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The role of the nuclear receptor CAR as a coordinate regulator of hepatic gene expression in defense against chemical toxicity.

Abstract：

:The nuclear receptor CAR (constitutive active receptor) mediates the induction of transcription of cytochrome P450 (CYP) genes by phenobarbital (PB) and PB-type inducers. A recent study using CAR-null mice has shown that CAR regulates not only the CYP genes but also other genes encoding various drug/steroid-metabolizing enzymes. In addition to coordinating these enzymes, CAR plays other roles in hepatic gene expression: CAR represses various genes including carnitine palmitoyltransferase 1a and phosphoenolpyruvate carboxykinase 1 in response to PB, and the receptor regulates the constitutive expression of genes such as squalene epoxidase. On the other hand, induction of certain genes such as amino levulinate synthase 1 by PB is not regulated by CAR. Here we describe diverse roles of CAR in hepatic gene expression with a particular focus on endogenous substances such as cholesterol, bilirubin, and steroid hormones.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Yamamoto Y,Kawamoto T,Negishi M

doi

10.1016/s0003-9861(02)00456-3

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

207-11

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003986102004563

journal_volume

409

pub_type

杂志文章

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