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 effect of glutathione depletor diethylmaleate on rat hepatic glutathione S-transferase and glutathione peroxidase was studied in vivo and in vitro. When diethylmaleate (600 mg/kg) was given i.p. to rats, liver glutathione was depleted within 2 h and recovered to the control level 5 h after diethylmaleate treatment. Both glutathione S-transferase and peroxidase activities in microsomes, not in cytosol, were markedly increased during glutathione depletion and only glutathione S-transferase activity remained at high levels after recovery of the glutathione content. The increase in microsomal glutathione S-transferase and peroxidase activities with concomitant exhaustion of glutathione was also observed by perfusion of the isolated liver with diethylmaleate (10 mM). When liver microsomes were incubated with diethylmaleate in vitro at 37 degrees C, glutathione S-transferase, but not peroxidase, activity was increased; the increase was not reversed by dithiothreitol. These results indicate that diethylmaleate activates microsomal glutathione S-transferase by direct reaction to the enzyme during glutathione depletion and suggest that glutathione S-transferase activity and glutathione peroxidase activity in the microsomal enzyme may be differently regulated.
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PMID:Activation of hepatic microsomal glutathione S-transferase of rats by a glutathione depletor, diethylmaleate. 128 82

Nuclear cataract formed in rat lens in response to a protocol of multiple, low doses of sodium selenite. Nuclear cataract occurred, in both Wistar and Sprague-Dawley rats, following five subcutaneous injections of selenite over an 8-day period with an accumulated dose of 40-50 nmol selenite g-1 body weight. Glutathione content decreased within the first 24 hr of treatment and remained at 60% of controls. Lipid peroxidation occurred in Wistar rats prior to nuclear cataract formation. A two to three-fold increase in calcium concentration and decreased protein content accompanied nuclear cataract development. Enzyme activities were measured for glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and only the peroxidase activity remained constant through the period of cataract formation. This protocol resulted in nuclear cataracts similar in appearance to those observed with a single, acute dose of selenite. The opportunity to control the rate of selenite-dependent cataract formation allows further definition of precataractous events.
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PMID:Biochemical changes and cataract formation in lenses from rats receiving multiple, low doses of sodium selenite. 147 77

We have previously demonstrated that geniposide (GP) inhibits the aflatoxin B1 (AFB1) induced-hepatotoxicity and hepatic DNA binding in rats. To address the mechanism of action, the effects of GP on AFB1-induced DNA repair synthesis and AFB1 biotransformation in cultured rat hepatocytes were investigated. By evaluation of unscheduled DNA synthesis (UDS), GP reduced AFB1-induced DNA repair synthesis in a dose-dependent manner in hepatocyte cultures. GP elevates the metabolism of AFB1 and decreases the formation of AFM1. The enzyme activities of glutathione S-transferase (GST) and GSH-peroxidase (GSH-Px) in AFB1-treated hepatocyte cultures are enhanced in the presence of GP. GP reduces AFB1-induced DNA repair synthesis through an increased AFB1 detoxication metabolism. It provides one possible mechanism for the chemopreventive activity of GP.
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PMID:Inhibitory effect of geniposide on aflatoxin B1-induced DNA repair synthesis in primary cultured rat hepatocytes. 151 17

Studies were undertaken to investigate the effect of t-butylated hydroxytoluene (BHT) on reduced glutathione (GSH) levels and related enzymes in rat ocular tissues. GSH levels were significantly enhanced when 1 microM BHT was included in the medium of rat lens cultures. BHT had a dose-dependent effect on GSH levels of lenses in cultures. Inclusion of 10 microM BHT in the culture medium resulted in a twofold increase in GSH levels of the lens within 24 hr. Increased gamma-glutamylcysteine synthetase activity concomitant with the increased amount of [35S]methionine incorporation in GSH strongly suggested that BHT caused enhanced levels of GSH in lenses by increasing de novo biosynthesis. A significant increase was also observed in glutathione S-transferase (GST) levels of lenses in culture containing BHT in the medium. Present studies also demonstrated that rat lens expresses only the mu and pi class GST isoenzymes and both these classes of isoenzymes were elevated by BHT. Oral administration of BHT to rats also resulted in enhanced in vivo levels of GSH in lens, retina and cornea. In addition, a significant in vivo increase in the levels of GST, GSH-peroxidase, GSH-reductase, gamma-glutamylcysteine synthetase, and glucose 6-phosphate dehydrogenase was observed in the lens, retina, and cornea of BHT-fed rats.
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PMID:t-butylated hydroxytoluene enhances intracellular levels of glutathione and related enzymes of rat lens in vitro organ culture. 154 39

The expression of glutathione transferase pi (GST pi) was studied in leukemic cells from 60 patients with acute nonlymphoblastic leukemia at diagnosis and at progressing stages of the disease. A polyclonal rabbit antibody to human placental GST pi coupled with peroxidase antiperoxidase staining was used for immunodetection of GST pi on sections of routinely fixed bone marrow clots. All patients had received induction therapy based on an anthracycline and a standard dose of ara-C. The expression of GST pi at diagnosis was significantly correlated with response to induction therapy, duration of first remission, and overall survival. Twenty-nine of 36 samples of bone marrow from patients that entered complete remission (CR) following primary induction therapy showed a low expression, whereas nine of 16 sections from patients with resistant disease showed a high expression of GST pi (P less than or equal to 0.03). Of 40 sections that showed a low expression of GST pi, 29 (73%) were taken from patients that achieved a CR, whereas 12 of 19 sections that showed a high expression of the enzyme were from patients with resistant disease or that entered CR only after additional therapy (P less than or equal to 0.02). The median duration of first CR was 18.2 mo for patients whose cells showed a low expression of GST pi compared with 6.7 mo for those that entered CR in spite of a high expression of the enzyme (P less than or equal to 0.005). Of cells from ten patients that at the time of study were in a continuous first CR, none expressed high concentrations of GST pi. The expression of GST pi remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GST pi and treatment results but, of ten patients that entered a second CR or achieved a partial remission, only one showed a high expression of the enzyme. We conclude that there was a significant correlation between the expression of GST pi at the time of diagnosis and the subsequent treatment results and that GST pi is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia.
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PMID:Expression of glutathione transferase pi as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia. 159 86

White suckers (Catostomus commersoni) are one of two species of bottom-feeding fish in which various liver neoplasms are more prevalent in urban/industrial sites in western Lake Ontario than in less polluted sites in the Great Lakes. Previous studies indicate that white suckers excrete metabolites of various polycyclic aromatic hydrocarbons (PAHs) in bile, and that glutathione transferase (GST)-mediated conjugation is a major detoxification pathway for the PAH benzo[alpha]pyrene. To determine whether hepatocarcinogenesis in these wild fish is associated with induced GST-dependent resistance to carcinogens, we examined the expression of immunoreactive GSTs in liver neoplasms and putatively preneoplastic altered hepatocellular foci from white suckers collected from several polluted sites in western Lake Ontario. Histological sections of liver with altered hepatocellular foci, hepatocellular adenomas, hepatocellular carcinomas, bile duct adenomas and bile duct carcinomas were examined for GST immunoreactivity by the peroxidase-antiperoxidase (PAP) technique with polyclonal antiserum specific for all major GST isoenzyme subunits found in normal liver of white suckers. All bile duct adenomas, bile duct carcinomas and hepatocellular carcinomas were markedly or completely deficient in immunoreactive GST in comparison with surrounding normal hepatocytes. The majority of the hepatocellular adenomas were also deficient. Most altered hepatocellular foci had normal GST staining, but several GST-deficient altered hepatocellular foci were observed. However, none of the preneoplastic or advanced liver neoplasms expressed induced GST, suggesting that carcinogenesis is not associated with selection for GST-dependent resistance. Loss of hepatocellular GSTs may be incidental to neoplastic progression in these fish, or might be important in increasing susceptibility of some preneoplastic populations of hepatocytes to further DNA damage by environmental or endogenous chemicals that are normally detoxified by GSTs.
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PMID:Loss of glutathione S-transferases in pollution-associated liver neoplasms in white suckers (Catostomus commersoni) from Lake Ontario. 166 Jul 92

Using the antibody for glutathione S-transferase (GST) purified from human kidney, normal testes and experimental cryptorchid testes from newborn to 20-week-old rats were immunohistochemically stained by the peroxidase antiperoxidase (PAP) method. The cryptorchidism was surgically created at 1 week of age. The localization of GST was particularly examined by light microscopy, and the amount of Leydig cells was measured by a stereological method. 1. Leydig cells in the normal and cryptorchid testes showed strong GST activity at all ages. The amount of these cells in normal testes increased from 4 to 8 weeks of age and then slightly decreased, whereas in cryptorchid testes it was significantly larger than in the normal testes at 20 weeks of age, indicating hyperplasia of Leydig cells. 2. In the normal and cryptorchid testes, degenerating primary spermatocytes with GST activity appeared in the seminiferous tubules at 2 to 4 weeks of age. In the cryptorchid testis, degenerating germ cells with GST activity were also found in the regressing seminiferous tubules after 4 weeks of age. It is possible that GST acts as a detoxification system in the degenerating germ cells. 3. The PAP staining of GST in the rat testes is considered to be useful method for evaluating metabolic function of the spermatogenic cells and the distribution and amount of Leydig cells. 4. Experimental cryptorchidism showed that germ cells become sensitive after 4 weeks of age.
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PMID:[Immunohistochemical study of glutathione S-transferase in normal and experimental cryptorchid testes rats]. 167 96

Using the antibody for glutathione S-transferase (GST) purified from the human kidney, the normal testes and experimental cryptorchid testes from newborn to 20 weeks-old rats were immunohistochemically stained by the peroxidase antiperoxidase (PAP) method. The cryptorchidism was surgically created at 1 week of age by cutting the gubernaculum testis. The localization of GST were particularly examined by light microscopy, and the amount of Leydig cells were measured by a stereological method. 1. Leydig cells in the normal and cryptorchid testes showed strong GST activity at all ages. The amount of these cells in normal testes increased from 4 to 8 weeks of age and then slightly decreased, whereas in cryptorchid testes it was significantly larger than in the normal's at 20 weeks of age, indicating hyperplasia of Leydig cells. 2. In the normal and cryptorchid testes, degenerating primary spermatocytes with GST activity appeared in the seminiferous tubules at 2 to 4 weeks of age. In the cryptorchid testes, degenerating germ cells with GST activity were also found in the regressing seminiferous tubules after 4 weeks of age. This is a possibility that GST act as a detoxification system in the degenerating germ cells. 3. The PAP staining of GST in the rat testes is considered to be an useful method for evaluating metabolic function of the spermatogenic cells and the distribution and amount of Leydig cells. 4. Experimental cryptorchidism showed that germ cells become sensitive to the abdominal environment after 4 weeks of age.
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PMID:[Immunohistochemical study on glutathione S-transferase in experimental cryptorchid testes in rats]. 168 11

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

Bovine adrenal cortex tissue expresses high levels of glutathione S-transferase (GST) from each of the alpha, mu and pi gene families. We describe the purification and characterization of an abundant alpha-class GST from this tissue that has not been identified previously because of its failure to bind to S-hexylglutathione-Sepharose 6B (S-hexG-Ag). This enzyme has been affinity purified on glutathione-Sepharose 6B (GSH-Ag) and was obtained in a highly purified form by employing S-hexG-Ag to remove the bulk of GST before chromatography on GSH-Ag. The purified GST eluted from GSH-Ag was found to exhibit marked peroxidase and delta 5-ketosteroid isomerase activities (19.2 and 1.67 U/mg respectively). The bovine enzyme also showed high GST activity towards 4-hydroxynonenal (5.09 U/mg). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that the bovine GST contains two distinct polypeptides, one with an Mr of 25,900 and the other with an Mr of 26,500. An abundant alpha-class GST was also purified from human adrenal cortex that possessed properties which were similar to the bovine alpha-class GST described above; however, unlike the bovine enzyme, the corresponding human alpha-class GST bound to S-hexG-Ag. As with the bovine enzyme, the purified human GST displayed marked peroxidase and isomerase activities (27 and 4.02 U/mg respectively). Further analysis on SDS-PAGE (Mr 25,800) and reverse-phase high-performance liquid chromatography established that this abundant alpha-class GST in human adrenal cortex is equivalent to the human liver GST B1B1 enzyme. As both human and bovine adrenal cortex contain high levels of alpha-class GST with similar catalytic properties, we discuss the possible functions of these enzymes in this tissue.
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PMID:Expression of an abundant alpha-class glutathione S-transferase in bovine and human adrenal cortex tissues. 173 63


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