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

Mol Cell Endocrinol. 2006 Jun 7;251(1-2):67-77. doi: 10.1016/j.mce.2006.02.011. Epub 2006 Apr 3.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Anticholesteremic Agents / pharmacology
  • Cell Line
  • Clofibrate / pharmacology
  • Gene Expression
  • Gene Expression Regulation*
  • Genes, Reporter
  • Humans
  • Luciferases
  • PPAR alpha / metabolism*
  • Plasmids
  • Promoter Regions, Genetic
  • Rats
  • Retinoid X Receptor alpha / metabolism*
  • Scavenger Receptors, Class B / genetics*
  • Scavenger Receptors, Class B / metabolism
  • Sequence Analysis, DNA
  • Transfection

Substances

  • Anticholesteremic Agents
  • PPAR alpha
  • Retinoid X Receptor alpha
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B
  • Luciferases
  • Clofibrate