2015年10月
Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- 巻
- 466
- 号
- 3
- 開始ページ
- 536
- 終了ページ
- 540
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bbrc.2015.09.065
- 出版者・発行元
- ACADEMIC PRESS INC ELSEVIER SCIENCE
HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. (C) 2015 Elsevier Inc. All rights reserved.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.bbrc.2015.09.065
- ISSN : 0006-291X
- eISSN : 1090-2104
- Web of Science ID : WOS:000363094400042