Activation of the rat scavenger receptor class B type I gene by PPARα

Peroxisomal proliferator activated receptor α (PPARα) is activated by fibrate drugs which are known to protect against atherosclerosis. The present study examines the effects of PPARα on SR-BI expression. For this study, a rat SR-BI promoter-luciferase reporter gene construct was co-transfected into different cell lines with expression vectors that encode for PPARα ± retinoic X receptor α (RXRα). PPARα/RXR increased the activity of the SR-BI promoter, an effect that was enhanced by clofibrate. Sequence analysis of the rat SR-BI promoter revealed the presence of a putative peroxisomal proliferator response element (PPRE) at bp −1622. Electrophoretic mobility shift assays demonstrated that PPARα and RXRα are able to bind to the SR-BI PPRE motif. In addition, mutational analysis studies confirmed that this PPRE motif is responsible for the PPARα/RXRα-dependent activation of the rat SR-BI promoter in the cell lines examined.