Cytochrome 3A and 2E1 in human liver tissue: Individual variations among normal Japanese subjects

Life Sciences
Shuko HataHironobu Sasano

Abstract

The metabolism of drugs, xenobiotic compounds, and other endogenous/exogenous substrates generally begins with their oxidation through cytochrome P450 (CYP). The results of recent pharmacogenetic analyses have demonstrated CYP's polymorphisms to be related to individual differences in metabolism, but only a limited number of CYP3A4 and CYP2E1 variant alleles influence enzymatic activities. Therefore, CYP gene expression profiling of both normal and pathological human livers should provide critical information for an evaluation of the biological significance of CYPs. In our present study, we first characterized the individual differences in CYP3A4 and CYP2E1 expression levels among Japanese normal or non-pathological liver tissue obtained from autopsy or surgery using immunohistochemistry and quantitative RT-PCR array of phase I metabolic enzymes with combined laser capture microscopy and qPCR analysis. Both CYP3A4 and CYP2E1 mRNA and proteins were predominantly detected in hepatocytes surrounding central veins in normal liver, but there were marked individual differences in both CYP3A4 and CYP2E1 mRNA and proteins among the 23 Japanese subjects examined. Individual differences in CYP3A and CYP2E1 subtypes were also detected in ...Continue Reading

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Citations

Nov 15, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Minako SakuraiHironobu Sasano
Aug 10, 2013·Cancer Medicine·Shuko HataHironobu Sasano
Jan 25, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Roberta D'AmbrosioPierre Bedossa
Jun 3, 2014·Pharmacology & Therapeutics·Payman ShahabiSophie Visvikis-Siest
Jun 1, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yoshiyuki ShirasakaA David Rodrigues
Jan 13, 2016·World Journal of Gastroenterology : WJG·Christoph G DietrichAndreas Geier
Feb 4, 2021·Drug Development Research·Daniela FanniMirko Manchia

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