Current Perspective : Mechanism of Statin-Induced Rhabdomyolysis
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- Sakamoto Kazuho
- Department of Pharmacology, Fukushima Medical University School of Medicine, Japan
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- Kimura Junko
- Department of Pharmacology, Fukushima Medical University School of Medicine, Japan
書誌事項
- タイトル別名
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- Mechanism of Statin-Induced Rhabdomyolysis
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Statins, a group of drugs used for the treatment of hypercholesterolemia, have adverse effects on skeletal muscle. The symptoms of these effects range from slight myalgia to severe rhabdomyolysis. The number of patients currently taking statins is estimated to be several millions worldwide. However, the mechanism of statins’ myotoxic effects is unclear. Statins inhibit biosynthesis of mevalonate, a rate-limiting step of cholesterol synthesis, by inhibiting HMG-CoA reductase. Mevalonate is also an essential precursor for producing isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate. These isoprenoids are especially important for anchoring small GTPases to the membrane before they function; e.g., Ras GTPases modulate proliferation and apoptosis, Rho GTPases control cytoskeleton formation, and Rab GTPases are essential for intracellular vesicle trafficking. Inactivation of these small GTPases alters cellular functions. Recently, we successfully reproduced statin-induced myotoxicity in culture dishes using in vitro skeletal muscle systems (e.g., skeletal myotubes and myofibers). This review summarizes our findings that statins induce depletion of isoprenoids and inactivation of small GTPases, especially Rab, which are critical for statin-induced myotoxicity. Although further study is required, our findings may contribute to the prevention and treatment of statins’ adverse effects on skeletal muscle and development of safer anti-hypercholesterolemia drugs.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 123 (4), 289-294, 2013
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680157600640
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- NII論文ID
- 130003382619
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- NII書誌ID
- AA11806667
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- COI
- 1:CAS:528:DC%2BC2cXktlOlug%3D%3D
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 025108947
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- PubMed
- 24257439
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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