Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response

被引：167

作者：

Beigneux, AP ^{[1
]}

Moser, AH ^{[1
]}

Shigenaga, JK ^{[1
]}

Grunfeld, C ^{[1
]}

Feingold, KR ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Metab Sect, Med Serv,Dept Vet Affairs Med Ctr, San Francisco, CA 94121 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 293卷 / 01期

关键词：

infection; endotoxin; cholestasis; drug metabolism; bile acid metabolism;

D O I：

10.1016/S0006-291X(02)00196-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Expression of P-450 (Cyp) enzymes is reduced in liver during the acute phase response, contributing to the decrease in bile acid levels and drug metabolism during infection, Nuclear hormone receptors CAR and PXR are key transactivators of Cyp2b and Cyp3a genes, respectively. Injection of bacterial lipopolysaccharide (LPS) induced the expected reduction in Cyp2b10 and Cyp3a mRNA levels in mouse liver. These decreases were associated with a marked reduction in CAR and PXR mRNA levels within 4 h following treatment. LPS-induced CAR and PXR repression were dose-dependent and sustained for at least 16 h, LPS treatment also reversed the up-regulation of Cyp3a in mice pre-treated with PXR ligand RU486. In addition, we observed a concomitant decrease in RXR (retinoid X receptor) mRNA levels, the obligatory partner of both CAR and PXR for high affinity binding to DNA. These findings represent one possible molecular mechanism underlying sepsis-induced repression of Cyp enzymes. (C) 2002 Elsevier Science (USA). All rights reserved.

引用

页码：145 / 149

页数：5

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