SB431542 TREATMENT PROMOTES THE HYPERTROPHY OF SKELETAL MUSCLE FIBERS BUT DECREASES SPECIFIC FORCE
Kevin I Watt, Richard T Jaspers, Phillip Atherton, Ken Smith, Michael J Rennie, Aivaras Ratkevicius, Henning Wackerhage
Muscle & Nerve | WILEY | Published : 2010
The small molecule inhibitor SB431542 inhibits activin type I receptors. The muscle growth-inhibitor myostatin binds to and signals via these receptors. The aim of this study was to test the hypothesis that SB431542 can inhibit myostatin-related Smad signaling and induce muscle growth in cultured C2C12 myotubes and increase growth and specific force in cultured Xenopus muscle fibers. The effect of SB431542 was assessed in vitro on C2C12 myotubes and ex vivo using mature Xenopus muscle fibers. SB431542 treatment reduced myostatin-induced C-terminal Smad2 phosphorylation and resulted in the formation of enlarged myotubes. However myogenin expression was unchanged, while p70 S6k phosphorylation..View full abstract
We thank Dr. K. Baar, University of Dundee, Dundee, UK, for his support, advice, and kind gift of a total myosin heavy chain antibody. We thank Dr. A. Hughes, University of Aberdeen, for his support and advice. We thank Dr. W.J. van der Laarse, Department of Physiology, VU University Medical Center, for his support in the culture of mature Xenopus muscle fibers. This work was presented in part at the European College of Sports Science Conference (ECSS) 12th July 2007, Jyvaskylia, Finland. This work was funded by the School of Medicine and Dentistry, University of Aberdeen and the Bone and Musculoskeletal Programme, University of Aberdeen.