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Role of SIRT1 in mitophagy in the skeletal muscle

Research Project

Project/Area Number 15K18992
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionSapporo Medical University

Principal Investigator

HOSODA RYUSUKE  札幌医科大学, 医学部, 助教 (20749428)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsマイトファジー / SIRT1 / オートファジー
Outline of Final Research Achievements

We found skeletal muscle dysfunction and impaired activation autophagy in skeletal muscle-specific SIRT1 knockout mice. These suggest that SIRT1 in skeletal muscle cells plays an important role in maintaining skeletal muscle function via autophagy. In myoblasts, resveratrol (RSV), a SIRT1 activator, promoted mitophagy. Mitochondrial reactive oxygen species (ROS) levels induced by antimycin A were significantly reduced by RSV. This effect of RSV was blocked by knockdown of PINK-1 which triggers mitophagy, suggesting that SIRT1 activation decrease mitochondrial ROS levels via mitophagy. We demonstrate using in vivo and in vitro models the relationship between SIRT1 and autophagy/mitophagy and its significance in skeletal muscle protection.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Pterostilbene and Its Glucoside Induce Type ⅩⅦ Collagen Expression2017

    • Author(s)
      Hiroki Hamada, Kei Shimoda, Yoshiyuki Horio, Tsubasa Ono, Ryusuke Hosoda, Noriyuki Nakayama and Koichi Urano
    • Journal Title

      Natural Product Communications

      Volume: 12 Pages: 85-86

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 筋ジストロフィーの新治療法の開発2016

    • Author(s)
      久野篤史、細田隆介、堀尾嘉幸
    • Journal Title

      Medical Science Digest

      Volume: 42 Pages: 642-646

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Sirt1-deficient mice have hypogonadotropic hypogonadism due to defective GnRH neuronal migration.2015

    • Author(s)
      Di Sante G, Wang L, Wang C, Jiao X, Casimiro MC, Chen K, Pestell TG, Yaman I, Di Rocco A, Sun X, Horio Y, Powell MJ, He X, McBurney MW, Pestell RG.
    • Journal Title

      Mol Endocrinol

      Volume: 29 Issue: 1 Pages: 200-212

    • DOI

      10.1007/s11060-014-1686-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Protective role of SIRT1 in the cardiomyocyte in doxorubicin-induced cardiotoxicity2017

    • Author(s)
      Ryusuke Hosoda, Kuno Atsushi, Sebori Rio, Yoshiyuki Horio
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホール アストピア (長崎県長崎市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Resveratrol restores autophagy and improve cardiac dysfunction in a mouse model of Duchenne muscular dystrophy2017

    • Author(s)
      久野 篤史, 細田 隆介, 瀬堀 理生, 堀尾 嘉幸
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホール アストピア (長崎県長崎市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心筋におけるSIRT1の欠損はドキソルビシン誘導性心筋障害を悪化させる2016

    • Author(s)
      細田 隆介, 久野 篤史, 瀬堀 理生, 堀尾 嘉幸
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 筋ジストロフィーの心筋障害におけるオートファジー不全の意義2016

    • Author(s)
      久野 篤史, 細田 隆介, 瀬堀 理生, 堀尾 嘉幸
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Ablation of SIRT1 in the cardiomyocyte aggravates doxorubicin cardiotoxicity in mice: Possible role of accumulation of deleted mtDNA.2016

    • Author(s)
      Ryusuke Hosoda, Atsushi Kuno, Rio Sebori, Yoshiyuki Horio
    • Organizer
      American Heart Association 2016 Scientific Sessions
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impaired autophagy induced by activated mTORC1 underlies development of dystrophic cardiomyopathy.2016

    • Author(s)
      Atsushi Kuno, Ryusuke Hosoda, Rio Sebori, Yoshiyuki Horio
    • Organizer
      American Heart Association 2016 Scientific Sessions
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス線維芽細胞での細胞老化におけるIGFBP5の役割2016

    • Author(s)
      細田隆介, 久野篤史, 戸田悠基, 斎藤慶樹, 瀬堀理生, 林貴士, 堀尾嘉幸
    • Organizer
      第89回日本薬理学年会
    • Place of Presentation
      パシフィコ横浜 会議センター(横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] ドキソルビシン誘導性心筋障害に対するSIRT1の役割解明2016

    • Author(s)
      細田隆介、久野篤史、瀬堀理生、堀尾嘉幸
    • Organizer
      第67回 薬理学会北部会
    • Place of Presentation
      北海道大学学術交流会館 (北海道札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ピセアタンノールとレスベラトロールの酸化ストレスに対する細胞保護効果の比較2015

    • Author(s)
      細田隆介, 久野篤史, 瀬堀理生, 濱田博喜, 堀尾嘉幸
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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