Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells. (24th December 2008)

• Record Type: Journal Article
• Authors: Seo, Makoto; Inoue, Ikuo; Ikeda, Masaaki; Nakano, Takanari; Takahashi, Seiichiro; Katayama, Shigehiro; Komoda, Tsugikazu
• Other Names: Glauert Howard Academic Editor.
• Is Part Of: PPAR research. Volume 2008(2008)
• Publication Date: 2008-12-24
• Subjects: Peroxisomes -- Periodicals; Peroxisomal disorders -- Periodicals; 571.65505
• DOI: 10.1155/2008/316306
• Languages: English
• ISSNs: 1687-4757

Abstract

Abstract : Statins increase peroxisome proliferator-activated receptorα (PPARα ) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin-induced HNF-4α . (2) PPARα mRNA expression was increased by statin treatment. (3) The PPARα levels in nuclear fractions were increased by statin treatment. (4) Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPARα /RXRα expression vectors. In summary, these data demonstrate that PPARα production and activation are upregulated through the PPARα promoter activity by statin treatment.