2013 Fiscal Year Final Research Report

Development of the inhibition of skeletal muscle atrophy with anti-ubiquitination oligopeptide

Research Project

Project/Area Number	24792289
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Orthodontic/Pediatric dentistry
Research Institution	The University of Tokushima
Principal Investigator	KAWAI Nobuhiko 徳島大学, ヘルスバイオサイエンス研究部, 助教 (40437588)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	骨格筋萎縮 / ユビキチンン-プロテアソーム経路 / IGF-1シグナル
Research Abstract	In atrophied muscles, ubiquitin ligase, Cbl-b, increases and it stimulates the ubiquitination and degradation of IRS-1, an intermediate in IGF-1 singnaling pathway, resulting in IGF-1 resistance. In this study, we evaluate the efficacy of application of anti-ubiquitination oligopeptide that inhibits the interaction between Cbl-b and IRS-1 into starved C2C12 myotubes and denervated tibialis anterior muscle of C57BL/6 wild-type mice. Oligopeptide significantly inhibited the decrease of AKT phosphorylation in starved myotubes. In addition, sectional area of denervated muscle fibers treated with oligopeptide was significantly larger compared to non-treated denervated muscles. These results suggest that application of anti-ubiquitination oligopeptide could be an effective tool for therapeutic use in muscular atrophy diseases.