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SHR Neuro Cancer Cardio Lipid Metab Microb
Mullen, PJ; Lüscher, B; Scharnagl, H; Krähenbühl, S; Brecht, K.
Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy.
Biochem Pharmacol. 2010; 79(8): 1200-1209.
Doi: 10.1016/j.bcp.2009.12.007
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PubMed
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- Co-authors Med Uni Graz
- Scharnagl Hubert
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Cells, Cultured -
- Cholesterol - metabolism
- Glycosylation -
- Hep G2 Cells -
- Humans -
- Hydroxymethylglutaryl-CoA Reductase Inhibitors - metabolism
- Muscle Fibers, Skeletal - drug effects
- Muscular Diseases - chemically induced
- Protein Prenylation -
- RNA, Messenger - analysis
- Receptors, LDL - genetics
- Simvastatin - toxicity
- Sterol Regulatory Element Binding Protein 2 - metabolism
- Ubiquinone - analysis
- Find related publications in this database (Keywords)
- Statins
- Prenylation
- Ubiquinone
- Cholesterol
- N-linked glycosylation