Genetic Variants of Glutathione S-Transferase GSTT1 and GSTT2 in Cynomolgus Macaques: Identification of GSTT Substrates and Functionally Relevant Alleles

Chemical Research in Toxicology
Yasuhiro UnoHiroshi Yamazaki

Abstract

Glutathione S-transferase (GST) is a family of important drug-metabolizing enzymes, conjugating endogenous and exogenous compounds. Genetic polymorphisms result in the inter-individual variability of GST activity in humans. Especially, human GSTT1 and GSTT2 null alleles are associated with toxicity and various cancers derived from chemicals. Cynomolgus macaque, a nonhuman primate species widely used in drug metabolism studies, has molecular and enzymatic similarities of GSTs to the human orthologs; however, genetic polymorphisms have not been investigated in this species. In this study, resequencing of GSTT1 and GSTT2 in 64 cynomolgus and 32 rhesus macaques found 15 nonsynonymous variants and 1 nonsense variant for GSTT1 and 15 nonsynonymous variants for GSTT2. Some of these GSTT variants were distributed differently in Indochinese and Indonesian cynomolgus macaques and rhesus macaques. For analysis of functional relevance of the GSTT variants, 1-iodohexane and dibromomethane were determined to be suitable substrates for cynomolgus GSTT1 and GSTT2. However, the conjugation activities were roughly correlated with GSTT protein levels immunochemically quantified in cynomolgus liver samples with no statistical significances, implyi...Continue Reading

References

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Oct 1, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoRyoichi Nagata
Aug 12, 2009·Archives of Biochemistry and Biophysics·P David JosephyBengt Mannervik
Nov 17, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoHiroshi Yamazaki
May 10, 2011·The Journal of Veterinary Medical Science·Yasuhiro UnoHiroshi Yamazaki
Aug 19, 2011·The Journal of Pharmacology and Experimental Therapeutics·Shotaro UeharaYasuhiro Uno
Nov 30, 2011·Drug Metabolism and Pharmacokinetics·Shotaro UeharaYasuhiro Uno
Apr 30, 2013·Biochemical Pharmacology·Yasuhiro UnoHiroshi Yamazaki
Jul 6, 2013·Biochemical Pharmacology·Yasuhiro UnoHiroshi Yamazaki
Jul 6, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoHiroshi Yamazaki
Feb 16, 2015·Molecular Biology Reports·Yasuhiro UnoHiroshi Yamazaki
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Yasuhiro UnoHiroshi Yamazaki

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Citations

Aug 20, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yasuhiro UnoHiroshi Yamazaki
Jan 13, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yasuhiro UnoHiroshi Yamazaki
Feb 7, 2020·Biochemical Pharmacology·Yasuhiro UnoHiroshi Yamazaki

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