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)

We have investigated the role of a glutathione S-transferase (GST) with inherent peroxidase activity in the cellular defense against lipid peroxidation and free radical-mediated oxidative damage. Stable transfectants of human T47D cells were generated which express recombinant rat GST-Yc from a human cytomegalovirus promoter-based expression vector. Among several GST-Yc transfectants characterized, two of them contained, respectively, 2- and 3-fold higher GST activity than parental cells or control transfectants and, respectively, 4-5- and 8-10-fold higher selenium-independent glutathione peroxidase activity. Cellular growth kinetics and rates of [3H]thymidine incorporation showed that both transfectants were more resistant to oxidative shocks mediated by cumene hydroperoxide or singlet oxygen generated by photosensitized rose bengal than were T47D cells and control transfectants. In contrast, a T47D transfectant, which expressed high levels of recombinant selenoglutathione peroxidase and showed enhanced resistance to cumene hydroperoxide (Mirault, M.-E., Tremblay, A., Beaudoin, N., and Tremblay, M. J. (1991) J. Biol. Chem. 266, 20752-20760), was as sensitive as parental cells to singlet oxygen. No difference was found in growth sensitivity to 1-h shock treatments with the quinonoid drug daunomycin, irrespective of GST-Yc or selenoglutathione peroxidase overexpression in these cells.
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PMID:Distinct oxidoresistance phenotype of human T47D cells transfected by rat glutathione S-transferase Yc expression vectors. 174 Apr 15

Activity of enzymes involved in metabolism of xenobiotics was not altered in liver tissue of rats kept on a ration enriched with selenium at a dose of 2.5 mg/kg. Both organic form of selenium (yeast meal, selenomethionine) and inorganic derivatives (sodium selenite) at a dose of 5 mg/kg of ration caused distinct activation of epoxide hydrolase, UDP-glucuronosyl transferase and glutathione transferase within 6 weeks after the experiment beginning, while content of cytochrome P-450, glutathione-SH and glutathione peroxidase activity were not significantly altered. Within 9 weeks the enzymatic activity remained at the higher rate only in rats kept on the ration with sodium selenite. Relationship between toxic effects of selenium high doses and alterations in activity of enzymes involved in metabolism of xenobiotics is discussed.
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PMID:[The effect of selenium on enzymes metabolizing xenobiotics in rat liver]. 175 7

Hepatic glutathione (GSH) S-transferase (GST) activity and the tissue distribution of a cationic GST were investigated in biopsy liver samples obtained from patients with alcoholic liver diseases. GST activities in alcoholic fatty liver were significantly high, whereas those in cirrhosis were significantly low compared with normal liver. In fatty liver, immunohistochemically, the staining of the enzyme was strongly positive in hepatocytes around intensive fatty metamorphosis. Then, using experimental chronic alcohol-fed rats, the changes in hepatic GST and GSH peroxidase (GPx) activities and lipid peroxide (LPO) and GSH contents in alcoholic fatty liver were evaluated. Hepatic GST isoenzymes were analyzed and tissue distribution of cationic and neutral GSTs was also investigated. Liver GSH content decreased at two weeks and increased at six weeks. Liver LPO content was elevated at four and six weeks and cytosolic GPx activity was enhanced at four weeks. Cytosolic GST activity was enhanced at six weeks. The cationic and neutral GST isoenzyme pattern was unchanged compared with normal liver. Immunohistochemically, the distribution and intensity of the staining of GSTs were essentially unchanged. There was no evidence of an increase in the GST isoenzyme with selen-independent GPx activity. However, GSTs were strongly stained in the hepatocytes with fatty droplets. Thus, in alcoholic fatty liver, hepatic GST and GPx activities are thought to be enhanced by different mechanisms. The elevated GPx activity may relate to the production of LPO. However, the enhancement of GST activity may result from some other causes which include the enzyme induction.
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PMID:Glutathione S-transferase in alcoholic fatty liver. 177 80

The activity of glutathione S-transferase (GST) decreased progressively in Schistosoma mansoni from mice treated with oltipraz (OPZ). However, the peroxidase activity of GST (selenium-independent) and selenium-dependent glutathione peroxidase was not affected by OPZ treatment. Purification and quantification of GST from worms after OPZ treatment indicated that the decrease in enzyme activity was greater than could be accounted for by the decrease in GST protein content. SDS-polyacrylamide gel electrophoresis followed by Western blot analysis with GST isoenzyme specific antisera revealed a slight decrease in the quantity of both 26 and 28 kDa GSTs. Fractionation of cytosolic GSTs from male S. mansoni by chromatofocusing resolved three major isoenzymes (SmI, II and III) and a minor form which eluted first from the column. SmI, II and III all had a molecular weight of about 28 kDa on SDS-polyacrylamide gel electrophoresis. However, on electrophoresis in the absence of SDS, the three GST forms exhibited different mobilities. The pattern of SmI, II and III was similar in untreated and OPZ-treated worms, but the activities of the isoenzymes from treated worms were lower. The results suggest that OPZ interacts with the GST isoenzymes SmI, II and III in a similar manner; thus, the effects are not isoenzyme specific. Taken together, these results suggest that OPZ and/or its metabolites interact directly with GST resulting in inhibition of activity and reduction in total enzyme protein. This mechanism may be important in the antischistosomal action of OPZ.
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PMID:Oltipraz-induced decrease in the activity of cytosolic glutathione S-transferase in Schistosoma mansoni. 178 33

Glutathione reductase (EC 1.6.4.2; GSSG-R), glutathione peroxidase (EC.1.11.1.9; GSHpx) and glutathione transferase (EC 2.5.1.18; GST) enzymatic activities and glutathione status were investigated in 11-day embryos and the yolk sac, placenta and perinatal liver in rats. It is observed that: (a) levels of GSSG differ between the embryo (lower) and yolk sac (higher); (b) GSH concentrations increased significantly in fetal livers with respect to the days of gestation; in contrast, GSSG hepatic concentrations showed a significant rise with respect to time only during lactation; (c) the specific enzymatic activity of both GSHpx and GSSG-R were higher in the visceral yolk sac than in the embryo; (d) hepatic GSSG-R activity increased significantly during gestation. In addition, hepatic GSHpx and GST activities showed statistically significant increases over the period studied.
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PMID:Glutathione and related enzyme activity in the 11-day rat embryo, placenta and perinatal rat liver. 179 27

Sixty patients with severe forms of acute viral hepatitis B (AVHB) without symptoms of acute hepatic encephalopathy (AHE) and 20 AVHB patients with such symptoms were examined for red blood cell and serum levels of dienic conjugates (DC), malonic dialdehyde (MDA), reduced glutathione (RG), activity of superoxydismutase (SOD), catalase, glutathione peroxidase-1 (GP1), glutathione peroxidase-2 (GP2), glutathione reductase (GR), glutathione transferase (GT). Elevated MDA and DC concentrations were found in grave AVHB, in coma and precoma DC reduced. MDA levels in precoma fell, in coma rose. The activity of SOD, GP1, GP2, GR and RG concentration were low, especially in AHE symptoms. GT and catalase activity proved high in severe AVHB with a trend to lowering in precoma and coma.
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PMID:[Status of the processes of free-radical oxidation and the antioxidation system in patients with a severe course of hepatitis B]. 180 52

It was suggested that increased Cu-Zn superoxide dismutase (SOD-1) might be involved in the various biological abnormalities found in Down's syndrome (DS) such as premature aging and Alzheimer-type neurological lesions. As a model system for testing this hypothesis we have developed two strains of transgenic mice carrying only one copy of the human SOD-1 gene. In the first strain (TG1), no expression has been found by northern blot analysis. The second strain (TG2) exhibited human SOD-1 mRNA and increased SOD-1 activity in the brain (1.93 fold), in the heart (1.69 fold), thymus (1.49 fold) and to a lesser extent in muscle (1.25 fold), liver (1.19 fold), kidney (1.18 fold), spleen (1.35 fold), lung (1.26 fold) and erythrocytes (1.09 fold). In this strain, increased SOD-1 activity in the brain did not induce modifications in the seleno-dependent glutathione peroxidase, glutathione reductase and glutathione S-transferase activities. In brain homogenates, we have focused our studies on Tau proteins which are known to be the major antigenic components of paired helical filaments (PHF), both in DS and Alzheimer's disease. Our results suggested that, in our experimental conditions, the overexpression of SOD-1 did not induce the modifications of Tau proteins similar to those seen during neurofibrillary degeneration.
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PMID:Expression of human Cu-Zn superoxide dismutase gene in transgenic mice: model for gene dosage effect in Down syndrome. 182 30

Dietary copper deficiency was produced in Swiss albino mice and Sprague Dawley rats to compare changes in selected antioxidant enzymes. A 5-wk dietary treatment was employed, starting approximately 1 wk after birth for mice (initially via dams) and 3 wk after birth for rats. An additional confirmatory experiment was conducted with mice using the postweanling paradigm. Mouse offspring (6 wk of age) and rats (8 wk of age) maintained on a Cu-deficient treatment were compared with Cu-adequate controls. Compared with Cu-adequate animals, Cu-deficient mice and rats were anemic, had lower ceruloplasmin activities and liver copper levels, and had higher relative weights of heart and small intestine. Activity of cytochrome c oxidase (mice) and Cu,Zn-superoxide dismutase (mice and rats) was lower in all seven organs examined from Cu-deficient animals compared with Cu-adequate animals, although there were organ and species differences. Compared with Cu-adequate controls, glutathione peroxidase activity was lower in liver and plasma of Cu-deficient mice and rats. Hepatic glutathione transferase activity was markedly lower in those Cu-deficient mice started on treatment at 1 wk of age but not in those mice or rats subjected to postweanling copper deficiency.
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PMID:Changes in Cu,Zn-superoxide dismutase, cytochrome c oxidase, glutathione peroxidase and glutathione transferase activities in copper-deficient mice and rats. 184 85

Glutathione transferases (GSTs) of a novel class, which it is proposed to term Theta, were purified from rat and human liver. Two, named GST 5-5 and GST 12-12, were obtained from the rat, and one, named GST theta, was from the human. Unlike other mammalian GSTs they lack activity towards 1-chloro-2,4-dinitrobenzene and are not retained by GSH affinity matrices. Only GST 5-5 retains full activity during purification, and its activities towards the substrates 1,2-epoxy-3-(p-nitrophenoxy)propane, p-nitrobenzyl chloride, p-nitrophenethyl bromide, cumene hydroperoxide, dichloromethane and DNA hydroperoxide are 185, 86, 67, 42, 11 and 0.03 mumol/min per mg of protein respectively. Earlier preparations of GST 5-5 or GST E were probably a mixture of GST 5-5 and GST 12-12, which was largely inactive, and may also have been contaminated by less than 1% with another GSH peroxidase of far greater activity. Partial analysis of primary structure shows that subunits 5, 12 and theta are related to each other, particularly at the N-terminus, where 25 of 27 residues are identical, but have little relationship to the Alpha, Mu and Pi classes of mammalian GSTs. They do, however, show some relatedness to subunit I of Drosophila melanogaster [Toung, Hsieh & Tu (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 31-35] and the dichloromethane dehalogenase of Methylobacterium DM4 [La Roche & Leisinger (1990) J. Bacteriol, 172, 164-171].
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PMID:Theta, a new class of glutathione transferases purified from rat and man. 184 57

The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13-fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH-Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation.
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PMID:The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse. 186 40


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