RRC ID 6569
Author Baba TT, Nemoto TK, Miyazaki T, Oida S.
Title Simvastatin suppresses the differentiation of C2C12 myoblast cells via a Rac pathway.
Journal J. Muscle Res. Cell. Motil.
Abstract Statins, which are known as cholesterol-lowering drugs, have several additional effects including the enhancement of bone formation and the stimulation of smooth muscle cell proliferation. In this study, we investigated the signal pathway of simvastatin operating in C2C12 myoblast cells. Myotube formation of C2C12 cells was efficiently blocked by 1 muM simvastatin, and mevalonic acid was able to cancel this effect. Geranylgeranyl pyrophosphate restored the myotube formation, whereas farnesyl pyrophosphate did not. These findings demonstrate that the Rho family, such as Rho, Rac and Cdc42, occurring downstream of geranylgeranyl pyrophosphate in the mevalonic acid pathway, was involved in the simvastatin-mediated blockage of myotube formation. An inhibitor of Rho kinase did not influence the myotube formation; whereas an inhibitor of Rac blocked this process. Taken together, we conclude that the differentiation of C2C12 cells into myotubes was blocked by simvastatin through the pathway mediated by Rac, not by Rho.
Volume 29(2-5)
Pages 127-34
Published 2008
DOI 10.1007/s10974-008-9146-9
PMID 18792797
MeSH Alkaline Phosphatase / metabolism Amides / pharmacology Aminoquinolines / pharmacology Animals Bone Morphogenetic Protein 2 / genetics Bone Morphogenetic Protein 2 / pharmacology Cell Differentiation / drug effects* Cells, Cultured Gene Expression / drug effects Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Mevalonic Acid / pharmacology Muscle Fibers, Skeletal / cytology Muscle Fibers, Skeletal / metabolism Myoblasts, Skeletal / cytology Myoblasts, Skeletal / drug effects* Myoblasts, Skeletal / metabolism Myogenin / genetics Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / metabolism Polyisoprenyl Phosphates / pharmacology Protein Kinase Inhibitors / pharmacology Pyridines / pharmacology Pyrimidines / pharmacology Recombinant Proteins / pharmacology Sesquiterpenes / pharmacology Signal Transduction / drug effects* Simvastatin / pharmacology* rac GTP-Binding Proteins / antagonists & inhibitors rac GTP-Binding Proteins / metabolism* rho-Associated Kinases / antagonists & inhibitors
IF 2.102
Times Cited 10
Human and Animal Cells