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)

Stromal cells from bone marrow are susceptible to toxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). We have previously shown that tert-butyl-hydroquinone (tBHQ) can induce quinone reductase (QR) in bone marrow stroma as well as protect stromal cells against HQ-induced toxicity. Current studies investigate the underlining mechanisms of chemoprotection against HQ in DBA/2- and C57Bl/6-derived bone marrow stromal cells. The chemoprotector 1,2-dithiole-3-thione (DTT) has been used in these studies due to tBHQ toxicity to stromal cells at higher concentrations. Pretreatment of cells with DTT prior to HQ administration protected cells against HQ-induced toxicity. DTT induced QR activity in a dose-dependent manner in stromal cells from both strains of mice. However, there were no corresponding changes in glutathione transferase activity. DTT also increased cytosolic glutathione (GSH) concentrations by approximately 85% in both strains. Since bone marrow stroma consists primarily of fibroblasts and macrophages, we also evaluated QR activity in the separate cell types from the two strains of mice. There were differences in basal and DTT-induced QR activity between fibroblasts and macrophage cells derived from the same strain of mice, as well as the expected differences between strains. Additionally, dicoumarol, an inhibitor of QR activity, potentiated HQ-induced toxicity in both strains of bone marrow stromal cells. Thus, cellular glutathione, QR activity, and their inducibility by chemoprotective agents such as DTT may prove to be important factors in chemically induced bone marrow toxicity and carcinogenicity.
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PMID:Induction of quinone reductase and glutathione in bone marrow cells by 1,2-dithiole-3-thione: effect on hydroquinone-induced cytotoxicity. 137 15

1. The inductive effect of N-benzylimidazole (NBI) on hepatic microsomal and cytosolic drug-metabolizing enzyme activities in aryl hydrocarbon (Ah)-responsive C57BL/6N (B6) and Ah-non-responsive DBA/2N (D2) mouse strains was determined and compared with that caused by beta-naphthoflavone (BNF). 2. Relative Ah-responsiveness of the two strains was confirmed by measurement of BNF-induced ethoxyresorufin deethylase (EROD) activity and ELISA immunoquantification. BNF markedly induced EROD activity only in the Ah-responsive B6 mouse strain (65-fold increase). 3. NBI (150 mg/kg per day for 3 days) increased cytochrome P450 concentration similarly in both strains (40 and 60% in B6 and D2 strains, respectively). Compared with BNF treatment of the B6 strain, increases in EROD activity following NBI treatment were only minor. In addition, EROD activity increases were greater in the Ah-nonresponsive D2 strain (300%) than in the Ah-responsive B6 strain (100%) suggesting the possibility of an induction mechanism different from that of recognized Ah receptor agonists. 4. Induction of UDP-glucuronosyltransferase activity (p-nitrophenol acceptor) by BNF was greater in the Ah-responsive B6 strain than in the Ah-non-responsive D2 strain. NBI failed to induce this activity in either strain. 5. Induction of glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene following NBI treatment occurred to the same extent (25% increase) as that seen following BNF treatment, in the Ah-responsive B6 strain. Neither xenobiotic affected this activity in the Ah-non-responsive D2 strain. 6. Although NBI is a major inducer, possessing Ah-like inducing properties in rat, it caused only minor changes in murine drug metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-benzylimidazole-mediated changes in hepatic drug-metabolizing enzyme activities in Ah-responsive and Ah-non-responsive mice. 149 85

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

Liver cytosol from mice fed on a normal diet contains Alpha-class glutathione S-transferase (GST) subunits of Mr 25,800, Mu-class GST subunits of Mr 26,400 and Pi-class GST subunits of Mr 24,800. Feeding female mice with a diet containing the anticarcinogenic antioxidant butylated hydroxyanisole (BHA) causes induction of the constitutively expressed Mu-class and Pi-class subunits. BHA also induces an Alpha-class GST comprising subunits of Mr 25,600, which is not expressed at detectable levels in normal mouse liver [McLellan & Hayes (1989) Biochem. J. 263, 393-402]. Data are now presented that show that administration of the anticarcinogen beta-naphthoflavone (BNF), like BHA, induces the Alpha-class 25,600-Mr subunits but not the constitutive Alpha-class GST with subunits of Mr 25,800. The effects of BNF on expression of hepatic GST were studied in both DBA/2 and C57BL/6 mice; these studies revealed a preferential induction of the Alpha-class 25,600-Mr subunits and of the Pi-class 24,800-Mr subunits in those mice in possession of a functional Ah receptor. The BHA/BNF-inducible Alpha-class GST can be resolved into two separate, non-interconvertible peaks by reverse-phase h.p.l.c. Automated amino acid sequence analysis of CNBr-derived peptides from each of these h.p.l.c.-purified peaks showed that the peaks contained at least two very similar subunits. These have been named Ya1 and Ya2. The amino acid sequence of the Ya1 subunit was compared with sequences deduced from a genomic clone, lambda mYa1 (Daniel, Sharon, Tichauer & Sarid (1987) DNA 6, 317-324], and a cDNA clone, pGT41 [Pearson, Reinhart, Sisk, Anderson & Adler (1988) J. Biol. Chem. 263, 13324-13332]. Our data suggest that the Ya1 subunit represents the subunit encoded by the genomic clone, lambda mYa1. Sequence analysis of the constitutive Alpha-class Ya3 subunit (Mr 25,800) shows that, although it is a member of the same gene family as the Ya1 and Ya2 subunits, it represents a distinct sub-family of Alpha-class GST, containing subunits that are more similar to rat Yc. Our data indicate that, of these Alpha-class GST subunits, the two with Mr 25,600 (Ya1 and Ya2) are selectively induced by BHA or BNF in mouse liver; neither BHA nor BNF induces significantly the GST subunit with Mr 25,800 (Ya3).
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PMID:Regulation of mouse glutathione S-transferases by chemoprotectors. Molecular evidence for the existence of three distinct alpha-class glutathione S-transferase subunits, Ya1, Ya2, and Ya3, in mouse liver. 204 74

The distribution of aminopyrine N-demethylase (APND), ethoxyresorufin O-deethylase (ERRD), epoxide hydrolase (EH) and glutathione transferase (GST) activities in parenchymal (PC) and non-parenchymal (NPC) cell populations of control and Aroclor 1254-treated C57BL/6N and DBA/2N mice was determined. Furthermore, the metabolism of benzo(a)-pyrene (BP) in PC and NPC of both Aroclor 1254-treated mice strains was examined. Measurable activities of all enzymes investigated were detected in control PC as well as NPC of both mice strains; in all instances the PC possessed greater enzyme activities than did the NPC. The PC and NPC of DBA/2N of C57BL/6N mice. In NPC of both strains a low ratio of oxidative (APND and ERRD) to post-oxidative (EH and GST) enzyme activities was observed. Hence, NPC of C57BL/6N and DBA/2N mice might have a relatively lower ability to oxidize xenobiotics to reactive electrophiles and a greater ability to conjugate or hydrolyze those products that may be formed. Treatment with Aroclor 1254 enhanced all the enzyme activities measured in PC and NPC of both mice strains with the exception of ERRD in PC and NPC of DBA/2N mice. This is due to the fact that the induction process of ERRD by aromatic and halogenated aromatic compounds such as Aroclor 1254 depends upon the presence of a cytosolic receptor with a high affinity for this type of inducers and the DBA/2N mice have a very poor affinity receptor. After incubating BP with PC or NPC of Aroclor 1254-treated C57BL/6N mice significant amounts of 9,10-dihydrodiol, 4,5-dihydrodiol, 7,8-dihydrodiol, quinone, 9-hydroxy and 3-hydroxy derivatives of BP were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distribution of carcinogen metabolizing enzymes in the mouse liver: comparison of parenchymal and non-parenchymal cell populations. 347 97

Hepatic glutathione S-transferase isoenzyme content has been investigated in both sexes of three inbred strains of mice (DBA/2, C3H/He, C57BL6). A polypeptide (Mr 24,800), which is immunologically related to Yf purified from rat lung, was found to be expressed as a major form in all male mouse livers but represented only a minor enzyme form in female mouse liver. Glutathione S-transferases comprising subunits with molecular masses of 25,800 (Ya) or 26,400 (Yb) were present in males and females of the three strains under investigation. Cytosolic isoenzymes from all strains and sexes were purified to apparent homogeneity and no significant inter-strain differences in the properties of the individual forms were observed. In addition, no differences were detected in the microsomal glutathione S-transferase content of the different strains or sexes.
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PMID:Sex-specific constitutive expression of the pre-neoplastic marker glutathione S-transferase, YfYf, in mouse liver. 366 66

The repeated oral administration of nafenopin, a hypolipidaemic compound, at a dose of 100 mg/kg to male C57BL/6, DBA/2, Balb c and C3H mice caused an increase in the specific activity of liver cytosolic epoxide hydrolase, the activity of microsomal epoxide hydrolase was also increased in all except the C3H mice. The dose dependence and the specificity of this induction was investigated in male DBA/2 mice. In the range of 10-200 mg/kg nafenopin the induction of the two hydrolase activities was found to increase with increasing doses of the test compound. Two other cytosolic enzyme activities, lactate dehydrogenase and glutathione S-transferase, remained essentially unchanged within the dose range investigated.
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PMID:Induction of cytosolic and microsomal epoxide hydrolases by the hypolipidaemic compound nafenopin in the mouse liver. 670 41

Three major forms of cytosolic glutathione S-transferase (designated F1, F2, and F3 transferases according to increasing isoelectric points) were purified to homogeneity from liver of DBA/2J mice, primarily by CM-cellulose and hydroxylapatite chromatography. The purified enzymes were shown to have specific activities of 104, 281, and 143 units/mg, respectively, when assayed with 1 mM each of 1-chloro-2,4-dinitrobenzene and reduced glutathione. Antisera against these three forms of mouse transferase were raised separately in rabbits. F1 and F2 transferases showed complete immunological identity either by double immunodiffusion or enzyme immunoinactivation tests. No cross-reactivity was observed between the antisera to F1 (or F2) transferase an F3 transferase or between the antisera to F3 transferase and F1 (or F2) transferase. F1 and F2 transferases were shown to be homodimers with an identical molecular weight of 44,000 +/- 1,000, whereas F3 transferase has a dimeric molecular weight of 51,000 +/- 2,000. The amino acid composition and tryptic peptide map of F1 transferase are similar to those of F2 transferase, but are distinct from those of F3 transferase. In addition to these major forms, a minor form of mouse transferase (F4) with a high isoelectric point (greater than 9.5) was shown to be a mixture of interconvertible isomers of F2 and F3 transferase. Different forms of mouse transferase were studied extensively with respect to their biochemical properties, including Michaelis constants, substrate specificity, thermal stability, and fluorometric ligand binding. The results of this study suggest great species variations regarding the multiple forms as well as the substrate specificity of this family of enzymes.
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PMID:Mouse liver glutathione S-transferases. Biochemical and immunological characterization. 679 May 31

The hepatic cytosolic glutathione S-transferase (GST) activity in four strains of the mouse and one strain of the rat was studied with the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethachrynic acid (ETHA), cumene hydroperoxide (CU) and atrazine as the in vitro substrates. In the mouse, significant gender, strain and age-related differences in the GST activity towards CDNB and atrazine were found between adolescent and sexually mature males and females of the CD-1, C57BL/6, DBA/2 and Swiss-Webster strains, and the differences were larger with atrazine as the substrate. With DCNB and CU a similar tendency was observed, however not significant for all strains. The GST activity towards ETHA was also gender and strain specific, but revealed no age-related differences. The herbicide atrazine seems to be a useful substrate in the study of strain and age-related differences in the mouse GST class Pi.
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PMID:A study of gender, strain and age differences in mouse liver glutathione-S-transferase. 774 1

Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C57BL/6 develop adverse immune reactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokinetics of gold in these strains under chronic GST treatment. Our results indicate that the susceptible strains A.SW and C57BL/6 accumulate significantly higher gold concentrations in the liver and spleen compared to the resistant strain DBA/2. In the kidney of DBA/2 mice, gold concentrations persisted at a plateau level, whereas in A.SW and, particularly, C57BL/6 mice early peaks of gold concentrations were followed by a transient decrease, suggestive of tubular toxicity. Whereas splenic T and B cells failed to contain measurable gold concentrations in all three strains, splenic and peritoneal macrophages contained relatively high levels, more so in the susceptible strain C57BL/6 than in the resistant DBA/2 strain. This finding is consistent with the concept that macrophages play an important role in both the adverse and the beneficial effects of gold drugs.
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PMID:Gold kinetics under long-term treatment with gold(I) disodium thiomalate: a comparison in three different mouse strains. 805 98


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