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Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification.

Abstract：

:The nuclear pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play central roles in protecting the body against environmental chemicals (xenobiotics). PXR and CAR are activated by a wide range of xenobiotics and regulate cytochrome P450 and other genes whose products are involved in the detoxification of these chemicals. In this report, we have used receptor-selective agonists together with receptor-null mice to identify PXR and CAR target genes in the liver and small intestine. Our results demonstrate that PXR and CAR regulate overlapping but distinct sets of genes involved in all phases of xenobiotic metabolism, including oxidative metabolism, conjugation, and transport. Among the murine genes regulated by PXR were those encoding PXR and CAR. We provide evidence that PXR regulates a similar program of genes involved in xenobiotic metabolism in human liver. Among the genes regulated by PXR in primary human hepatocytes were the aryl hydrocarbon receptor and its target genes CYP1A1 and CYP1A2. These findings underscore the importance of these two nuclear receptors in defending the body against a broad array of potentially harmful xenobiotics.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Maglich JM,Stoltz CM,Goodwin B,Hawkins-Brown D,Moore JT,Kliewer SA

doi

10.1124/mol.62.3.638

keywords:

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

638-46

issue

3

eissn

0026-895X

issn

1521-0111

journal_volume

62

pub_type

杂志文章

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