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β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver

  • Albert Braeuning and Michael Schwarz
Published/Copyright: February 26, 2010

Abstract

The liver is the major organ for metabolism of drugs and other xenobiotics. Expression of many drug-metabolizing enzymes is not equally distributed throughout the liver: under normal conditions, many of them, including the most relevant members of the cytochrome P450 superfamily, are exclusively expressed in a hepatocyte subpopulation located near branches of the efferent central vein. Activation of different ligand-dependent transcription factors by exogenous compounds stimulates high expression of certain cytochrome P450 isoforms. This process also occurs preferentially in perivenous hepatocytes. The mechanisms, however, which determine the zone-specificity of basal and xenobiotic-induced expression of cytochrome P450 enzymes, have remained largely unknown for decades. Very recently, signaling through the Wnt/β-catenin pathway has been implicated in the regulation of zonal gene expression in mouse liver. In this review, current knowledge of cytochrome P450 regulation by β-catenin-dependent transcription is summarized and underlying molecular mechanisms are discussed.


Corresponding author

Received: 2010-08-21
Accepted: 2010-10-07
Published Online: 2010-02-26
Published in Print: 2010-02-26

©2010 by Walter de Gruyter Berlin New York

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