Identification of theta-class glutathione S-transferase in liver cytosol of the marmoset monkey.
The presence of theta-class glutathione S-transferase (GST) in marmoset monkey liver cytosol was investigated. An anti-peptide antibody targeted against the C-terminus of rGSTT1 reacted with a single band in marmoset liver cytosol that corresponded to a molecular weight of 28 kDa. The intensity of the immunoreactive band was not affected by treatment of marmoset monkeys with 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbitone, rifampicin or clofibric acid. Similarly, activity towards methyl chloride (MC) was unaffected by these treatments. However, GST activity towards 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP) was increased in marmosets treated with phenobarbitone (2.6-fold) and rifampicin (2.6-fold), activity towards dichloromethane (DCM) was increased by 50% after treatment of marmosets with clofibric acid, and activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was raised slightly (30-42% increases) after treatment with phenobarbitone, rifampicin or clofibric acid. Compared with humans, marmoset liver cytosol GST activity towards DCM was 18-fold higher, activity towards MC was 7 times higher and activity towards CDNB was 4 times higher. Further, EPNP activity was clearly detectable in marmoset liver cytosol samples, but was undetectable in human samples. Immunoreactive marmoset GST was partially purified by affinity chromatography using hexylglutathione-Sepharose and Orange A resin. The interaction of immunoreactive marmoset GST was similar to that found previously for rat and human GSTT1, suggesting that this protein is also a theta class GST. However, unlike rat GSTT1, the marmoset enzyme was not the major catalyst of EPNP conjugation. Instead, immunoreactivity was closely associated with activity towards MC. In conclusion, these results provide evidence for the presence of theta-class GST in the marmoset monkey orthologous to rGSTT1 and hGSTT1.
Schulz
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TG
Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK. tschulz1@gwdg.de
Wiebel
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Thier
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Neubert
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Davies
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Edwards
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RJ
D000818:Animals; D002144:Callithrix; D002846:Chromatography, Affinity; D002995:Clofibric Acid / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology*; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism; D005982:Glutathione Transferase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008737:Methyl Chloride / Q000378:metabolism; D008752:Methylene Chloride / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009596:Nitrophenols / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology; D013045:Species Specificity
D004137:Dinitrochlorobenzene; D004852:Epoxy Compounds; D009596:Nitrophenols; D000072317:Polychlorinated Dibenzodioxins; D002995:Clofibric Acid; D008752:Methylene Chloride; C007606:1,2-epoxy-3-(p-nitrophenoxy)propane; D008737:Methyl Chloride; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D012293:Rifampin; D010634:Phenobarbital