Phosphorylation/dephosphorylation steps are crucial for the induction of CYP2B1 and CYP2B2 gene expression by phenobarbital

The effects of several protein kinase activators and protein phosphatase in hibitors on the phenobarbital (PB)-induced gene expression of CYP2B1 and CY P2B2 (CYP2B1/2B2) in adult rat hepatocytes were investigated. Insulin, epid ermal growth factor, interleukin 6, cAMP, phorbol la-myristate 13-acetate, tumor necrosis factor alpha, vanadate, and okadaic acid were found to suppr ess the induction of CYP2B1/2B2 at mRNA and protein levels in hepatocytes. cAMP and vanadate completely suppressed the induction of CYP2B1/2B2 gene ex pression in both rat hepatocytes and liver. The addition of genistein to va nadate-treated hepatocytes partially recovered the induction of CYP-2B1/2B1 gene expression by PB. These results of the present study demonstrate that phosphorylation/dephosphorylation steps are crucial for the induction of C YP2B1/2B2 gene expression by PB. (C) 1999 Academic Press.