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Elucidation of the cell protective mechanism of acetylcholinesterase variants in cardiomyocyte and approach to therapy for myocardial infarction

Research Project

Project/Area Number 18K15850
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKochi University

Principal Investigator

Todaka Hiroshi  高知大学, 教育研究部医療学系基礎医学部門, 助教 (80769662)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsAChE / AChE-R / 細胞保護作用 / 虚血ストレス / 心筋細胞 / 虚血性心疾患 / 細胞保護 / アセチルコリンエステラーゼ / アセチルコリン / 虚血 / 再灌流障害
Outline of Final Research Achievements

Acetylcholinesterase (AChE), an enzyme acting on rapid acetylcholine hydrolysis, expresses in the central and peripheral nervous system. Recently, it is reported that the expression of alternative splicing variants of AChE is elevated by multiple stress in the non-neural cell and are involved in the cell protection. However, the function of AChE variants in cardiomyocyte under ischemic stress remained unclear. In the present study, we found that the expression of readthrough-AChE (AChE-R) variant was increased in cardiomyocyte under ischemic stress. Furthermore, overexpression of AChE-R in the cardiomyocyte suppressed cell death under ischemic stress through the repression of apoptosis related-proteins levels. These results suggest that AChE-R may have a role to play in the cardioprotection under ischemic stress.

Academic Significance and Societal Importance of the Research Achievements

現代の虚血性心不全の治療においては、心筋保護療法の重要性が認識されつつある。本研究より心臓AChE-Rが虚血ストレス刺激に対して細胞保護に作用することが見出された。さらに心筋細胞へのAChE-Rの遺伝子導入は、細胞保護作用の増強を促した。以上の結果より、AChE-Rの遺伝子導入は虚血性心不全の病態改善および予後改善が期待され、虚血性心不全への新規治療法開発の足掛かりになると想定される。

Report

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

    (13 results)

All 2021 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Candidate plasticity gene 16 mediates suppression of insulin gene expression in rat insulinoma INS-1 cells under glucotoxic conditions.2019

    • Author(s)
      Nakane T, Ido A, Higuchi T, Todaka H, Morisawa K, Nagamine T, Fukunaga K, Sakamoto S, Murao K, Sugiyama Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 512 Issue: 2 Pages: 189-195

    • DOI

      10.1016/j.bbrc.2019.03.036

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship Between the Fall in Blood Pressure in the Standing Position and Diaphragmatic Muscle Thickness: Proof of Concept Study2019

    • Author(s)
      Ichikawa A, Yamasaki F, Ueda M, Todaka H, Miyao E, Yoshinaga Y, Yamanaka S, Matsumura Y, Sato T.
    • Journal Title

      Blood Press Monit

      Volume: 24 Issue: 6 Pages: 284-288

    • DOI

      10.1097/mbp.0000000000000403

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A negative feedback loop between nuclear factor 90 (NF90) and an anti-oncogenic microRNA, miR-72018

    • Author(s)
      Takuma Higuchi, Keiko Morisawa, Hiroshi Todaka, Sylvia Lai, Eunsup Chi, Kazutsugu Matsukawa, Yasunori Sugiyama, Shuji Sakamoto
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 503 Issue: 3 Pages: 1819-1824

    • DOI

      10.1016/j.bbrc.2018.07.119

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Donepezil, a drug for Alzheimer’s disease, promotes muscle differentiation during the process of regeneration2021

    • Author(s)
      Hiroshi Todaka, Mikihiko Arikawa, Tatsuya Noguchi, Atsushi Ichikawa, Takayuki Sato
    • Organizer
      the 126th Annual Meeting of The Japanese Association of Anatomists・the 98th Annual Meeting of The Physiological Society of Japan
    • Related Report
      2020 Annual Research Report
  • [Presentation] Donepezil, anti-Alzheimer drug, enhances myogenesis in C2C12 myoblasts2019

    • Author(s)
      Todaka H , Arikawa M , Noguchi T , Ichikawa A , Sato T
    • Organizer
      10th International Congress of Comparative Physiology and Biochemistry (ICCPB2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨格筋の分化・成熟化における細胞融合促進因子の新たな発現制御機構2019

    • Author(s)
      坂本修士、山口輝、樋口琢磨、森澤啓子、Sylvia Lai、戸高寛、藤田浩志、池恩燮、杉山康憲、松川和嗣、津田雅之
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨格筋の細胞融合及び成熟化におけるRNA結合タンパク質の役割の解明2019

    • Author(s)
      坂本修士、山口輝、森澤啓子、樋口琢磨、戸高寛、Sylvia Lai、池恩燮、藤田浩志、杉山康憲、松川和嗣、津田雅之
    • Organizer
      日本筋学会 第5回学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 糖毒性状態の膵臓β細胞においてCPG16はJDP2を介してインスリン発現を抑制する2019

    • Author(s)
      中根 達人、井戸 彩詠、樋口 琢磨、戸髙 寛、坂本 修士、村尾 孝児、杉山 康憲
    • Organizer
      第60回日本生化学会中国・四国支部会例会
    • Related Report
      2019 Research-status Report
  • [Presentation] 神経関連因子Bri3は膵臓β細胞におけるアポトーシスを促進する2019

    • Author(s)
      井上 楓、中根 達人、飯田 悟史、戸高 寛、樋口 琢磨、坂本 修士、村尾 孝児、杉山 康憲
    • Organizer
      第60回日本生化学会中国・四国支部会例会
    • Related Report
      2019 Research-status Report
  • [Presentation] Acetylcholinesterase inhibitor accelerates muscle differentiation in C2C12 myoblasts2019

    • Author(s)
      Hiroshi Todaka, Mikihiko Arikawa, Tatsuya Noguchi, Atsushi Ichikawa, Takayuki Sato
    • Organizer
      9th FAOPS CONGRESS
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] コリンエステラーゼ阻害剤を用いた筋再生機構の解明2018

    • Author(s)
      戸高寛, 有川幹彦, 野口達哉, 市川厚, 佐藤隆幸
    • Organizer
      第70回日本生理学会中四国地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵臓β細胞におけるCPG16-JDP2を介した新規インスリン発現抑制機構の解明2018

    • Author(s)
      中根達人, 井戸彩詠, 樋口琢磨, 戸高寛, 坂本修士, 村尾孝児, 杉山康憲
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Nuclear Factor 90(NF90)の発現はmiR-7を介したフィードバックループにより制御される2018

    • Author(s)
      樋口琢磨, 戸高寛, 森澤啓子, Sylvia Lai, 池恩燮, 杉山康憲, 坂本修士
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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