کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2513547 | 1118421 | 2010 | 10 صفحه PDF | دانلود رایگان |
The mechanism of statin-induced skeletal muscle myopathy is poorly understood. We investigated how simvastatin affects cholesterol metabolism, ubiquinone levels, and the prenylation and N-linked glycosylation of proteins in C2C12 myotubes. We used liver HepG2 cells for comparison, as their responses to statins are well-characterized in terms of their cholesterol metabolism (in contrast to muscle cells), and statins are well-tolerated in the liver. Differences between the two cell lines could indicate the mechanism behind statin-induced myopathy. Simvastatin reduced de novo cholesterol production in C2C12 myotubes by 95% after 18 h treatment. The reduction was 82% in the HepG2 cells. Total cholesterol pools, however, remained constant in both cell lines. Simvastatin treatment similarly did not affect total ubiquinone levels in the myotubes, unlike in HepG2 cells (22% reduction in CoQ10). Statin treatment reduced levels of Ras and Rap1 prenylation in both cell lines, whereas N-linked glycosylation was only affected in C2C12 myotubes (21% reduction in rate). From these observations, we conclude that total cholesterol and ubiquinone levels are unlikely to be involved in statin-mediated myopathy, but reductions in protein prenylation and especially N-linked glycosylation may play a role. This first comparison of the responses to simvastatin between liver and skeletal muscle cell lines may be important for future research directions concerning statin-induced myopathy.
Simvastatin reduces protein prenylation and N-linked glycosylation in C2C12 myotubes, whereas the total cholesterol and ubiquinone levels are not altered.Figure optionsDownload as PowerPoint slide
Journal: Biochemical Pharmacology - Volume 79, Issue 8, 15 April 2010, Pages 1200–1209