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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• 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 / ユビキチン-プロテアソーム経路 / Cbl-b / 機能性ペプチド

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.

Research Products

• [Journal Article] Local Applications of Myostatin-siRNA with Atelocollagen Increse Skeletal Muscle Mass and Recovery of Muscle Function (2013)
  • Author(s): Kawakami E, Kawai N, Kinouchi N, Mori H, Ohsawa Y, Ishimaru N, Sunada Y, Noji S, Tanaka E
  • Journal Title: PLoS One Volume: 8 Issue: 5 Pages: e64719-e64719
  • DOI: 10.1371/journal.pone.0064719
  • Peer Reviewed
• [Journal Article] Changes in activity and structure of jaw muscles in Parkinson's disease model rats (2013)
  • Author(s): Nakamura S, Kawai N, Ohnuki Y, Saeki Y, Korfage JA, Langenbach GE, Kitayama T, Watanabe M, Sano R, Tanne K, Tanaka E
  • Journal Title: Journal of Oral Rehabilitation Volume: 40 Issue: 3 Pages: 205-213
  • DOI: 10.1111/joor.12030
  • Peer Reviewed
• [Presentation] 抗ユビキチン化ペプチドによる骨格筋萎縮抑制法の開発 (2013)
  • Author(s): 川合 暢彦, 平坂 勝也, 七條 なつ子, 塩田 智子, 森 博世, 木内 奈央, 二川健, 田中 栄二
  • Organizer: 第72回日本矯正歯科学会大会
  • Place of Presentation: 長野県. 松本市
• [Presentation] アテロコラーゲンを担体とした抗ユビキチン化ペプチドによる骨格筋萎縮抑制 (2013)
  • Author(s): 川合 暢彦, 平坂 勝也, 塩田 智子, 越智 ありさ, 安倍 知紀, 真板 綾子, 近藤 茂忠, 田中 栄二 , 二川 健
  • Organizer: 日本宇宙生物科学会・第27回大会
  • Place of Presentation: 茨城県. つくば市
• [Presentation] アテロコラーゲンを担体とした抗ユビキチン化ペプチドによる骨格筋萎縮抑制 (2013)
  • Author(s): 川合 暢彦, 平坂 勝也, 塩田 智子, 越智 ありさ, 安倍 知紀, 真板 綾子, 近藤 茂忠, 田中 栄二 , 二川 健
  • Organizer: 日本宇宙生物科学会・第27回大会
  • Place of Presentation: 筑波大学 (茨城県)
• [Presentation] 抗ユビキチン化ペプチドによる骨格筋萎縮抑制法の開発 (2013)
  • Author(s): 川合 暢彦, 平坂 勝也, 七條 なつ子, 塩田 智子, 森 博世, 木内 奈央, 二川 健, 田中 栄二
  • Organizer: 第72回日本矯正歯科学会大会
  • Place of Presentation: キッセイ文化ホール (長野県)