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)

Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.
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PMID:Effects of modifying agents on conformity of enzyme phenotype and proliferative potential in focal preneoplastic and neoplastic liver cell lesions in rats. 133 90

The c14CoS/c14CoS mouse has a homozygous deletion of about 1.2 cM on chromosome 7 that includes the albino (c) locus. The untreated 14CoS/14CoS newborn has been reported to exhibit a marked transcriptional activation of the hepatic NAD(P)H:menadione oxidoreductase (Nmo-1; DT diaphorase; quinone reductase; azo dye reductase) gene, as well as elevated UDP glucuronosyl-transferase (UGT1*06) and glutathione transferase (GT1) activities, when compared with the cch/cch wild-type and the cch/c14CoS heterozygote. We show here that the newborn hepatic activities of seven enzymes that play a role in the oxidative stress response--NMO1, UGT1*06, GT1, copper-zinc superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase--are increased 1.5- to 25-fold in 14CoS/14CoS, as compared with ch/ch and ch/14CoS mice. The activities of four additional enzymes having no known association with the oxidative stress response--benzo[a]pyrene hydroxylase (CYP1A1, cytochrome P(1)450), acetanilide 4-hydroxylase (CYP1A2, cytochrome P(3)450), lactate dehydrogenase (LDH), and NADPH-cytochrome c reductase--are not significantly different among the three genotypes. These data suggest that there exists an "oxidative stress" response in the untreated 14CoS/14CoS newborn. We postulate that a chromosome 7 regulatory gene, which we have named Nmo-1n, might encode a trans-acting negative effector of the Nmo-1 gene, and genes corresponding to the other elevated enzymic activities described above. When both copies of Nmo-1n are deleted, as is the case in 14CoS/14CoS mice, a battery of genes involved in oxidative stress is released from negative control and becomes activated--despite the absence of any apparent oxidative insult by foreign chemicals.
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PMID:"Oxidative stress" response in liver of an untreated newborn mouse having a 1.2-centimorgan deletion on chromosome 7. 154 Jan 61

The effect of age on the glutathione antioxidant system and its acinar distribution in rat liver was studied. GSH/GSSG ratio in blood and liver was lower in old than in young rats. Hepatic glutathione peroxidase and glutathione S-transferase activities were higher in old than in young rats, whereas hepatic gamma-glutamyl transpeptidase activity was lower in old than in young rats. Glutathione reductase and glucose-6-phosphate dehydrogenase activities did not change with age in rat liver. Total glutathione levels and glutathione peroxidase activity were higher in periportal than in perivenous areas of young rats, but this heterogeneous distribution did not occur in old rats. No change with age was found in hepatic zonation of glutathione reductase and glucose-6-phosphate dehydrogenase.
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PMID:Effect of aging on metabolic zonation in rat liver: acinar distribution of GSH metabolism. 156 87

Studies were performed to determine the effects of chronic hypoxia on enzymes that catalyze various detoxication reactions. Rats were exposed to room air or 10.5% O2 for 10 days, and microsomes and postmicrosomal supernatants were isolated from liver. Detoxication enzyme activities were measured by radiochemical and spectrophotometric assays, and immunoreactive protein amounts were measured by Western blot analysis. Total cytochrome P450, as measured by the CO-difference spectrum, and activities of superoxide dismutase (EC 1.15.1.1), epoxide hydrolase (EC 4.2.1.63), catalase (EC 1.11.1.6), glutathione disulfide reductase (EC 1.6.4.2), and glutathione (GSH) S-transferase (EC 2.5.1.18) were not affected by this extent of hypoxia. In contrast, 10 days of hypoxia decreased activities or immunoreactivities (% of aerobic) of GSH peroxidase (EC 1.11.1.9) (54%), cytochrome P450EtOH2 (42%), CYP3A1 (53%), sulfotransferase (EC 2.8.2.1) (77%) and UDP-glucuronosyltransferase (EC 2.4.1.17) (65%). Activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), an important enzyme in NADPH production was also decreased to 56% of the aerobic value, but Western blot analysis showed that the amount of protein reactive with antibodies to glucose-6-phosphate dehydrogenase was not affected by hypoxia. Thus, hypoxia may decrease activity of enzymes by regulatory mechanisms even though the amount of immuno-detectable enzyme is unchanged. Liver cells isolated from rats exposed to hypoxia also gave lower GSH synthetic rates than cells from normoxic rats. This result, together with the effect of hypoxia on glucose-6-phosphate dehydrogenase, indicates that the GSH supply for GSH-dependent detoxication reactions may be limited due to chronic hypoxia. To test directly whether chronic hypoxia increased sensitivity to a compound normally detoxified by a GSH-dependent reaction, sensitivity to tert-butyl hydroperoxide (t-BuOOH) of hepatocytes from rats exposed to in vivo hypoxia was compared to that from normoxic rats. The results showed that the cells from the hypoxic rats were much more sensitive to injury. Taken together, these results suggest that decreases in amounts and/or activities of detoxication enzymes during chronic hypoxia may result in increased susceptibility of cells to chemical injury.
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PMID:Effect of chronic hypoxia on detoxication enzymes in rat liver. 161 Apr 6

1. Interstrain differences in red blood cell enzyme activities were studied in mice (BALB/c, C57BL/6, C3H/He, DBA/2 and ddY) and rats (Donryu, F344/N, SD, Wistar and Wistar/ST), and were also compared with hamster, guinea-pig and rabbit. 2. The enzyme activities measured were: glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD), NADPH-diaphorase (ND), hexokinase (Hx), glutamate oxaloacetate transaminase (GOT), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE). 3. There were marked variations in the activities of some red cell enzymes (e.g. GST, Hx, ND), while others (e.g. G-6-PD, 6-PGD) were much less variable both within different strains and species.
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PMID:Interstrain differences in red cell enzyme activities in mice and rats. 178 55

This study investigated the influence of the location of the sampling site during enzymatic analyses of 31 human term placentae. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase were measured in fetal membranes, umbilical cords and placental disc. The disc samples were obtained from central (peri-insertion and mid-disc fetal and maternal halves), and peripheral regions. Significant variations were found. This study demonstrates the importance of defining the location of the sampling site in studies involving enzymatic analysis of the placenta.
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PMID:Regional variations in the activities of antioxidant enzymes in the term human placenta. 196 20

Glutathione metabolism was studied in isolated hepatocytes from foetal, newborn and adult rats. The GSH/GSSG ratio decreased 15-20-fold through the foetal-neonatal-adult transition. This was mainly due to an increase in GSSG. All enzyme activities involved in the glutathione redox cycle tend to increase during that transition, but the relative increases in glutathione peroxidase and glutathione S-transferase were 3-5 times those of glutathione reductase or glucose-6-phosphate dehydrogenase. GSH synthesis from methionine as a sulphur source was 6 times lower in foetal than in adult hepatocytes. However, when N-acetylcysteine was used as a sulphur donor to by-pass the cystathionine pathway, the rates of GSH synthesis were similar in foetal and adult cells. This is due to the fact that cystathionase activity in foetal cells is very low. This low activity is reflected in the blood amino acid pattern, where the concentration of cysteine rises from 8 to 52 microM from foetuses to adult rats. This supports the idea that cysteine may be an essential amino acid for the premature animal.
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PMID:Physiological changes in glutathione metabolism in foetal and newborn rat liver. 201 16

Lipid peroxide production, antioxidant contents and activities of antioxidative protective enzymes were examined in lungs of rats exposed to clean air (control group), 0.05 ppm O3, 0.05 ppm O3 + 0.04 ppm NO2 and 0.05 ppm O3 + 0.4 ppm NO2 for 22 months. The results were compared with our previous data in rats exposed to 0.04 ppm NO2, 0.4 ppm NO2 and 4 ppm NO2 for their life span (Sagai et al., Toxicol. Appl. Pharmacol., 73, (1984) 444-456). TBA values used as an index of lipid peroxidation in the lungs were increased maximally at 9 months, but were decreased below control values in animals exposed for 18 and 22 months. Nonprotein sulfhydryl (NPSH) contents were increased maximally at 9 months, and after 18 and 22 months were decreased significantly below control values. Vitamin E (VE) contents showed a similar trend. On the other hand, enzyme activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione peroxidase measured by using cumene hydroperoxide (cum.OOH) substrate (GPx-cum.OOH), glutathione peroxidase measured by using H2O2 as a substrate (GPx-H2O2), glutathione S-transferase (GSH-Tase) and superoxide dismutase (SOD) did not show any significant changes during this experiment. The results show that lipid peroxidation in lungs was increased synergistically by a combination of NO2 and O3 at ambient levels, and that the time of maximum lipid peroxide production was shorter than with NO2 alone. The protective ability against lipid peroxides was higher with increased lipid peroxide levels, but the inducibility was not maintained through a life span exposure to the combined gases. Additionally, two small adenomas were observed in 2 out of 18 rats in the 0.05 ppm O3 + 0.04 ppm NO2 group and a large adenoma was observed in 1 out of 18 animals in the 0.05 ppm + 0.4 ppm NO2 group exposed for 22 months.
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PMID:Biochemical effects of combined gases of nitrogen dioxide and ozone. IV. Changes of lipid peroxidation and antioxidative protective systems in rat lungs upon life span exposure. 201 15

Two paraquat-resistant clones, PR-1 and PR-2, were selected from CHO K1 cells pretreated with ethyl methanesulfonate. PR-1 and PR-2, routinely cultured in a normal medium without paraquat, were six fold more resistant to paraquat than the parental CHO K1 cells. There was no difference in the uptake of [3H]paraquat among PR-1, PR-2, and CHO K1 cells. Both PR-1 and PR-2 cells showed no cross resistance to free radical generating agents and no increase in total activity of superoxide dismutase. The activities of paraquat-dependent NADPH oxidase and glucose-6-phosphate dehydrogenase were significantly reduced in PR-1 and PR-2 cells, hence the rate of paraquat radical formation will be limited. In addition, an elevation of glutathione levels in PR-1 cells or an increase in glutathione S-transferase activity in PR-2 cells may also play a certain role in protective mechanisms against the toxicity of paraquat.
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PMID:Paraquat-resistant cell lines derived from Chinese hamster ovary cells. 216 Aug 62

Free radicals are found to be involved in both initiation and promotion of multistage carcinogenesis. These highly reactive compounds can act as initiators and/or promoters, cause DNA damage, activate procarcinogens, and alter the cellular antioxidant defense system. Antioxidants, the free radical scavengers, however, are shown to be anticarcinogens. They function as the inhibitors at both initiation and promotion/transformation stage of carcinogenesis and protect cells against oxidative damage. Altered antioxidant enzymes were observed during carcinogenesis or in tumors. When compared to their appropriate normal cell counterparts, tumor cells are always low in manganese superoxide dismutase activity, usually low in copper and zinc superoxide dismutase activity and almost always low in catalase activity. Glutathione peroxidase and glutathione reductase activities are highly variable. In contrast, glutathione S-transferase 7-7 is increased in many tumor cells and in chemically induced preneoplastic rat hepatocyte nodules. Increased glucose-6-phosphate dehydrogenase activity is also found in many tumors. Comprehensive data on free radicals, antioxidant enzymes, and carcinogenesis are reviewed. The role of antioxidant enzymes in carcinogenesis is discussed.
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PMID:Free radicals, antioxidant enzymes, and carcinogenesis. 219 55


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