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)

The effects of geniposide pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Sprague-Dawley rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase (AST), alanine amino-transferase (ALT) and gamma-glutamyltranspeptidase (gamma-GT). After pretreatment of animals with geniposide (10 mg/kg) daily for 3 consecutive days, the enzyme elevations were significantly suppressed. This suggested that the geniposide possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevation of the activities of glutathione S-transferase (GST) and gamma-glutamylcysteine synthetase but not glutathione peroxidase (GSH-Px) and gamma-glutamyltranspeptidase were observed. Treatment of rats with geniposide significantly lowered hepatic GSH and GSSG levels, but the ratio of GSH to GSSG was not changed. Geniposide treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of geniposide on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that involve the enhanced GST activity for AFB1 detoxication and induction gamma-glutamylcysteine synthetase for GSH biosynthesis.
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PMID:Suppressive effect of geniposide on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. 168 34

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and sub-lines isolated in vitro by selection with Adriamycin were studied for reversal of intrinsic and acquired Adriamycin resistance, using buthionine sulfoximine (BSO) to deplete cellular glutathione alone and in combination with the P-glycoprotein antagonist verapamil. GSH levels varied among the parental cell lines but did not increase with resistance. In the parental SW620, DLD-I and HCT-15 and their drug-resistant derivatives, there was no relation between the effect of the glutathione-depleting agent BSO, the mRNA expression of both selenium-dependent glutathione peroxidase (GPx) and glutathione S-transferase pi (GST pi), bulk glutathione S-transferase (GST) activity, and the degree of resistance. However, in LS 180 and its derivative sub-lines, which do not principally rely on P-glycoprotein (Pgp) for Adriamycin resistance, treatment with BSO demonstrated a relatively diminished GSH depletion and enhanced recovery. In comparison with the other acquired cell lines, BSO specifically reversed acquired resistance in the LS 180 Adriamycin-resistant subline (LS 180 Ad150) after short-term drug exposure. Furthermore, the LS 180 Ad150 cells demonstrated an increase in both GPx and GST pi mRNA expression. These observations suggest that glutathione-mediated detoxification of Adriamycin may play a role in the resistance of this sub-line. Verapamil enhanced Adriamycin cytotoxicity 1.2- to 12-fold in the intrinsically resistant cells and as much as 15-fold in cell lines with acquired resistance. Combination of BSO with verapamil resulted in additive, but not synergistic, reversal of resistance. The results underscore the complex nature of Adriamycin resistance, and suggest a role for drug-resistance-modulating agents in the treatment of colon carcinoma.
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PMID:Contribution of glutathione and glutathione-dependent enzymes in the reversal of adriamycin resistance in colon carcinoma cell lines. 168 79

The authors hypothesized that rat plasma or tissue glutathione metabolism could change with age due to possible decreases in glutathione-related enzyme activities. To test this hypothesis, the authors measured plasma and tissue concentrations of glutathione and glutathione-related enzymes. Animals were 3 months, 12 months, or 24 months old at the time of experiments. Plasma glutathione was found to be significantly increased in both the 12-month-old and 24-month-old groups compared to the 3-month-old rats. Tissue enzyme measurements showed no significant differences between the groups in lung or liver glutathione peroxidase or glutathione S-transferase. gamma-Glutamyl transpeptidase activity was significantly decreased in kidney and lung with aging. Decreases in tissue gamma-glutamyl transpeptidase activity occur with age; this may contribute to increases in plasma glutathione concentrations.
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PMID:Effects of age on rat glutathione metabolism. 168 7

A B16 melanoma line was repeatedly transplanted subcutaneously in C57BL/6 mice. On day 4 after every transplant, the animals were treated with doxorubicin (DXR), 10 mg/kg i.p. The aim of the work was to develop an in-vivo model of resistance to the antiblastic in order to analyze some possible mechanistic aspects of the process in the course of time. After 16 transplants and treatments the melanoma completely lost its sensitivity to the antiproliferative effects of maximal tolerated doses of DXR and showed over-expression of P-glycoprotein. Compared to the parental line, the in vitro resistance index was 4.6. After 27 transplants and treatments the melanoma did not increase its in vitro resistance to DXR further, and this resistance was completely reversed by verapamil. The behavior of the antioxidant defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, glutathione reductase and glutathione) was evaluated after 4, 16 and 27 transplants and treatments with DXR. At no stage did the treated melanoma show any variation in the antioxidant enzymes. Compared to the parental counterpart its glutathione levels were elevated after four treatments (+80%), when, however, the line was still sensitive to the in vivo effects of DXR, and after 16 treatments (+30%). Instead, no variation of the glutathione content was seen after 27 treatments with DXR. These results seem to exclude the possibility that the antioxidant defenses play a major role in the resistance of this B16 melanoma line to DXR. On the other hand, the low but, however, 'clinically' significant resistance of the tumor to the antiblastic seems mainly related to the mechanisms linked to the P-glycoprotein over-expression.
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PMID:Antioxidant defenses in a B16 melanoma line resistant to doxorubicin: an in vivo study. 168 13

Activities of red cell glutathione-dependent enzymes, glutathione peroxidase (GP), glutathione reductase, and glutathione transferase (GT), were measured in 70 children suffering from chronic hepatitis and liver cirrhosis with various forms and activities of the conditions. Manifest changes in GP and GT activities were revealed. Measurements of GT activities are recommended for assessment of the liver process severity and for early detection of the liver detoxifying function stress.
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PMID:[The activity of the glutathione-dependent enzymes of erythrocytes in chronic liver diseases in children]. 170 92

As a means to understand the fundamental mechanisms of bleomycin cell killing, we previously isolated 19 bleomycin-sensitive mutants which represent at least six genetically distinct complementation groups (T.D. Stamato, B. Peters, P. Patil, N. Denko, R. Weinstein, and A. Giaccia. Cancer Res., 47: 1588-1592, 1987). One class of mutants represented by the cell line BL-10 displays only hypersensitivity to killing by bleomycin in both acute (16 h) and chronic treatments but no sensitivity to killing by other DNA-damaging agents. Complementation studies between this mutant and human fibroblasts suggested that the human gene which corrects the defect of BL-10 rested on human chromosome 6. It has been reported that the gene for human glutathione S-transferase (GST) alpha also resides on chromosome 6. Measurements of selenium-independent peroxidase (alpha-GST + glutathione peroxidase) activity in wild-type Chinese hamster ovary (CHO) cells, using cumene hydrogen peroxide as a substrate, gave a value of 112 nmol of glutathione oxidized/min/mg protein compared with 88.1 nmol of glutathione oxidized/min/mg protein for BL-10. Measurement of the selenium-dependent peroxidase activity, using H2O2 as a substrate, resulted in 65.9 nmol of reduced glutathione oxidized/min/mg protein in CHO and 81.5 nmol of reduced glutathione oxidized/min/mg protein for BL-10. In other words, BL-10 cells did not exhibit a difference in their ability to metabolize both substrates in contrast to CHO cells. This indicates that BL-10 possesses little alpha-GST activity. Transfection of BL-10 cells with a mammalian expression vector containing the alpha-GST gene increases the survival of BL-10 to bleomycin and does not increase the bleomycin resistance of two other bleomycin mutants which lie in different genetic complementation groups. These data strongly implicate a role for alpha-GST in the resistance of cells to bleomycin.
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PMID:The hypersensitivity of the Chinese hamster ovary variant BL-10 to bleomycin killing is due to a lack of glutathione S-transferase-alpha activity. 171 44

The relation among glutathione-related enzyme activities, thiobarbituric acid-reactive substances of the human aorta and internal mammary artery, and serum lipids was studied in 40 male patients undergoing coronary revascularization. Glutathione peroxidase and glutathione reductase activities were significantly higher in the internal mammary artery, whereas glutathione transferase activity was elevated in the aortic wall. Moreover, non-selenium-dependent glutathione peroxidase activity was detectable only in the aorta. The levels of thiobarbituric acid-reactive substances were significantly higher in the aorta. A positive correlation was found among the activity of glutathione peroxidase, glutathione reductase, and thiobarbituric acid-reactive substances in the internal mammary artery and total cholesterol, low density lipoprotein cholesterol, and triglycerides. In the aortic wall, a positive correlation among the activity of glutathione peroxidase, glutathione transferase, thiobarbituric acid-reactive substances, and the previously mentioned serum lipids was evident. In contrast, high density lipoprotein cholesterol was inversely related to enzymatic activities and thiobarbituric acid-reactive substances in both the internal mammary artery and aorta. In conclusion, significant differences in the levels of glutathione-related enzyme activities and thiobarbituric acid-reactive substances in the internal mammary artery and aorta were found, suggesting a different ability of the two tissues to counteract oxidative stress: the glutathione-related antioxidant properties and the level of lipid peroxidation in the arterial tissue seem to be specifically influenced by serum lipids.
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PMID:Glutathione-related enzyme activities and lipoperoxide levels in human internal mammary artery and ascending aorta. Relations with serum lipids. 173 63

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

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


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