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

Peroxisomal proliferator activated receptor alpha (PPAR alpha) is activated by fibrate drugs which are known to protect against atherosclerosis. The present study examines the effects of PPARa 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 PPAR alpha retinoic X receptor alpha (RXR alpha). PPAR alpha/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 PPAR alpha and RXRa are able to bind to the SR-BI PPRE motif. In addition, mutational analysis studies confirmed that this PPRE motif is responsible for the PPAR alpha/RXR alpha-dependent activation of the rat SR-BI promoter in the cell lines examined. (c) 2006 Elsevier Ireland Ltd. All rights reserved.