| Project/Area Number |
15500449
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Sports science
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| Research Institution | The University of Tokuahima |
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Principal Investigator |
NIKAWA Takeshi The University of Tokushima, Department of Health Bioscience, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (20263824)
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| Co-Investigator(Kenkyū-buntansha) |
KISHI Kyoichi The University of Tokushima, Department of Health Bioscience, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (80035435)
NAKAYA Yutaka The University of Tokushima, Department of Health Bioscience, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (50136222)
YASUI Natsuo The University of Tokushima, Department of Health Bioscience, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (00157984)
SAIRYO Koichi The University of Tokushima, Department of Health Bioscience, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 講師 (10304528)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Cbl-b / unloading / ubiquitin-ligase / spaceflight / tail-suspension / insulin resistance / muscle atrophy / ユビチキンリガーゼ / インスリン / インスリン様増殖因子 / Unloading |
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| Research Abstract |
Skeletal muscle unloading during prolonged bed rest, paralysis, or spaceflight can result in debilitating skeletal muscle atrophy. Reduced muscle mass is characterized by a combination of decreased protein synthesis and increased protein degradation. Currently, there is no treatment to reverse the progression of atrophy. Here we show that Cbl-b, a RING-type member of the ubiquitin ligase family, is essential for skeletal muscle atrophy. Expression of Cbl-b in vivo induces significant atrophy in rat tibialis anterior muscle. In contrast, Cbl-b deficient mice are resistant to muscle atrophy and dysfunction induced during unloading by tail suspension. Upon tail suspension or zero gravity, Cbl-b interacts with and thereby degrades the skeletal muscle growth factor signaling intermediate IRS-1. Thus, Cbl-b activation appears to underlie the refractoriness of atrophic muscle tissue to growth factor stimulation by IGF/insulin and likely accounts for the overall decrease in protein synthesis observed during muscle wasting. These data suggest that Cbl-b may be a novel target for the development of therapeutics aimed at the preservation of muscle mass and function during a variety of muscle wasting diseases.
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