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PPAR Research
Volume 2008 (2008), Article ID 316306, 11 pages
http://dx.doi.org/10.1155/2008/316306
Research Article

Statins Activate Human PPAR 𝛼 Promoter and Increase PPAR 𝛼 mRNA Expression and Activation in HepG2 Cells

1Department of Biochemistry, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan
2Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan
3Department of Physiology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan
4Molecular Clock Project, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan

Received 17 June 2008; Revised 17 September 2008; Accepted 2 October 2008

Academic Editor: Howard Glauert

Copyright © 2008 Makoto Seo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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