DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation.

摘要: The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction human CYP 2B6 and mouse 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced 2B1 rat primary hepatocytes is down-regulated both n-6 n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, mechanism for this down-regulation DHA was previously unknown. objective present determine whether change CAR translocation involved PUFAs hepatocytes. We used 100 microM arachidonic acid, linoleic eicosapentaenoic test hypothesis. PB triggered from cytosol into nucleus a dose-dependent time-dependent manner our hepatocyte system, distribution significantly affected DHA. treatment decreased PB-inducible accumulation nuclear fraction increased it cytosolic manner. occurred manner, similar pattern found results immunoprecipitation CAR/RXR heterodimer bound binding site 1 (NR-1) PB-responsive enhancer module (PBREM) 2B1gene. EMSA NR-1 attenuated Taken together, these suggest attenuation subsequent are DHA's expression.