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)

Microsomal and cytosolic enzymes that metabolize xenobiotics were measured in composite samples representing entire livers and in samples from three lobes, using livers of cattle, goats and sheep. Within individual species, concentrations of cytochrome P-450 and b5 and activities of NADPH cytochrome c reductase, aldrin epoxidase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase, microsomal and cytosolic stilbene oxide (epoxide) hydrolase and glutathione S-transferase were not different (P greater than .05) among the various hepatic lobes. Among species, several activities differed (P less than .05), with cattle livers generally having lower values than sheep or goats.
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PMID:Interlobular distribution of hepatic xenobiotic-metabolizing enzyme activities in cattle, goats and sheep. 381 84

The ability of S-9 fractions isolated from the livers of 4-, 12-, and 26-month-old male inbred F344 rats to activate and metabolize the hepatocarcinogen aflatoxin B1 [(AFB1) CAS: 1162-65-8] was studied. The following observations were made: The activation of AFB1 to compounds that are mutagenic in the Ames Salmonella-microsome test and to compounds that covalently bind DNA in vitro was similar for liver S-9 from 4- and 12-month-old rats. A 30-50% decrease in the activation of AFB1 occurred in rats between 12 and 26 months of age. The in vitro metabolism of AFB1 to chloroform-soluble and water-soluble metabolites was similar for 4- and 12-month-old rats and decreased significantly in rats after 12 months of age. The proportion of most of the chloroform-soluble metabolites of AFB1 formed by liver S-9 from 4-, 12-, and 26-month-old rats was similar. However, the proportion of aflatoxicol (CAS: 29611-03-8) produced by liver S-9 increased approximately twofold in rats between 12 and 26 months of age. The cytochrome P450 content and the NADPH cytochrome c reductase activity of liver microsomes decreased 40-45% in rats between 12 and 26 months of age. However, the activities of UDPglucuronyltransferases and most forms of glutathione S-transferase did not change significantly with increasing age in liver microsomes and cytosol, respectively.
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PMID:Metabolism, covalent binding, and mutagenicity of aflatoxin B1 by liver extracts from rats of various ages. 391 13

The effect of chloroform treatment on the hepatic glutathione S-transferases was studied in phenobarbital-treated rats. The apparent isozymic composition of glutathione S-transferases in hepatic cytosol was changed after chloroform treatment. Glutathione S-transferases AA, A, B, C, and D + E were observed in hepatic cytosol from untreated rats; in contrast, the catalytic activity associated with basic glutathione S-transferases, such as AA, A, B, and C, decreased with time after chloroform treatment. Glutathione S-transferase B was not detectable 2 hr after chloroform treatment, and glutathione S-transferases AA and C were scarcely detectable after 5 hr. Twenty-four hours after chloroform treatment, glutathione S-transferases A and C were clearly detectable as was D + E and a small amount of B. Hepatic cytosolic glutathione S-transferase activity was decreased by chloroform treatment, and reached a minimum at 5 hr after treatment. Corresponding to the decrease of hepatic cytosol glutathione S-transferase activity, serum glutathione S-transferase activity was elevated maximally 5 hr after chloroform treatment and returned to almost normal by 24 hr. Treatment of rats with SKF 525-A or cysteine inhibited the chloroform-induced elevation of serum glutathione S-transferase activity. The chromatographic properties of the glutathione S-transferases present in serum were similar to glutathione S-transferase D + E. Furthermore, after incubation of partially purified cytosolic glutathione S-transferases with chloroform in the presence of hepatic microsomes and NADPH, only transferase D + E was detected. The addition of bilirubin to partially purified cytosolic glutathione S-transferase decreased the basic character of glutathione S-transferases B and C. In conclusion, chloroform caused a release of hepatic cytosolic glutathione S-transferases into serum. Both the active metabolite of chloroform, which was produced by the microsomal cytochrome P-450 system, and bilirubin, which was increased by chloroform treatment, played roles in altering the properties of the glutathione S-transferases.
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PMID:Chloroform-induced alteration of glutathione S-transferase activity. 396 26

The effect of intratracheal instillation of different doses of benzo(a)pyrene (0.1, 1.0 and 2.0 mg) on the drug metabolizing enzymes of lung and liver was analysed in rats fed diet with or without vitamin A for 5-6 weeks. Benzo(a)pyrene exposure at 2.0 mg dose only elevated the level of cytochrome P-450 and b5, and activity of benzopyrene hydroxylase in liver, and extent of increase was similar in normal and vitamin A deficient groups. Contrary to this, pulmonary contents of cytochrome P-450 and b5, and benzopyrene hydroxylase activity increased over control values in both the groups even at lower doses of benzo(a)pyrene. Moreover, their values were higher in vitamin A deficient-treated groups compared to normal-treated controls. Increase in these parameters was greater in lung as compared to increase in liver. NADPH cytochrome C-reductase in lung and liver was not affected either by inducing vitamin A deficiency or exposing these rats further to benzo(a)pyrene. Uridine-diphospho-glucuronosyl-transferase (UDP-GT) activity in normal and vitamin A deficient groups was enhanced following exposure to benzo(a)pyrene both in lung and liver. However, activity of this enzyme remained impaired in vitamin A deficient groups, benzo(a)pyrene exposed or not exposed when compared to respective normal controls. Glutathione S-transferase activity remained unchanged following exposure to benzo(a)pyrene both in lung and liver. The apparent increase in hepatic glutathione S-transferase and decrease in pulmonary glutathione S-transferase activity in vitamin A deficiency was only due to vitamin A deficient status of rats with no further effect of benzo(a)pyrene.
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PMID:Effect of intratracheally instilled benzo(a)pyrene on the pulmonary and hepatic drug-metabolizing enzymes in normal and vitamin A deficient rats. 401 64

The effects of diethylhydroxylamine (DEHA), a potent free-radical scavenger, on lipid peroxidation of rat liver microsomes were investigated in vitro. DEHA strongly inhibited ascorbate-dependent nonenzymatic microsomal lipid peroxidation. DEHA also completely inhibited nonenzymatic lipid peroxidation of heat-denatured microsomes, indicating that inhibition is protein-independent. DEHA only moderately inhibited NADPH-dependent enzymatic microsomal lipid peroxidation. DEHA has been shown to exhibit antitumorogenic properties. However, it had no significant effect on hepatic glutathione S-transferase, selenium-independent glutathione peroxidase, or selenium-dependent glutathione peroxidase activity in the DEHA-treated CD-1 (lCR) Br male mouse. This suggests that the mode of action of DEHA as an antitumorogenic agent may be different from that of butylated hydroxyanisole, whose antitumor function is attributed to induction of glutathione S-transferase activity.
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PMID:Effects of diethylhydroxylamine on hepatic microsomal lipid peroxidation and glutathione S-transferases. 403 93

Incubations with goat lung and liver microsomes were conducted to trap with exogenous glutathione (GSH) the electrophilic intermediate produced via cytochrome P-450-dependent metabolic activation of 3-methylindole (3MI). Microsomal incubation mixtures with [14C]3MI, a NADPH-generating system, and [3H]GSH produced a dual-labeled adduct which was isolated by reverse-phase high-performance liquid chromatography. Reactive 3MI intermediates were also trapped with cysteine. Adduct formation increased in proportion to the concentration of either thiol. Covalent binding of activated 3MI metabolites to microsomal protein was inversely related to adduct production. There were both qualitative and quantitative differences in the formation of GSH adducts by lung and liver microsomes. In the presence of 2 mM GSH, the adduct was produced at a rate of 1.8 nmol/mg protein/min by lung microsomes but only at 0.1 nmol/mg protein/min by hepatic microsomes. The addition of cytosolic fractions containing glutathione S-transferase activity increased GSH adduct formation by approximately 30%. These results support the view that electrophilic 3MI intermediates are trapped by conjugation with GSH, and that organ-selective toxicity is primarily due to much faster rates of cytochrome P-450 oxidation of 3MI in the lung than in the liver.
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PMID:Glutathione adduct formation with microsomally activated metabolites of the pulmonary alkylating and cytotoxic agent, 3-methylindole. 404 23

Duplicate groups of rainbow trout (Salmo gairdneri) (mean weight 11 g) were given for 40 weeks one of four partially purified diets that were either adequate or low in selenium or vitamin E or both. Weight gains of trout given the dually deficient diet were significantly lower than those of trout given a complete diet or a diet deficient in Se. No mortalities occurred and the only pathology seen was exudative diathesis in the dually deficient trout. There was significant interaction between the two nutrients both with respect to packed cell volume and to malondialdehyde formation in the in vitro NADPH-dependent microsomal lipid peroxidation system. Tissue levels of vitamin E and Se decreased to very low levels in trout given diets lacking these nutrients. For plasma there was a significant effect of dietary vitamin E on Se concentration. Glutathione (GSH) peroxidase (EC 1.11.1.9) activity in liver and plasma was significantly lower in trout receiving low dietary Se but was independent of vitamin E intake. The ratios of hepatic GSH peroxidase activity measured with cumene hydroperoxide and hydrogen peroxide were the same for all treatments. This confirms the absence of a Se-independent GSH peroxidase activity in trout liver. Se deficiency did not lead to any compensatory increase in hepatic GSH transferase (EC 2.5.1.18) activity; values were essentially the same in all treatments. Plasma pyruvate kinase (EC 2.7.1.40) activity increased significantly in the trout deficient in both nutrients. This was thought to be due to leakage of the enzyme from the muscle and may be indicative of incipient (subclinical) muscle damage.
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PMID:Some effects of vitamin E and selenium deprivation on tissue enzyme levels and indices of tissue peroxidation in rainbow trout (Salmo gairdneri). 406 58

Benzo[a]pyrene will bind covalently to rat liver cytosolic proteins when incubated with microsomes and NADPH. The binding is most extensive when microsomes from 3-methylcholanthrene-treated rather than phenobarbital-treated or control rats are used. The binding to cytosolic proteins increases when incubations are performed with increasing concentrations of cytosol. At the same time the covalent binding of benzo[a]pyrene to microsomal proteins decreases. Two cytosolic polypeptides are the main targets for benzo[a]pyrene. These have the same mobility in polyacrylamide gels as the subunits of purified glutathione S-transferase B. These subunits also react covalently with benzo[a]pyrene when the transferase is incubated with microsomes and NADPH.
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PMID:Covalent binding of benzo[a]pyrene to rat liver cytosolic proteins and its effect on the binding to microsomal proteins. 630 70

Results of various studies have shown that male Swiss Webster mice are more susceptible to toxic effects of vinylidene chloride (VDC) than are females of the same mouse strain, females and males of the C57BL mouse strain, Chinese hamsters and rats. The main targets of toxicity are kidney and liver. The kidney of male Swiss Webster mice is the only organ where VDC unambiguously induces tumours. In the present study we have investigated the ability of NADPH-foritifed postmitochondrial supernatant fractions (S-9 mix) of kidney and liver from susceptible and nonsusceptible animals to activate VDC to a bacterial mutagen. The following sequence of activating potencies was observed: mouse liver (both strains and sexes) and Chinese hamster liver greater than rat liver greater than human liver greater than Chinese hamster kidney greater than kidney from male mice of both strains greater than kidney from rats and female mice. The last two preparations only occasionally showed weak activation of VDC. Addition of purified microsomal epoxide hydrolase to S-9 mix did not affect the mutagenicity of VDC; addition of glutathione reduced the mutagenicity up to 50%. Pretreatment of animals (male rats, male and female Swiss Webster mice) with VDC did not potentiate the ability of the subcellular preparations to activate this compound. In fact, in some cases, a weaker activation was observed. Following this treatment, microsomal 7-ethoxy-coumarin O-dealkylase was decreased in mouse kidney and in rat liver. The enzyme was not affected in mouse liver and was not measurable in rat kidney. Microsomal epoxide hydrolase activity (with styrene 7,8-oxide as substrate) was not affected in mouse liver and rat kidney. In the kidney of male mice treated with a high concentration of VDC, epoxide hydrolase activity was decreased initially, but after longer treatment, in some cases a weak increase above control was noticed. A stronger increase in activity of epoxide hydrolase was observed in the rat liver and the kidney of female mice. Cytosolic glutathione transferase activity (with 2,4-dinitrochlorobenzene as substrate) was not affected by the VDC treatment in the liver of male mice, but was decreased in the kidney of male mice, and was elevated in the kidney and liver of rats and of female mice. The different effects of VDC on this enzyme may be one of the reasons for the differences in susceptibility towards the toxic and carcinogenic actions of this compound in different species, strains and sexes.
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PMID:Vinylidene chloride: changes in drug-metabolizing enzymes, mutagenicity and relation to its targets for carcinogenesis. 634 25

1,2-Dibromo-[1,2-14C]ethane was bound irreversibly to DNA when glutathione S-transferase or rat liver cytosolic components were added to incubations of calf thymus DNA and glutathione at 37 degrees C. There was no DNA binding of 1,2-dibromoethane when glutathione was absent or in incubations of DNA with microsomal proteins with or without NADPH, thus supporting the proposal that the major route of DNA binding by 1,2-dibromoethane occurs via conjugation to glutathione. In vitro binding of 1,2-dibromoethane occurred most effectively when the YaYc (or 'B') isozyme of glutathione S-transferase was included in incubations of DNA with 1,2-dibromoethane and glutathione. Other dihaloalkanes were incubated with DNA in the presence of glutathione S-transferase and [35S]glutathione. Of these, only 1,2-dibromo-3-chloropropane and tris-(2,3-dibromopropyl)-phosphate led to significant DNA binding of [35S]glutathione. 1,2-Dibromo-3-chloro-[1,3-14C]propane was bound to DNA when glutathione and glutathione S-transferase were present. However, even higher 1,2-dibromo-3-chloropropane binding to DNA occurred when cytosol or microsomes were included in incubations without glutathione. When glutathione was added to incubations containing cytosol and 1,2-dibromo-3-chloropropane, total DNA binding was decreased. Thus, the actual amount of DNA binding by dihaloethanes in vivo may be the result of a complicated balance among the opposing roles of glutathione conjugation in detoxicating and activating processes.
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PMID:Glutathione-mediated binding of dibromoalkanes to DNA: specificity of rat glutathione-S-transferases and dibromoalkane structure. 637 44


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