Activation of the rat scavenger receptor class B type I gene by PPARalpha.
Peroxisomal proliferator activated receptor alpha (PPARalpha) is activated by fibrate drugs which are known to protect against atherosclerosis. The present study examines the effects of PPARalpha 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 PPARalpha+/-retinoic X receptor alpha (RXRalpha). PPARalpha/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 -1,622. Electrophoretic mobility shift assays demonstrated that PPARalpha and RXRalpha are able to bind to the SR-BI PPRE motif. In addition, mutational analysis studies confirmed that this PPRE motif is responsible for the PPARalpha/RXRalpha-dependent activation of the rat SR-BI promoter in the cell lines examined.
Department of Obstetrics and Gynecology, University of South Florida, College of Medicine, 12901 Bruce B Downs Blvd., MDC 37, Tampa, 33612, USA.
Dayami
D
Lopez
Mark P
MP
McLean
D020816:Amino Acid Motifs; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002460:Cell Line; D002994:Clofibrate / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases; D047493:PPAR alpha / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D051381:Rats; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014162:Transfection
D000924:Anticholesteremic Agents; D047493:PPAR alpha; D047490:Retinoid X Receptor alpha; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D008156:Luciferases; D002994:Clofibrate