyrate was significantly formed at initial lactate concentration from 66 to 104 mM, but substantially declined when initial lactate exceeded 133 mM. At initial lactate concentration of 66 mM, lactate conversion was independent on initial pH from 5.5 to 7.0, but the conversion was completely inhibited when pH dropped below 4.8. Nevertheless, the inhibition on lactate conversion was largely relieved by the addition of acetate, suggesting that exogenous acetate could enhance lactate conversion at low pH condition. Additionally, lactate in CSFL-brewing wastewater was dramatically removed when inoculated with strain BPY5. These results implicate that the isolate may be applied for the industrial production of butyrate or the recovery of butyrate from lactate-containing wastewater. PMID:26842597

  14. New holographic polymeric composition based on plexiglass, polyvinyl butyral, and phenanthrenquinone

    NASA Astrophysics Data System (ADS)

    Matusevich, Vladislav; Tolstik, Elen; Kowarschik, Richard; Egorova, Elena; Matusevich, Yuri I.; Krul, Leonid

    2013-05-01

    The newly developed Plexiglas films containing polyvinyl butyral resins and phenanthrenequinone molecules as photosensitive dopant, which are proposed for the practical application as interlayer of laminated safety glass, are shown for the first time. The injection of the phenanthrenequinone-poly(methyl methacrylate) into the polyvinyl butyral protective interlayer provides a homogenous distribution of the recording holographic medium in the layer and allows fixing the entire surface grating in the laminated glass. In addition, the original properties of polyvinyl butyral as a connecting material were preserved during manufacturing of the laminated glass. This allows a recording of holographic structures directly after baking of the laminated glass, thus reducing the destruction of the gratings due to the elevated temperatures. The diffractive structures in phenanthrenequinone-poly(methyl methacrylate)-polyvinyl butyral polymeric layers with thicknesses of hundreds of microns are sealed between two panels of glass (so-called laminated glass) and are generated by illumination with an Argon-laser of 514 nm. Efficiently fixed and long-term stable holographic gratings recorded in the phenanthrenequinone-poly(methyl methacrylate)-polyvinyl butyral layer enable to produce transparent laminated glass with inserted diffractive elements, which can be used e.g. for Head-up Displays in automobile windshields or as holographic light concentrators for solar cells.

  15. 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

  16. SKW 6.4 cell differentiation induced by interleukin 6 is stimulated by butyrate.

    PubMed

    Kawamoto, T; Gohda, E; Iji, H; Fujiwara, M; Yamamoto, I

    1998-08-01

    We investigated if sodium butyrate (NaBu), an inhibitor of histone deacetylase, and its analogs modulate cytokine-induced differentiation of the human B cell line SKW 6.4 transformed by the Epstein-Barr virus. NaBu markedly enhanced interleukin (IL)-6-induced IgM production with an accompanying increase in the level of histone H4 acetylation and augmented IgM production induced by IL-4 and phorbol 12-myristate 13-acetate. From both the enhancing effect of cell differentiation and the effect of inducing histone hyperacetylation in SKW 6.4 cells, other histone deacetylase inhibitors and NaBu analogs were divided into three groups: those that increased both IL-6-induced antibody production and histone acetylation, those that caused histone hyperacetylation, but failed to induce the differentiation, and those that were ineffective at inducing either activity. No agent that enhanced IgM production without inducing histone hyperacetylation was found among the inhibitors and analogs we tested. These results suggest that the increase in the histone acetylation is necessary, but it is insufficient to augment differentiation of SKW 6.4 cells. Thus another activity of NaBu in addition to the inhibition of histone deacetylase may be involved in promoting IL-6-induced differentiation. Our results also suggest that fatty acids that have a straight chain of four carbon atoms or are branched with four and five carbon atoms, which contain no hydrophilic substituents, or those with similar structures, show this other activity. PMID:9826026

  17. Crystal structure of bis­[tris­(1,10-phenanthroline-κ2 N,N′)cobalt(II)] tetra­nitrate N,N′-(1,4-phenyl­enedicarbon­yl)diglycine solvate octa­hydrate

    PubMed Central

    Pook, Niels-Patrick; Hentrich, Philipp; Gjikaj, Mimoza

    2015-01-01

    The complex cation of the title compound, [Co(C12H8N2)3]2(NO3)4·C12H12N2O6·8H2O, contains a CoII atom with a distorted octa­hedral coordination environment defined by six N atoms from three bidentate 1,10-phenanthroline ligands. The asymmetric unit of the title compound is completed by one-half of the N,N′-(1,4-phenyl­enedicarbon­yl)diglycine solvent mol­ecule, which is located on a centre of inversion, by two nitrate counter-anions and four solvent water mol­ecules. Two [Co(C12H8N2)3]2+ cations are connected through C—H⋯O contacts and through lone-pair⋯π inter­actions involving the non-coordinating N,N′-(1,4-phenyl­enedicarbon­yl)diglycine and phenanthroline mol­ecules. The different aromatic ring systems are involved in π–π stacking and C—H⋯π inter­actions, with centroid-to-centroid distances in the range 3.7094 (8)–3.9973 (9) Å. The crystal structure is stabilized by further anion⋯π inter­actions and C—H⋯O contacts, as well as O—H⋯O and N—H⋯O hydrogen bonds between water mol­ecules, the non-coordinating nitrate anions, N,N′-(1,4-phenyl­enedicarbon­yl)diglycine and phenanthroline mol­ecules. These non-covalent inter­actions give rise to a three-dimensional supra­molecular network. PMID:26396753

  18. Butyrate production from high-fiber diet protects against lymphoma tumor.

    PubMed

    Wei, Wei; Sun, Wei; Yu, Shanshan; Yang, Yu; Ai, Limei

    2016-10-01

    Gut microbiota and dietary fiber are critical for protecting body from obesity, diabetes and cancer. Butyrate, produced in the gut by bacterial fermentation of dietary fibers, is demonstrated to be protective against the development of colorectal cancer as a histone deacetylase (HDAC) inhibitor. We report that high-fiber diet and butyrate significantly inhibited the growth lymphoma tumors. Butyrate induced apoptosis of lymphoma tumor cells and significantly up-regulated histone 3 acetylation (H3ac) level and target genes such as Fas, P21, P27. Our results unravel an instrumental role of fiber diet and their metabolites on lymphoma tumor and demonstrate an intervention potential on the prevention and therapy of lymphoma. PMID:26885564

  19. Bis{μ-2-[3-carboxyl­atometh­yl-4-(phenyl­sulfan­yl)phen­yl]propano­ato-κ4 O,O′:O′′,O′′′}bis­[(2,2′-bipyridine-κ2 N,N′)cadmium

    PubMed Central

    Li, Long; Ding, Yu-Qiu; Diao, Kai-Sheng

    2012-01-01

    In the title complex, [Cd2(C17H14O4S)2(C10H8N2)2], which was hydro­thermally synthesized, the CdII cation is hexa­coordinated in a distorted octa­hedral geometry by two N atoms from a 2,2′-bipyridine ligand and by four O atoms from two different 2-[3-carboxyl­atometh­yl-4-(phenyl­sulfan­yl)phen­yl]propano­ate ligands, forming a cyclic dimetallic complex. PMID:22589863

  20. 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

  1. 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

  2. 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

  3. Nonprotein amino acids from spark discharges and their comparison with the murchison meteorite amino acids.

    PubMed

    Wolman, Y; Haverland, W J; Miller, S L

    1972-04-01

    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 alpha-amino-n-butyric acid, alpha-aminoisobutyric acid, norvaline, isovaline, pipecolic acid, beta-alanine, beta-amino-n-butyric acid, beta-aminoisobutyric acid, gamma-aminobutyric acid, sarcosine, N-ethylglycine, and N-methylalanine. In addition, norleucine, alloisoleucine, N-propylglycine, N-isopropylglycine, N-methyl-beta-alanine, N-ethyl-beta-alanine alpha,beta-diaminopropionic acid, isoserine, alpha,gamma-diaminobutyric acid, and alpha-hydroxy-gamma-aminobutyric acid are produced by the electric discharge, but have not been found in the meteorite. PMID:16591973

  4. 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

  5. MicroRNA (miRNA) expression is regulated by butyrate induced epigenetic modulation of gene expression in bovine cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present evidence that butyrate induced histone acetylation regulates miRNA expression. MicroRNA expression microarray profiling revealed that 35 miRNA transcripts are significantly (p <0.05) differentially expressed after cells were treated with 10 mM butyrate. Among them, 11 transcripts are dif...

  6. Communities stimulated with ethanol to perform direct interspecies electron transfer for syntrophic metabolism of propionate and butyrate.

    PubMed

    Zhao, Zhiqiang; Zhang, Yaobin; Yu, Qilin; Dang, Yan; Li, Yang; Quan, Xie

    2016-10-01

    Direct interspecies electron transfer (DIET) has been considered as an alternative to interspecies H2 transfer (IHT) for syntrophic metabolism, but the microorganisms capable of metabolizing the key intermediates, such as propionate and butyrate, via DIET have yet to be described. A strategy of culturing the enrichments with ethanol as a DIET substrate to stimulate the communities for the syntrophic metabolism of propionate and/or butyrate was proposed in this study. The results showed that the syntrophic propionate and/or butyrate degradation was significantly improved in the ethanol-stimulated reactor when propionate/butyrate was the sole carbon source. The conductivity of the ethanol-stimulated enrichments was as 5 folds (for propionate)/76 folds (for butyrate) as that of the traditional enrichments (never ethanol fed). Microbial community analysis revealed that Geobacter species known to proceed DIET were only detected in the ethanol-stimulated enrichments. Together with the significant increase of Methanosaeta and Methanosarcina species in these enrichments, the potential DIET between Geobacter and Methanosaeta or Methanosarcina species might be established to improve the syntrophic propionate and/or butyrate degradation. Further experiments demonstrated that granular activated carbon (GAC) could improve the syntrophic metabolism of propionate and/or butyrate of the ethanol-stimulated enrichments, while almost no effects on the traditional enrichments. Also, the high H2 partial pressure could inhibit the syntrophic propionate and/or butyrate degradation of the traditional enrichments, but its effect on that of the ethanol-stimulated enrichments was negligible. PMID:27403870

  7. 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

  8. 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

  9. Enhancing Butanol Production under the Stress Environments of Co-Culturing Clostridium acetobutylicum/Saccharomyces cerevisiae Integrated with Exogenous Butyrate Addition

    PubMed Central

    Luo, Hongzhen; Ge, Laibing; Zhang, Jingshu; Zhao, Yanli; Ding, Jian; Li, Zhigang; He, Zhenni; Chen, Rui; Shi, Zhongping

    2015-01-01

    In this study, an efficient acetone-butanol-ethanol (ABE) fermentation strategy integrating Clostridium acetobutylicum/Saccharomyces cerevisiae co-culturing system with exogenous butyrate addition, was proposed and experimentally conducted. In solventogenic phase, by adding 0.2 g-DCW/L-broth viable S. cerevisiae cells and 4.0 g/L-broth concentrated butyrate solution into C. acetobutylicum culture broth, final butanol concentration and butanol/acetone ratio in a 7 L anaerobic fermentor reached the highest levels of 15.74 g/L and 2.83 respectively, with the increments of 35% and 43% as compared with those of control. Theoretical and experimental analysis revealed that, the proposed strategy could, 1) extensively induce secretion of amino acids particularly lysine, which are favorable for both C. acetobutylicum survival and butanol synthesis under high butanol concentration environment; 2) enhance the utilization ability of C. acetobutylicum on glucose and over-produce intracellular NADH for butanol synthesis in C. acetobutylicum metabolism simultaneously; 3) direct most of extra consumed glucose into butanol synthesis route. The synergetic actions of effective amino acids assimilation, high rates of substrate consumption and NADH regeneration yielded highest butanol concentration and butanol ratio in C. acetobutylicum under this stress environment. The proposed method supplies an alternative way to improve ABE fermentation performance by traditional fermentation technology. PMID:26489085

  10. Electron transport phosphorylation in rumen butyrivibrios: unprecedented ATP yield for glucose fermentation to butyrate

    PubMed Central

    Hackmann, Timothy J.; Firkins, Jeffrey L.

    2015-01-01

    From a genomic analysis of rumen butyrivibrios (Butyrivibrio and Pseudobutyrivibrio sp.), we have re-evaluated the contribution of electron transport phosphorylation (ETP) to ATP formation in this group. This group is unique in that most (76%) genomes were predicted to possess genes for both Ech and Rnf transmembrane ion pumps. These pumps act in concert with the NifJ and Bcd-Etf to form a electrochemical potential (ΔμH+ and ΔμNa+), which drives ATP synthesis by ETP. Of the 62 total butyrivibrio genomes currently available from the Hungate 1000 project, all 62 were predicted to possess NifJ, which reduces oxidized ferredoxin (Fdox) during pyruvate conversion to acetyl-CoA. All 62 possessed all subunits of Bcd-Etf, which reduces Fdox and oxidizes reduced NAD during crotonyl-CoA reduction. Additionally, 61 genomes possessed all subunits of the Rnf, which generates ΔμH+ or ΔμNa+ from oxidation of reduced Fd (Fdred) and reduction of oxidized NAD. Further, 47 genomes possessed all six subunits of the Ech, which generates ΔμH+ from oxidation of Fdred. For glucose fermentation to butyrate and H2, the electrochemical potential established should drive synthesis of ∼1.5 ATP by the F0F1-ATP synthase (possessed by all 62 genomes). The total yield is ∼4.5 ATP/glucose after accounting for three ATP formed by classic substrate-level phosphorylation, and it is one the highest yields for any glucose fermentation. The yield was the same when unsaturated fatty acid bonds, not H+, served as the electron acceptor (as during biohydrogenation). Possession of both Ech and Rnf had been previously documented in only a few sulfate-reducers, was rare in other rumen prokaryotic genomes in our analysis, and may confer an energetic advantage to rumen butyrivibrios. This unique energy conservation system might enhance the butyrivibrios’ ability to overcome growth inhibition by unsaturated fatty acids, as postulated herein. PMID:26157432

  11. Morphological development of polypropylene in immiscible blends with cellulose acetate butyrate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Isotactic polypropylenes (iPP) with different melt flow indexes were melt blended with cellulose acetate butyrate (CAB) and then prepared into microspheres or nanofibers following a novel process of producing well dispersed CAB/iPP immiscible blends and subsequent removal of the CAB matrix. The morp...

  12. Intermediary Metabolism in Clostridium acetobutylicum: Levels of Enzymes Involved in the Formation of Acetate and Butyrate

    PubMed Central

    Hartmanis, Maris G. N.; Gatenbeck, Sten

    1984-01-01

    The levels of seven intermediary enzymes involved in acetate and butyrate formation from acetyl coenzyme A in the saccharolytic anaerobe Clostridium acetobutylicum were investigated as a function of time in solvent-producing batch fermentations. Phosphate acetyltransferase and acetate kinase, which are known to form acetate from acetyl coenzyme A, both showed a decrease in specific activity when the organism reached the solvent formation stage. The three consecutive enzymes thiolase, β-hydroxybutyrylcoenzyme A dehydrogenase, and crotonase exhibited a coordinate expression and a maximal activity after growth had ceased. Only low levels of butyryl coenzyme A dehydrogenase activity were found. Phosphate butyryltransferase activity rapidly decreased after 20 h from 5 to 11 U/mg of protein to below the detection limit (1 mU/mg). Butyrate no longer can be formed, and the metabolic flux may be diverted to butanol. Butyrate kinase showed a 2.5- to 10-fold increase in specific activity after phosphate butyryltransferase activity no longer could be detected. These results suggest that the uptake of acetate and butyrate during solvent formation can not proceed via a complete reversal of the phosphate transferase and kinase reactions. The activities of all enzymes investigated as a function of time in vitro are much higher than the metabolic fluxes through them in vivo. This indicates that none of the maximal activities of the enzymes assayed is rate limiting in C. acetobutylicum. PMID:16346566

  13. Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal

    PubMed Central

    Bui, Thi Phuong Nam; Ritari, Jarmo; Boeren, Sjef; de Waard, Pieter; Plugge, Caroline M.; de Vos, Willem M.

    2015-01-01

    Human intestinal bacteria produce butyrate, which has signalling properties and can be used as energy source by enterocytes thus influencing colonic health. However, the pathways and the identity of bacteria involved in this process remain unclear. Here we describe the isolation from the human intestine of Intestinimonas strain AF211, a bacterium that can convert lysine stoichiometrically into butyrate and acetate when grown in a synthetic medium. Intestinimonas AF211 also converts the Amadori product fructoselysine, which is abundantly formed in heated foods via the Maillard reaction, into butyrate. The butyrogenic pathway includes a specific CoA transferase that is overproduced during growth on lysine. Bacteria related to Intestinimonas AF211 as well as the genetic coding capacity for fructoselysine conversion are abundantly present in colonic samples from some healthy human subjects. Our results indicate that protein can serve as a source of butyrate in the human colon, and its conversion by Intestinimonas AF211 and related butyrogens may protect the host from the undesired side effects of Amadori reaction products. PMID:26620920

  14. Simultaneous Clostridial fermentation, lipase-catalyzed esterification, and ester extraction to enrich diesel with butyl butyrate.

    PubMed

    van den Berg, Corjan; Heeres, Arjan S; van der Wielen, Luuk A M; Straathof, Adrie J J

    2013-01-01

    The recovery of 1-butanol from fermentation broth is energy-intensive since typical concentrations in fermentation broth are below 20 g L(-1). To prevent butanol inhibition and high downstream processing costs, we aimed at producing butyl esters instead of 1-butanol. It is shown that it is possible to perform simultaneously clostridial fermentation, esterification of the formed butanol to butyl butyrate, and extraction of this ester by hexadecane. The very high partition coefficient of butyl butyrate pulls the esterification towards the product side even at fermentation pH and relatively low butanol concentrations. The hexadecane extractant is a model diesel compound and is nontoxic to the cells. If butyl butyrate enriched diesel can directly be used as car fuel, no product recovery is required. A proof-of-principle experiment for the one-pot bio-ester production from glucose led to 5 g L(-1) butyl butyrate in the hexadecane phase. The principle may be extended to a wide range of esters, especially to longer chain ones. PMID:22833369

  15. Allergic contact dermatitis to topical corticosteroids: clobetasol propionate and clobetasone butyrate.

    PubMed

    Dooms-Goossens, A; Vanhee, J; Vanderheyden, D; Gevers, D; Willems, L; Degreef, H

    1983-11-01

    2 case reports are given of patients with positive patch test reactions to clobetasol propionate. One of the patients also reacted to clobetasone butyrate. 30 other steroids that were chemically very closely related to these two 21-chloro-9-alpha-fluoro-corticosteroids, were patch test negative. The literature on contact dermatitis reactions to corticosteroids is reviewed. PMID:6653104

  16. Effects of 5-azacytidine and butyrate on differentiation and apoptosis of hepatic cancer cell lines.

    PubMed Central

    Wang, X M; Wang, X; Li, J; Evers, B M

    1998-01-01

    OBJECTIVE: To determine the cellular effects of 5-azacytidine (5-azaC) and sodium butyrate on two human liver cancers, HepG2 and Hep3B. SUMMARY BACKGROUND DATA: Primary liver cancer is a significant health problem; treatment options are limited and prognosis is poor. Recent studies have focused on the role that programmed cell death (i.e., apoptosis) plays in both normal and neoplastic growth: certain genes can either suppress (e.g., Bcl-2, Bcl-xL) or promote (e.g., Bik, Bax, Bak) apoptosis. The identification of novel agents targeted to specific molecular pathways may be beneficial in the treatment of this disease. METHODS: Human liver cancer cell lines HepG2 and Hep3B were treated with 5-azaC alone, butyrate alone, or 5-azaC and butyrate. Morphologic and proliferative changes were assessed by light microscopy and 5-bromo-2'-deoxyuridine staining; flow cytometry was used to determine cell cycle characteristics. Apoptosis was assessed by DNA laddering and the in situ apoptosis detection assay using the TdT-mediated dUTP nick end labeling method. In addition, total RNA and protein were analyzed by ribonuclease protection and Western blot, respectively, to assess changes in the expression of apoptosis-related genes. RESULTS: Treatment with either 5-azaC or butyrate inhibited cell growth and induced apoptosis in both HepG2 and Hep3B cells; the combination of 5-azaC and butyrate was not more effective than either agent alone. 5-azaC alone resulted in a more differentiated-appearing morphology and G2 cell cycle arrest in both cell lines. Treatment with 5-azaC or butyrate affected the expression levels of proteins of the Bcl-2 family. CONCLUSIONS: Both 5-azaC and butyrate induced apoptosis in the HepG2 and Hep3B liver cancer cells; 5-azaC treatment alone produced G2 arrest in both cell lines. Proteins of the Bcl-2 family may play a role in the cellular changes that occur with treatment, but further studies are required to define this potential role. Products of the

  17. Stimulation of butyrate production in the large intestine of weaning piglets by dietary fructooligosaccharides and its influence on the histological variables of the large intestinal mucosa.

    PubMed

    Tsukahara, Takamitsu; Iwasaki, Yoshie; Nakayama, Keizo; Ushida, Kazunari

    2003-12-01

    Fructooligosaccharides (FOS) reach the large intestine and are fermented into short-chain fatty acids (SCFA), lactate, and carbon dioxide. As the major energy source for the epithelial cells of the large intestine, n-butyrate stimulates the proliferation of cells as well as mineral and water absorption from the lumen. We examined the effect of dietary FOS supplementation on luminal SCFA production and its influence on the morphometrical variables of mucosa of the large intestine in commercially available pigs. Six weaning piglets were used. After 7 d of adaptation, three pigs were given a test diet containing FOS (10%) ad libitum for 10 d. The other three remained on the basal diet and were used as controls. At the end of the experiment, their large intestines were removed, and the cecum, gyri centripetales, gyri centrifugales, and rectum were separated. The contents of each portion were collected and measured for SCFA concentration, pH, and moisture. A micrometer was used to measure the crypt depth. The numbers of epithelial and mitotic cells in the crypt columns were also counted. The concentration of SCFA was significantly higher in piglets fed FOS than in the controls. The concentration of n-butyrate was markedly stimulated by FOS. The number of epithelial. mitotic, and mucin-containing cells was higher in piglets fed FOS than in the controls. Accordingly, the crypt depth was larger in the FOS-fed piglets. The luminal n-butyrate concentration showed a significantly positive correlation with the crypt depth and the number of epithelial, mitotic, and mucin-containing cells. PMID:14974732

  18. Cloning and expression of clostridium acetobutylicum ATCC 824 acetoacetyl-coenzyme A:acetate/butyrate:coenzyme A-transferase in Escherichia coli

    SciTech Connect

    Cary, J.W.; Petersen, D.J.; Bennett, G.N. ); Papoutsakis, E.T. )

    1990-06-01

    Coenzyme A (CoA)-transferase (acetoacetyl-CoA:acetate/butyrate:CoA-transferase (butyrate-acetoacetate CoA-transferase) (EC 2.8.3.9)) of Clostridium acetobutylicum ATCC 824 is an important enzyme in the metabolic shift between the acid-producing and solvent-forming states of this organism. The genes encoding the two subunits of this enzyme have been cloned and subsequent subcloning experiments established the position of the structural genes for CoA-transferase. Complementation of Escherichia coli ato mutants with the recombinant plasmid pCoAT4 (pUC19 carrying a 1.8-kilobase insert of C. acetobutylicum DNA encoding CoA-transferase activity) enabled the transformants to grow on butyrate as a sole carbon source. Despite the ability of CoA-transferase to complement the ato defect in E. coli mutants, Southern blot and Western blot (immunoblot) analyses showed showed that neither the C. acetobutylicum genes encoding CoA-transferase nor the enzyme itself shared any apparent homology with its E. coli counterpart. Polypeptides of M{sub r} of the purified CoA-transferase subunits were observed by Western blot and maxicell analysis of whole-cell extracts of E.coli harboring pCoAT4. The proximity and orientation of the genes suggest that the genes encoding the two subunits of CoA-transferase may form an operon similar to that found in E. coli. In the plasmid, however, transcription appears to be primarily from the lac promoter of the vector.

  19. Eumovate (clobetasone butyrate 0.05%) cream: a review of clinical efficacy and safety.

    PubMed

    Goustas, P; Cork, M J; Higson, D

    2003-06-01

    Topical steroid creams and ointments have been available as over-the-counter (OTC) medications for the self treatment of acute dermatitis and other steroid responsive skin disorders for more than ten years. Despite earlier fears, widespread availability and use of these creams is not associated with clinically significant adverse effects. In dermatological practice, hydrocortisone 1% remains the mainstay of treatment for facial eczema, but it is often not effective in eczema affecting other body areas. Eumovate(TM) (clobetasone butyrate 0.05%) cream has recently been made available as a pharmacy medication for the short-term management of acute eczema and allergic dermatitis by adults and children aged 10 or older, based on evidence derived from clinical trials involving over 3500 patients. This review summarises the key efficacy and safety data derived from 29 clinical trials and the post-licensing pharmacovigilance safety information, which supported the reclassification of this product for OTC use. These data show clobetasone butyrate 0.05% is more effective than 1.0% hydrocortisone in the treatment of eczema and more effective than flurandrenolone 0.0125% (p=0.01%) and a potent topical steroid hydrocortisone butyrate (p<0.05), in the treatment of psoriasis. A review of the effect of topical steroids on skin thickness concluded that, following short term application, there was no clinically significant difference between hydrocortisone 1.0% and clobetasone butyrate 0.05% in terms of potential for skin thinning. Similarly, even under extreme conditions, clobetasone butyrate 0.05% has negligible systemic absorption and has almost no effect on HPA axis function. PMID:12775314

  20. Multiple Facets of Arabidopsis Seedling Development Require 
Indole-3-Butyric Acid–Derived Auxin[W

    PubMed Central

    Strader, Lucia C.; Wheeler, Dorthea L.; Christensen, Sarah E.; Berens, John C.; Cohen, Jerry D.; Rampey, Rebekah A.; Bartel, Bonnie

    2011-01-01

    Levels of auxin, which regulates both cell division and cell elongation in plant development, are controlled by synthesis, inactivation, transport, and the use of storage forms. However, the specific contributions of various inputs to the active auxin pool are not well understood. One auxin precursor is indole-3-butyric acid (IBA), which undergoes peroxisomal β-oxidation to release free indole-3-acetic acid (IAA). We identified ENOYL-COA HYDRATASE2 (ECH2) as an enzyme required for IBA response. Combining the ech2 mutant with previously identified iba response mutants resulted in enhanced IBA resistance, diverse auxin-related developmental defects, decreased auxin-responsive reporter activity in both untreated and auxin-treated seedlings, and decreased free IAA levels. The decreased auxin levels and responsiveness, along with the associated developmental defects, uncover previously unappreciated roles for IBA-derived IAA during seedling development, establish IBA as an important auxin precursor, and suggest that IBA-to-IAA conversion contributes to the positive feedback that maintains root auxin levels. PMID:21406624

  1. Involvement of the Antioxidant Effect and Anti-inflammatory Response in Butyrate-Inhibited Vascular Smooth Muscle Cell Proliferation

    PubMed Central

    Mathew, Omana P.; Ranganna, Kasturi; Milton, Shirlette G.

    2014-01-01

    Epigenetic mechanisms by altering the expression and, in turn, functions of target genes have potential to modify cellular processes that are characteristics of atherosclerosis, including inflammation, proliferation, migration and apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone deacetylase inhibitor (HDACi), is an inhibitor of vascular smooth muscle cell (VSMC) proliferation, a critical event in atherogenesis. Here, we examined whether glutathione peroxidases (GPxs), a family of antioxidant enzymes, are modulated by butyrate, contributing to its antiproliferation action on VSMC through the regulation of the inflammatory response by using western blotting, immunostaining methods and activity assay. Treatment of VSMC with butyrate not only upregulates glutathione peroxidase (GPx) 3 and GPx4, but also increases the overall catalytic activity of GPx supporting involvement of antioxidant effect in butyrate arrested VSMC proliferation. Moreover, analysis of the redox-sensitive NF-κB transcription factor system, the target of GPx, reveals that butyrate causes downregulation of IKKα, IKKβ, IkBα and NF-κBp65 expression and prevents NF-κBp65 phosphorylation at serine536 causing inhibition of the expression NF-κB target inflammatory genes, including inducible nitric oxide synthase, VCAM-1 and cyclooxygenase-2. Overall, these observations suggest a link between the antioxidant effect and anti-inflammatory response in butyrate-arrested VSMC proliferation, accentuating the atheroprotective and therapeutic potential of natural products, like butyrate, in vascular proliferative diseases. PMID:25390157

  2. Butyrate downregulates α2β1 integrin: a possible role in the induction of apoptosis in colorectal cancer cell lines

    PubMed Central

    Buda, A; Qualtrough, D; Jepson, M A; Martines, D; Paraskeva, C; Pignatelli, M

    2003-01-01

    Background: Integrins mediate cell matrix adhesion and regulate cell growth and survival. In colonic epithelial cells, α2β1 integrin controls glandular differentiation and proliferation. Butyrate stimulates differentiation and induces apoptosis in vitro. Aims: We investigated whether butyrate induction of apoptosis was associated with perturbation of integrin mediated cell matrix adhesion. Methods: Three colonic cancer cell lines (SW1222, SW620, LS174T) were studied. Adhesion to extracellular matrix proteins, expression of α2β1 integrin, and apoptosis were studied in adherent cells after treatment with 4 mM butyrate. Results: Butyrate decreased the attachment to type I collagen in SW620 cells and type I and IV collagen in LS174T cells. The decreased cell attachment was associated with downregulation of α2β1 integrin and increased apoptosis in adherent cells. No changes in α2β1 expression or matrix adhesion were seen in SW1222 cells, which were also found to be less sensitive to butyrate induction of apoptosis. Downregulation of α2β1 integrin preceded the detection of apoptosis. Conclusion: Apoptosis induced by butyrate is associated with downregulation of expression and functional activity of α2β1 integrin. Perturbation of cell matrix adhesion may be a novel mechanism by which butyrate induces apoptosis in colorectal cancer cells. PMID:12692060

  3. Comparison of the butyrate effects on neurotransmitter receptors in neurohybrids NG108-15 and NCB-20 cells

    SciTech Connect

    Zhu, X.Z.; Chuang, D.M.

    1987-08-31

    The authors previous study demonstrated that long term treatment of NCB-20 cells with sodium butyrate resulted in a marked increase in the density of delta-opioid receptors with a much lesser effect on muscarinic cholinergic and no effect on alpha/sub 2/-adrenergic receptors. In the present study the authors investigated the effect of sodium butyrate on these three types of receptors in NG108-15 cells whose neuroblastoma parent is the same as that of NCB-20 cells. Long term treatment of NG108-15 cells with sodium butyrate (0.5 mM) induced a 2-fold increase in the density of the specific binding of /sup 3/H-clonidine. A comparable increase in the number of binding sites was detected when /sup 3/H-yohimbine was used as the receptor ligand. The butyrate-induced increase in the alpha/sub 2/-adrenergic receptor binding could be totally abolished by treatment with a protein synthesis inhibitor, cycloheximide, suggesting that synthesis of receptor protein is involved. The same butyrate treatment had no significant effect on opioid and muscarinic cholinergic receptor bindings. Thus, butyrate effects on the expression of these three types of receptors in NG108-15 and NCB-20 cells are dramatically different. These data suggest that induction by butyrate of neurotransmitter receptors requires concerted action of genetic factors of both parents of the neurohybrids. 22 references, 2 figures, 2 tables.

  4. Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2012-01-01

    Background Treatment of shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration Clinical

  5. The hypophagic response to heat stress is not mediated by GPR109A or peripheral β-OH butyrate.

    PubMed

    Hepler, Chelsea; Foy, Caroline E; Higgins, Mark R; Renquist, Benjamin J

    2016-05-15

    Rising temperatures resulting from climate change will increase the incidence of heat stress, negatively impacting the labor force and food animal production. Heat stress elevates circulating β-OH butyrate, which induces vasodilation through GPR109a. Interestingly, both heat stress and intraperitoneal β-OH butyrate administration induce hypophagia. Thus, we aimed to investigate the role of β-OH butyrate in heat stress hypophagia in mice. We found that niacin, a β-OH butyrate mimetic that cannot be oxidized to generate ATP, also reduces food intake. Interestingly, the depression in food intake as a result of 8-h intraperitoneal niacin or 48-h heat exposure did not result from changes in hypothalamic expression of orexigenic or anorexigenic signals (AgRP, NPY, or POMC). Genetically eliminating GPR109a expression did not prevent the hypophagic response to heat exposure, intraperitoneal β-OH butyrate (5.7 mmol/kg), or niacin (0.8 mmol/kg). Hepatic vagotomy eliminated the hypophagic response to β-OH butyrate and niacin but did not affect the hypophagic response to heat exposure. We subsequently hypothesized that the hypophagic response to heat stress may depend on direct effects of β-OH butyrate at the central nervous system: β-OH butyrate induced hormonal changes (hyperinsulinemia, hypercorticosteronemia, and hyperleptinemia), or gene expression changes. To test these possibilities, we blocked expression of hepatic hydroxyl methyl glutaryl CoA synthase II (HMGCS2) to prevent hepatic β-OH butyrate synthesis. Mice that lack HMGCS2 maintain a hypophagic response to heat stress. Herein, we establish that the hypophagia of heat stress is independent of GPR109a, the hepatic vagus afferent nerve, and hepatic ketone body synthesis. PMID:26936786

  6. The impact of a specific blend of essential oil components and sodium butyrate in feed on growth performance and Salmonella counts in experimentally challenged broilers.

    PubMed

    Cerisuelo, A; Marín, C; Sánchez-Vizcaíno, F; Gómez, E A; de la Fuente, J M; Durán, R; Fernández, C

    2014-03-01

    Essential oils (EO) and short-chain fatty acids have potential antimicrobial activity in broilers. This study aimed to investigate the effect of a specific blend of EO and a combination of this blend of EO with sodium-butyrate on growth performance and Salmonella colonization in broilers. A total of 480 one-day-old male broilers were distributed into 5 treatments (8 pens per treatment and 12 birds per pen) and reared during 42 d in experimental conditions. Dietary treatments consisted of the addition of different doses of EO (0 mg/kg, control; 50 mg/kg, EO50 and 100 mg/kg, EO100) or a combination of EO with 1 g/kg of sodium-butyrate (B; EO50 + B, EOB50 and EO100 + B, EOB100) to a basal diet. All birds were orally infected with 10(8) cfu of Salmonella Enteritidis on d 7 of study. Individual BW and feed intake per pen were measured at arrival and on a weekly basis. The prevalence and enumeration of Salmonella in feces was determined per treatment at 72 h postinfection and on d 23 and 37 of study. At slaughter, cecal content and liver samples from 16 birds per treatment were cultured for Salmonella and cecal pH was measured. No differences were observed on growth performance among treatments. All fecal samples analyzed were positive for Salmonella from d 10 to the end of the rearing period. At slaughter, Salmonella contamination (positive samples) in cecum was lower in birds fed EOB50 compared with the other treatments (P < 0.05), whereas birds fed the control diet showed the highest colonization rates. The pH of the cecal content was not different among treatments. Thus, EO or its combination with sodium-butyrate did not affect growth performance. However, a clear effectiveness of these products was observed in Salmonella control, especially when low doses of EO were combined with sodium-butyrate (EOB50). PMID:24604853

  7. Clinical evaluation of clobetasone butyrate eye drops in the treatment of anterior uveitis and its effects on intraocular pressure.

    PubMed Central

    Eilon, L A; Walker, S R

    1981-01-01

    Clobetasone butyrate has been formulated as a new steroid preparation of use in ophthalmology and has been compared with prednisolone phosphate and betamethasone phosphate in the treatment of anterior uveitis. The results from 4 double-blind, between-patient studies have shown that all 3 treatments are effective in reducing the signs and symptoms of this intraocular disease. 87% of those patients receiving clobetasone butyrate had a good or satisfactory response, but no differences in therapeutic efficacy were observed between these 3 steroid treatments. Clobetasone butyrate had little effect on intraocular pressure when compared with dexamethasone or hydrocortisone, both of which cause a significant rise in intraocular pressure. PMID:7028089

  8. Use of Sodium Butyrate as an Alternative to Dietary Fiber: Effects on the Embryonic Development and Anti-Oxidative Capacity of Rats

    PubMed Central

    Lin, Yan; Fang, Zheng-feng; Che, Lian-qiang; Xu, Sheng-yu; Wu, De; Wu, Cai-mei; Wu, Xiu-qun

    2014-01-01

    In this study, we evaluated the effect of replacing dietary fiber with sodium butyrate on reproductive performance and antioxidant defense in a high fat diet during pregnancy by using a rat model. Eighty virgin female Sprague Dawley rats were fed one of four diets—(1) control diet (C group), (2) high fat + high fiber diet (HF group), (3) high-fat +5% sodium butyrate diet (SB group), and (4) HF diet + α-cyano-4-hydroxy cinnamic acid (CHC group)—intraperitoneally on days 8, 10, 12, 14, and 16 of gestation. SB and dietary fiber had similar effects on improving fetal number and reducing the abortion rate; however, the anti-oxidant capacity of maternal serum, placenta, and fetus was superior in the HF group than in the SB group. In comparison, CHC injection decreased reproductive performance and antioxidant defense. Both dietary fiber (DF) and SB supplementation had a major but different effect on the expression of anti-oxidant related genes and nutrient transporters genes. In summary, our data indicate that SB and DF showed similar effect on reproductive performance, but SB cannot completely replace the DF towards with respect to redox regulation in high-fat diet; and SB might influence offspring metabolism and health differently to DF. PMID:24852604

  9. Short-chain fatty acids induce cytoskeletal and extracellular protein modifications associated with modulation of proliferation on primary culture of rat intestinal smooth muscle cells.

    PubMed

    Le Blay, G; Blottière, H M; Ferrier, L; Le Foll, E; Bonnet, C; Galmiche, J P; Cherbut, C

    2000-08-01

    Short-chain fatty acids are the main end products of bacterial fermentation of carbohydrates. Their role on the metabolism and biology of colonocytes is now well characterized. However, the functional consequences of their presence on intestinal smooth muscle cells remain poorly studied. We aimed to assess the effect of different short-chain fatty acids on ileal and colonic smooth muscle cells in primary culture and on A7R5 line. Butyrate (above 0.1 mM) inhibited A7R5 cell proliferation, while at low concentration (0.05 to 0.5 mM) butyrate significantly stimulated the proliferation of ileal and colonic myocytes in primary culture. An inhibition was observed at higher concentrations. Collagenous and noncollagenous protein synthesis was stimulated by butyrate. Moreover, butyrate stimulated actin and myosin expression. Thus, butyrate, which is produced by dietary fiber fermentation, may affect intestinal muscles by directly acting at the molecular level on myocytes. PMID:11007115

  10. Photosynthetic mixed culture polyhydroxyalkanoate (PHA) production from individual and mixed volatile fatty acids (VFAs): substrate preferences and co-substrate uptake.

    PubMed

    Fradinho, J C; Oehmen, A; Reis, M A M

    2014-09-20

    This work studied the effect of the substrate feeding composition on the polyhydroxyalkanoate (PHA) accumulation capacity of an acetate enriched photosynthetic mixed culture (PMC). From the six tested organic acids - malate, citrate, lactate, acetate, propionate and butyrate - only the three volatile fatty acids (VFAs) enabled PHA production, with acetate and butyrate leading to polyhydroxybutyrate (PHB) formation and propionate leading to a HB:HV copolymer with a 51% fraction of hydroxyvalerate (HV). Also, results showed an acceleration of butyrate and propionate consumption when fed in the presence of acetate, suggesting that the latter can act as a co-substrate for butyrate and propionate uptake. Furthermore, results suggest that some PMC bacterial groups present a substrate preference for butyrate in relation to acetate and propionate. These findings indicate the possibility of feeding the PMC with cheap VFA rich fermented wastes, leading to a more cost-effective and environmentally sustainable PHA production system. PMID:24915131

  11. 40 CFR 180.331 - 4-(2,4-Dichlorophenoxy) butyric acid; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... million Alfalfa, forage 0.7 Alfalfa, hay 2.0 Cattle, meat byproducts 0.05 Clover, forage 0.2 Clover, hay 0... Peppermint, tops 0.2 Sheep, meat byproducts 0.05 Soybean, forage 0.7 Soybean, hay 2.0 Soybean, seed 0.5 Spearmint, tops 0.2 Trefoil, forage 0.7 Trefoil, hay 2.0 (b) Section 18 emergency exemptions. (c)...

  12. 40 CFR 180.331 - 4-(2,4-Dichlorophenoxy) butyric acid; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... million Alfalfa, forage 0.7 Alfalfa, hay 2.0 Cattle, meat byproducts 0.05 Clover, forage 0.2 Clover, hay 0... Peppermint, tops 0.2 Sheep, meat byproducts 0.05 Soybean, forage 0.7 Soybean, hay 2.0 Soybean, seed 0.5 Spearmint, tops 0.2 Trefoil, forage 0.7 Trefoil, hay 2.0 (b) Section 18 emergency exemptions. (c)...

  13. 40 CFR 180.331 - 4-(2,4-Dichlorophenoxy) butyric acid; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... million Alfalfa, forage 0.7 Alfalfa, hay 2.0 Cattle, meat byproducts 0.05 Clover, forage 0.2 Clover, hay 0... Peppermint, tops 0.2 Sheep, meat byproducts 0.05 Soybean, forage 0.7 Soybean, hay 2.0 Soybean, seed 0.5 Spearmint, tops 0.2 Trefoil, forage 0.7 Trefoil, hay 2.0 (b) Section 18 emergency exemptions. (c)...

  14. 40 CFR 180.331 - 4-(2,4-Dichlorophenoxy) butyric acid; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... million Alfalfa, forage 0.7 Alfalfa, hay 2.0 Cattle, meat byproducts 0.05 Clover, forage 0.2 Clover, hay 0... Peppermint, tops 0.2 Sheep, meat byproducts 0.05 Soybean, forage 0.7 Soybean, hay 2.0 Soybean, seed 0.5 Spearmint, tops 0.2 Trefoil, forage 0.7 Trefoil, hay 2.0 (b) Section 18 emergency exemptions. (c)...

  15. 40 CFR 180.331 - 4-(2,4-Dichlorophenoxy) butyric acid; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Peppermint, tops 0.2 Sheep, meat byproducts 0.05 Soybean, forage 0.7 Soybean, hay 2.0 Soybean, seed 0.5 Spearmint, tops 0.2 Trefoil, forage 0.7 Trefoil, hay 2.0 (b) Section 18 emergency exemptions. (c)...

  16. Anaerobic conversion of lignocellulosic corn fiber to butyric acid, a substrate for microbial butanol production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many factors, including sharply fluctuating fuel prices and questions regarding the sustainability of fuel produced from potential food crops, have bolstered interest in renewable fuels from alternative feedstocks. We tested pretreated and nonpretreated corn fiber for its susceptibility to hydrolys...

  17. Carboxymethyl Cellulose Acetate Butyrate: A Review of the Preparations, Properties, and Applications

    PubMed Central

    Kamel, Samir; Salama, Ahmed; Sarhan, Hebat-Allah

    2014-01-01

    Carboxymethyl cellulose acetate butyrate (CMCAB) has gained increasing importance in several fields, particularly in coating technologies and pharmaceutical research. CMCAB is synthesized by esterification of CMC sodium salt with acetic and butyric anhydrides. CMCAB mixed esters are relatively high molecular weight (MW) thermoplastic polymers with high glass transition temperatures (Tg). CMCAB ester is dispersible in water and soluble in a wide range of organic solvents, allowing varied opportunity to the solvent choice. It makes application of coatings more consistent and defect-free. Its ability to slow down the release rate of highly water-soluble compounds and to increase the dissolution of poorly soluble compounds makes CMCAB a unique and potentially valuable tool in pharmaceutical and amorphous solid dispersions (ASD) formulations. PMID:25548679

  18. Resorufin butyrate as a soluble and monomeric high-throughput substrate for a triglyceride lipase.

    PubMed

    Lam, Vincent; Henault, Martin; Khougaz, Karine; Fortin, Louis-Jacques; Ouellet, Marc; Melnyk, Roman; Partridge, Anthony

    2012-02-01

    Triglyceride lipases such as lipoprotein lipase, endothelial lipase, and hepatic lipase play key roles in controlling the levels of plasma lipoprotein. Accordingly, small-molecule modulation of these species could alter patient lipid profiles with corresponding health effects. Screening of these enzymes for small-molecule therapeutics has historically involved the use of lipid-based particles to mimic native substrates. However, particle-based artifacts can complicate the discovery of therapeutic molecules. As a simplifying solution, the authors sought to develop an approach involving a soluble and monomeric lipase substrate. Using purified bovine lipoprotein lipase as a model system, they show that the hydrolysis of resorufin butyrate can be fluorescently monitored to give a robust assay (Z' > 0.8). Critically, using parallel approaches, they show that resorufin butyrate is soluble and monomeric under assay conditions. The presented assay should be useful as a simple and inexpensive primary or secondary screen for the discovery of therapeutic lipase modulators. PMID:21956174

  19. Structural Analysis and Quantitative Determination of Clevidipine Butyrate Impurities Using an Advanced RP-HPLC Method.

    PubMed

    Zhou, Yuxia; Zhou, Fan; Yan, Fei; Yang, Feng; Yao, Yuxian; Zou, Qiaogen

    2016-03-01

    Eleven potential impurities, including process-related compounds and degradation products, have been analyzed by comprehensive studies on the manufacturing process of clevidipine butyrate. Possible formation mechanisms could also be devised. MS and NMR techniques have been used for the structural characterization of three previously unreported impurities (Imp-3, Imp-5 and Imp-11). To separate and quantify the potential impurities in a simultaneous fashion, an efficient and advanced RP-HPLC method has been developed. In doing so, four major degradation products (Imp-2, Imp-4, Imp-8 and Imp-10) can be observed under varying stress conditions. This analytical method has been validated according to ICH guidelines with respect to specificity, accuracy, linearity, robustness and stability. The method described has been demonstrated to be applicable in routine quality control processes and stability evaluation studies of clevidipine butyrate. PMID:26489435

  20. Enantiomeric excesses in meteoritic amino acids

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Pizzarello, S.

    1997-01-01

    Gas chromatographic-mass spectral analyses of the four stereoisomers of 2-amino-2,3-dimethylpentanoic acid (dl-alpha-methylisoleucine and dl-alpha-methylalloisoleucine) obtained from the Murchison meteorite show that the L enantiomer occurs in excess (7.0 and 9.1%, respectively) in both of the enantiomeric pairs. Similar results were obtained for two other alpha-methyl amino acids, isovaline and alpha-methylnorvaline, although the alpha hydrogen analogs of these amino acids, alpha-amino-n-butyric acid and norvaline, were found to be racemates. With the exception of alpha-amino-n-butyric acid, these amino acids are either unknown or of limited occurrence in the biosphere. Because carbonaceous chondrites formed 4.5 billion years ago, the results are indicative of an asymmetric influence on organic chemical evolution before the origin of life.

  1. Isolation of lipase producer and its performance in enantioselective hydrolysis of glycidyl butyrate.

    PubMed

    Jia, Shi-Ying; Xu, Jian-He; Li, Qing Shan; Yu, Jun Tang

    2003-01-01

    A racemic glycidyl butyrate resolving strain, preliminarily identified as a Rhizopus sp., had been isolated from soil. Its extracellular lipase was found to enantioselectively hydrolyze the (S)-enantiomer of the chiral ester, with optimal activities at pH 5.3 and 42 degrees C. Higher enantioselectivity of the enzyme was observed at lower temperatures, while the best enantioselectivity was obtained at pH 5.5-6.0, with an E value (enantiomeric ratio) of 57. PMID:12495206

  2. An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations.

    PubMed

    McIntyre, Iain M; Trochta, Amber; Gary, Ray D; Wright, Jennifer; Mena, Othon

    2016-03-01

    In this case report, we present an evaluation of the distribution of postmortem concentrations of butyr-fentanyl in a fatality attributed principally to the drug. A man who had a history of intravenous drug abuse was found unresponsive on the bathroom floor of his home. Drug paraphernalia was located on the bathroom counter. Toxicology testing, which initially screened positive for fentanyl by enzyme-linked immunosorbent assay, subsequently confirmed butyr-fentanyl, which was then quantitated by gas chromatography-mass spectrometry-specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. The butyr-fentanyl peripheral blood concentration was quantitated at 58 ng/mL compared with the central blood concentration of 97 ng/mL. The liver concentration was 320 ng/g, the vitreous was 40 ng/mL, the urine was 670 ng/mL and the gastric contained 170 mg. Acetyl-fentanyl was also detected in all biological specimens tested. Peripheral blood concentration was quantitated at 38 ng/mL compared with the central blood concentration of 32 ng/mL. The liver concentration was 110 ng/g, the vitreous was 38 ng/mL, the urine was 540 ng/mL and the gastric contained <70 mg. The only other drug detected was a relatively low concentration of benzoylecgonine. The cause of death was certified as acute butyr-fentanyl, acetyl-fentanyl and cocaine intoxication, and the manner of death was certified as accident. PMID:26683128

  3. Performance of cellulose acetate butyrate membranes in hyperfiltration of sodium chloride and urea feed solution

    NASA Technical Reports Server (NTRS)

    Wydeven, T.; Leban, M.

    1973-01-01

    Cellulose acetate butyrate (CAB) membranes are shown to give high salt and urea rejection with water flux of about 3 gallons/sq ft per day at 600 psig. Membranes prepared from a formulation containing glyoxal show a significant increase in flux and decrease in salt and urea rejection with drying time. Zero drying time gives maximum urea and salt rejection and is therefore most suitable for hyperfiltration of sodium chloride and urea feed solution.

  4. Sodium Butyrate Ameliorates L-Arginine-Induced Pancreatitis and Associated Fibrosis in Wistar Rat: Role of Inflammation and Nitrosative Stress.

    PubMed

    Kanika, Gayathri; Khan, Sabbir; Jena, Gopabandhu

    2015-08-01

    Several reports indicated that histone deacetylases (HDACs) play a crucial role in inflammation and fibrogenesis. Sodium butyrate (SB) is a short-chain fatty acid having HDAC inhibition potential. The present study aimed to evaluate the protective effect of SB against L-arginine (L-Arg)-induced pancreatic fibrosis in Wistar rats. Pancreatic fibrosis was induced by twice intraperitoneal (i.p.) injections of 20% L-Arg (250 mg/100 g) at 2-h interval on day 1, 4, 7, and 10, whereas SB (800 mg/kg/day) was administrated for 10 days. At the end of the study, biochemical estimations, histological alterations, DNA damage, and the expression of various proteins were evaluated. Posttreatment of SB decreased L-Arg-induced oxidative and nitrosative stress, DNA damage, histological alterations, and fibrosis. Interestingly, posttreatment of SB significantly decreased the expression of α-smooth muscle actin, interleukin-1β, inducible nitric oxide synthase, and 3-nitrotyrosine. The present study demonstrated that posttreatment of SB alleviates L-Arg-induced pancreatic damage and fibrosis in rat. PMID:25774002

  5. Impact of butyrate on microbial selection in enhanced biological phosphorus removal systems.

    PubMed

    Begum, Shamim A; Batista, Jacimaria R

    2014-01-01

    Microbial selection in an enhanced biological phosphorus removal system was investigated in a laboratory-scale sequencing batch reactor fed exclusively with butyrate as a carbon source. As reported in the few previous studies, butyrate uptake was slow and phosphorus (P) release occurred during the entire anaerobic period. Polyphosphate-accumulating organism (PAO), i.e. Candidatus Accumulibacter phosphatis (named as Accumulibacter), glycogen-accumulating organisms (GAOs), i.e. Candidatus Competibacter phosphatis (named as Competibacter) and Defluviicoccus-related, tetrad-forming alphaproteobacteria (named as Defluviicoccus) were identified using fluorescence in situ hybridization analysis. The results show that Accumulibacter and Defluviicoccus were selected in the butyrate-fed reactor, whereas Competibacter was not selected. P removal was efficient at the beginning of the experiment with an increasing percentage relative abundance (% RA) of PAOs. The % RA of Accumulibacter and Defluviicoccus increased from 13% to 50% and 8% to 16%, respectively, and the % RA of Competibacter decreased from 8% to 2% during the experiment. After 6 weeks, P removal deteriorated with the poor correlation between the percentage of P removal and % RA of GAOs. PMID:25189844

  6. Converting Carbon Dioxide to Butyrate with an Engineered Strain of Clostridium ljungdahlii

    PubMed Central

    Nevin, Kelly P.; Woodard, Trevor L.; Lovley, Derek R.

    2014-01-01

    ABSTRACT Microbial conversion of carbon dioxide to organic commodities via syngas metabolism or microbial electrosynthesis is an attractive option for production of renewable biocommodities. The recent development of an initial genetic toolbox for the acetogen Clostridium ljungdahlii has suggested that C. ljungdahlii may be an effective chassis for such conversions. This possibility was evaluated by engineering a strain to produce butyrate, a valuable commodity that is not a natural product of C. ljungdahlii metabolism. Heterologous genes required for butyrate production from acetyl-coenzyme A (CoA) were identified and introduced initially on plasmids and in subsequent strain designs integrated into the C. ljungdahlii chromosome. Iterative strain designs involved increasing translation of a key enzyme by modifying a ribosome binding site, inactivating the gene encoding the first step in the conversion of acetyl-CoA to acetate, disrupting the gene which encodes the primary bifunctional aldehyde/alcohol dehydrogenase for ethanol production, and interrupting the gene for a CoA transferase that potentially represented an alternative route for the production of acetate. These modifications yielded a strain in which ca. 50 or 70% of the carbon and electron flow was diverted to the production of butyrate with H2 or CO as the electron donor, respectively. These results demonstrate the possibility of producing high-value commodities from carbon dioxide with C. ljungdahlii as the catalyst. PMID:25336453

  7. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria.

    PubMed

    Nylund, L; Nermes, M; Isolauri, E; Salminen, S; de Vos, W M; Satokari, R

    2015-02-01

    The reports on atopic diseases and microbiota in early childhood remain contradictory, and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r = -0.54, P = 0.002) and with the abundance of butyrate-producing bacteria (r = -0.52, P = 0.005). During the 3-month follow-up, microbiota diversity increased (P < 0.001) and scoring atopic dermatitis values decreased (P < 0.001) in all infants. This decrease coincided with the increase in bacteria related to butyrate-producing Coprococcus eutactus (r = -0.59, P = 0.02). In conclusion, the high diversity of microbiota and high abundance of butyrate-producing bacteria were associated with milder eczema, thus suggesting they have a role in alleviating symptoms of atopic eczema. PMID:25413686

  8. Feed-drug interaction of orally applied butyrate and phenobarbital on hepatic cytochrome P450 activity in chickens.

    PubMed

    Mátis, G; Kulcsár, A; Petrilla, J; Hermándy-Berencz, K; Neogrády, Zs

    2016-08-01

    The expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes may be affected by several nutrition-derived compounds, such as by the commonly applied feed additive butyrate, possibly leading to feed-drug interactions. The aim of this study was to provide some evidence if butyrate can alter the activity of hepatic CYPs in chickens exposed to CYP-inducing xenobiotics, monitoring for the first time the possibility of such interaction. Ross 308 chickens in the grower phase were treated with daily intracoelomal phenobarbital (PB) injection (80 mg/kg BW), applied as a non-specific CYP-inducer, simultaneously with two different doses of intra-ingluvial sodium butyrate boluses (0.25 and 1.25 g/kg BW) for 5 days. Activity of CYP2H and CYP3A subfamilies was assessed by specific enzyme assays from isolated liver microsomes. According to our results, the lower dose of orally administered butyrate significantly attenuated the PB-triggered elevation of both hepatic CYP2H and CYP3A activities, which might be in association with the partly common signalling pathways of butyrate and CYP-inducing drugs, such as that of PB. Based on these data, butyrate may take part in pharmacoepigenetic interactions with simultaneously applied drugs or other CYP-inducing xenobiotics, with possible consequences for food safety and pharmacotherapy. Butyrate was found to be capable to maintain physiological CYP activity by attenuating CYP induction, underlining the safety of butyrate application in poultry nutrition. PMID:26614344

  9. Butyrate alleviates metabolic impairments and protects pancreatic β cell function in pregnant mice with obesity

    PubMed Central

    Li, Hua-Ping; Chen, Xuan; Li, Ming-Qing

    2013-01-01

    The relative or absolute deficiency of pancreatic β-cell mass function underlies the pathogenesis of diabetes. It is necessary to alleviate the metabolic stress and reduce the demand for insulin to decrease the effects of mutations affecting β-cell expansion. Butyrate is a natural nutrient existed in food and can also be produced physiologically through the intestinal fermentation of fiber. Pregnancy and obesity model would be helpful for understanding how β-cell adapt to insulin resistance and how butyrate alleviate the metabolic impairment and protect pancreatic β cell function in pregnant mice with obesity. C57BL/6J female mice were divided into three groups and fed with high fat food (HF group, 40% energy from fat), high fat with sodium butyrate food (HSF group, 95% HF with 5% butyrate), or control food (CF group, 14% energy from fat), respectively. The feeding would last for 14 weeks before mating and throughout the gestation period. A subset of dams were sacrificed at gestational day (GD) 14.5 to evaluate the changes of metabolism and β-cell function, mass, proliferation and apoptosis, inflammatory reaction of islet from different diet. Pancreases were double immuno-labeled to assess the islet morphology, insulin expression, expression of proliferation gene PCNA and anti-apoptosis gene bcl-2. Moreover, we detected the expression of NF-κB, phosphorylated NF-κB (pNF-κB) to evaluate the islet inflammatory response with immunohistochemistry. Mice fed with HSF showed obviously changes including the decreased values of weight gain, glucose, insulin, triglyceride and total cholesterol level of blood compared with high fat diet group, and the reduced circulating maternal pro-inflammation factors at GD14.5. Mice fed with HF displayed β-cell hyperplasia with a greater β-cell size and β-cell area in pancreas. Furthermore, the higher ratio of apoptosis and inflammatory response were found in HF group compared with HSF and CF group, while the proliferation

  10. Aerobic catabolism of phenylacetic acid in Pseudomonas putida U: biochemical characterization of a specific phenylacetic acid transport system and formal demonstration that phenylacetyl-coenzyme A is a catabolic intermediate.

    PubMed Central

    Schleissner, C; Olivera, E R; Fernández-Valverde, M; Luengo, J M

    1994-01-01

    The phenylacetic acid transport system (PATS) of Pseudomonas putida U was studied after this bacterium was cultured in a chemically defined medium containing phenylacetic acid (PA) as the sole carbon source. Kinetic measurement was carried out, in vivo, at 30 degrees C in 50 mM phosphate buffer (pH 7.0). Under these conditions, the uptake rate was linear for at least 3 min and the value of Km was 13 microM. The PATS is an active transport system that is strongly inhibited by 2,4-dinitrophenol, 4-nitrophenol (100%), KCN (97%), 2-nitrophenol (90%), or NaN3 (80%) added at a 1 mM final concentration (each). Glucose or D-lactate (10 mM each) increases the PATS in starved cells (140%), whereas arsenate (20 mM), NaF, or N,N'-dicyclohexylcarbodiimide (1 mM) did not cause any effect. Furthermore, the PATS is insensitive to osmotic shock. These data strongly suggest that the energy for the PATS is derived only from an electron transport system which causes an energy-rich membrane state. The thiol-containing compounds mercaptoethanol, glutathione, and dithiothreitol have no significant effect on the PATS, whereas thiol-modifying reagents such as N-ethylmaleimide and iodoacetate strongly inhibit uptake (100 and 93%, respectively). Molecular analogs of PA with a substitution (i) on the ring or (ii) on the acetyl moiety or those containing (iii) a different ring but keeping the acetyl moiety constant inhibit uptake to different extents. None of the compounds tested significantly increase the PA uptake rate except adipic acid, which greatly stimulates it (163%). The PATS is induced by PA and also, gratuitously, by some phenyl derivatives containing an even number of carbon atoms on the aliphatic moiety (4-phenyl-butyric, 6-phenylhexanoic, and 8-phenyloctanoic acids). However, similar compounds with an odd number of carbon atoms (benzoic, 3-phenylpropionic, 5-phenylvaleric, 7-phenylheptanoic, and 9-phenylnonanoic acids) as well as many other PA derivatives do not induce the system

  11. Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy.

    PubMed

    Gomez-Arango, Luisa F; Barrett, Helen L; McIntyre, H David; Callaway, Leonie K; Morrison, Mark; Dekker Nitert, Marloes

    2016-10-01

    The risk of developing pregnancy-induced hypertension and preeclampsia is higher in obese pregnant women. In obesity, the composition of the gut microbiota is altered. Obesity is also associated with low-grade inflammation. Metabolites from the gut microbiota may contribute to both hypertension and inflammation. The aim of this study is to investigate whether the composition of the gut microbiota in overweight and obese pregnant women is associated with blood pressure and levels of plasminogen activator inhibitor-1. The composition of the gut microbiota was determined with 16S ribosomal RNA sequencing in 205 women at 16 weeks gestation from the SPRING study (the Study of Probiotics in Gestational Diabetes). Expression of butyrate-producing genes in the gut microbiota was assessed by real-time polymerase chain reaction. Plasminogen activator inhibitor-1 levels were measured in fasting serum of a subset of 70 women. Blood pressure was slightly but significantly higher in obese compared with overweight women. The abundance of the butyrate-producing genus Odoribacter was inversely correlated with systolic blood pressure. Butyrate production capacity was decreased, but plasminogen activator inhibitor-1 concentrations increased in obese pregnant women. Plasminogen activator inhibitor-1 levels were inversely correlated with expression of butyrate kinase and Odoribacter abundance. This study shows that in overweight and obese pregnant women at 16 weeks gestation, the abundance of butyrate-producing bacteria and butyrate production in the gut microbiota is significantly negatively associated with blood pressure and with plasminogen activator inhibitor-1 levels. Increasing butyrate-producing capacity may contribute to maintenance of normal blood pressure in obese pregnant women. PMID:27528065

  12. Exposure to sodium butyrate leads to functional downregulation of calcium-activated potassium channels in human airway epithelial cells.

    PubMed

    Roy, Jeremy; Denovan-Wright, Eileen M; Linsdell, Paul; Cowley, Elizabeth A

    2006-11-01

    Cystic fibrosis (CF) is caused by genetic mutations that lead to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. The most common mutation, DeltaF508, causes inefficient trafficking of mutant CFTR protein from the endoplasmic reticulum to the cell membrane. Therapeutic efforts have been aimed at increasing the level of DeltaF508-CFTR protein in the membrane using agents such as sodium butyrate. In this study, we investigated the effects of culturing a human airway epithelial cell line, Calu-3, in the presence of 5 mM sodium butyrate. Within 24 h, butyrate exposure caused a significant decrease in the basal, as well as Ca(2+)-activated, anion secretion by Calu-3 cell monolayers, determined by the change in transepithelial short-circuit current in response to the Ca(2+)-elevating agent thapsigargin. The secretory response to 1-ethyl-2-benzimidazolinone, an activator of the basolateral Ca(2+)-activated K(+) channel KCNN4, was similarly reduced by butyrate treatment. Quantitative PCR revealed that these functional effects were associated with dramatic decreases in mRNA for both KCNN4 and CFTR. Furthermore, the KCNQ1 K(+) channel was upregulated after butyrate treatment. We suggest that prolonged exposure to sodium butyrate downregulates the expression of both KCNN4 and CFTR, leading to a functional loss of Ca(2+)-activated anion secretion. Thus, butyrate may inhibit, rather than stimulate, the anion secretory capacity of human epithelial cells that express wild-type CFTR, particularly in tissues that normally exhibit robust Ca(2+)-activated secretion. PMID:17047984

  13. Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia

    PubMed Central

    Vital, Marius; Gao, Jiarong; Rizzo, Mike; Harrison, Tara; Tiedje, James M

    2015-01-01

    Butyrate-producing bacteria have an important role in maintaining host health. They are well studied in human and medically associated animal models; however, much less is known for other Vertebrata. We investigated the butyrate-producing community in hindgut-fermenting Mammalia (n=38), Aves (n=8) and Reptilia (n=8) using a gene-targeted pyrosequencing approach of the terminal genes of the main butyrate-synthesis pathways, namely butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). Most animals exhibit high gene abundances, and clear diet-specific signatures were detected with but genes significantly enriched in omnivores and herbivores compared with carnivores. But dominated the butyrate-producing community in these two groups, whereas buk was more abundant in many carnivorous animals. Clustering of protein sequences (5% cutoff) of the combined communities (but and buk) placed carnivores apart from other diet groups, except for noncarnivorous Carnivora, which clustered together with carnivores. The majority of clusters (but: 5141 and buk: 2924) did not show close relation to any reference sequences from public databases (identity <90%) demonstrating a large ‘unknown diversity'. Each diet group had abundant signature taxa, where buk genes linked to Clostridium perfringens dominated in carnivores and but genes associated with Ruminococcaceae bacterium D16 were specific for herbivores and omnivores. Whereas 16S rRNA gene analysis showed similar overall patterns, it was unable to reveal communities at the same depth and resolution as the functional gene-targeted approach. This study demonstrates that butyrate producers are abundant across vertebrates exhibiting great functional redundancy and that diet is the primary determinant governing the composition of the butyrate-producing guild. PMID:25343515

  14. Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia.

    PubMed

    Vital, Marius; Gao, Jiarong; Rizzo, Mike; Harrison, Tara; Tiedje, James M

    2015-04-01

    Butyrate-producing bacteria have an important role in maintaining host health. They are well studied in human and medically associated animal models; however, much less is known for other Vertebrata. We investigated the butyrate-producing community in hindgut-fermenting Mammalia (n = 38), Aves (n = 8) and Reptilia (n = 8) using a gene-targeted pyrosequencing approach of the terminal genes of the main butyrate-synthesis pathways, namely butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). Most animals exhibit high gene abundances, and clear diet-specific signatures were detected with but genes significantly enriched in omnivores and herbivores compared with carnivores. But dominated the butyrate-producing community in these two groups, whereas buk was more abundant in many carnivorous animals. Clustering of protein sequences (5% cutoff) of the combined communities (but and buk) placed carnivores apart from other diet groups, except for noncarnivorous Carnivora, which clustered together with carnivores. The majority of clusters (but: 5141 and buk: 2924) did not show close relation to any reference sequences from public databases (identity <90%) demonstrating a large 'unknown diversity'. Each diet group had abundant signature taxa, where buk genes linked to Clostridium perfringens dominated in carnivores and but genes associated with Ruminococcaceae bacterium D16 were specific for herbivores and omnivores. Whereas 16S rRNA gene analysis showed similar overall patterns, it was unable to reveal communities at the same depth and resolution as the functional gene-targeted approach. This study demonstrates that butyrate producers are abundant across vertebrates exhibiting great functional redundancy and that diet is the primary determinant governing the composition of the butyrate-producing guild. PMID:25343515

  15. Engineered Production of Short Chain Fatty Acid in Escherichia coli Using Fatty Acid Synthesis Pathway

    PubMed Central

    Jawed, Kamran; Mattam, Anu Jose; Fatma, Zia; Wajid, Saima; Abdin, Malik Z.; Yazdani, Syed Shams

    2016-01-01

    Short-chain fatty acids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fatty acid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fatty acid production, such as deletion of the fadD and fadE that initiates the fatty acid degradation cycle and overexpression of fadR that is a global transcriptional activator of fatty acid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fatty acid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fatty acid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product. PMID:27466817

  16. Engineered Production of Short Chain Fatty Acid in Escherichia coli Using Fatty Acid Synthesis Pathway.

    PubMed

    Jawed, Kamran; Mattam, Anu Jose; Fatma, Zia; Wajid, Saima; Abdin, Malik Z; Yazdani, Syed Shams

    2016-01-01

    Short-chain fatty acids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fatty acid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fatty acid production, such as deletion of the fadD and fadE that initiates the fatty acid degradation cycle and overexpression of fadR that is a global transcriptional activator of fatty acid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fatty acid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fatty acid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product. PMID:27466817

  17. Use of Additives to Improve Performance of Methyl Butyrate-Based Lithium-Ion Electrolytes

    NASA Technical Reports Server (NTRS)

    Smart, Marshall C.; Bugga, Ratnakumar V.

    2011-01-01

    This work addresses the need for robust rechargeable batteries that can operate well over a wide temperature range. To this end, a number of electrolyte formulations have been developed that incorporate the use of electrolyte additives to improve the high-temperature resilience, low-temperature power capability, and life characteristics of methyl butyrate-based electrolyte solutions. These electrolyte additives include mono-fluoroethylene carbonate (FEC), lithium oxalate, vinylene carbonate (VC), and lithium bis(oxalato)borate (LiBOB), which have been shown to result in improved high-temperature resilience of all carbonate-based electrolytes. Improved performance has been demonstrated of Li-ion cells with methyl butyrate-based electrolytes, including 1.20M LiPF6 in EC+EMC+MB (20:20:60 v/v %); 1.20M LiPF6 in EC+EMC+MB (20:20:60 v/v %) + 2% FEC; 1.20M LiPF6 in EC+EMC+MB (20:20:60 v/v %) + 4% FEC; 1.20M LiPF6 in EC+EMC+MB (20:20:60 v/v %) + lithium oxalate; 1.20M LiPF6 in EC+EMC+MB (20:20:60 v/v %) + 2% VC; and 1.20M LiPF6 in EC+EMC+MB (20:20:60 v/v %) + 0.10M LiBOB. These electrolytes have been shown to improve performance in MCMB-LiNiCoO2 and graphite-LiNi1/3Co1/3Mn1/3O2 experimental Li-ion cells. A number of LiPF6-based mixed carbonate electrolyte formulations have been developed that contain ester co-solvents, which have been optimized for operation at low temperature, while still providing reasonable performance at high temperature. For example, a number of ester co-solvents were investigated, including methyl propionate (MP), ethyl propionate (EP), methyl butyrate (MB), ethyl butyrate (EB), propyl butyrate (PB), and butyl butyrate (BB) in multi-component electrolytes of the following composition: 1.0M LiPF6 in ethylene carbonate (EC) + ethyl methyl carbonate (EMC) + X (20:60:20 v/v %) [where X = ester co-solvent]. ["Optimized Car bon ate and Ester-Based Li-Ion Electrolytes", NASA Tech Briefs, Vol. 32, No. 4 (April 2008), p. 56.] Focusing upon improved rate

  18. Butyrivibrio hungatei sp. nov. and Pseudobutyrivibrio xylanivorans sp. nov., butyrate-producing bacteria from the rumen.

    PubMed

    Kopecný, Jan; Zorec, Masa; Mrázek, Jakub; Kobayashi, Yasuo; Marinsek-Logar, Romana

    2003-01-01

    Two novel Gram-negative, anaerobic, non-spore-forming, butyrate-producing bacterial species, strains Mz 5T and JK 615T, were isolated from the rumen fluid of cow and sheep. Both strains were curved rods that were motile by means of single polar or subpolar flagellum and common in the rumen microbial ecosystem. Strain Mz 5T produced high xylanase, proteinase, pectin hydrolase and DNase activities; 1,4-beta-endoglucanase was also detected in the culture medium. The bacterium utilized a wide range of carbohydrates. Glucose was fermented to formate, butyrate, lactate, succinate and ethanol. The DNA G + C content was 42.1 mol%. The complete 16S rDNA sequence was obtained and phylogenetic relationships were determined. Strain Mz 5T and related isolates were located in clostridial cluster XIVa and were closely related to Pseudobutyrivibrio ruminis, Butyrivibrio crossotus, Roseburia cecicola and Eubacterium rectale. The name proposed for this novel bacterium is Pseudobutyrivibrio xylanivorans; the type strain is Mz 5T (=DSM 14809T =ATCC BAA-455T). Strain JK 615T produced no fibrolytic activity, but utilized a wide range of carbohydrates. Glucose was fermented to formate, acetate, butyrate and ethanol. The DNA G + C content was 44-8 mol%. The complete 16S rDNA sequence was obtained and phylogenetic relationships were determined. Strain JK 615T was located in clostridial cluster XIVa and was closely related to Clostridium proteoclasticum, Butyrivibrio fibrisolvens and Eubacterium halii. The name proposed for this novel bacterium is Butyrivibrio hungatei; the type strain is JK 615T (=DSM 14810T =ATCC BAA-456T). PMID:12656174

  19. Direct interspecies electron transfer accelerates syntrophic oxidation of butyrate in paddy soil enrichments.

    PubMed

    Li, Huijuan; Chang, Jiali; Liu, Pengfei; Fu, Li; Ding, Dewen; Lu, Yahai

    2015-05-01

    Syntrophic interaction occurs during anaerobic fermentation of organic substances forming methane as the final product. H2 and formate are known to serve as the electron carriers in this process. Recently, it has been shown that direct interspecies electron transfer (DIET) occurs for syntrophic CH4 production from ethanol and acetate. Here, we constructed paddy soil enrichments to determine the involvement of DIET in syntrophic butyrate oxidation and CH4 production. The results showed that CH4 production was significantly accelerated in the presence of nanoFe3 O4 in all continuous transfers. This acceleration increased with the increase of nanoFe3 O4 concentration but was dismissed when Fe3 O4 was coated with silica that insulated the mineral from electrical conduction. NanoFe3 O4 particles were found closely attached to the cell surfaces of different morphology, thus bridging cell connections. Molecular approaches, including DNA-based stable isotope probing, revealed that the bacterial Syntrophomonadaceae and Geobacteraceae, and the archaeal Methanosarcinaceae, Methanocellales and Methanobacteriales, were involved in the syntrophic butyrate oxidation and CH4 production. Among them, the growth of Geobacteraceae strictly relied on the presence of nanoFe3 O4 and its electrical conductivity in particular. Other organisms, except Methanobacteriales, were present in enrichments regardless of nanoFe3 O4 amendment. Collectively, our study demonstrated that the nanoFe3 O4 -facilitated DIET occurred in syntrophic CH4 production from butyrate, and Geobacter species played the key role in this process in the paddy soil enrichments. PMID:25059331

  20. Tarsi of Male Heliothine Moths Contain Aldehydes and Butyrate Esters as Potential Pheromone Components.

    PubMed

    Choi, Man-Yeon; Ahn, Seung-Joon; Park, Kye-Chung; Meer, Robert Vander; Cardé, Ring T; Jurenka, Russell

    2016-05-01

    The Noctuidae are one of the most speciose moth families and include the genera Helicoverpa and Heliothis. Females use (Z)-11-hexadecenal as the major component of their sex pheromones except for Helicoverpa assulta and Helicoverpa gelotopoeon, both of which utilize (Z)-9-hexadecenal. The minor compounds found in heliothine sex pheromone glands vary with species, but hexadecanal has been found in the pheromone gland of almost all heliothine females so far investigated. In this study, we found a large amount (0.5-1.5 μg) of hexadecanal and octadecanal on the legs of males of four heliothine species, Helicoverpa zea, Helicoverpa armigera, H. assulta, and Heliothis virescens. The hexadecanal was found on and released from the tarsi, and was in much lower levels or not detected on the remaining parts of the leg (tibia, femur, trochanter, and coxa). Lower amounts (0.05-0.5 μg) of hexadecanal were found on female tarsi. This is the first known sex pheromone compound to be identified from the legs of nocturnal moths. Large amounts of butyrate esters (about 16 μg) also were found on tarsi of males with lower amounts on female tarsi. Males deposited the butyrate esters while walking on a glass surface. Decapitation did not reduce the levels of hexadecanal on the tarsi of H. zea males, indicating that hexadecanal production is not under the same neuroendocrine regulation system as the production of female sex pheromone. Based on electroantennogram studies, female antennae had a relatively high response to hexadecanal compared to male antennae. We consider the possible role of aldehydes and butyrate esters as courtship signals in heliothine moths. PMID:27155602

  1. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces lesions in the substantia nigra of the cat which are visible by nuclear magnetic resonance imaging (MRI)

    SciTech Connect

    Sharp, D.E.; Ali, I.I.; Hadjiconstantinou, M.; Keller, P.J.; Hunter, W.W.; Neff, N.H.

    1986-03-05

    Male cats aged 6-8 months were administered two doses of MPTP (10 mg/kg) ip in saline 48 hrs apart. The cats exhibited drooling, dilation of pupils, incontinence, heightened sensitivity to touch and light, hypo- and bradykinesia and ataxia. After the second injection marked rigidity was observed, especially in the hind limbs. The cats were anesthesized and imaged with a 1.5%T MR imager using a spin-echo sequence with TR 2500ms and Te 25ms. MRI showed an increase in signal intensity extending from the periaqueductal grey matter through the region of the substantia nigra. Further an acute decrease in the differentiation of white and grey matter was observed. This is commonly associated with generalized cerebral edema. Measurement of striatal biogenic amine contents showed 20-30% decreases in striatal dopamine, 77% decreases in DOPAC, and 73-80% decrease in HVA. The content of the serotonin metabolite 5-hydroxyindoleacetic acid was unchanged indicating that the toxic effects are specific to dopaminergic neurons. Pathological examinations of the brains showed no macro or microscopic changes. These findings could represent the first observation of the actual processes involved in the degeneration of dopaminergic neurons in Parkinsonism.

  2. Butyrate Induced IGF2 Activation Correlated with Distinct Chromatin Signatures Due to Histone Modification.

    PubMed

    Shin, Joo Heon; Li, Robert W; Gao, Yuan; Bickhart, Derek M; Liu, George E; Li, Weizhong; Wu, Sitao; Li, Cong-Jun

    2013-01-01

    Histone modification has emerged as a very important mechanism regulating the transcriptional status of the genome. Insulin-like growth factor 2 (IGF2) is a peptide hormone controlling various cellular processes, including proliferation and apoptosis. H19 gene is closely linked to IGF2 gene, and IGF2 and H19 are reciprocally regulated imprinted genes. The epigenetic signature of H19 promoter (hypermethylation) on the paternal allele plays a vital role in allowing the expression of the paternal allele of IGF2.46 Our previous studies demonstrate that butyrate regulates the expression of IGF2 as well as genes encoding IGF Binding proteins. To obtain further understanding of histone modification and its regulatory potentials in controlling IGF2/H19 gene expression, we investigated the histone modification status of some key histones associated with the expression of IGF2/H19 genes in bovine cells using RNA-seq in combination with Chip-seq technology. A high-resolution map of the major chromatin modification at the IGF2/H19 locus induced by butyrate was constructed to illustrate the fundamental association of the chromatin modification landscape that may play a role in the activation of the IGF2 gene. High-definition epigenomic landscape mapping revealed that IGF2 and H19 have distinct chromatin modification patterns at their coding and promoter regions, such as TSSs and TTSs. Moreover, the correlation between the differentially methylated regions (DMRs) of IGF2/H19 locus and histone modification (acetylation and methylation) indicated that epigenetic signatures/markers of DNA methylation, histone methylation and histone acetylation were differentially distributed on the expressed IGF2 and silenced H19 genes. Our evidence also suggests that butyrate-induced regional changes of histone acetylation statusin the upstream regulation domain of H19 may be related to the reduced expression of H19 and strong activation of IGF2. Our results provided insights into the mechanism

  3. Converting carbon dioxide to butyrate with an engineered strain of Clostridium ljungdahlii.

    PubMed

    Ueki, Toshiyuki; Nevin, Kelly P; Woodard, Trevor L; Lovley, Derek R

    2014-01-01

    Microbial conversion of carbon dioxide to organic commodities via syngas metabolism or microbial electrosynthesis is an attractive option for production of renewable biocommodities. The recent development of an initial genetic toolbox for the acetogen Clostridium ljungdahlii has suggested that C. ljungdahlii may be an effective chassis for such conversions. This possibility was evaluated by engineering a strain to produce butyrate, a valuable commodity that is not a natural product of C. ljungdahlii metabolism. Heterologous genes required for butyrate production from acetyl-coenzyme A (CoA) were identified and introduced initially on plasmids and in subsequent strain designs integrated into the C. ljungdahlii chromosome. Iterative strain designs involved increasing translation of a key enzyme by modifying a ribosome binding site, inactivating the gene encoding the first step in the conversion of acetyl-CoA to acetate, disrupting the gene which encodes the primary bifunctional aldehyde/alcohol dehydrogenase for ethanol production, and interrupting the gene for a CoA transferase that potentially represented an alternative route for the production of acetate. These modifications yielded a strain in which ca. 50 or 70% of the carbon and electron flow was diverted to the production of butyrate with H2 or CO as the electron donor, respectively. These results demonstrate the possibility of producing high-value commodities from carbon dioxide with C. ljungdahlii as the catalyst. Importance: The development of a microbial chassis for efficient conversion of carbon dioxide directly to desired organic products would greatly advance the environmentally sustainable production of biofuels and other commodities. Clostridium ljungdahlii is an effective catalyst for microbial electrosynthesis, a technology in which electricity generated with renewable technologies, such as solar or wind, powers the conversion of carbon dioxide and water to organic products. Other electron donors

  4. Discoloration of poly(vinyl butyral) in cells exposed to real and simulated solar environments

    NASA Technical Reports Server (NTRS)

    Kim, Q.; Shumka, A.

    1984-01-01

    The discoloration of poly(vinl butyral) (PVB) films used in solar cell modules is described. Transmission absorption, Fourier transformation IR absorption and atomic absorption spectroscopy as well as scanning electron microscopy were used for this study. The discoloration of the PVB has been found to be affected by oxygen, moisture, temperature and light. However, the most severe discoloration observed is clearly associated with the migration of positive silver ions, which can be accelerated in the presence of electric fields. The metallization is the source of the silver, and the data are consistent with an interfacial reaction between the silver and PVB followed by transport into the polymer.

  5. Converting Carbon Dioxide to Butyrate with an Engineered Strain of Clostridium ljungdahlii

    SciTech Connect

    Ueki, T; Nevin, KP; Woodard, TL; Lovley, DR

    2014-08-26

    Microbial conversion of carbon dioxide to organic commodities via syngas metabolism or microbial electrosynthesis is an attractive option for production of renewable biocommodities. The recent development of an initial genetic toolbox for the acetogen Clostridium ljungdahlii has suggested that C. ljungdahlii may be an effective chassis for such conversions. This possibility was evaluated by engineering a strain to produce butyrate, a valuable commodity that is not a natural product of C. ljungdahlii metabolism. Heterologous genes required for butyrate production from acetyl-coenzyme A (CoA) were identified and introduced initially on plasmids and in subsequent strain designs integrated into the C. ljungdahlii chromosome. Iterative strain designs involved increasing translation of a key enzyme by modifying a ribosome binding site, inactivating the gene encoding the first step in the conversion of acetyl-CoA to acetate, disrupting the gene which encodes the primary bifunctional aldehyde/alcohol dehydrogenase for ethanol production, and interrupting the gene for a CoA transferase that potentially represented an alternative route for the production of acetate. These modifications yielded a strain in which ca. 50 or 70% of the carbon and electron flow was diverted to the production of butyrate with H-2 or CO as the electron donor, respectively. These results demonstrate the possibility of producing high-value commodities from carbon dioxide with C. ljungdahlii as the catalyst. IMPORTANCE The development of a microbial chassis for efficient conversion of carbon dioxide directly to desired organic products would greatly advance the environmentally sustainable production of biofuels and other commodities. Clostridium ljungdahlii is an effective catalyst for microbial electrosynthesis, a technology in which electricity generated with renewable technologies, such as solar or wind, powers the conversion of carbon dioxide and water to organic products. Other electron donors

  6. Untangling the fiber yarn: butyrate feeds Warburg to suppress colorectal cancer.

    PubMed

    Sebastián, Carlos; Mostoslavsky, Raul

    2014-12-01

    Dietary composition has an important role in shaping the gut microbiota. In turn, changes in the diet directly impinge on bacterial metabolites present in the intestinal lumen. Whether such metabolites play a role in intestinal cancer has been a topic of hot debate. In this issue of Cancer Discovery, Donohoe and colleagues show that dietary fiber protects against colorectal carcinoma in a microbiota-dependent manner. Furthermore, fiber-derived butyrate acts as a histone deacetylase inhibitor, inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells experiencing the Warburg effect. PMID:25477104

  7. Digital mRNA profiling of N-glycosylation gene expression in recombinant Chinese hamster ovary cells treated with sodium butyrate.

    PubMed

    Lee, Sang Min; Kim, Yeon-Gu; Lee, Eun Gyo; Lee, Gyun Min

    2014-02-10

    To understand the effects of sodium butyrate (NaBu) on protein glycosylation, recombinant Chinese hamster ovary (rCHO) cells producing Fc-fusion glycoprotein were subjected to 3mM NaBu. The addition of NaBu to the cultures reduced the relative proportion of acidic isoforms and sialic acid content of the glycoprotein. Fifty-two N-glycosylation-related gene expressions were also assessed by the NanoString nCounter system, which can provide a direct digital readout using custom-designed color-coded probes. Among them, ten genes (ugp, slc35a2, ganc, man1a, man1c, mgat5a, st3gal5, glb1, neu1, and neu3) were up-regulated and three genes (b4galt2, st3gal3, and neu2) were down-regulated significantly. Altered expression patterns in st3gal3, neu1, and neu3, which have roles in the sialic acid biosynthesis pathway, correlated with reduced sialic acid content of the glycoprotein by NaBu. Taken together, the results obtained in this study provide a better understanding of the detrimental effect of NaBu on N-glycosylation in rCHO cells. PMID:24333461

  8. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium.

    PubMed

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong

    2016-01-01

    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates. PMID:27264309

  9. Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells

    PubMed Central

    Li, Robert W; Li, CongJun

    2006-01-01

    Background Global gene expression profiles of bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The bovine microarray with 86,191 distinct 60mer oligonucleotides, each with 4 replicates, was designed and produced with Maskless Array Synthesizer technology. These oligonucleotides represent approximately 45,383 unique cattle sequences. Results 450 genes significantly regulated by butyrate with a median False Discovery Rate (FDR) = 0 % were identified. The majority of these genes were repressed by butyrate and associated with cell cycle control. The expression levels of 30 selected genes identified by the microarray were confirmed using real-time PCR. The results from real-time PCR positively correlated (R = 0.867) with the results from the microarray. Conclusion This study presented the genes related to multiple signal pathways such as cell cycle control and apoptosis. The profound changes in gene expression elucidate the molecular basis for the pleiotropic effects of butyrate on biological processes. These findings enable better recognition of the full range of beneficial roles butyrate may play during cattle energy metabolism, cell growth and proliferation, and possibly in fighting gastrointestinal pathogens. PMID:16972989

  10. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium

    PubMed Central

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong

    2016-01-01

    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn’t induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates. PMID:27264309

  11. The Origin of Amino Acids in Lunar Regolith Samples

    NASA Technical Reports Server (NTRS)

    Cook, Jamie E.; Callahan, Michael P.; Dworkin, Jason P.; Glavin, Daniel P.; McLain, Hannah L.; Noble, Sarah K.; Gibson, Everett K., Jr.

    2016-01-01

    We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7 ppb in hot-water extracts and 14.5 ppb to 651.1 ppb in 6M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, D- and L-alanine, D- and L-aspartic acid, D- and L-glutamic acid, D- and L-serine, L-threonine, and L-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: -aminoisobutyric acid (AIB), D-and L-amino-n-butyric acid (-ABA), DL-amino-n-butyric acid, -amino-n-butyric acid, -alanine, and -amino-n-caproic acid. We observed an excess of the L enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic -ABA were present in some samples.

  12. Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation.

    PubMed

    Blottière, Hervé M; Buecher, Bruno; Galmiche, Jean-Paul; Cherbut, Christine

    2003-02-01

    Short-chain fatty acids (SCFA), particularly butyrate, were shown to regulate cell proliferation in vitro and in vivo. Indeed, butyrate is the major fuel for colonic epithelial cells, and it can influence cell proliferation through the release of growth factors or gastrointestinal peptides such as gastrin, or through modulation of mucosal blood flow. Lastly, SCFA can act directly on genes regulating cell proliferation, and butyrate is the main SCFA to display such an effect. Butyrate inhibits histone deacetylase, which will allow histone hyperacetylation. Such hyperacetylation leads to transcription of several genes, including p21/Cip1. Moreover, it will allow cyclin D3 hyper-expression by inhibiting its degradation. The induction of the cyclin-dependent kinase inhibitory protein p21/Cip1 accounts for cell arrest in the G1 phase of the cell cycle. However, in the absence of p21 other mechanisms are initiated, leading to inhibition of cell proliferation. PMID:12740064

  13. Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella.

    PubMed

    Rivera-Chávez, Fabian; Zhang, Lillian F; Faber, Franziska; Lopez, Christopher A; Byndloss, Mariana X; Olsan, Erin E; Xu, Gege; Velazquez, Eric M; Lebrilla, Carlito B; Winter, Sebastian E; Bäumler, Andreas J

    2016-04-13

    The mammalian intestine is host to a microbial community that prevents pathogen expansion through unknown mechanisms, while antibiotic treatment can increase susceptibility to enteric pathogens. Here we show that streptomycin treatment depleted commensal, butyrate-producing Clostridia from the mouse intestinal lumen, leading to decreased butyrate levels, increased epithelial oxygenation, and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by tributyrin treatment. Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission. We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth. PMID:27078066

  14. Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome

    PubMed Central

    Pozuelo, Marta; Panda, Suchita; Santiago, Alba; Mendez, Sara; Accarino, Anna; Santos, Javier; Guarner, Francisco; Azpiroz, Fernando; Manichanh, Chaysavanh

    2015-01-01

    The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS. PMID:26239401

  15. Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA.

    PubMed

    Ying, Mingyao; Xu, Rener; Wu, Xiaohui; Zhu, Huaxing; Zhuang, Yuan; Han, Min; Xu, Tian

    2006-05-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disease caused by polyglutamine expansion within the Atrophin-1 protein. To study the mechanism of this disease and to test potential therapeutic methods, we established Atro-118Q transgenic mice, which express in neurons a mutant human Atrophin-1 protein that contains an expanded stretch of 118 glutamines. Consistent with the results from previous studies on transgenic mice that expressed mutant Atrophin-1 with 65 glutamines, Atro-118Q mice exhibited several neurodegenerative phenotypes that are commonly seen in DRPLA patients, including ataxia, tremors, and other motor defects. Overexpression of wild-type human Atrophin-1 could not rescue the motor and survival defects in Atro-118Q mice, indicating that the mutant protein with polyglutamine expansion does not simply function in a dominant negative manner. Biochemical analysis of Atro-118Q mice revealed hypoacetylation of histone H3 in brain tissues and thus suggested that global gene repression is an underlying mechanism for neurodegeneration in this mouse model. We further show that intraperitoneal administration of sodium butyrate, a histone deacetylase inhibitor, ameliorated the histone acetylation defects, significantly improved motor performance, and extended the average life span of Atro-118Q mice. These results support the hypothesis that transcription deregulation plays an important role in the pathogenesis of polyglutamine expansion diseases and suggest that reversion of transcription repression with small molecules such as sodium butyrate is a feasible approach to treating DRPLA symptoms. PMID:16407196

  16. Melatonin and its precursors in Y79 human retinoblastoma cells: Effect of sodium butyrate

    NASA Technical Reports Server (NTRS)

    Deng, Mei Hua; Coviella, Ignacio Lopez G.; Lynch, Harry J.; Wurtman, Richard J.

    1991-01-01

    The release of melatonin and the production of its precursors, S-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells were studied. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for 3 days. This protocol dramatically increased the release of melatonin, and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine (10 micro-M) or L-DOPA (100 micro-M) markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation (e.g. treatment with sodium butyrate) can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 cells. The inhibition of melatonin release by dopamine supports the hypothesis that in these cells, melatonin and dopamine are components of a retinal feedback loop.

  17. Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro.

    PubMed

    Scott, Karen P; Martin, Jennifer C; Duncan, Sylvia H; Flint, Harry J

    2014-01-01

    Dietary macronutrients affect the composition of the gut microbiota, and prebiotics are used to improve and maintain a healthy gut. The impact of prebiotics on dominant gut bacteria other than bifidobacteria, however, is under-researched. Here, we report carbohydrate utilisation patterns for representative butyrate-producing anaerobes, belonging to the Gram-positive Firmicutes families Lachnospiraceae and Ruminococcaceae, by comparison with selected Bacteroides and Bifidobacterium species. Growth assessments using anaerobic Hungate tubes and a new rapid microtitre plate assay were generally in good agreement. The Bacteroides strains tested showed some growth on basal medium with no added carbohydrates, utilising peptides in the growth medium. The butyrate-producing strains exhibited different growth profiles on the substrates, which included starch, inulin, fructooligosaccharides (FOS), galactooligosaccharides (GOS) and xylooligosaccharides (XOS). Eleven were able to grow on short-chain FOS, but this number decreased as the chain length of the fructan substrates increased. Long-chain inulin was utilised by Roseburia inulinivorans, but by none of the Bifidobacterium species examined here. XOS was a more selective growth substrate than FOS, with only six of the 11 Firmicutes strains able to use XOS for growth. These results illustrate the selectivity of different prebiotics and help to explain why some are butyrogenic. PMID:23909466

  18. The proteomic study of sodium butyrate antiproliferative/cytodifferentiation effects on K562 cells.

    PubMed

    Grebenová, Dana; Kuzelová, Katerina; Pluskalová, Michaela; Peslová, Gabriela; Halada, Petr; Hrkal, Zbynek

    2006-01-01

    Employing methods of cell biology and proteome analysis tools, we examined effects of an inhibitor of histone deacetylases, sodium butyrate (SB), on the proliferation/differentiation characteristics of chronic myelogenous leukemia (CML)-derived cells K562. SB suppressed proliferation of K562 cells by inducing cell cycle arrest in G1 phase, which was followed by their transition to G0 phase (decrease of Ki-67 antigen-positive cells) and erythroid differentiation (increased glycophorin A expression and synthesis of hemoglobins). Neither terminal apoptosis (low counts of TUNEL-positive cells) nor necrosis (moderate counts of propidium iodide-positive cells) occurred. Importantly, SB attenuated protein expression of CML-related chimeric kinase BCR-ABL that is responsible for the deregulated proliferation of CML cells. The proteomic analysis (2-D electrophoresis combined with MALDI-TOF mass spectrometry and/or Western blotting) revealed several proteins that were differentially expressed or their mobility was altered due to butyrate treatment, namely, HSP90, HSP70, p23, cyclophilin A (CYPA), prefoldin2 (PFD2) and alpha-, gamma-, epsilon-human globin chains. Perturbation of HSP90 multichaperone complex of which BCR-ABL is the client protein is presumably a cause of BCR-ABL suppression. Changes in other proteins with chaperonic functions, CYPA and PFD2, may reflect SB antiproliferative and cytodifferentiation effects. PMID:16978890

  19. Dietary toxicity of calcium beta-hydroxy-beta-methyl butyrate (CaHMB).

    PubMed

    Baxter, J H; Carlos, J L; Thurmond, J; Rehani, R N; Bultman, J; Frost, D

    2005-12-01

    HMB, 3-hydroxy-3-methyl butyrate, is of interest as a dietary supplement and a possible component of functional and medical foods. The purpose of this study was to evaluate the toxicity of the calcium salt of HMB, calcium 3-hydroxy-3-methyl butyrate (CaHMB, monohydrate, food grade), when administered daily in the diet of rats for at least 90 days. Male and female Crl:CD (SD)IGS BR animals were assigned to four groups. Each group received diets containing the carrier or 1%, 2%, or 5% of CaHMB mixed with diet. Assessment of toxicity was based on mortality, clinical observations, body weights, food consumption, and clinical and anatomic pathology evaluations. Administration of CaHMB in basal diet for 91 days was tolerated well. There were no unscheduled sacrifices or deaths. There were no CaHMB-related adverse effects on clinical observations, body weights, food consumption, clinical chemistry, hematology, absolute or relative organ weights, or macroscopic or microscopic observations. A statistically significant increase in inorganic phosphorous was observed in male animals in the 5% feeding group; however, this effect was not considered adverse. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 5% of CaHMB mixed with diet (3.49 g/kg BW for males and 4.16 g/kg BW for females). PMID:16006030

  20. Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate

    PubMed Central

    Liu, Jiaming; Sun, Jing; Wang, Fangyan; Yu, Xichong; Ling, Zongxin; Li, Haixiao; Zhang, Huiqing; Jin, Jiangtao; Chen, Wenqian; Pang, Mengqi; Yu, Junjie; He, Yiwen; Xu, Jiru

    2015-01-01

    Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD. PMID:26523278

  1. Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn's mucosa through modulation of antioxidant defense machinery.

    PubMed

    Russo, Ilaria; Luciani, Alessandro; De Cicco, Paola; Troncone, Edoardo; Ciacci, Carolina

    2012-01-01

    Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB), which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia coli (EC-LPS) in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa. PMID:22412931

  2. Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats

    PubMed Central

    Perrin, P; Pierre, F; Patry, Y; Champ, M; Berreur, M; Pradal, G; Bornet, F; Meflah, K; Menanteau, J

    2001-01-01

    BACKGROUND—Dietary fibres have been proposed as protective agents against colon cancer but results of both epidemiological and experimental studies are inconclusive.
AIMS—Hypothesising that protection against colon cancer may be restricted to butyrate producing fibres, we investigated the factors needed for long term stable butyrate production and its relation to susceptibility to colon cancer.
METHODS—A two part randomised blinded study in rats, mimicking a prospective study in humans, was performed using a low fibre control diet (CD) and three high fibre diets: starch free wheat bran (WB), type III resistant starch (RS), and short chain fructo-oligosaccharides (FOS). Using a randomised block design, 96 inbred rats were fed for two, 16, 30, or 44 days to determine the period of adaptation to the diets, fermentation profiles, and effects on the colon, including mucosal proliferation on day 44. Subsequently, 36 rats fed the same diets for 44 days were injected with azoxymethane and checked for aberrant crypt foci 30 days later.
RESULTS—After fermentation had stabilised (44 days), only RS and FOS produced large amounts of butyrate, with a trophic effect in the large intestine. No difference in mucosal proliferation between the diets was noted at this time. In the subsequent experiment one month later, fewer aberrant crypt foci were present in rats fed high butyrate producing diets (RS, p=0.022; FOS, p=0.043).
CONCLUSION—A stable butyrate producing colonic ecosystem related to selected fibres appears to be less conducive to colon carcinogenesis.


Keywords: fibre; fermentation; butyrate; colon carcinogenesis; aberrant crypt foci; rat PMID:11115823

  3. Clinical evaluation of clobetasone butyrate: a comparative study of its effects in postoperative inflammation and on intraocular pressure.

    PubMed Central

    Ramsell, T G; Bartholomew, R S; Walker, S R

    1980-01-01

    Clobetasone butyrate, a new corticosteroid with a high topical activity, has been compared with prednisolone phosphate and a placebo in the treatment of inflammation following cataract extraction. These 2 steroids were more effective in relieving postoperative inflammation than placebo (P less than 0.05), though no obvious clinical differences between the 2 compounds emerged from this investigation. However, a single-blind comparative study against betamethasone phosphate in patients suspected of having steroid-induced glaucoma showed that, while betamethasone phosphate significantly raised intraocular pressure, clobetasone butyrate had only a minimal effect, and this difference was statistically significant (P less than 0.02). PMID:6986899

  4. Synthesis and crystal structure of trans-di­chlorido[3-methyl-1-(4-vinyl­benz­yl)-1H-imidazol-3-ium-2-yl-κC 2](4-phenyl­pyridine-κN)palladium(II)

    PubMed Central

    Majeed, Maitham H.; Wendt, Ola F.

    2016-01-01

    The title compound, [PdCl2(C11H9N)(C13H14N2)], represents a new class of palladium-based polymerizable monomer which could give a potentially catalytically active polymer. It was synthesized via transmetallation from the corresponding silver complex. The PdII ion coordinates two Cl anions, one C atom from the N-heterocyclic carbene (NHC) ligand and one N atom from the 4-phenyl­pyridine ligand, displaying a slightly distorted square-planar geometry. The dihedral angle between the imidazole ring and the pyridine ring is 34.53 (8)°. The Pd—C bond length between the NHC ligand and the PdII ion is 1.9532 (16) Å. In the crystal, weak non-classical C—H⋯Cl hydrogen bonds link the mol­ecules into a tape structure along [101]. A weak π–π inter­action is also observed [centroid–centroid distance = 3.9117 (11) Å]. PMID:27375883

  5. Crystal structure of cis-bis­{4-phenyl-1-[(3R)-1,7,7-tri­methyl-2-oxobi­cyclo­[2.2.1]heptan-3-ylidene]thio­semicarbazidato-κ3 O,N 1,S}cadmium(II) with an unknown solvent mol­ecule

    PubMed Central

    Nogueira, Vanessa Senna; Bresolin, Leandro; Näther, Christian; Jess, Inke; de Oliveira, Adriano Bof

    2015-01-01

    The reaction between the racemic mixture of the camphor-4-phenyl­thio­semicarbazone derivative and cadmium acetate dihydrate yielded the title compound, [Cd(C17H20N3OS)2]. The CdII ion is six-coordinated in a distorted octa­hedral environment by two deprotonated thio­semicarbazone ligands acting as an O,N,S-donor in a tridentate chelating mode, forming five-membered chelate rings. In the crystal, the mol­ecules are connected via pairs of N—H⋯S and C—H⋯S inter­actions, building centrosymmetric dimers. One of the ligands is disordered in the campher unit over two sets of sites with site-occupancy factors of 0.7 and 0.3. The structure contains additional solvent mol­ecules, which are disordered and for which no reasonable split model was found. Therefore, the data were corrected for disordered solvent using the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9–18] in PLATON. Since the disordered solvents were removed by data processing, and the number of solvent entities was a suggestion only, they were not considered in the chemical formula and subsequent chemical or crystal information. PMID:26870441

  6. Crystal structure of cis-bis-{4-phenyl-1-[(3R)-1,7,7-tri-methyl-2-oxobi-cyclo-[2.2.1]heptan-3-ylidene]thio-semicarbazidato-κ(3) O,N (1),S}cadmium(II) with an unknown solvent mol-ecule.

    PubMed

    Nogueira, Vanessa Senna; Bresolin, Leandro; Näther, Christian; Jess, Inke; de Oliveira, Adriano Bof

    2015-12-01

    The reaction between the racemic mixture of the camphor-4-phenyl-thio-semicarbazone derivative and cadmium acetate dihydrate yielded the title compound, [Cd(C17H20N3OS)2]. The Cd(II) ion is six-coordinated in a distorted octa-hedral environment by two deprotonated thio-semicarbazone ligands acting as an O,N,S-donor in a tridentate chelating mode, forming five-membered chelate rings. In the crystal, the mol-ecules are connected via pairs of N-H⋯S and C-H⋯S inter-actions, building centrosymmetric dimers. One of the ligands is disordered in the campher unit over two sets of sites with site-occupancy factors of 0.7 and 0.3. The structure contains additional solvent mol-ecules, which are disordered and for which no reasonable split model was found. Therefore, the data were corrected for disordered solvent using the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] in PLATON. Since the disordered solvents were removed by data processing, and the number of solvent entities was a suggestion only, they were not considered in the chemical formula and subsequent chemical or crystal information. PMID:26870441

  7. Prebiotic Synthesis of Hydrophobic and Protein Amino Acids

    PubMed Central

    Ring, David; Wolman, Yecheskel; Friedmann, Nadav; Miller, Stanley L.

    1972-01-01

    The formation of amino acids by the action of electric discharges on a mixture of methane, nitrogen, and water with traces of ammonia was studied in detail. The presence of glycine, alanine, α-amino-n-butyric acid, α-aminoisobutyric acid, valine, norvaline, isovaline, leucine, isoleucine, alloisoleucine, norleucine, proline, aspartic acid, glutamic acid, serine, threonine, allothreonine, α-hydroxy-γ-aminobutyric acid, and α,γ-diaminobutyric acid was confirmed by ion-exchange chromatography and gas chromatography-mass spectrometry. All of the primary α-amino acids found in the Murchison Meteorite have been synthesized by this electric discharge experiment. PMID:4501592

  8. Molar extinction coefficients of some fatty acids

    NASA Astrophysics Data System (ADS)

    Sandhu, G. K.; Singh, Kulwant; Lark, B. S.; Gerward, L.

    2002-10-01

    The attenuation of gamma rays in some fatty acids, viz. formic acid (CH 2O 2), acetic acid (C 2H 4O 2), propionic acid (C 3H 6O 2), butyric acid (C 4H 8O 2), n-hexanoic acid (C 6H 12O 2), n-caprylic acid (C 8H 16O 2), lauric acid (C 12H 24O 2), myristic acid (C 14H 28O 2), palmitic acid (C 16H 32O 2), oleic acid (C 18H 34O 2) and stearic acid (C 18H 36O 2), has been measured at the photon energies 81, 356, 511, 662, 1173 and 1332 keV. Experimental values for the molar extinction coefficient, the effective atomic number and the electron density have been derived and compared with theoretical calculations. There is good agreement between experiment and theory.

  9. Engineering E. coli strain for conversion of short chain fatty acids to bioalcohols