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Phenobarbital induction of drug/steroid-metabolizing enzymes and nuclear receptor CAR
- Source :
-
BBA - General Subjects . Feb2003, Vol. 1619 Issue 3, p239. 4p. - Publication Year :
- 2003
-
Abstract
- Phenobarbital (PB) increases hepatic drug/steroid-metabolic capability by coordinately activating transcription of the genes encoding various metabolizing enzymes. The nuclear receptor CAR was first implicated as a transcription factor that activates the cytochrome P450 Cyp2b10 gene. In response to PB, CAR forms a heterodimer with the retinoid X receptor (RXR), binds to a PB response element (typified by DR-4 motif), and activates transcription of the gene. In the CAR-null mouse, PB does not only induce the Cyp2b10 gene, but also induces genes encoding various metabolizing enzymes. Thus, CAR is a general nuclear receptor that is essential for PB induction of drug/steroid metabolizing enzymes. PB also induces amino levulinate synthase 1 (ALAS-1), the rate-limiting enzyme in heme biosynthesis, to increase heme supply. However, PB induction of the synthase occurs in CAR-null mice, suggesting that CAR does not coordinate the heme synthesis for the induction of drug/steroid metabolism. [Copyright &y& Elsevier]
- Subjects :
- *NUCLEAR receptors (Biochemistry)
*ENZYMES
Subjects
Details
- Language :
- English
- ISSN :
- 03044165
- Volume :
- 1619
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- BBA - General Subjects
- Publication Type :
- Academic Journal
- Accession number :
- 9010842
- Full Text :
- https://doi.org/10.1016/S0304-4165(02)00482-8