Stimulation of cardiac cardiolipin biosynthesis by PPARα activation

Journal of Lipid Research

William A. Taylor¹  Grant M. Hatch¹  Patrick C. Choy²  Jennifer Gartshore²  Biao Lu³  Frank J. Gonzalez³  Jun Takasaki⁴  Fred Y. Xu⁴  Yan J. Jiang⁵  Andrew J. Halayko⁵ 

[1] Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan;National Cancer Institute, National Institutes of Health, Bethesda, MD;Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;Center for Research and Treatment of Atherosclerosis and Departments of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;

关键词: phospholipid;    heart;    lipid metabolism;    gene expression;    gene regulation;   

DOI  :  

来源: DOAJ

【 摘 要 】

The role of peroxisome proliferator-activated receptor α (PPARα)-stimulated phospholipase A2 (PLA2) in cardiac mitochondrial cardiolipin (CL) biosynthesis was examined in both in vivo and in vitro models. Treatment of rat heart H9c2 cells with clofibrate increased the expression and activity of 14 kDa PLA2 but did not affect the pool size of CL. Clofibrate treatment stimulated de novo CL biosynthesis via an increase in phosphatidylglycerolphosphate (PGP) synthase activity, accounting for the unaltered CL content. Cardiac PLA2, PGP synthase, and CDP-1,2-diacyl-sn-glycerol synthase (CDS-2) activities and CDS-2 mRNA levels were elevated in mice fed clofibrate for 14 days compared with controls. In PPARα-null mice, clofibrate feeding did not alter cardiac PLA2, PGP synthase activities, or CDS-2 activity and mRNA level, confirming that these enzymes are regulated by PPARα activation. In contrast to mouse heart, clofibrate treatment did not affect the activity or mRNA levels of CDS-2 in H9c2 cells, indicating that CDS-2 is regulated differently in rat heart H9c2 cells in vitro and in mouse heart in vivo.These results clearly indicate that cardiac CL de novo biosynthesis is stimulated by PPARα activation in responsive rodent models and that CDS-2 is an example of an enzyme that exhibits alternative regulation in vivo and in cultured cell lines. This study is the first to demonstrate that CL de novo biosynthesis is regulated by PPARα activation.

【 授权许可】

Unknown