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)

Water solubility and non-toxic properties of ascorbic acid are taken as criteria for beneficial effects of large doses of the vitamin. In the present study, male guinea pigs, dosed daily with 15, 30 or 50 mg/100g body weight for 10 weeks, demonstrated no differences in effect on liver and lung weights, body growth and microsomal protein contents of liver and lung when compared with controls. When guinea pigs were fed excessive ascorbic acid, there was a small non-significant increase (p less than 0.05) in hepatic and pulmonary cytochrome P-450, and significant increase (p less than 0.05) in hepatic cytochrome b5 which was accompanied with a significant increase in arylhydrocarbon hydroxylase activity in the two organs. Activity of NADPH-dependent cytochrome c-reductase was decreased in liver and remained unaffected in lung and colon. Drug detoxifying enzymes responded in different ways to increased intake of ascorbic acid. Activity of UDP-glucuronyltransferase remained unchanged on feeding excessive ascorbic acid, whereas glutathione S-transferase was decreased significantly in liver and was unaltered in lung and colon. Reduced glutathione was decreased only in the lung. The observed changes in drug activating and detoxifying enzymes appear to be important from drug pharmacokinetics and carcinogenesis point of view.
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PMID:Effect of large doses of ascorbic acid on the hepatic and extra-hepatic drug-metabolizing enzymes in guinea pig. 380 Oct 39

The ontogeny and endocrine regulation of sex-differentiated hepatic metabolism is mediated via the hypothalamic-pituitary axis. Using in vitro-in vivo systems, we demonstrate alterations in activity levels of six sex-differentiated enzyme systems in male rats bearing ectopic pituitary tumors after the injection of a pituitary cell line, C811RAP. Activity levels of hepatic glutathione S-transferase, UDP-glucuronyltransferase, and aryl hydrocarbon hydroxylase are reduced to activity levels of control females, while histidase, 5 alpha-reductase, and serum cholinesterase levels are increased to levels of control females, i.e. feminization of all of these enzymes. RIAs of testosterone, estrogen, FSH, and PRL are similar in tumor-bearing and control animals, but GH levels are significantly higher in tumor-bearing animals than in the controls. It is suggested that GH may be the pituitary factor responsible for the expression of sex-differentiated hepatic metabolism.
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PMID:Modulation (feminization) of hepatic enzymes by an ectopic pituitary tumor. 392 55

The effect of intratracheal instillation of different doses of benzo(a)pyrene (0.1, 1.0 and 2.0 mg) on the drug metabolizing enzymes of lung and liver was analysed in rats fed diet with or without vitamin A for 5-6 weeks. Benzo(a)pyrene exposure at 2.0 mg dose only elevated the level of cytochrome P-450 and b5, and activity of benzopyrene hydroxylase in liver, and extent of increase was similar in normal and vitamin A deficient groups. Contrary to this, pulmonary contents of cytochrome P-450 and b5, and benzopyrene hydroxylase activity increased over control values in both the groups even at lower doses of benzo(a)pyrene. Moreover, their values were higher in vitamin A deficient-treated groups compared to normal-treated controls. Increase in these parameters was greater in lung as compared to increase in liver. NADPH cytochrome C-reductase in lung and liver was not affected either by inducing vitamin A deficiency or exposing these rats further to benzo(a)pyrene. Uridine-diphospho-glucuronosyl-transferase (UDP-GT) activity in normal and vitamin A deficient groups was enhanced following exposure to benzo(a)pyrene both in lung and liver. However, activity of this enzyme remained impaired in vitamin A deficient groups, benzo(a)pyrene exposed or not exposed when compared to respective normal controls. Glutathione S-transferase activity remained unchanged following exposure to benzo(a)pyrene both in lung and liver. The apparent increase in hepatic glutathione S-transferase and decrease in pulmonary glutathione S-transferase activity in vitamin A deficiency was only due to vitamin A deficient status of rats with no further effect of benzo(a)pyrene.
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PMID:Effect of intratracheally instilled benzo(a)pyrene on the pulmonary and hepatic drug-metabolizing enzymes in normal and vitamin A deficient rats. 401 64

1-Chloro-2,4-dinitrobenzene (CDNB) was used to conjugate glutathione (GSH) through the catalysis of lens glutathione S-transferase without the untoward oxidative damage to the lens mediated by GSH oxidants. A 2 hr treatment of the rat lens with 1 mM CDNB resulted in a nearly total depletion of lens GSH with neither formation of GSSG nor glutathione-protein mixed disulfides. Rubidium uptake was found to decrease linearly with the loss of GSH; nevertheless, ionic imbalance did not commence until more than 30% cation pump activity was lost. Glycolytic rate dropped following CDNB treatment, due probably to a decline in demand for ATP by the deactivated cation pump. 31P-NMR studies confirmed the irreversible loss of ATP. CDNB depletion of GSH resulted in a two-fold increase in 14CO2 production from [14C]-1-glucose. Whereas oxidative stress resulted in a six-fold increase in glucose utilization through the hexose monophosphate shunt (HMPS), CDNB-treated lenses showed no such stimulation. This indicated that the residual GSH following CDNB treatment was insufficient for the activation of the glutathione peroxidase-reductase-HMPS mechanism and raised the possibility that the increased glucose utilization might be due to mechanisms other than the HMPS. These results indicate an intimate correlation between the GSH content and major metabolic functions in the lens.
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PMID:Effect of glutathione deprivation on lens metabolism. 609 26

The level of NADPH-cytochrome c reductase, glutathione reductase and hepatic B2 was significantly decreased in rats fed a B2-deficient diet. The synthesis of ester forms of B2 was decreased more in the lenses of rats fed this diet for 8 weeks than in those fed this diet for 4 weeks. The glutathione reductase activity in the lens decreased as the duration of a B2-deficient diet increased; this may be ascribable to a decrease in the formation in the lenticular riboflavin ester as a coenzyme. The level of lipid peroxides increased in the serum and lenses of rats on the B2-deficient diet, however, compared to the controls, the changes in the activities of superoxide dismutase and glutathione S-transferase were not significant. Lenticular glutathione peroxidase activity was decreased significantly in rats fed the B2-deficient diet for 8 weeks. We suggest that B2 deficiency brings about metabolic disorders in the redox system to maintain lens transparency, that lipoperoxide is accumulated, and that the efficiency of the scavenging system and the activities of glutathione peroxidase and reductase are decreased.
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PMID:Effects of B2-deficiency on lipoperoxide and its scavenging system in the rat lens. 642 65

This article is a summary of laboratory methods for the hepatic drug metabolizing enzymes which are reliable, sensitive, and reasonably straightforward to perform. Assay conditions are given for which the enzyme rate determinations are linear with respect to time and protein concentration for hepatic tissue preparations from Charles River Sprague Dawley CD male rats. In selecting these particular assay methods, factors such as disposal of radioactive wastes, safety of laboratory personnel, and cost of required equipment were considered. Thus 9 of the 10 hepatic parameters utilize simple spectrophotometric techniques; the remaining assay (ethoxyresorufin O-deethylase) requires a spectrophotofluorometer. The hepatic toxification/detoxification assays are cytochrome P-450 and reduced glutathione content, NADPH-cytochrome C reductase, aminopyrine N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase (3 substrates) and UDP-glucuronyltransferase (2 substrates).
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PMID:Laboratory methods for ten hepatic toxification/detoxification parameters. 642 71

The present study was designed to prepare and characterize subcellular fractions from the trunk kidney of the Northern pike (Esox lucius), with special emphasis on the preparation of a microsomal fraction suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation, as well as the recovery of different organelles, was determined using both enzyme markers and morphological examination with the electron microscope. Finally, the subcellular distributions of several drug-metabolizing enzymes (NADPH-cytochrome c reductase, NADH-ferricyanide reductase, glutathione transferase, epoxide hydrolase) were determined. With the exception of NADPH-cytochrome c reductase, the subcellular distributions obtained here for drug metabolizing and marker enzymes closely resembled those reported for rat liver. NADPH-cytochrome c reductase was apparently partially solubilized here from microsomal vesicles by an endogenous protease, which reduced its usefulness as a marker enzyme and raises questions concerning the measurement of activities catalyzed by the cytochrome P-450 system in these subfractions. In other respects the microsomes and supernatant fraction prepared here from the trunk kidney of the pike seem to be as well suited for investigations of drug metabolism as are the corresponding fractions from rat and pike liver.
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PMID:Preparation and characterization of subcellular fractions suitable for studies of drug metabolism from the trunk kidney of the Northern pike (Esox lucius) and assay of certain enzymes of xenobiotic metabolism in these subfractions. 643 81

The effects of the synthetic dibromo-pyrethroid insecticide deltamethrin on some hepatic phase I and II enzyme activities were studied in rat liver. The animals were treated with daily doses of 5 and 10 mg/kg of both pure insecticide or its commercial formulation (Decis), administered i.p. in corn oil for 7 days. The following enzyme activities were studied: NADPH-cytochrome-P450 reductase, aryl-hydrocarbon hydroxylase, aminopyrine N-demethylase, glutamyl cysteine synthetase, glutathione S-transferase, glutathione peroxidase, peroxisomal acyl-CoA oxidase, catalase, and urate oxidase. Both deltamethrin and its commercial formulation were effective in modifying the activities of several of these hepatic xenobiotic-metabolizing enzymes. However, some differences in enzyme modifications were found between treatment with pure or commercial deltamethrin, the latter being more active. This effect could be ascribed to additives, solvents, and chemical intermediates present in the Decis formulation. These results suggest that exposure to this deltamethrin commercial formulation could be more dangerous than exposure to deltamethrin alone, both in terms of its hepatotoxicity and/or alterations in the hepatic biotransformation of other occupational/environmental xenobiotics.
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PMID:Studies on hepatic xenobiotic-metabolizing enzymes in rats treated with insecticide deltamethrin. 747 74

Transfection of murine NIH3T3 fibroblasts and human MCF7 breast carcinoma cells with a pSV2-derived eukaryotic expression vector for human cytosolic glutathione peroxidase resulted in clones with increased glutathione peroxidase activity. This heterologous expression indicates that murine cells recognize the human "selenocysteine insertion sequence" in the 3' untranslated region of the mRNA which facilitates insertion of selenocysteine directed by the opal codon. Though most clones from both cell lines eventually lost their enhanced glutathione peroxidase activity despite continuous selection on G418, some NIH3T3 clones retained enhanced enzyme activity without continuous G418 exposure. Transfection of MCF7 cells with an Epstein-Barr virus (EBV)-derived episomally replicating expression vector carrying the glutathione peroxidase gene also revealed increased glutathione peroxidase activity. These MCF7 cells, however, all required exposure to G418 to maintain enhanced glutathione peroxidase activity. Detailed biochemical analysis of a stably expressing NIH3T3 clone and MCF7 expressing cells revealed no alterations in activities of copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, phospholipid-glutathione peroxidase, glutathione reductase, glutathione transferase, or NADPH-P450 reductase. Both pSV2- and EBV-derived glutathione peroxidase-expressing clones exhibited enhanced resistance to paraquat as well as to peroxides.
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PMID:Heterologous expression of selenium-dependent glutathione peroxidase affords cellular resistance to paraquat. 748 71

The emergence of drug resistance is a major obstacle to effective cancer chemotherapy. The identification of novel agents that serve as selective, potent and nontoxic modulators of drug resistance is thus an important goal for improving the success of cancer treatment. Thaliblastine (TBL), a plant alkaloid and P-glycoprotein (P-gp) inhibitor, is presently shown to fully reverse 490-fold resistance to Adriamycin (AdR) in a multidrug-resistant (MDR) human breast cancer cell line (MCF/AdR) that overexpresses P-gp, whereas the same treatment had no effect on AdR cytotoxicity in the drug-sensitive parental MCF-7 cells. Mechanistic studies showed that this striking resistance reversal was achieved without alteration of cellular levels of glutathione and without inhibition of glutathione S-transferase, glutathione peroxidase or P450 reductase by TBL, each of which is significantly altered in MCF/AdR cells, and each of which has been proposed to contribute to AdR resistance in this MDR line. Rather, resistance reversal by TBL can be entirely explained by this drug's capacity to restore the intracellular accumulation of AdR in the resistant cells. These results establish that MDR associated with P-gp overexpression can be fully reversed by the potent P-gp inhibitor TBL. They further indicate that although changes in multiple drug-metabolizing enzymes may accompany the development of MDR, these multiple biochemical alterations need not correspond to multiple functional determinants for drug resistance.
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PMID:Complete reversal by thaliblastine of 490-fold adriamycin resistance in multidrug-resistant (MDR) human breast cancer cells. Evidence that multiple biochemical changes in MDR cells need not correspond to multiple functional determinants for drug resistance. 756 98


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