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.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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5-Aminolevulinate Synthetase / metabolism
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Animals
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Blotting, Northern
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Calcium / metabolism
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Carnitine O-Palmitoyltransferase / metabolism
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Cells, Cultured
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Cholesterol / metabolism
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Constitutive Androstane Receptor
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Cytoplasm / metabolism
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Dose-Response Relationship, Drug
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Estrogens / pharmacology
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Gene Expression Regulation*
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Liver / metabolism*
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Male
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Mice
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Mice, Transgenic
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Models, Biological
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Oligonucleotide Array Sequence Analysis
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Oxygenases / metabolism
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Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Cytoplasmic and Nuclear / physiology*
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Squalene Monooxygenase
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Transcription Factors / metabolism*
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Transcription Factors / physiology*
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Transcription, Genetic
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Two-Hybrid System Techniques
Substances
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Constitutive Androstane Receptor
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Estrogens
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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KN 62
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Cholesterol
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Oxygenases
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Squalene Monooxygenase
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Carnitine O-Palmitoyltransferase
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5-Aminolevulinate Synthetase
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Phosphoenolpyruvate Carboxykinase (ATP)
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Calcium