Suppression of the Expression of the CYP2B1/2 Gene by Retinoic Acids

Publisher： Elsevier

ISSN： 0006-291X

Source： Biochemical and Biophysical Research Communications, Vol.277, Iss.1, 2000-10, pp. : 66-71

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

The effects of 5α-androsten-3α-ol (ASE), and retinoic acids (RAs) and their precursors on the phenobarbital (PB)-mediated induction of CYP2B1 and 2B2 were examined in cultured rat hepatocytes. Two isomers of RA, 9-cis- and all-trans-RA, suppressed markedly the effect of PB on CYP2B1/2 expression, while ASE had no suppressive effect. The effect of 9-cis-RA appeared at a lower concentration than the all-trans-isomer, indicating the dominant action of the former isomer. Suppression with 9-cis-retinal was also observed, but all-trans-retinol and -retinal were without effect. These results suggest that: (1) ASE, an inverse agonist for the constitutive androstane receptor (CAR), does not play a major role in the suppression of the CYP2B; (2) 9-cis-RA suppresses CYP2B induction by reducing ligand-free retinoid X-receptors (RXR) available for dimerization with the CAR; and (3) enzymes responsible for RA formation play an important role in the mechanism governing CYP2B regulation.