Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy
العنوان: | Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy |
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المؤلفون: | Peter J. Mullen, Barbara Lüscher, Karin Brecht, Hubert Scharnagl, Stephan Krähenbühl |
المصدر: | Biochemical Pharmacology. 79:1200-1209 |
بيانات النشر: | Elsevier BV, 2010. |
سنة النشر: | 2010 |
مصطلحات موضوعية: | Simvastatin, medicine.medical_specialty, Glycosylation, Ubiquinone, Muscle Fibers, Skeletal, Protein Prenylation, Biochemistry, chemistry.chemical_compound, Muscular Diseases, Internal medicine, medicine, Humans, Myocyte, RNA, Messenger, cardiovascular diseases, Myopathy, Cells, Cultured, Pharmacology, biology, Cholesterol, Myogenesis, nutritional and metabolic diseases, Skeletal muscle, Hep G2 Cells, Endocrinology, medicine.anatomical_structure, Receptors, LDL, chemistry, HMG-CoA reductase, biology.protein, Protein prenylation, lipids (amino acids, peptides, and proteins), Hydroxymethylglutaryl-CoA Reductase Inhibitors, medicine.symptom, Sterol Regulatory Element Binding Protein 2, medicine.drug |
الوصف: | 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 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. |
تدمد: | 0006-2952 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c1063186061476f284f227509ab0244Test https://doi.org/10.1016/j.bcp.2009.12.007Test |
حقوق: | CLOSED |
رقم الانضمام: | edsair.doi.dedup.....4c1063186061476f284f227509ab0244 |
قاعدة البيانات: | OpenAIRE |
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