کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10771119 | 1050838 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, and fatigability) occur frequently. We hypothesized that the iatrogenic effects of statins could result from alterations in Ca2+ homeostasis. Acute applications of simvastatin on human skeletal muscle fibers triggered a Ca2+ wave of intra-cellular Ca2+ that mostly originates from sarcoplasmic reticulum (SR) Ca2+-release. In addition, simvastatin increased mitochondrial NADH content and induced mitochondrial membrane depolarization (EC50 = 1.96 μM) suggesting an altered mitochondrial function. Consequently on simvastatin application, a weak mitochondrial Ca2+ efflux (EC50 = 7.8μM) through permeability transient pore and Na+/Ca2+ exchanger was triggered, preceding the large SR-Ca2+ release. Increased SR Ca2+ content after acute application of statin is also suggested by the increased Ca2+ spark amplitude and by the effect of cyclopiazonic acid. We thus conclude that simvastatin induced alterations in mitochondrial function which lead to an increase in cytoplasmic Ca2+, SR-Ca2+ overload, and Ca2+ waves. Taken together, these statin-induced muscle dysregulations may contribute to myotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 3, 15 April 2005, Pages 1067-1075
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 3, 15 April 2005, Pages 1067-1075
نویسندگان
Pascal Sirvent, Jacques Mercier, Guy Vassort, Alain Lacampagne,