Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were performed to investigate the effects of 60 min severe global ischemia followed by 30 min reperfusion on the antioxidant enzymatic system in the isolated perfused rat heart. Ischemia induced a significant increase of cytoplasmic and mitochondrial selenium-dependent glutathione peroxidase (EC 1.11.1.9) activity. In reperfused hearts, only the mitochondrial form showed a further significant increase. Glutathione reductase (EC 1.6.4.2) was increased in ischemic hearts, whilst the reperfused hearts showed a decrease towards the level found in aerobic hearts. Mitochondrial superoxide dismutase (EC 1.15.1.1) activity was depressed in ischemic as well as in reperfused hearts, though the cytoplasmic form was unmodified. Catalase (EC 1.11.1.6), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and glutathione transferase (EC 2.5.1.18) activities were unchanged throughout the experiment. Ischemia and reperfusion induced a significant fall in tissue-reduced glutathione content concomitant with an increase of its oxidized form. We have also studied the mitochondrial inner membrane proteins for both molecular weight, with Coomassie blue, and thiol status, with monobromobimane stain, using a sodium dodecyl sulfate polyacrylamide gel electrophoresis technique. Neither ischemia nor reperfusion effected any relevant modification of the molecular weight of the mitochondrial inner-membrane proteins either in the presence or absence of a reducing agent. However, two of these proteins with an apparent molecular weight of 52,0000 and 12,000 showed a decrease in the monobromobimane stain, probably due to the oxidation of their thiol groups.
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PMID:Effect of ischemia and reperfusion on antioxidant enzymes and mitochondrial inner membrane proteins in perfused rat heart. 338 95

Periportal and perivenous hepatocytes were isolated by the digitonin-collagenase perfusion technique. The activity of the cytosolic glutathione S-transferase was higher in perivenous cells, but the cytosolic glutathione reductase and the microsomal glutathione S-transferase activities were evenly distributed. In contrast, both the Se-dependent and the microsomal Se-independent glutathione peroxidase activity and the glucose-6-phosphate dehydrogenase activity was much lower in perivenous hepatocytes, suggesting that these cells have a lowered detoxification capacity, which may contribute to their greater susceptibility to damage by xenobiotics. The mechanism of the ethanol-induced GSH depletion in vivo was studied by incubating conventionally isolated hepatocytes. In the absence of glutathione precursors, ethanol (80 mM) did not influence the GSH content, despite accumulation of acetaldehyde (10-100 MicroM). L-Methionine or L-cysteine stimulated GSH replenishment to in vivo rates. Ethanol oxidation resulted in acetaldehyde accumulation, but did not inhibit GSH replenishment from L-methionine and even stimulated that from L-cysteine. This seems to exclude conjugation of GSH with acetaldehyde as a mechanism by which ethanol suppresses GSH levels in vivo.
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PMID:Glutathione metabolism in isolated rat hepatocytes: acinar heterogeneity of detoxifying enzymes and effects of ethanol. 342 86

The acinar distribution of glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G-6-PDH) was examined by analyzing periportal (p.p.) and perivenous (p.v.) rat hepatocytes selectively isolated by the digitonin-collagenase perfusion. The cytosolic GST activity was higher in p.v. cells, but the microsomal GST and cytosolic GR were found to be evenly distributed in the acinus. In contrast, the activity of both the Se-dependent GPx and the microsomal (Se-independent) GPx, as well as G-6-PDH, was much lower in the p.v. than in the p.p. cells. The heterogeneous distribution of GST, GPx and G-6-PDH was confirmed by analyzing liver perfusion effluents collected after ante- or retrograde digitonin infusion. The relatively low activities of GPx and G-6-PDH in the p.v. cells could partly explain the susceptibility of this region to chemical injury.
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PMID:Acinar distribution of glutathione-dependent detoxifying enzymes. Low glutathione peroxidase activity in perivenous hepatocytes. 359 5

The effect of (1-benzoyl-1H-indazol-3-yl)oxylacetate L-Lysine (bendazac-lysine) on some enzymatic activities involved in the metabolism of reduced glutathione (GSH) was studied in the rabbit lens during developing cataract induced by a single dose of X-rays (2000 rads). The specific activities of glutathione reductase (G.R.), glutathione peroxidase (GSH.Px) and glutathione S-transferase (GSHS-tr.) do not change following irradiation and treatment with bendazac-lysine. The activity of the same enzymes expressed as a function of water soluble proteins (WSP) per lens significantly decreases (P less than 0.01) as compared to controls in the irradiated lens not treated with bendazac-lysine (ILNTB) at the 8th week, whereas no significant decrease as compared to controls is observed in the irradiated lens treated with bendazac-lysine (ILTB). In the ILNTB the specific activity of glucose-6-phosphate dehydrogenase (G6PDH) is reduced by 10% after 0.3 weeks and by 29% after 12 weeks. In the ILTB the specific activity of G6PDH is reduced by 8% after 0.3 weeks and by 14.5% after 12 weeks. The specific activity of superoxide dismutase (SOD) in the ILNTB is reduced by 19% after 0.3 weeks and reached 31% after 12 weeks. In the ILTB the specific activity of SOD is reduced by 11% after 0.3 weeks and 19.8% after 12 weeks. The mechanism of protective effect of bendazac-lysine on cataract is discussed.
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PMID:Effects of bendazac L-lysine salt on some metabolic enzymes of glutathione in the rabbit lens after X-irradiation. 361 May 98

We found that Adriamycin increased the pentose phosphate shunt activity in both Adriamycin-sensitive (WT) and Adriamycin-resistant (ADRR) human breast cancer MCF-7 cells. In contrast, hydrogen peroxide and cumene hydroperoxide markedly stimulated pentose-shunt activity in ADRR but only moderately increased the activity in WT cells. Furthermore, the altered oxidation-reduction regulation is associated with changes intrinsic to the key enzymes of the pentose-shunt pathway, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase and with glutathione peroxidase. We found the Vmax values for glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were 50- and 4-fold lower, respectively, in ADRR than WT cells and the Kms of NADP+ were 10-fold lower in ADRR than WT. The activity of glutathione reductase in ADRR is 42% of that in WT. In spite of these changes, the response of the cells to both hydrogen peroxide and organic peroxide is not limited by either the capacity of the pentose shunt or glutathione reductase, but is determined by the activity of glutathione peroxidase and a glutathione transferase which possess peroxidase activity. The kinetic properties of the glucose-6-phosphate dehydrogenase in ADRR may, however, seriously limit the activity of cytochrome P-450 reductase, a major enzyme of Adriamycin conversion to a free radical.
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PMID:Adriamycin resistance in human tumor cells associated with marked alteration in the regulation of the hexose monophosphate shunt and its response to oxidant stress. 366 3

The activity of antioxidative enzymes SOD, catalase, glutathione peroxidase and the related glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase was examined in liver cytosol and large granule fraction (mitochondria) from control and copper-loaded rats. An increase of SOD activity (more than 100%) and a decrease of both catalase (by 60%) and glutathione peroxidase activity (by 30%) in large granule fraction were observed after copper loading. The cytosolic glutathione peroxidase activity was also markedly decreased: glutathione peroxidase I (EC 1.11.1.9)--by 35% and glutathione peroxidase II (EC 2.5.1.18)--by 75%. Cytosolic catalase activity and the glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase activities in cytosol and in mitochondria of copper-loaded rats were unchanged. It is concluded that under chronic copper loading the primary mechanisms of copper toxicity are accompanied by disturbances of the antioxidative enzyme function.
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PMID:Effect of chronic copper loading on the activity of rat liver antioxidative enzymes. 375 26

The effects of dietary administration of 3,5-di-tert-butyl-4-hydroxytoluene (BHT), 2(3)-tert-butyl-4-hydroxyanisole (BHA), ethoxyquin (EQ) and 5-(2-pyrizinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) on aflatoxin B1 (AFB1) - DNA adduct formation in vivo in livers and kidneys of rats were investigated. Male F344 rats were treated with 1 mg/kg AFB1 by i.p. administration and nucleic acids isolated 2 h post dosing. Animals were fed a semipurified diet supplemented with either 0.5% EQ, 0.45% BHT, 0.45% BHA or 0.1% oltipraz for 2 weeks prior to AFB1 treatment. Analysis of nucleic acid bases by h.p.l.c. showed that several AFB1 metabolite-DNA adducts were formed in both tissues. The principal and related adducts of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 represented approximately 80-90% of all adducts in both tissues and in all treatment groups. However, inclusion of the antioxidants in the diet resulted in substantial reductions in overall AFB1 modified DNA levels. EQ, BHT, BHA and oltipraz reduced the covalent binding of AFB1 to liver DNA by 91, 85, 65 and 76% and to kidney DNA by 80, 35, 62 and 64%, respectively. Concordantly, the specific activities of hepatic enzymes of presumed importance to AFB1 detoxification, epoxide hydrase, and glucuronyl and glutathione transferases were significantly elevated by all antioxidants. Reduced glutathione levels were unchanged except by oltipraz, although activities of enzymes contributing to the maintenance of reduced glutathione pools, glutathione reductase and glucose-6-phosphate dehydrogenase, were elevated in most treatment groups. An excellent correlation (r = 0.95) was observed between the degree of inhibition of DNA binding by AFB1 and the induction of hepatic glutathione S-transferase activities by the four antioxidants.
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PMID:Modification of aflatoxin B1 binding to DNA in vivo in rats fed phenolic antioxidants, ethoxyquin and a dithiothione. 392 31

Phenylhydrazine when injected into the mouse acts in two phases. At an early stage it provokes directly in the erythrocytes as well as in the liver a decrease in the concentration of acid soluble nonprotein thiol groups. Indirectly it causes a later and more lasting increase in glutathione S-transferase and glucose-6-phosphate dehydrogenase activities in the erythrocytes, due mostly to a renewal of the population of these cells, and in glucose-6-phosphate dehydrogenase activity in the liver due to a decrease in hepatic glutathione. Thus, modifications in the erythrocytes are mainly due first to a strong oxidation of hemoglobin and afterwards to the renewal of the population. In the liver, modifications are mostly induced by consumption of reduced glutathione and secondary activation of the pentose cycle. It is suggested that there is a similarity between this chemical aggression and an inflammatory process.
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PMID:Influence of phenylhydrazine on the antioxidant system of the erythrocytes and the liver in mice. 671 4

Effects of feeding mice and rats with 2(3)-tert-butyl-4-hydroxyanisole (BHA) and 3,5-di-tert-butyl-4-hydroxytoluene (BHT), the two most commonly used food-additive phenolic antioxidants with known anticarcinogenic properties but with only minor differences in their chemical structures, have been compared to search for common effects between the two agents in two different rodent species and then applied toward better understanding of the mechanisms involved in their protective actions. In liver microsomes of treated mice, both BHA and BHT enhanced the relative activity of aniline ring hydroxylation but decreased the relative benzo(a)pyrene monooxidase activities. However, in rats, although aniline ring hydroxylation activity was decreased by both compounds, the decrease of benzo(a)pyrene monooxidase activity was observed only with BHT. Thus, common effects could not be recognized at the microsomal mixed-function oxidase level. Contrary to expectations based on chemical structures, BHT feeding elevated by epoxide hydrolase activity to an even greater extent than that produced by BHA, especially in rats. However, enzyme activities involved in the glucuronide conjugation system (uridine diphosphate:glucuronyl transferase, uridine diphosphate:glucose dehydrogenase, and quinone reductase) are all elevated by both antioxidants in both rodent species. With BHA treatment, the levels of acid-soluble thiols were increased in both rats and mice. However, with BHT, the level was increased only in mice but not in rats. Similar trends were produced for glucose-6-phosphate dehydrogenase activity, but glutathione reductase activity was increased even for BHT-treated rats. Additionally, the glutathione S-transferase activities were also increased by both antioxidant treatments and in both rodent species. Based on these results, the elevations of epoxide hydrolase activity along with the enhanced glucuronide conjugation and glutathione oxidation and reduction conjugation system enzyme activities were common to both compounds in both rodent species. This suggests their involvement in anticarcinogenic mechanisms. Increases of these detoxification enzyme activities appeared to be all designed to accelerate the elimination of administered antioxidants but, inadvertantly, conferring protective effects from xenobiotics such as carcinogens.
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PMID:Comparative effects of dietary administration of 2(3)-tert-butyl-4-hydroxyanisole and 3,5-di-tert-butyl-4-hydroxytoluene on several hepatic enzyme activities in mice and rats. 680 43

Pretreating female Balb/c mice with schisandrin B (Sch B) at increasing daily doses (1-4 mmol/kg) for 3 days caused dose-dependent increases in hepatic glutathione S-transferase (GST) and glutathione reductase (GRD) activities. However, the activities of glucose-6-phosphate dehydrogenase (G6PDH), Se-glutathione peroxidase (GPX), and gamma-glutamylcysteine synthetase (GCS) were down-regulated to varying degrees in a dose-dependent manner. While there were biphasic changes in hepatic reduced glutathione (GSH) level as well as susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion, a gradual decrease in hepatic malondialdehyde content was observed. The beneficial effect of Sch B on the hepatic GSH anti-oxidant system became more evident after CCl4 challenge. The same Sch B pretreatment regimen caused a dose-dependent protection against carbon tetrachloride (CCl4)-induced hepatotoxicity. The hepatoprotection was associated with significant enhancement in hepatic GSH status, as indicated by the substantial increase in tissue GSH levels and the corresponding decrease in susceptibility of tissue homogenates to GSH depletion. Where the activities of GST and GRD were increased linearly over non-CCl4 control values, there was also a gradual elevation in G6PDH activity upon administration of increasing doses of Sch B. In contrast, GPX activity was moderately down-regulated. The ensemble of results suggests that the hepatoprotection afforded by Sch B pretreatment may mainly be attributed to the enhancement in the functioning of the hepatic GSH anti-oxidant system, possibly through stimulating the activities of GSH related enzymes.
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PMID:Effect of schisandrin B on hepatic glutathione antioxidant system in mice: protection against carbon tetrachloride toxicity. 748 Jan 97


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