| Project/Area Number |
24390355
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
NIKAWA Takeshi 徳島大学, ヘルスバイオサイエンス研究部, 教授 (20263824)
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| Co-Investigator(Kenkyū-buntansha) |
SOKABE Masahiro 名古屋大学, 大学院医学研究科, 教授 (10093428)
KOBAYASHI Takeshi 名古屋大学, 大学院医学研究科, 助教 (40402565)
SUZUKI Yutaka 東京大学, 大学院新領域創成科学研究科, 教授 (40323646)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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| Keywords | 筋萎縮 / メカノセンシング / ユビキチンリガーゼ / ミトコンドリア / メカノセンサー / 酸化ストレス / 無重力 / 次世代シークエンサー |
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| Outline of Final Research Achievements |
Ubiquitin ligase Cbl-b plays a crucial role in disuse-mediated muscle atrophy: Cbl-b caused ubiquitination and subsequent degradation of IRS-1, resulting in skeletal muscle atrophy. Since Cbl-b in skeletal muscle is preferentially expressed under unloading conditions, we hypothesized that elucidating the regulation pathway of Cbl-b expression leads to the clarification of the sensing mechanism for unloading stress. Here we report the mechanism of sensing for microgravity, using rat or mouse skeletal myotubes cultured under unloading conditions. Microgravity or simulated microgravity conditions significantly caused decrease in myotube diameter, indicating that skeletal muscle myotubes per se can sense microgravity stress. Furthermore, there was a potent oxidative stress responsive element from -110 to -60 bp of the Cbl-b promoter. We suggest that unloading stress induced muscle atrophy through oxidative stress-mediated Cbl-b expression and mitochondria dysfunction.
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