ArticleAmerican journal of physiology. Endocrinology and metabolism2011
Simvastatin represses protein synthesis in the muscle-derived C₂C₁₂ cell line with a concomitant reduction in eukaryotic initiation factor 2B expression.
Article in American journal of physiology. Endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Key genes and processes affected by atorvastatin treatment in mouse diaphragm muscle.Archives of toxicology · 2025Article
- Article
- Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases.Inflammopharmacology · 2023Review
- Management of Hypercholesterolemia Through Dietary ß-glucans-Insights From a Zebrafish Model.Frontiers in nutrition · 2021Article
- Diabetogenic effect of pravastatin is associated with insulin resistance and myotoxicity in hypercholesterolemic mice.Journal of translational medicine · 2019Article
- Insulin prevents and reverts simvastatin-induced toxicity in C2C12 skeletal muscle cells.Scientific reports · 2019Article
- Gene Co-expression Analysis Indicates Potential Pathways and Regulators of Beef Tenderness in Nellore Cattle.Frontiers in genetics · 2018Article
- A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles.BMC musculoskeletal disorders · 2016Article
- A Peculiar Formula of Essential Amino Acids Prevents Rosuvastatin Myopathy in Mice.Antioxidants & redox signaling · 2016Article
- Muscle rupture associated with statin use.British journal of clinical pharmacology · 2016Article
- The metabolic demands of cancer cells are coupled to their size and protein synthesis rates.Cancer & metabolism · 2013Article
- Identification of ubiquitin-modified lysine residues and novel phosphorylation sites on eukaryotic initiation factor 2B epsilon.Biochemical and biophysical research communications · 2013Article
- Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.The Journal of biological chemistry · 2012Article
- Article
- Considerations for Clinical Therapeutic Development of Statins for Neurodevelopmental Disorders.eNeuroArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Statins are a widely prescribed class of cholesterol lowering drugs whose use is frequently associated with muscle-related ailments. A number of mechanisms have been implicated in statin-induced myotoxicity including alterations in both protein synthesis and protein degradation. The objective of the present study was to explore the mechanism(s) contributing to the statin-induced reduction in protein synthesis in the muscle-derived C₂C₁₂ cell line. Cells were treated with 10 μM simvastatin or vehicle alone for 24 h in 1% serum. Cells exposed to simvastatin exhibited reduced rates of protein synthesis, as evidenced by [(35)S]methionine and [(35)S]cysteine incorporation into protein. The reduction in protein synthesis occurred with a concomitant decrease in expression and activity of eukaryotic initiation factor 2B (eIF2B), a regulated and rate-controlling guanine nucleotide exchange factor known to affect global rates of protein synthesis. The reductions in protein synthesis and eIF2B expression were prevented by coincubation with mevalonate. Simvastatin treatment also resulted in a proteasome-sensitive reduction in the protein expression of all the subunits of the eIF2B heteropentameric complex. Finally, increased phosphorylation of the catalytic ε-subunit at Ser(535) was observed, an event consistent with an observed reduction in eIF2B activity. These results suggest that repression of eIF2B expression and activity may contribute, at least in part, to the statin-induced reduction in protein synthesis.
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