Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male Sprague-Dawley rats were injected ip with benzene, toluene, or a mixture of xylene isomers at 20 mmol hydrocarbon/kg daily for 3 days. The effects of administration of these hydrocarbons upon their own in vitro metabolism, as well as upon cytochrome P-450, NADPH-cytochrome c reductase, aminopyrine N-demethylase, aniline hydroxylase, glutathione, glutathione S-transferase, and UDPglucuronyltransferase in liver were studied. Each hydrocarbon studied increased its own in vitro metabolism. Benzene had no effect on the metabolism of toluene or xylenes. Toluene and xylenes increased the metabolism of benzene, toluene, and xylenes. Cytochrome P-450 was elevated by toluene and xylenes, but was not affected by benzene. NADPH-cytochrome c reductase was induced by all three hydrocarbons. Aminopyrine N-demethylase and aniline hydroxylase were induced by toluene and xylenes and were not affected by benzene. Glutathione was elevated by benzene, decreased by xylenes, and not affected by toluene. Glutathione S-transferase was induced differentially by these hydrocarbons toward various substrates: toward 1-chloro-2,4-dinitrobenzene by benzene and toluene, toward 1,2-dichloro-4-nitrobenzene by benzene and xylenes, and no effect toward 1,2-epoxy-3-(p-nitrophenoxy)propane by any hydrocarbons. UDPglucuronyltransferase was induced by benzene and toluene when o-aminophenol and phenol were used as the substrate. Xylenes had no effect. Benzene was more effective at inducing conjugation enzymes. Xylenes were more effective at inducing cytochrome P-450 dependent enzymes. Toluene was equipotent at inducing both types of enzymes. The results indicate that the addition of methyl groups to the aromatic ring affects the inductive pattern of these monocyclic aromatic hydrocarbons.
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PMID:A comparative study of the effects of benzene, toluene, and xylenes on their in vitro metabolism and drug-metabolizing enzymes in rat liver. 308 Aug 23

The effects of food deprivation, carbohydrate restriction and ethanol consumption on the metabolism of eight volatile hydrocarbons (benzene, toluene, styrene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene and trichloroethylene) in rats were compared with the effects of enzyme induction by phenobarbital (PB), polychlorinated biphenyl (PCB) and 3-methylcholanthrene (MC) on the metabolism of these compounds. Although causing a marked increase both in microsomal protein and cytochrome p-450 contents, PB (80 mg/kg per day for three days) and PCB (a single dose of 500 mg/kg) induced only a limited range of enzyme activity: PB increased the metabolism of toluene, styrene, chloroform, carbon tetrachloride and trichloroethylene, and PCB only increased those of toluene, styrene and trichloroethylene. MC (20 mg/kg per day for three days) had no effect on the metabolism of any of the hydrocarbons studied. In contrast, food deprivation, carbohydrate restriction and three-week ingestion of ethanol (2.0 g/day), each enhanced the metabolism of all the hydrocarbons with little or no increase in microsomal protein and cytochrome P-450 contents. PB, PCB and MC treatments enhanced the activity of enzymes involved in conjugation reactions, UDP-glucuronyltransferase and glutathione S-transferase, whereas the dietary manipulation and ethanol consumption produced no significant effect on these enzymes. It is concluded that ethanol consumption. lowered carbohydrate intake and food deprivation affect the metabolism and toxicity of volatile hydrocarbons differently from PB, PCB or MC.
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PMID:Enhanced metabolism of volatile hydrocarbons in rat liver following food deprivation, restricted carbohydrate intake, and administration of ethanol, phenobarbital, polychlorinated biphenyl and 3-methylcholanthrene: a comparative study. 392 Aug 36

The far-ranging distribution of genes for aromatic hydrocarbon catabolism, predominantly studied in soil pseudomonads, is extended to a marine oligobacterium by finding five homologous sequences in a 5.7-kb chromosomal DNA from a new isolate, Cycloclasticus oligotrophus RB1. RB1 is capable of growth in unamended seawater or mineral salts media supplemented with a variety of aromatic compounds, including toluene, o-, m-, or p-xylenes, as sole carbon sources. The five open reading frames, designated xylM, K, G, C1, and C2, are 57% A+T-rich. XylM is predicted to be an integral membrane protein; XylK and XylG possess glutathione S-transferase (GST) and 2-hydroxy-5methyl-6-oxohexa2,4-dienoate dehydrogenase activities, respectively; XylC1C2 are homologs of the large and small subunits of the iron sulfur protein component of the biphenyl dioxygenase (e.g., BphA1A2).
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PMID:A marine oligobacterium harboring genes known to be part of aromatic hydrocarbon degradation pathways of soil pseudomonads. 878 14

In this experiment, we studied the different changes in activities and protein levels of each subform of hepatic cytochrome P450 and glutathione S-transferase (GST), in chemical-induced liver injury in rats. Rats were administered 1,1-dichloroethylene (DCE), allyl alcohol (AA), bromobenzene (BB) and N,N-dimethylformamide (DMF) p.o. once every two days for 7 times, and decapitated 18 hr after the last administration. DCE and AA showed stronger hepatic toxicity than BB and DMF, as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher in DCE and AA treated rats than in BB and DMF groups. Anti-cytochrome P450 inhibitable activity of toluene metabolism and/or immunoblot analysis showed that CYP2E1 and CYP2B1/2 were induced by BB and DMF, but not by the other two chemicals; CYP2C11 was greatly decreased by all of the four toxicants; and CYP1A1/2 was slightly reduced by the four treatments. These changes were reflected in testosterone metabolism. Formation of 6 beta- and 7 alpha-hydroxytestosterone from testosterone was enhanced only in DMF-treated rats, whereas that of 2 alpha- and 16 alpha-hydroxytestosterone was reduced by all of the four chemicals. Serum GST activity was increased only in BB and DMF treated rats, but liver cytosolic GST activity was enhanced by all of the four hepatotoxicants, with higher values in BB and DMF groups than in DCE and AA groups. Immunoblot analysis demonstrated that GST Yp was induced by BB and DMF treatments, and Ya and Yc were increased only by BB. GST Yk and Yb1 were not affected by the treatments. The different change patterns of enzymes by a specific toxin and the similar modifying effect on a specific enzyme by different toxins were discussed in relation to the liver damage and to the heterogeneous distribution of enzymes in liver.
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PMID:Different change patterns of the isozymes of cytochrome P450 and glutathione S-transferases in chemically induced liver damage in rat. 1054 60

The overall objective of this study was to evaluate a continuum of biomarkers in blood and urine for their sensitivities as indicators of low level occupational exposures to 1,3 butadiene (BD). The study design was largely cross-sectional, with biological samples collected within a short timeframe. Personal 8-h BD exposure measures were made on several occasions over a 60-day period for each potentially exposed worker in order provide maximum accuracy for this independent variable and to accommodate the different expression intervals of the several biomarkers. Co-exposures to styrene, toluene and benzene were also measured. The study included 24 BD monomer production workers (mean BD exposure=0.642 mg/m(3)), 34 polymerization workers (mean BD exposure=1.794 mg/m(3)) and 25 controls (mean BD exposure=0.023 mg/m(3)). The several biomarkers were measured by a consortium of investigators at different locations in the US and Europe. These biomarkers included: (1) metabolic genotypes (CYP2E1, EH, GST M1, GST T1, ADH2, ADH3), determined in Prague and Burlington, VT; (2) urinary M1 and M2 metabolites (1,2-dihydroxy-4-[N-acetylcysteinyl]-butane and 1-hydroxy-2-[N-acetylcysteinyl]-3-butene, respectively), determined in Albuquerque, NM and Leiden; (3) hemoglobin adducts (N-[2-dihydroxy-3-butenyl]valine=HBVal and N-[2,3,4-trihydroxybutyl]valine=THBVal), determined in Amsterdam and Chapel Hill, NC, respectively; (4) HPRT mutations determined by autoradiographic assay in Galveston, TX, with slides re-read in Burlington, VT; (6) hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations determined by cloning assay in Leiden with mutational spectra characterized in Burlington, VT; (7) sister chromatid exchanges and chromosome aberrations determined by standard methods and FISH analysis in Prague. Urinary M1 and M2 metabolites and HBVal and THBVal hemoglobin adducts were all significantly correlated with BD exposure levels, with adducts being the most highly associated. No significant relationships were observed between BD exposures and HPRT mutations or any of the cytogenetic endpoints, regardless of method of assay.
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PMID:Biomarkers for assessing occupational exposures to 1,3-butadiene. 1139 5

We observed previously that polymorphisms in glutathione S-transferase (GST) genes modified allergic responses to diisocyanate exposure. Here, we extended the study to examine the possible role of N-acetyltransferase (NAT) genotypes in the development of diisocyanate-induced ill effects, both separately and in combination with the previously examined GSTM1, GSTM3, GSTP1 and GSTT1 genotypes. The study population comprised 182 diisocyanate-exposed workers, 109 of whom were diagnosed with diisocyanate-induced asthma and 73 of whom had no symptoms of asthma. The diisocyanates to which the workers had been exposed to were diphenylmethane diisocyanate (MDI), hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI). The NAT2 genotype did not have any significant effect on the risk of developing asthma, but the putative slow acetylator NAT1 genotypes posed a 2.54-fold risk of diisocyanate-induced asthma (95% confidence interval [CI] 1.32 to 4.91). The effect of the NAT1 genotype was especially marked for workers exposed to TDI, among whom the NAT1 slow acetylator genotypes posed a 7.77-fold risk of asthma (95% CI 1.18 to 51.6). Statistically significant increases in asthma risk were also observed among the whole study population for the concurrent presence of the GSTM1 null genotype and either NAT1 (odds ratio [OR] 4.53, 95% CI 1.76 to 11.6) or NAT2 (OR 3.12, 95% CI 1.11 to 8.78) slow acetylator genotypes, and of NAT1 and NAT2 slow acetylator genotypes (OR 4.20, 95% CI 1.51 to 11.6). The results suggest for the first time that in addition to GSTs, the NATs play an important role in inception of asthmatic reactions related to occupational exposure to diisocyanates.
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PMID:N-Acetyltransferase genotypes as modifiers of diisocyanate exposure-associated asthma risk. 1192 38

We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.
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PMID:Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents. 1194 Apr 58

Aerobic, co-metabolic bioremediation of trichloroethylene (TCE), cis-1,2-dichloroethylene (cis-DCE) and other chlorinated ethenes with monooxygenase-expressing microorganisms is limited by the toxic epoxides produced as intermediates. A recombinant Escherichia coli strain less sensitive to the toxic effects of cis-DCE, TCE and trans-1,2-dichloroethylene (trans-DCE) degradation has been created by engineering a novel pathway consisting of eight genes including a DNA-shuffled toluene ortho-monooxygenase from Burkholderia cepacia G4 (TOM-Green), a newly discovered glutathione S-transferase (GST) from RhodococcusAD45 (IsoILR1), found to have activity towards epoxypropane and cis-DCE epoxide, and an overexpressed E. coli mutant gamma-glutamylcysteine synthetase (GSHI*). Along with IsoILR1, another new RhodococcusAD45 GST, IsoILR2, was cloned that lacks activity towards cis-DCE epoxide and differs from IsoILR1 by nine amino acids. The recombinant strain in which TOM-Green and IsoILR1 were co-expressed on separate plasmids degraded 1.9-fold more cis-DCE compared with a strain that lacked IsoILR1. In the presence of IsoILR1 and TOM-Green, the addition of GSH1* resulted in a sevenfold increase in the intracellular GSH concentration and a 3.5-fold improvement in the cis-DCE degradation rate based on chloride released (2.1 +/- 0.1 versus 0.6 +/- 0.1 nmol min(-1) mg(-1) protein at 540 microM), a 1.8-fold improvement in the trans-DCE degradation rate (1.29 +/- 0.03 versus 0.71 +/- 0.04 nmol x min(-1) mg(-1) protein at 345 microM) and a 1.7-fold improvement in the TCE degradation rate (6.8 +/- 0.24 versus 4.1 +/- 0.16 nmol x min(-1) mg(-1) protein at 339 microM). For cis-DCE degradation with TOM-Green (based on substrate depletion), V(max) was 27 nmol x min(-1) mg(-1) protein with both IsoILR1 and GSHI* expressed compared with V(max) = 10 nmol x min(-1) mg(-1) protein for the GST(-)GSHI*(-) strain. In addition, cells expressing IsoILR1 and GSHI* grew 78% faster in rich medium than a strain lacking these two heterologous genes.
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PMID:Metabolic pathway engineering to enhance aerobic degradation of chlorinated ethenes and to reduce their toxicity by cloning a novel glutathione S-transferase, an evolved toluene o-monooxygenase, and gamma-glutamylcysteine synthetase. 1504 22

The control of size and size distribution of microspheres is necessary for obtaining repeatable controlled release behavior. The chitosan microspheres were prepared by a membrane emulsification technique in this study. Chitosan was dissolved in 1 wt.% aqueous acetic acid containing 0.9 wt.% sodium chloride, which was used as a water phase. A mixture of liquid paraffin and petroleum ether 7:5 (v/v) containing PO-500 emulsifier was used as an oil phase. The water phase was permeated through the uniform pores of a porous glass membrane into the oil phase by the pressure of nitrogen gas to form W/O emulsion. Then GST (Glutaraldehyde Saturated Toluene) as crosslinking agent was slowly dropped into the W/O emulsion to solidify the chitosan droplets. The preparation condition for obtaining uniform-sized microspheres was optimized. The microspheres with different size were prepared by using the membranes with different pore size, and there was a linear relationship between the diameter of microspheres and pore size of the membranes when the microspheres were in the range of micron size. The smallest chitosan microspheres obtained was 0.4 mum in diameter. This is the first report for preparing the uniform-sized chitosan microspheres by membrane emulsification technique. Uniform chitosan microspheres were further used as a carrier of protein drug. Bovine serum albumin (BSA) as a model drug was loaded in the microspheres and released in vitro. The effects of pH value, diameter and crosslinking degree of microspheres, and BSA concentration on loading efficiency and release behavior were discussed.
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PMID:Preparation of uniform sized chitosan microspheres by membrane emulsification technique and application as a carrier of protein drug. 1592 72

Metabolically engineered Escherichia coli has previously been used to degrade cis-1,2-dichloroethylene (cis-DCE). The strains express the six genes of an evolved toluene ortho-monooxygenase from Burkholderia cepacia G4 (TOM-Green, which formed a reactive epoxide) with either (1) gamma-glutamylcysteine synthetase (GSHI, which forms glutathione) and the glutathione S-transferase IsoILR1 from Rhodococcus AD45 (which adds glutathione to the reactive cis-DCE epoxide) or (2) with an evolved epoxide hydrolase from Agrobacterium radiobacter AD1 (EchA F108L/I219L/C248I which converts the reactive cis-DCE epoxide to a diol). Here, the impact of this metabolic engineering for bioremediation was assessed by investigating the changes in the proteome through a quantitative shotgun proteomics technique (iTRAQ) by tracking the changes due to the sequential addition of TOM-Green, IsoILR1, and GSHI and due to adding the evolved EchA versus the wild-type enzyme to TOM-Green. For the TOM-Green/EchA system, 8 proteins out of 268 identified proteins were differentially expressed in the strain expressing EchA F108L/I219L/C248I relative to wild-type EchA (e.g., EchA, protein chain elongation factor EF-Ts, 50S ribosomal subunits L7/L12/L32/L29, cysteine synthase A, glycerophosphodiester phosphodiesterase, iron superoxide dismutase). For the TOM-Green/IsoILR1/GSHI system, the expression level of 49 proteins was changed out of 364 identified proteins. The induced proteins due to the addition of TOM-Green, IsoILR1, and GSHI were involved in the oxidative defense mechanism, pyruvate metabolism, and glutathione synthesis (e.g., 30S ribosomal subunit proteins S3 and S16, 50S ribosomal subunit protein L20, alkyl hydroperoxide reductase, lactate dehydrogenase, acetate kinase, cysteine synthase A). Enzymes involved in indole synthesis, fatty acid synthesis, gluconeogenesis, and the tricarboxylic acid cycle were repressed (e.g., tryptophanase, acetyl-CoA carboxylase, phosphoenolpyruvate carboxykinase, malate dehydrogenase). Hence, the metabolic engineering that leads to enhanced aerobic degradation of 1 mM cis-DCE (2.4-4-fold more chloride ions released) and reduced toxicity from cis-DCE epoxide results in enhanced synthesis of glutathione coupled with an induced stress response as well as repression of fatty acid synthesis, gluconeogenesis, and the tricarboxylic acid cycle.
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PMID:Proteome changes after metabolic engineering to enhance aerobic mineralization of cis-1,2-dichloroethylene. 1673 90


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