期刊
TOXICOLOGY LETTERS
卷 212, 期 3, 页码 288-297出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2012.06.001
关键词
Constitutive androstane receptor; Pregnane X receptor; Drug-metabolizing enzyme; Cytochrome P450; Drug transporters; Nuclear receptor
类别
资金
- Ministry of Education, Science, Sports and Culture of the Japanese Government [20590759]
- Grants-in-Aid for Scientific Research [20590759] Funding Source: KAKEN
Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are key regulators of drug-metabolizing enzymes and transporters. These two receptors are closely associated with each other and also have overlapping functions. This study investigated the overall hepatic gene expression profiles and the regulatory roles of these nuclear receptors using CAR/PXR single and double knockout mice. Basal and ligand-stimulated gene expression profiles were obtained in each mouse using cDNA microarrays and a reverse transcriptase-polymerase chain reaction. Enzymes such as Cyp2b10, Cyp3a11, Cdc20 and Cdk1 displayed both CAR- and PXR-dependent induction. Inversely, enzymes such as Cyp4a10, Fos and Mme displayed both CAR- and PXR-dependent repression. Enzymes such as Cyp1a1, Cyp1a2 and c-Myc represented the group of genes only induced by CAR. Enzymes such as Aacs represented the group of genes induced only by the PXR. CAR and PXR are closely associated and have diverse roles, both as positive and negative regulators of hepatic genes including xenobiotic metabolism, apoptosis, cholesterol biosynthesis, lipid metabolism, and cytokine signaling pathways. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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