statins activate human ppar promoter and increase ppar mrna expression and activation in hepg2 cells他汀类药物激活人类ppar启动子和增加ppar mrna表达和激活hepg2细胞.pdfVIP

Hindawi Publishing Corporation PPAR Research Volume 2008, Article ID 316306, 11 pages doi:10.1155/2008/316306 Research Article Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells Makoto Seo,1 Ikuo Inoue,2 Masaaki Ikeda,3, 4 Takanari Nakano,1 Seiichiro Takahashi,2 Shigehiro Katayama,2 and Tsugikazu Komoda1 1 Department of Biochemistry, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan 2 Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan 3 Department of Physiology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan 4 Molecular Clock Project, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan Correspondence should be addressed to Makoto Seo, mkt.s.lev5060@ Received 17 June 2008; Revised 17 September 2008; Accepted 2 October 2008 Recommended by Howard Glauert Statins increase peroxisome proliferator-activated receptor α (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 sta