Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.

ABSTRACT: Nuclear receptors regulate metabolic pathways in response to changes in the environment by appropriate alterations in gene expression of key metabolic enzymes. Here, a computational search approach based on iteratively built hidden Markov models of nuclear receptors was used to identify a human nuclear receptor, termed hPAR, that is expressed in liver and intestines. hPAR was found to be efficiently activated by pregnanes and by clinically used drugs including rifampicin, an antibiotic known to selectively induce human but not murine CYP3A expression. The CYP3A drug-metabolizing enzymes are expressed in gut and liver in response to environmental chemicals and clinically used drugs. Interestingly, hPAR is not activated by pregnenolone 16alpha-carbonitrile, which is a potent inducer of murin

SUBMITTER: Bertilsson G 

PROVIDER: S-EPMC22810 | biostudies-literature | 1998 Oct

REPOSITORIES: biostudies-literature