IN-VIVO PHENOBARBITAL TREATMENT INCREASES PROTEIN-BINDING TO A PUTATIVE AP-1 SITE IN THE CYP2B2 PROMOTER

Phenobarbital (PB) is a potent inducer of cytochrome P450 enzymes, par ticularly CYP2B1/2B2. Although the mechanism(s) of PB Induction of CYP 2B1/2B2 is not fully understood, current research is focusing on the r ole PB may plap in altering the binding of nuclear proteins to critica l DNA response elements in the 5'-flanking region of these genes. Ln t his study, rat liver nuclear proteins were analyzed for DNA binding ab ility using both a general consensus and a CYP2B2 sequence-specific AP -1 oligonucleotide. We demonstrate that in vivo PB treatment enhances protein binding activity to the consensus AP-1 oligonucleotide. Likewi se, a putative AP-1 site, identified at -1441 in the CYP2B2 5'-flankin g region, also formed a sequence specific DNA/protein complex which wa s enhanced after PB exposure. These data may support a role of AP-1 in the PB induction mechanism of CYP2B1/2B2. (C) 1996 Academic Press, In c.