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 cytotoxicity of 8 natural dyes, commercially available as food additives in Japan, was studied on cultured fetal rat hepatocytes. Laccaic acid, one of the carminic acid samples and monascus pigments were found to be very toxic to cultured hepatocytes. Laccaic acid caused an increase in gamma-glutamyl transpeptidase activity. An 11-fold increase was seen 4 days after such addition, a significantly greater elevation than that produced by either the water or acetone solvents employed, or other dyes which have no toxic effects. On the other hand, monascus pigments had an increasing effect on both gamma-glutamyl transpeptidase and glutathione S-transferase, the later enzyme being elevated approximately 9 times greater than control values within 2-4 days. The increases in gamma-glutamyl transpeptidase and glutathione S-transferase activities by laccaic acid and monascus pigments could be inhibited by the simultaneous addition of either actinomycin D or cycloheximide. This suggests that the induction of these enzymes requires transcription and translation processes.
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PMID:Induction of gamma-glutamyl transpeptidase and glutathione S-transferase in cultured fetal rat hepatocytes by laccaic acid and monascus pigments. 613 34

4-Tertiary butyl catechol (TBC) causes depigmentation in humans and animals and stimulates formation of pheomelanosomes. In this study, we investigated the effects of noncytotoxic doses of TBC on glutathione S-transferase (GST) activity in the skin of Uscd strain mice and B16 murine melanoma cells in culture, in relation to changes in activities of glutathione reductase (GR) and gamma-glutamyl transpeptidase (GGT) reported to be involved in pheomelanogenesis. Occurrence of pheomelanosomes in skin melanocytes was demonstrated by electron microscopy and reduction (25%) of eumelanin content in melanoma cells was shown by spectrophotometry. Topical application of 1 M TBC-DMSO-acetone solution on the ear skin elevated GST activity about 27%, and activities of GGT and GR to 35% and 19%, respectively, within 1 week. Melanoma cells cultured in 10(-4) M TBC-containing medium for 2 h showed no changes in GST and GGT activities, but 12% increase of GR activity during the first 12 h. Activities of all 3 enzymes was elevated (11-17%) 24 h later. The elevation detected by 48 h was 25% for GST, 26% for GGT, and 14% for GR. The findings were interpreted to show that depigmentation produced by the antioxidant results from stimulated pheomelanogenesis through activation of glutathione-metabolizing enzymes and suppressed oxidation of eumelanin intermediates.
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PMID:Effects of 4-tertiary butyl catechol on glutathione-metabolizing enzymes in vivo and in vitro. 614 Feb 89

Effects of an antioxidant, butylated (3-tert-butyl-4-) hydroxyanisole (BHA) on the induction of specific molecular forms of glutathione S-transferase (GST), UDP-glucuronyltransferase (UDP-GT) and other glutathione-related enzymes in rat liver were investigated. The development of gamma-glutamyl transpeptidase (gamma-GTP)-positive foci and hyperplastic nodules induced by diethylnitrosamine, 200 mg/kg i.p., followed by 0.02% N-2-fluorenylacetamide (FAA) in diet plus partial hepatectomy was inhibited by the administration of 0.75% BHA in the FAA-containing diet. Inhibition was reflected in decreased area of gamma-GTP-positive foci which correlated with a decrease in gamma-GTP activity measured biochemically. Under the present experimental conditions, total activities of GSTs, especially that of GST-A form, and of UDP-GTs, especially that of the late fetal form (o-GT), were markedly increased, together with glutathione levels in the whole liver, within one week after BHA administration. Without BHA administration the activities of GST-A and o-GT, as well as glutathione levels, were also increased by FAA treatment, primarily localized within gamma-GTP-positive foci. These results suggest that the induction of specific molecular forms of detoxicating enzymes either in enzyme-altered foci or in the whole liver may play an important role in determining the extent of development of preneoplastic nodules from initiated foci under the short term induction conditions used.
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PMID:Induction by butylated hydroxyanisole of specific molecular forms of glutathione S-transferase and UDP-glucuronyltransferase and inhibition of development of gamma-glutamyl transpeptidase-positive foci in rat liver. 614 73

Whole tissue reduced glutathione (GSH) concentration was found to be lowest in rabbit renal inner medulla and progressively higher in outer medulla and cortex. Activities of cytosolic glutathione reductase in inner medulla and outer medulla were similar, and each was only approximately 50% of that of cortex. Whole tissue and microsomal gamma-glutamyl transpeptidase activities were high in cortex and outer medulla but were low in inner medulla. Cytosolic activity of selenium-dependent glutathione peroxidase ( GPx -I) was similar in both outer medulla and inner medulla but was only 50% of that of cortex. Activity of cytosolic selenium-independent glutathione peroxidase ( GPx -II) was highest in cortex and lowest in inner medulla (approximately 15% of cortex and approximately 50% of outer medulla). Cytosolic glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene as substrate was high in all three regions of kidney. With 1,2-dichloro-4-nitrobenzene and 1,2-epoxy-(4-nitrophenoxy)propane as substrates, cytosolic glutathione S-transferase activities were very low in cortex, outer medulla, and inner medulla. Microsomal activities of glutathione reductase, GPx -I, GPx -II and glutathione S-transferases were much lower than activities of corresponding cytosolic enzymes. Activities of the glutathione peroxidases in renal inner medulla would hence be expected to cause little interference to prostaglandin endoperoxide synthetase mediated cooxidative activation of paracetamol. It has been demonstrated that the paracetamol metabolite can react rapidly with GSH, forming not only glutathione conjugate but also paracetamol itself and oxidized glutathione. Low GSH concentrations, as well as low activities of glutathione reductase, GPx -I, GPx -II, and gamma-glutamyl transpeptidase, may therefore render the inner medullary region of kidney particularly vulnerable to paracetamol-related analgesic nephropathy.
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PMID:Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney. Possible implications in analgesic nephropathy. 614 22

A comparative study of reduced glutathione (GSH) concentrations and activities of GSH related-enzymes in urinary bladder transitional epithelium (UBTE), urinary bladder nontransitional tissue (UBNT), and liver of the rabbit, was carried out to investigate the reasons for the susceptibility of UBTE towards peroxidase-mediated chemical carcinogenesis. Cooxidative activation of chemical carcinogens by prostaglandin H synthase occurs at high levels in UBTE and minimally in UBNT. Other peroxidases are also likely to activate carcinogenic xenobiotics in the urinary bladder. GSH concentrations in UBTE and UBNT were low compared to that in the liver. gamma-Glutamyl transpeptidase activities were much lower in UBTE and in UBNT than those in the liver. Activities of selenium-dependent and selenium-independent glutathione peroxidases were very low in UBTE and UBNT. Cytosolic glutathione S-transferase activity towards 1,2-epoxy-(4-nitrophenoxy)propane was very low in UBTE. Microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene was much lower in UBTE than in the liver. We propose that the low GSH concentration and diminished activities of glutathione peroxidases, gamma-glutamyl transpeptidase, and certain isozymes of glutathione S-transferase could be responsible for the vulnerability of UBTE towards chemical carcinogenesis.
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PMID:Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. 614 17

Changes in molecular forms of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDP-GT) as hepatic detoxicating enzymes were investigated during chemical hepatocarcinogenesis in the rat. The activity and the protein amount (formula; see text) itself of the GST-A form, which has fetal characteristics and is separable from other forms by CM-Sephadex column chromatography and by immunologic techniques, was much increased in gamma-glutamyl transpeptidase (gamma-GTP)-positive foci or hyperplastic nodules (HNs) induced by diethylnitrosamine and 2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene. The activity of enzyme 1 (late fetal form) of UDP-GT assayed with o-aminophenol (o-GT) also increased with increased number of the foci or HNs, while the activity of enzyme 2 (neonatal form) assayed with phenolphthalein (p-GT) changed but little. The foci and HNs were stained more strongly than the nonnodular areas immunohistochemically using the antibody against purified GST-A or o-GT. The two activities were also increased in well-differentiated hepatomas, but they were decreased in moderately and poorly differentiated hepatomas, and activating enzymes such as cytochrome P-450 were markedly decreased from HN. GST-A and o-GT differ from fetal enzymes such as those of carbohydrate metabolism in that they are inducible in the short-term by drugs, including carcinogens, and they show the highest activities in HNs, and so they may be considered as hepatic preneoplastic (PN) antigens.
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PMID:Molecular forms of glutathione S-transferase and UDP-glucuronyltransferase as hepatic preneoplastic marker enzymes. 642 25

Five different dose levels of 2-acetylaminofluorene (2-AAF) were fed to weanling mice of 4 different genotypes from three unrelated F1 hybrids for 13 wk to determine differences in susceptibility to induction of bladder hyperplasia. Differences in the prevalence of hyperplasia per se and in the average grade of hyperplasia were interpreted as indicating greater susceptibility. On this basis, males of all genotypes were more susceptible than females. Among the genotypes, (AEX YS)F1 mice (AY) were most susceptible, followed closely by yellow A vy/A(BALB/cXVY)F1 mice (CV). Agouti A/a(BALB/cXVY)F1 mice were less susceptible than their yellow siblings and similar to the (C57BL/6XC3H)F1 mice. Neither body weight gain nor any of the biochemical parameters measured appeared to be affected at any dose level of 2-AAF. However, quantitative differences in several biochemical characteristics were detected among the genotypes. Serum gamma-glutamyl transpeptidase activity was higher in the AY mice than in the other hybrids. Among the CV mice, the yellow animals had lower glutathione S-transferase (GST) activity than their agouti siblings. Hepatic GST activity was lower in CV mice than in either of the other hybrids. Hepatic cytochrome P-450 and bs activities were similar in all hybrids.
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PMID:Controlled genetic variation in a subchronic toxicity assay: susceptibility to induction of bladder hyperplasia in mice by 2-acetylaminofluorene. 665 34

The present study was designed to examine changes in glutathione metabolism in the liver of mice as influenced by supplementation of their diet with 1 of 4 antioxidants: butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin E and selenium. In addition to determination of the acid-soluble thiol levels, 5 different enzymes involved with glutathione utilization and synthesis were measured: glutathione transferase, gamma-glutamyl transpeptidase, selenium-dependent glutathione peroxidase, gamma-glutamylcysteine synthetase and glutathione reductase. All 4 antioxidants produced significant increases in glutathione transferase activity, with BHA and BHT being much more effective than the other two. With the exception of vitamin E, BHA, BHT and selenium all resulted in a slight enhancement in the activity of glutathione reductase as well as in the acid-soluble thiol level. On the other hand, the induction of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase was responsive to only vitamin E and selenium supplementation, respectively. Although the influence of each of these antioxidants in glutathione metabolism appears to be specific and somewhat compartmentalized, the overall impression is that of an increased capacity for glutathione-conjugate formation and recovery of reduced glutathione. These biochemical changes in glutathione metabolism may be relevant to the anticarcinogenic effects observed with BHA, BHT and selenium.
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PMID:Comparative effects of antioxidants on enzymes involved in glutathione metabolism. 672 79

Age and sex differences in the hepatic glutathione level and related enzyme activities in rats of both sexes were investigated. At 7 weeks of age there was no significant difference in GSH levels between males and females, although a higher level of intracellular GSH was observed in male rats at 12 weeks of age. Hepatic gamma-glutamyl transpeptidase activities were significantly higher in females than in males at only 7 weeks of age. Glutathione peroxidase showed higher activities in females than in males. Conversely, glutathione S-transferase, glutathione reductase and glutathione synthesis rates were markedly higher in males than in females.
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PMID:Sex-related difference in the hepatic glutathione level and related enzyme activities in rat. 684 36

Glutathione and its related enzymes play a major role in the detoxification of toxic chemicals. In rat brain the pattern of distribution of reduced glutathione exhibits cellular heterogeneity, suggesting also the possibility of cellular differences in glutathione conjugating capacity. To understand the potential role of GSH in detoxification of neurotoxicants, the distributions of the glutathione conjugating and metabolizing enzymes, glutathione S-transferase (GST; alpha-, mu- and pi-classes) and gamma-glutamyl transpeptidase (gamma-GT) were determined immunohistochemically in brain, lumbar spinal cord and dorsal root ganglia (DRG) of adult Sprague-Dawley rats using polyclonal antibodies. The influence of tissue fixation on apparent distribution was also examined. Glial cells and neurons throughout the nervous system were only weakly positive with alpha-GST in frozen sections. No immunoreactivity for the alpha-class GSTs was observed in any of the paraformaldehyde-fixed neural specimens examined. In microwave-fixed frozen sections, immunoreactivity to mu-GST was found in astrocytes and neurons throughout the brain and spinal cord, and in the neurons and satellite cells of the DRG. Immunoreactivity for pi-GST was seen in oligodendrocytes but not in astrocytes in any region of the CNS examined. Similarly, satellite cells of the DRG were positive for pi-GST. Neuronal perikarya of the entire neopallium, hippocampus, cerebellum, brainstem, spinal cord and DRG were also positively stained for pi-GST. The differential staining of astrocytes and oligodendrocytes with pi- and mu-GST was unaltered in paraformaldehyde fixed tissues, but the neuronal immunostaining was lost. The ependyma, pia and choroid plexus stained positively with all three GST antibodies regardless of fixation. Gamma-Glutamyl transpeptidase-like immunoreactivity was confined to non-neuronal elements of both central and peripheral nervous systems. Ependymal cells throughout the central nervous systems stained intensely with antibodies directed against gamma-GT. Satellite and Schwann cells of the DRG and glial cells of the spinal cord and brain exhibited moderate to intense immunoreactivity for gamma-GT. The heterogeneous cellular distribution of glutathione and its metabolizing enzymes may reflect cellular differences in capacity for metabolic processing of both endogenous compound and xenobiotics.
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PMID:Glutathione S-transferases and gamma-glutamyl transpeptidase in the rat nervous systems: a basis for differential susceptibility to neurotoxicants. 756 94


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