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Elucidation of regulatory mechanisms of mitochondria regulation by ERAD in failing heart and its therapeutic application.

Research Project

Project/Area Number 20K22902
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionKyushu University

Principal Investigator

Ikeda Soichiro  九州大学, 医学研究院, 共同研究員 (00885410)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords心不全 / 小胞体 / ミトコンドリア / 心筋リモデリング / 小胞体ストレス / 小胞体関連分解
Outline of Research at the Start

重症心不全は未だ予後不良であり新たな治療戦略が求められているが、細胞内小器官(オルガネラ)をターゲットとした治療戦略は皆無である。近年小胞体とミトコンドリアの相互作用が細胞機能維持に重要であることが明らかとなっている。また小胞体関連分解(ER-associated degradation: ERAD)は小胞体の不良タンパクのみならず分泌タンパクや細胞質タンパクを制御することが明らかとなっている。本研究は不全心筋においてERADの構成タンパクであるHERPUD1がミトコンドリア機能を制御することで細胞機能維持を担っている可能性を検証するものである。

Outline of Final Research Achievements

In failing heart after myocardial infarction, HERPUD1 protein levels were increased. HERPUD1 was also increased in cardiomyocytes treated with H2O2. Homozygous HERPUD1 knockout mice exacerbated cardiac dysfunction after myocardial infarction. Overexpression of HERPUD1 by adenovirus ameliorated mitochondria dysfunction and cell death in cardiomyocytes treated with H2O2. HERPUD1 may have a protective role in failing heart after myocardial infarction by attenuating mitochondria dysfunction and cardiomyocytes death.

Academic Significance and Societal Importance of the Research Achievements

本研究は心筋細胞における小胞体およびミトコンドリア制御機構を明らかにすることで、心不全の新たな病態機序を明らかにし、加えて新たな新規治療法の開発に発展する可能性がある。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] GFAT2 mediates cardiac hypertrophy through HBP-O-GlcNAcylation-Akt pathway2021

    • Author(s)
      Ishikita Akihito、Matsushima Shouji、Ikeda Soichiro、Okabe Kosuke、Nishimura Ryohei、Tadokoro Tomonori、Enzan Nobuyuki、Yamamoto Taishi、Sada Masashi、Tsutsui Yoshitomo、Miyake Ryo、Ikeda Masataka、Ide Tomomi、Kinugawa Shintaro、Tsutsui Hiroyuki
    • Journal Title

      iScience

      Volume: 24 Issue: 12 Pages: 103517-103517

    • DOI

      10.1016/j.isci.2021.103517

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Excessive Hypoxia‐Inducible Factor‐1α Expression Induces Cardiac Rupture via p53‐Dependent Apoptosis After Myocardial Infarction2021

    • Author(s)
      Ikeda Masataka、Ide Tomomi、Tadokoro Tomonori、Miyamoto Hiroko Deguchi、Ikeda Soichiro、Okabe Kosuke、Ishikita Akihito、Sato Midori、Abe Ko、Furusawa Shun、Ishimaru Kosei、Matsushima Shouji、Tsutsui Hiroyuki
    • Journal Title

      Journal of the American Heart Association

      Volume: 10 Issue: 17 Pages: 1-15

    • DOI

      10.1161/jaha.121.020895

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heart Rate Reduction with Ivabradine Prevents Cardiac Rupture after Myocardial Infarction in Mice2021

    • Author(s)
      Ikeda Masataka、Ide Tomomi、Furusawa Shun、Ishimaru Kosei、Tadokoro Tomonori、Miyamoto Hiroko Deguchi、Ikeda Soichiro、Okabe Kosuke、Ishikita Akihito、Abe Ko、Matsushima Shouji、Tsutsui Hiroyuki
    • Journal Title

      Cardiovascular Drugs and Therapy

      Volume: - Issue: 2 Pages: 257-262

    • DOI

      10.1007/s10557-020-07123-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Downregulation of HERPUD1 exacerbates oxidative stress-induced mitochondrial dysfunction and cardiomyocyte death2020

    • Author(s)
      池田 宗一郎
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report

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Published: 2020-09-29   Modified: 2023-01-30  

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