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Role of autophagy adaptor in skeletal muscle

Research Project

Project/Area Number 18H03153
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59020:Sports sciences-related
Research InstitutionNagoya City University

Principal Investigator

Okutsu Mitsuharu  名古屋市立大学, 大学院理学研究科, 准教授 (80409755)

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)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
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)
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
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.

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。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (31 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (20 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Book (1 results) Remarks (5 results)

  • [Int'l Joint Research] University of Iowa(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Iowa(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The University Iowa(米国)

    • Related Report
      2018 Annual Research Report
  • [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
    • Journal Title

      American Journal of Physiology. Regulatory, Integrative and Comparative Physiology

      Volume: 317 Issue: 6 Pages: R770-R779

    • DOI

      10.1152/ajpregu.00155.2019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] p62/SQSTM1 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in oxidative muscle2019

    • Author(s)
      Mami Yamada, Masahiro Iwata, Eiji Warabi, Hisashi Oishi, Vitor A. Lira, Mitsuharu Okutsu
    • Journal Title

      The FASEB Journal

      Volume: 印刷中 Issue: 7 Pages: 8022-8032

    • DOI

      10.1096/fj.201900133r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 運動による骨格筋の新たな抗酸化酵素の産生機構2021

    • Author(s)
      奥津光晴、山田麻未
    • Organizer
      第25回日本体力医学会東海地方会学術集会シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] Lack of muscle p62/SQSTM1 protects against high fat diet‐induced muscle wasting2020

    • Author(s)
      Yamada M, Okutsu M
    • Organizer
      Experimental Biology 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Muscle‐specific Nrf2 deficiency exacerbates cancer cachexia‐induced skeletal muscle atrophy2020

    • Author(s)
      Okutsu M, Yamada M
    • Organizer
      Experimental Biology 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オートファジー基質と骨格筋の恒常性維持2020

    • Author(s)
      奥津光晴、山田麻未
    • Organizer
      第75回日本体力医学会シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 骨格筋の筋量維持に対するオートファジーアダプターの役割2020

    • Author(s)
      奥津光晴
    • Organizer
      第6回日本筋学会シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 加齢性筋萎縮に対するオートファジー基質の役割2020

    • Author(s)
      山田麻未、奥津光晴
    • Organizer
      第75回日本体力医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Muscle contractile activity-mediated regulation of antioxidant enzymes in oxidative muscle requires p62 phosphorylation-induced Nrf2 activation2019

    • Author(s)
      Okutsu M.
    • Organizer
      14th symposium for International Society of Exercise and Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Muscle contractile activity-mediated regulation of antioxidant enzymes in oxidative muscle requires p62 phosphorylation-induced Nrf2 activation2019

    • Author(s)
      Okutsu M.
    • Organizer
      Hallym University-Nagoya City University International Joint Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Muscle contractile activity-mediated regulation of antioxidant enzymes in oxidative muscle requires p62/SQSTM1 phosphorylation-induced Nrf2 activation2019

    • Author(s)
      Yamada M, Iwata M, Warabi E, Oishi H, Lira VA, and Okutsu M
    • Organizer
      Experimental Biology 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but is not required for exercise training-induced angiogenesis2019

    • Author(s)
      Okutsu M, Yamada M, Hokazono C, Tokizawa K, Marui S, Iwata M, Lira VA, Suzuki K, Miura S, and Nagashima K
    • Organizer
      Experimental Biology 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高脂肪食摂取による筋萎縮に対するp62の役割2019

    • Author(s)
      山田麻未,奥津光晴.
    • Organizer
      第74回日本体力医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌カヘキシーによる筋萎縮に対するNrf2の役割2019

    • Author(s)
      奥津光晴,山田麻未.
    • Organizer
      第74回日本体力医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高脂肪食摂取による筋萎縮に対するオートファジー基質の役割2019

    • Author(s)
      山田麻未,奥津光晴.
    • Organizer
      第42回日本分子生物学年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌カヘキシーによる骨格筋萎縮におけるNrf2の役割2019

    • Author(s)
      奥津光晴,山田麻未.
    • Organizer
      第42回日本分子生物学年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Muscle contractile activity-mediated p62 phosphorylation im prove antioxidant enzymes in skeletal muscle thorough the activation of Keap1/Nrf2 pathway2019

    • Author(s)
      Yamada M, Iwata M, Okutsu M
    • Organizer
      第7回骨格筋生物学研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The role of Nrf2 in exercise training-mediated regulation of antioxidant enzymes in skeletal muscle2018

    • Author(s)
      Okutsu M, Yamada M, Iwata M
    • Organizer
      Experimental Biology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] p62/SQSTM1 is required for exercise training-mediated regulation of antioxidant enzymes in skeletal muscle2018

    • Author(s)
      Yamada M, Iwata M, Okutsu M
    • Organizer
      Experimental Biology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 運動による抗酸化物質の増加におけるNrf2の役割2018

    • Author(s)
      奥津光晴、山田麻未、岩田全広
    • Organizer
      第73回日本体力医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 運動によるp62の活性化と抗酸化物質の発現制御2018

    • Author(s)
      山田麻未、岩田全広、奥津光晴
    • Organizer
      第73回日本体力医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨格筋の収縮刺激による抗酸化物質の産生制御に対するNrf2の活性化2018

    • Author(s)
      山田麻未、岩田全広、奥津光晴
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [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
    • Related Report
      2019 Annual Research Report
  • [Remarks] 名古屋市立大学大学院 理学研究科 分子生理学

    • URL

      https://www.nsc.nagoya-cu.ac.jp/~okutsu/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 【プレスリリース】EurekAlert! by AAAS

    • URL

      https://www.eurekalert.org/pub_releases/2019-04/ncu-pan042519.php

    • Related Report
      2019 Annual Research Report
  • [Remarks] 【プレスリリース】日本の研究者.com

    • URL

      https://research-er.jp/articles/view/79014

    • Related Report
      2019 Annual Research Report
  • [Remarks] 【プレスリリース】名古屋市立大学

    • URL

      https://www.nagoya-cu.ac.jp/about/press/press/release/h31/#014852

    • Related Report
      2019 Annual Research Report
  • [Remarks] 名古屋市立大学大学院システム自然科学研究科分子生理学研究室

    • URL

      https://www.nsc.nagoya-cu.ac.jp/~okutsu/

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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