2019 Fiscal Year Final Research Report
Mechanisms of mechanostress transmissions from nerves to muscles - metabolisms and adaptive responses
| Project Area | "LIVING IN SPACE" - Integral Understanding of life-regulation mechanism from "SPACE" |
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| Project/Area Number |
15H05937
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Complex systems
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
東端 晃 国立研究開発法人宇宙航空研究開発機構, 有人宇宙技術部門, 主任研究開発員 (30360720)
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| Project Period (FY) |
2015-06-29 – 2020-03-31
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| Keywords | 重力 / 筋萎縮 / メカノトランスダクション / ドーパミン / BMP/TGF-b / カルシウムシグナル / 宇宙滞在 |
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| Outline of Final Research Achievements |
The purpose of this study is to investigate the mechanism by which the C. elegans mechanosensor molecule/neuronal system adapts to changes in muscle and metabolism under space experiments and various culture conditions on the ground. As a result, in C. elegans grown under space microgravity, both gene and protein expression levels for muscular thick filaments, cytoskeletal elements, and mitochondrial metabolic enzymes decreased relative to parallel cultures on the 1G centrifuge. In addition, a growth factor BMP released from motor nerves and sensory nerve dopamine are reduced in the spaceflown C. elegans. Furthermore, the mechanism from mitochondrial damage to muscle atrophy has been demonstrated that Ca2+ overaccumulation in the muscular cells, activation of furin and MMPs, and ECM degradation are the major processes of muscle collapse.
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| Free Research Field |
分子遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
筋細胞におけるミトコンドリア障害からその萎縮に向かうメカニズムの解明は、老化に伴う筋萎縮機構に通じる。今回、Ca2+過剰が筋細胞のECM分解を促し、最終的に筋細胞の崩壊プロセスが進行することを明らかにしたが、この機構は加齢や筋ジストロフィー症においても同様にみられることから、ECMの分解に関わるMatrix Metalloprotease (MMP)やその活性化酵素FurinもいずれもCa2+依存性のendopeptidasesなど分解に関わる酵素の抑制は、宇宙フライト時における筋細胞の萎縮、崩壊のみならず加齢や疾病による筋萎縮を抑えるターゲット分子になることが示唆された。
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