Regulation of Bcl-2 and Bcl-xL anti-apoptotic protein expression by nuclear receptor PXR in primary cultures of human and rat hepatocytes.

摘要: The pregnane X receptor (PXR) plays a major role in the protection of body by regulating genes involved metabolism and elimination potentially toxic xeno- endobiotics. We previously described that PXR activator dexamethasone protects hepatocytes from spontaneous apoptosis. hypothesise PXR-dependent co-regulation process between detoxication programmed cell death. Using primary cultured human rat hepatocytes, we investigated to determine if is implicated regulation Bcl-2 Bcl-xL, two crucial apoptosis inhibitors. In present study demonstrated treatment with agonists increased hepatocyte viability them staurosporine-induced anti-apoptotic capacity activation was correlated Bcl-xL induction at both transcriptional protein levels man rats, respectively. inhibition expression antisense oligonucleotide abolished activators induction. Accordingly, overexpression HepG2 cells led bcl-2 upon clotrimazole against Fas-induced Our results demonstrate required for up-regulation hepatocytes. They also suggest may protect liver chemicals simultaneously apoptotic pathway.