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Development of a remedy for ischemic necrosis using cell volume regulation ability created from intermolecular cooperation

Research Project

Project/Area Number 21K06792
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionAkita University

Principal Investigator

Numata Tomohiro  秋田大学, 医学系研究科, 教授 (20455223)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords細胞容積調節 / TRPM7 / LRRC8 / VSOR
Outline of Research at the Start

虚血性疾患は、世界で最も大きな死因の一つである。虚血性傷害は、壊死に陥った組織を回復させることは極めて困難であるため、壊死を未然に抑えるための治療法が求められている。虚血誘発性細胞死は、虚血後に急速な細胞膨大が続き、最終的に壊死となる。その
ため壊死を防ぐためには、細胞膨大させる機構を知る必要性が高まった。細胞膨大に働くイオンチャネルは、最近の研究結果によりTRPが分子実体であることが分かり、より詳細な解析が可能である。今回の研究では、①細胞膨大過程で働くカチオン流入抑制、②膨大した細胞を元の容積へ戻す機構の開発により虚血誘発性細胞膨大壊死からの救済することを目的とする。

Outline of Final Research Achievements

The research aimed to investigate the role of two proteins, namely TRPM7 and VSOR, in the cell volume regulation mechanism. TRPM7 protein has the ability to sense mechanical stimulation, while VSOR protein is an anion channel that helps cells to recover their original size. The study found that these two proteins work together to suppress cell swelling and allow cells to return to their original volume. They achieve this through a physical interaction between TRPM7 and the VSOR core molecule LRRC8A during cell swelling. Additionally, the functional coupling of TRPM7-VSOR was revealed through the measurement of two types of ion channels that work together.

Academic Significance and Societal Importance of the Research Achievements

細胞は、からだを作る最小単位として、その大きさが変化しても元の大きさに戻る仕組みを備えている。しかし、種々の病理的条件下でこの調節機能を失うと、細胞は死滅し、そのことが原因で病気となる。細胞の大きさを調節するメカニズムを理解することは、細胞の生死の制御を行うことにつながるため、がん細胞の治療法開発などへの応用が期待される。この研究成果は、細胞の生存メカニズムの解明に貢献し、将来的にはさまざまな病気の治療法の革新に寄与する可能性がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (58 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (7 results) Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (38 results) (of which Int'l Joint Research: 14 results,  Invited: 6 results) Remarks (2 results)

  • [Int'l Joint Research] ウズベキスタン国立科学アカデミー生物有機化学研究所(ウズベキスタン)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Paracelsus Medical University(オーストリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ハワイ大学(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] マックスプランク分子生理学/労働生理学研究所(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Louisiana State University(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] ハワイ大学(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] ウズベキスタン大学(ウズベキスタン)

    • Related Report
      2021 Research-status Report
  • [Journal Article] 漢方便秘薬 潤腸湯による腸の水分分泌メカニズムの解明2024

    • Author(s)
      沼田 朋大
    • Journal Title

      Akita Med.J

      Volume: 74 Pages: 1-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intermediate Conductance Ca2+-Activated Potassium Channels Are Activated by Functional Coupling with Stretch-Activated Nonselective Cation Channels in Cricket Myocytes2023

    • Author(s)
      T. Numata, K. Sato-Numata, M. Yoshino
    • Journal Title

      Front. Insect Sci.

      Volume: 2 Pages: 1100671-1100671

    • DOI

      10.3389/finsc.2022.1100671

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca2+ homeostasis in cardiomyocytes2023

    • Author(s)
      Tagashira Hideaki、Bhuiyan Md. Shenuarin、Shinoda Yasuharu、Kawahata Ichiro、Numata Tomohiro、Fukunaga Kohji
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 151 Issue: 2 Pages: 128-133

    • DOI

      10.1016/j.jphs.2022.12.005

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Classes on “Structure and Function of the Animal Body” in 2nd Grade Junior High School Science Classes Based on Measurement of Human Phonocardiogram and Electrocardiogram: Application of the ICST System2023

    • Author(s)
      YOSHINO M, KATSUKI T, ASAHI S, NUMATA T, MATSUKAWA M, HARADA K,HASEGAWA T
    • Journal Title

      Bull. Tokyo Gakugei Univ. Div. Nat. Sci.

      Volume: 75 Pages: 63-75

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy2023

    • Author(s)
      Tagashira H, Abe F, Sato-Numata K, Aizawa K, Hirasawa K, Kure Y, Iwata D, Numata T.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 11 Pages: 1264076-1264076

    • DOI

      10.3389/fcell.2023.1264076

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM72023

    • Author(s)
      Okada Yasunobu、Numata Tomohiro、Sabirov Ravshan Z.、Kashio Makiko、Merzlyak Peter G.、Sato-Numata Kaori
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 11 Pages: 1246955-1246955

    • DOI

      10.3389/fcell.2023.1246955

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of the Role of Ion Channels in Cell Volume Regulation and Development of New Methods for Controlling Ion Channel Activity for Medical Applications2022

    • Author(s)
      沼田 朋大
    • Journal Title

      秋田医学

      Volume: 49 Issue: 1 Pages: 1-9

    • DOI

      10.20569/00006052

    • URL

      https://air.repo.nii.ac.jp/records/5740

    • Year and Date
      2022-06-30
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death2021

    • Author(s)
      Okada Yasunobu、Sato-Numata Kaori、Sabirov Ravshan Z.、Numata Tomohiro
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 702317-702317

    • DOI

      10.3389/fcell.2021.702317

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasopressin Neurons Respond to Hyperosmotic Stimulation with Regulatory Volume Increase and Secretory Volume Decrease by Activating Ion Transporters and Ca2+ Channels2021

    • Author(s)
      Sato-Numata Kaori, Numata Tomohiro, Ueta Yoichi, Okada Yasunobu
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 55 Issue: S1 Pages: 119-134

    • DOI

      10.33594/000000342

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] BK Channels Are Activated by Functional Coupling With L-Type Ca2+ Channels in Cricket Myocytes2021

    • Author(s)
      Numata Tomohiro、Sato-Numata Kaori、Yoshino Masami
    • Journal Title

      Frontiers in Insect Science

      Volume: 1 Pages: 662414-662414

    • DOI

      10.3389/finsc.2021.662414

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM7 is an essential regulator for volume-sensitive outwardly rectifying anion channel2021

    • Author(s)
      Numata Tomohiro、Sato-Numata Kaori、Hermosura Meredith C.、Mori Yasuo、Okada Yasunobu
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 599-599

    • DOI

      10.1038/s42003-021-02127-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Elucidation of the mechanism of 5-HT-mediated activity of parasympathetic-like PC12 cells and the effect of Hange-Shashin-To2024

    • Author(s)
      Kaori Sato-Numata, Ryo Takayama, Keitatsu Ishikawa, Hirono Sugawara, Ayako Sakai, Tomohiro Numata
    • Organizer
      The 101th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] U937細胞のヒスタミン誘発性細胞縮小における分子メカニズムと小青竜湯、柴胡桂枝湯の効果2024

    • Author(s)
      青山碧透、小薮賢太郎、岡田龍馬、菅原弘乃、酒井 彩子、佐藤(沼田)かお理、沼田朋大
    • Organizer
      The 101th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel Approaches to Alleviate Heart Failure: A Focus on Moku-boi-to and Angiotensin II Receptor Blockade2024

    • Author(s)
      Fumiha Abe, Hideaki Tagashira, Tomohiro Numata
    • Organizer
      The 101th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional coupling between mechanosensitive channels and IK channels in the regulation of oviduct contraction2024

    • Author(s)
      Ayako Sakai, Kaori Sato-Numata, Masami Yoshino, Tomohiro Numata
    • Organizer
      The 101th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of K+ channels and Cl- channels in the water excretion effect of Boui-Ougi-To2024

    • Author(s)
      Taro Suzuki, Haruna Saito, Ayako Sakai, Kaori Sato-Numata, Yasunobu Okada, Tomohiro Numata
    • Organizer
      The 101th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Moku-boi-to's Defensive Mechanism Against ET-1-Induced Cardiac Damage2024

    • Author(s)
      Hideaki Tagashira, Fumiha Abe, Tomohiro Numata
    • Organizer
      The 101th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The exacerbation mechanism of cardiomyocyte injury by cardiac Sigma-1 receptor knockdown.2023

    • Author(s)
      Hideaki Tagashira, Yasuharu Shinoda, Tomohiro Numata, Kohji Fukunaga
    • Organizer
      The 100th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional coupling between BK and L-type Ca2+ channels found in cricket oviducts2023

    • Author(s)
      Tomohiro Numata, Kaori Sato-Numata, Masami Yoshino
    • Organizer
      The 100th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of LRRC8D in the regulatory volume decrease in human epithelial cells.2023

    • Author(s)
      Kaori Sato-Numata, Taro Suzuki, Ayako Sakai, Shuntaro Mori, Yasunobu Okada, Tomohiro Numata
    • Organizer
      The 100th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of the water secretion mechanism of Boui-ougi-to and its application to cancer therapeutic agents2023

    • Author(s)
      Taro Suzuki, Haruna Saito, Kaori Sato-Numata, Tomohiro Numata
    • Organizer
      The 100th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 心筋小胞体-ミトコンドリア近接形成とCa2+恒常性維持におけるSigma-1受容体の役割2023

    • Author(s)
      Hideaki Tagashira, Yasuharu Shinoda, Tomohiro Numata, Kohji Fukunaga
    • Organizer
      JTRAQ13
    • Related Report
      2023 Annual Research Report
  • [Presentation] 漢方便秘薬による腸の水分分泌メカニズムの解明2023

    • Author(s)
      沼田 朋大
    • Organizer
      第 87 回秋田県医学会総会 秋田県医師会設立76周年記念医学大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 動的エキシトンを利用した細胞膜機能の光制御2023

    • Author(s)
      村上 達也, 福田 亮介, 沼田 朋大
    • Organizer
      学術変革A領域会議「動的エキシトン」(台湾)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒスタミン誘発性細胞縮小に対する小青竜湯と柴胡桂枝湯の効果2023

    • Author(s)
      岡田龍馬、小薮賢太郎、青山碧透、菅原弘乃、佐藤(沼田)かお理、 沼田朋大
    • Organizer
      第55回東北生理談話会
    • Related Report
      2023 Annual Research Report
  • [Presentation] HEK293T細胞の八味地黄丸による水分分泌機構の解明2023

    • Author(s)
      渡邉俊介、佐藤(沼田)かお理、沼田朋大
    • Organizer
      第55回東北生理談話会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 防已黄耆湯の細胞死とCl-チャネルへの影響2023

    • Author(s)
      鈴木太郎、齊藤遥菜、佐藤(沼田)かお理、沼田朋大
    • Organizer
      第55回東北生理談話会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 漢方薬「木防已湯」の心筋保護作用とその作用機序の解明2023

    • Author(s)
      阿部史葉、田頭秀章、沼田朋大
    • Organizer
      第55回東北生理談話会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Hypotonicity-induced mechano-sensitivity of cultured Schwann cells2023

    • Author(s)
      Chawapun Suttinont, Tomohiro Numata, Moe Tsutsumi
    • Organizer
      Neuroscience 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of protective mechanism against AngII-induced cardiomyocyte injury by Moku-boi-to2023

    • Author(s)
      Hideaki Tagashira, Fumiha Abe, Tomohiro Numata
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細胞内分子シャペロン蛋白質に着目した新規腎疾患治療薬の開発2023

    • Author(s)
      田頭 秀章、福永浩司、沼田 朋大
    • Organizer
      第74回日本薬理学会北部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The exacerbation mechanism of cardiomyocyte injury by cardiac Sigma-1 receptor knockdown.2023

    • Author(s)
      H. Tagashira, Y. Shinoda, T. Numata, K. Fukunaga
    • Organizer
      "The 100th Annual Meeting for The Physiological Society of Japan  "
    • Related Report
      2022 Research-status Report
  • [Presentation] Functional coupling between BK and L-type Ca2+ channels found in cricket oviducts2023

    • Author(s)
      T. Numata, K. Sato-Numata, M. Yoshino
    • Organizer
      "The 100th Annual Meeting for The Physiological Society of Japan  "
    • Related Report
      2022 Research-status Report
  • [Presentation] The role of LRRC8D in the regulatory volume decrease in human epithelial cells.2023

    • Author(s)
      K. Sato-Numata, T. Suzuki, A. Sakai, S. Mori, Y. Okada, T. Numata
    • Organizer
      "The 100th Annual Meeting for The Physiological Society of Japan  "
    • Related Report
      2022 Research-status Report
  • [Presentation] Elucidation of the water secretion mechanism of Boui-ougi-to and its application to cancer therapeutic agents2023

    • Author(s)
      T. Suzuki, H. Saito, K. Sato-Numata, T. Numata
    • Organizer
      "The 100th Annual Meeting for The Physiological Society of Japan  "
    • Related Report
      2022 Research-status Report
  • [Presentation] The regulation mechanisms of mitochondrial Ca2+ signaling mediated by cardiac Sigma-1 receptor2022

    • Author(s)
      H. Tagashira, Y. Shinoda, T. Numata, K. Fukunaga
    • Organizer
      The 96th Annual Meeting for the Japanese Phrmacological Society
    • Related Report
      2022 Research-status Report
  • [Presentation] 様々な炎症反応に対する大防風湯の効果2022

    • Author(s)
      佐々木花純, 佐藤(沼田)かお理, 沼田朋大
    • Organizer
      第54回東北生理談話会
    • Related Report
      2022 Research-status Report
  • [Presentation] LRRC8Dチャネルの細胞容積調節能における役割の解明2022

    • Author(s)
      鈴木太郎, 佐藤(沼田)かお理, 酒井彩子, 森俊太郎, 沼田朋大
    • Organizer
      第54回東北生理談話会
    • Related Report
      2022 Research-status Report
  • [Presentation] 防已黄耆湯による水分分泌機構の解明2022

    • Author(s)
      齊藤 遥菜, 佐藤(沼田)かお理, 沼田朋大
    • Organizer
      第54回東北生理談話会
    • Related Report
      2022 Research-status Report
  • [Presentation] New role of TRPM7 in cell volume regulation mechanism2022

    • Author(s)
      T. Numata
    • Organizer
      "The 99th Annual Meeting for The Physiological Society of Japan  "
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Search for intracellular signals affecting the activity of acid-sensitive outwardly rectifying anion channel (ASOR)2022

    • Author(s)
      T. Numata, K. Sato-Numata, Y. Okada
    • Organizer
      "The 99th Annual Meeting for The Physiological Society of Japan  "
    • Related Report
      2022 Research-status Report
  • [Presentation] イオンチャネルの細胞容積調節能における意義と医療応用を目指した新たな活性制御法の開発2022

    • Author(s)
      T. Numata
    • Organizer
      令和3年度 秋田医学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] イオンチャネルの細胞容積調節能における意義と医療応用を目指した新たな活性制御法の開発2022

    • Author(s)
      沼田朋大
    • Organizer
      令和3年度 秋田医学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] New role of TRPM7 in cell volume regulation mechanism2022

    • Author(s)
      Tomohiro Numata
    • Organizer
      The 99th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Search for intracellular signals affecting the activity of acid-sensitive outwardly rectifying anion channel (ASOR)2022

    • Author(s)
      Kaori Sato-Numata, Tomohiro Numata, Yasunobu Okada
    • Organizer
      The 99th Annual Meeting for The Physiological Society of Japan
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 光誘導性電荷分離分子の細胞への応用とその活性化メカニズムの解明2021

    • Author(s)
      沼田朋大
    • Organizer
      第4回動的エキシトン若手セミナー
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 光誘導性D-A分子による細胞膜脱分極と再分極メカニズムの解明2021

    • Author(s)
      沼田 朋大, 佐藤(沼田)かお理, 今堀 博, 村上 達也
    • Organizer
      学術変革領域(A)「動的エキシトンの学理構築と機能開拓」第3回領域会議
    • Related Report
      2021 Research-status Report
  • [Presentation] 細胞生理機能制御のための光誘導性分子による脱分極機構の解明2021

    • Author(s)
      沼田朋大、佐藤(沼田)かお理
    • Organizer
      第53回東北談話会
    • Related Report
      2021 Research-status Report
  • [Presentation] 細胞容積調節機構におけるTRPM7の新たな役割2021

    • Author(s)
      沼田朋大
    • Organizer
      生理研研究会 構造情報を基盤とした膜機能分子の生理機能理解に向けて
    • Related Report
      2021 Research-status Report
  • [Remarks] 秋田大学大学院医学系研究科 器官・統合生理学講座

    • URL

      https://www.med.akita-u.ac.jp/~seiri2/index.html

    • Related Report
      2022 Research-status Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/read0125113

    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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