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pubmed-article:20018177pubmed:abstractTextThe 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 18h 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.lld:pubmed
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pubmed-article:20018177pubmed:authorpubmed-author:KrähenbühlSte...lld:pubmed
pubmed-article:20018177pubmed:authorpubmed-author:BrechtKarinKlld:pubmed
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pubmed-article:20018177pubmed:authorpubmed-author:MullenPeter...lld:pubmed
pubmed-article:20018177pubmed:authorpubmed-author:LüscherBarbar...lld:pubmed
pubmed-article:20018177pubmed:copyrightInfo2009 Elsevier Inc. All rights reserved.lld:pubmed
pubmed-article:20018177pubmed:issnTypeElectroniclld:pubmed
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pubmed-article:20018177pubmed:year2010lld:pubmed
pubmed-article:20018177pubmed:articleTitleEffect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy.lld:pubmed
pubmed-article:20018177pubmed:affiliationDepartment of Research, University Hospital Basel, Switzerland. peter.mullen@unibas.chlld:pubmed
pubmed-article:20018177pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20018177pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed