Striated muscle activator of Rho signaling is required for myotube survival but does not influence basal protein synthesis or degradation

• DOI: 10.1152/ajpcell.00421.2012
• Publication Date: 2013-05-30T02:46:41Z
• Authors: Marita A. Wallace; Aaron P. Russell
• Keywords: 0301 basic medicine; Serum Response Factor; Cell Survival; Myoblasts, Skeletal; Microfilament Proteins; Muscle Fibers, Skeletal; Muscle Proteins; Ribosomal Protein S6 Kinases, 70-kDa; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Actins; Cell Line; Polymerization; Mice; 03 medical and health sciences; Gene Expression Regulation; Receptors, Estrogen; Animals; RNA Interference; RNA, Messenger; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction

Skeletal muscle mass is regulated by sensing and transmitting extracellular mechanical stress signals to intracellular signaling pathways controlling protein synthesis degradation. Striated activator of Rho (STARS) a muscle-specific actin-binding that sensitive signals. STARS stimulates actin polymerization influences serum response factor (SRF) peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α transcription genes involved in growth, structure, contraction. The role skeletal cells not well understood. This study investigated whether influenced C2C12 myotube growth regulating influence on Pgc-1α, Srf, Errα mRNA levels, as several their downstream targets cell contraction, metabolism, was also investigated. overexpression increased polymerization, with no effect synthesis, degradation, or Akt phosphorylation. Ckmt2, Cpt-1β, Mhc1 mRNA. knockdown reduced death dead protease activity. It markers inflammation ( Casp1, Il-1β, Mcp-1), regeneration Socs3 Myh8), fast myosin isoforms Mhc2a Mhc2x). We show for the first time increases shifts more oxidative phenotype. suppression causes necrosis, inflammation, regeneration. As levels are suppressed clinical models associated necrosis such aging limb immobilization, rescuing maybe future therapeutic strategy maintain function attenuate contraction-induced damage.