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)

The effects of enflurane and isoflurane on heme metabolism, its regulation, and on some parameters involved in the hepatic drug metabolising system in animals under GSH depletion were investigated. A single dose of the anaesthethics (1 ml kg(-1), i.p.) was administered to control and GSH depleted mice, animals were sacrificed 20 min after. As a consequence of GSH depletion, a significant inhibition in delta-Aminolevulinic acid synthetase activity, the first enzyme of heme biosynthesis, and a striking induction in Heme oxygenase activity, the main enzyme of heme metabolism, were observed. Cytochrome P-450 levels and the activities of P-4502E1 and glutathione S-transferase were increased. These changes in heme metabolism and drug metabolising enzyme system were not altered further by the administration of enflurane or isoflurane. These findings would indicate that the status of oxidative stress produced by GSH depletion could not be affected by these anaesthetics and/or that disturbances in heme metabolism were already too important to undergo further variations.
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PMID:Glutathione depletion and anaesthesia in mice alter heme and drug metabolising enzymes. 1577 21

Cytochrome P-450 and glutathione S-transferase (GST) activities were investigated in stomach tumor and tumor-adjacent tissues of patients (n = 211) with gastric adenocarcinoma, and in the stomach tissues of unaffected individuals (normal tissues, n = 113). A significant reduction in total cytochrome P-450 activity was observed in tumor and tumor-adjacent tissues versus normal stomach. In all cases, cytochrome P-450 activity was significantly higher in males than in females. In the case of smokers, cytochrome P-450 activity was 1.8-fold higher in tumor-adjacent than in corresponding tumor tissues, but no difference was observed in nonsmokers. Patients had significantly lower GST activity in tumor and tumor-adjacent tissues compared to normal tissues. Smokers showed lower GST activity in both tumor and tumor-adjacent tissues compared to nonsmokers. In addition, GST activity was significantly lower in tissues positive for Helicobacter pylori infection than in H. pylori-negative tissues. However, the frequency of H. pylori infection was higher in tumor-adjacent (69%) than in tumor (45%) or normal tissues (44%). Our data suggest that diminished GST enzymes activity and increased cytochrome P-450 activity in normal and tumor-adjacent tissues might be due to the direct effect of the H. pylori infection and cigarette smoking, respectively. Data indicate that alterations in the activities of cytochrome P450 and GST may in part be associated with an increased risk for gastric cancer.
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PMID:Alteration of cytochrome P-450 and glutathione S-transferase activity in normal and malignant human stomach. 1619 17

The enzymatic mechanisms involved in the degradation of phenanthrene by the white rot fungus Pleurotus ostreatus were examined. Phase I metabolism (cytochrome P-450 monooxygenase and epoxide hydrolase) and phase II conjugation (glutathione S-transferase, aryl sulfotransferase, UDP-glucuronosyltransferase, and UDP-glucosyltransferase) enzyme activities were determined for mycelial extracts of P. ostreatus. Cytochrome P-450 was detected in both cytosolic and microsomal fractions at 0.16 and 0.38 nmol min(sup-1) mg of protein(sup1), respectively. Both fractions oxidized [9,10-(sup14)C]phenanthrene to phenanthrene trans-9,10-dihydrodiol. The cytochrome P-450 inhibitors 1-aminobenzotriazole (0.1 mM), SKF-525A (proadifen, 0.1 mM), and carbon monoxide inhibited the cytosolic and microsomal P-450s differently. Cytosolic and microsomal epoxide hydrolase activities, with phenanthrene 9,10-oxide as the substrate, were similar, with specific activities of 0.50 and 0.41 nmol min(sup-1) mg of protein(sup-1), respectively. The epoxide hydrolase inhibitor cyclohexene oxide (5 mM) significantly inhibited the formation of phenanthrene trans-9,10-dihydrodiol in both fractions. The phase II enzyme 1-chloro-2,4-dinitrobenzene glutathione S-transferase was detected in the cytosolic fraction (4.16 nmol min(sup-1) mg of protein(sup-1)), whereas aryl adenosine-3(prm1)-phosphate-5(prm1)-phosphosulfate sulfotransferase (aryl PAPS sulfotransferase) UDP-glucuronosyltransferase, and UDP-glucosyltransferase had microsomal activities of 2.14, 4.25, and 4.21 nmol min(sup-1) mg of protein(sup-1), respectively, with low activity in the cytosolic fraction. However, when P. ostreatus culture broth incubated with phenanthrene was screened for phase II metabolites, no sulfate, glutathione, glucoside, or glucuronide conjugates of phenanthrene metabolites were detected. These experiments indicate the involvement of cytochrome P-450 monooxygenase and epoxide hydrolase in the initial phase I oxidation of phenanthrene to form phenanthrene trans-9,10-dihydrodiol. Laccase and manganese-independent peroxidase were not involved in the initial oxidation of phenanthrene. Although P. ostreatus had phase II xenobiotic metabolizing enzymes, conjugation reactions were not important for the elimination of hydroxylated phenanthrene.
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PMID:Enzymatic Mechanisms Involved in Phenanthrene Degradation by the White Rot Fungus Pleurotus ostreatus. 1653 34

Liver cell aggregates were established from freshly isolated adult rat hepatocytes and non-parenchymal liver cells (NPC) in rotating cultures. One-third of the inoculated cells formed spheroidal aggregates and one-third of the aggregates remained in culture for up to 12 days, expressing a high intracellular lactate dehydrogenase (LDH) activity and ATP content. The 7-ethoxyresorufin O-deethylase (EROD) activity was doubled on day 8 compared with that in freshly isolated cells, and the glutathione S-transferase (GST) activity was preserved to initial level at day 12. Cytochrome P-450 (CYP) isoforms were differentially affected: at day 8, CYP1A1/2 and CYP2B1/2 contents were close to freshly isolated cell contents; CYP3A1/2 and 4A1/2/3 were preserved at half of the original levels; CYP2C6 and 2C11/2B1/2 were reduced. Enzyme inductions were effective throughout the whole culture period: EROD activity increased fivefold after exposure to phenobarbital (PB) and up to 20-fold after 3-methylcholanthrene (3-MC) exposure; GST activity was stimulated approximately twofold by both inducers. Compound-specific inductions were found for aldrin epoxidase (by PB only), ethoxycoumarin O-deethylase (ECOD) and UDP-glucuronyltransferase (by 3-MC only). Experiments with hepatocyte aggregates showed that the NPC in heterotypic aggregates preserve liver-specific functions more efficiently in long-term experiments. Accordingly, these aggregate cultures from adult rat liver cells could serve as a suitable in vitro model for long-term studies on xenobiotic metabolism or on the interaction of hepatotoxic chemicals with the cross-talk between hepatocytes and NPC.
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PMID:Preservation and inducibility of xenobiotic metabolism in long-term cultures of adult rat liver cell aggregates. 2065 95

Specific characteristics of cells vary as a function of time in culture. We have determined the stability of selected Phase I and Phase II biotransformation capacities in rabbit renal proximal tubule cells in primary culture. When grown in hormonally-defined medium, proximal tubule cells lost Phase I metabolic capacity. Cytochrome P-450 content and associated mixed-function oxidase activities present in kidney cortex microsomes were not detectable after 14 days in culture. Phase II glutathione-dependent metabolic functions were well retained in cultured cells compared with freshly isolated proximal tubules (FIPT). Cellular total glutathione content was 2.8 mug/mg protein in FIPT compared with approximately 10 mug/mg protein in stable confluent cultures. A higher total glutathione content of 20.6 mug/mg was noted in preconfluent cultures. The glutathione redox state was initially perturbed in FIPT with 37% of the total glutathione present found in its oxidized form. Tubule cells recovered to a normal ratio (6-13% of total glutathione in the oxidized form) while in culture. The glutathione S-transferase activity in 4-day-old cells in culture was reduced to 50% of the 4 U/mg protein level found in FIPT. No appreciable further decline in glutathione S-transferase activity was detected during 15 days in culture. The level of gamma-glutamyl-transpeptidase (a brush-border enzyme necessary for glutathione uptake into proximal tubule cells) declined from 1499 mU/mg protein in homogenates of FIPT to 636 mU/mg in homogenates of 8-day-old cultured cells. A further decline in activity occurred during the next 7 days in culture. In conclusion, although Phase I metabolic functions were diminished in primary cultured rabbit proximal tubule cells, Phase II metabolic functions were retained at levels comparable with FIPT and well above those found in several established kidney cell lines.
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PMID:Primary cultures of rabbit renal proximal tubule cells: II. Selected phase I and phase II metabolic capacities. 2070 58

Kidney cells were isolated from rat kidney cortex and maintained in short-term monolayer cultures. A number of important parameters were studied in order to establish the usefulness of these cells for toxicity studies. Despite morphological differences between the cultured cells and similar cells in vivo, many relevant enzyme systems remained present and functional. Intracellular glutathione levels were stable up to 5 days in culture. The glutathione S-transferase activity during culture remained stable although at a lower level than in freshly isolated cells. Whereas rat kidney cytosol contained subunits 4, 7, 2 and 1, 3- and 5-day-old cultures contained glutathione transferase subunits 7, 2 and a small amount of subunit 1. Cytochrome P-450, although measurable in microsomes from freshly isolated cells, could not be determined after 1 day in culture. Organic anion transporters on the basolateral side and gamma-glutamyl transpeptidase on the apical side were present. Through cytotoxicity studies, beta-lyase activity could be demonstrated in the culture. Hence this monolayer culture system, which can be used in combination with filters, seems to be suitable for studying various mechanisms of nephrotoxicity.
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PMID:Use of monolayers of primary rat kidney cortex cells for nephrotoxicity studies. 2070 91

The present study was undertaken to evaluate the subacute toxicity of arsenic (As) and chlorpyrifos (CPF) alone or in combination. In addition, the ameliorative effect of ascorbic acid on As and/or CPF-induced hepatic microsomal xenobiotic metabolizing enzymes in rats was examined. Rats were divided into 9 groups of 6 animals each: control (deionized water), vehicle control (groundnut oil), ascorbic acid (100 mg/kg body weight), As (40 ppm in water), CPF (5 mg/kg body weight), As (40 ppm) + CPF (5 mg/kg body weight), As + ascorbic acid, CPF + ascorbic acid, and As + CPF + ascorbic acid. After 28 d of exposure, rats were sacrificed and liver was extracted for isolation of hepatic microsomes. Exposure to As or CPF alone as well as both of these in combination significantly altered microsomal proteins and activity of phase I and phase II xenobiotic-metabolizing enzymes. Cytochrome P-450 and cytochrome b 5 levels and activities of aniline p-hydroxylase (APH) and uridine diphosphate glucuronosyltransferase (UGT) were significantly decreased in groups treated with As, CPF, and As plus CPF, while glutathione S-transferase (GST) was not markedly altered. Enzymatic activity of aminopyrine N-demethylase (ANDM) was also significantly reduced in As- and CPF-only groups. Co-administration of ascorbic acid effectively countered the As- and CPF-induced alterations in xenobiotic-metabolizing enzymes.
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PMID:Differential modulation of xenobiotic-metabolizing enzymes in rats following single and concurrent exposure to chlorpyrifos, arsenic, and ascorbic acid. 2428 77


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