Role of autophagy adaptor in skeletal muscle
| Project/Area Number |
18H03153
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 59020:Sports sciences-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Okutsu Mitsuharu 名古屋市立大学, 大学院理学研究科, 准教授 (80409755)
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| Co-Investigator(Kenkyū-buntansha) |
山田 崇史 札幌医科大学, 保健医療学部, 准教授 (50583176)
岩田 全広 日本福祉大学, 健康科学部, 准教授 (60448264)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 骨格筋 / オートファジーアダプター / 抗酸化物質 / オートファジー基質 / 運動 |
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| Outline of Final Research Achievements |
Antioxidants reduce oxidative stress and protect muscle from atrophy. However, a functional role and molecular mechanism regulating the production antioxidants remains to be determined. Here, we demonstrated that Lewis lung carcinoma (LLC) cells implantation in mice induced severe muscle atrophy, as well as atrogenes and oxidative marker in associated with poor antioxidants expression. LLC implantation increased superoxide dismutase (SOD) protein expression in association with Nrf2 activation. Muscle-specific Nrf2 knockout (Nrf2mKO) mice induced severe cachexia-induced muscle atrophy in associated with blunted cachexia-induced SOD expression. Muscle-specific p62 overexpression (p62mTg) mice increased phosphorylated p62, Nrf2 activity, and SOD expression. Importantly, p62mTg mice protected cancer cachexia-induced muscle atrophy. Collectively, these findings indicate that Nrf2 activation by p62 plays an important role for the protection of cachexia-induced muscle atrophy.
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| Academic Significance and Societal Importance of the Research Achievements |
p62の機能に関するこれまでの報告は癌細胞などの悪化した細胞を対象にした研究が多く、骨格筋のような正常細胞を対象にした研究は少ない。また運動による骨格筋の適応について、p62に着目しその役割を遺伝子組換えマウスを作成して立証した報告は少なく、学術的意義がある。
癌、心不全や糖尿病などの疾患や加齢は骨格筋量を減少する。筋量の減少は廃用性症候群やロコモティブ症候群を発症することから、筋量を規定する分子メカニズムを解明し予防や治療に応用することは、健康寿命の延伸や医療費削減の観点から重要な課題である。本研究の成果は、当該分野に応用することで上記の課題を解決できる可能性があることから社会的意義がある。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but not exercise training-induced angiogenesis2019
Author(s)
Mami Yamada, Chihiro Hokazono, Ken Tokizawa, Shuri Marui, Masahiro Iwata, Vitor A. Lira, Katsuhiko Suzuki, Shinji Miura, Kei Nagashima, Mitsuharu Okutsu
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Journal Title
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Volume: 317
Issue: 6
Pages: R770-R779
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] 筋肉研究最前線2019
Author(s)
奥津光晴，山田麻未.（森谷敏夫編集）
Total Pages
341
Publisher
株式会社エヌ・ティー・エス
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