| Project/Area Number |
17500430
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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 Tokushima |
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Principal Investigator |
NIKAWA Takeshi The University of Tokushima, Institute of Health Biosciences, 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) |
YASUI Natsuo The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (00157984)
NAKAYA Yutaka The University of Tokushima, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (50136222)
NEMOTO Hisao The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (30208293)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | training / cerebellar ubiquitin ligase / Cbl-b-knochout mice / ataxia / ubiquitin ligase inhibitor / unloading / 神経細胞ユビキチンリガーゼ / ユビキチンリガーゼ阻害剤 / Cbl-b / トレーニング / 小脳 / Ataxin-7 / 尾部懸垂 |
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| Research Abstract |
Skeletal muscle unloading during prolonged bed rest, paralysis, or spaceflight can result in debilitating ataxia. Central nerve system senses unloading stress and represents ataxia characterized by both a decreased responsiveness to growth factors and increased proteolysis in neuron. Here we show that cerebellum senses unloading stress of skeletal muscle through the activation of neuron and induce Cbl-b, a cerebellar ubiquitin ligase. Upon unloading of skeletal muscle, Cbl-b interacted with and degrades ataxin-1, a responsible gene of spino cerebellar degeneration, and Cbl-associated protein (Cap) in cerebellum, leading to ataxia. In fact, Cbl-b deficiency prevented ataxia after unloading. In Cbl-b-overexpressing neural cells, Cbl-b interacted with Cap more strongly than ataxin-1, indicating that Cbl-b may indirectly bind to ataxin-1. In contrast, Cbl-b preferentially interacted with IRS-1 in skeletal muscle cells. To develop countermeasures against unloading-mediated ataxia, we finally found two oligopeptides (Patent pending), which possessed inhibitory action of Cbl-b-mediated ubiquitination. These data suggest that Cbl-b may be novel targets for the development of therapeutic strategies aimed at the preservation of ataxia during a variety of nerve degeneration as well as muscle wasting.
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