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Analysis of regulation mechanisms of thermosensitive TRP channels and their involvement in immune responses

Research Project

Project/Area Number 23249012
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOkazaki Research Facilities, National Institutes of Natural Sciences

Principal Investigator

TOMINAGA Makoto  大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 教授 (90260041)

Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥48,490,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥11,190,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2012: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2011: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Keywords生理学 / 神経科学
Outline of Final Research Achievements

Thermosensitive TRPM2 channels expressed in mouse mucosal mast cells were found to participate in antigen-induced extracellular Ca2+ influx and subsequent degranulation. In addition, hydrogen peroxide was found to lower the temperature threshold for TRPM2 activation through methionine oxidation, indicating that temperature threshold for TRPM2 activation is regulated by redox signals that enable channel activity at physiological body temperatures. Loss of TRPM2 attenuated zymosan-evoked macrophage functions, including cytokine release and fever-enhanced phagocytic activity. The hydrogen peroxide-induced TRPM2-sensitization mechanism through oxidation was also found to work in mouse pancreatic  cells where glucose-induced oscillation of intracellular Ca2+ concentrations and insulin release was TRPM2- and redox status-dependent.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (12 results)

All 2015 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (5 results) Remarks (3 results)

  • [Journal Article] Redox signal-mediated enhancement of the temperature sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) elevated glucose-induced insulin secretion from pancreatic islets.2015

    • Author(s)
      Kashio M, Tominaga M.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 19 Pages: 12435-12442

    • DOI

      10.1074/jbc.m115.649913

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRPM2 contributes to antigen-stimulated Ca2+ influx in mucosal mast cells.2013

    • Author(s)
      Oda S, Uchida K, Wang X, Lee J, Shimada Y, Tominaga M, Kadowaki M.
    • Journal Title

      Pflugers Archiv. Eur. J. Physiol.

      Volume: 465 Issue: 7 Pages: 1023-1030

    • DOI

      10.1007/s00424-013-1219-y

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox signal-mediated sensitization of Transient Receptor Potential Melastatin 2 (TRPM2) to temperature affects macrophage functions2012

    • Author(s)
      Makiko Kashio, et al
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: (In press) Issue: 17 Pages: 6745-6750

    • DOI

      10.1073/pnas.1114193109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox signal-mediated sensitization of Transient Receptor Potential Melastatin 2 (TRPM2) to temperature affects macrophage functions

    • Author(s)
      Kashio M, Sokabe T, Shintaku K, Uematsu T, Fukuta N, Kobayashi N, Mori Y, Tominaga M
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Redox signal-mediated sensitization of Transient Receptor Potential Melastatin 2 (TRPM2) to temperatures affects insulin secretion from the pancreatic βcells.2015

    • Author(s)
      加塩麻紀子、丸中良典、富永真琴
    • Organizer
      第92回日本生理学大会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] レドックスシグナルを介したTRPM2感作の分子機構とマクロファージ機能への寄与2012

    • Author(s)
      加塩麻紀子、曽我部隆彰、森泰生、富永真琴
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      松本市総合体育館(長野県)
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Redox signal-mediated sensitization of Transient Receptor Potential Melastatin 2 (TRPM2) to temperatures affects insulin secretion from the pancreatic β-cells.

    • Author(s)
      加塩麻紀子、富永真琴
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学(鹿児島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] レドックスシグナルによるTRPM2 感作機構とマクロファージ機能への寄与

    • Author(s)
      加塩麻紀子、富永真琴
    • Organizer
      第59回日本中部生理学会
    • Place of Presentation
      岡崎カンファレンスセンター(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 過酸化水素によるTRPM2機能制御と生理機能

    • Author(s)
      加塩麻紀子、曽我部隆彰、森泰生、富永真琴
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Related Report
      2012 Annual Research Report
  • [Remarks] 細胞生理部門 富永研究室ホームページ

    • URL

      http://www.nips.ac.jp/cs/

    • Related Report
      2014 Annual Research Report
  • [Remarks] http://www.nips.ac.jp/cs/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 自然科学研究機構岡崎統合バイオサイエンスセンター 細胞生理研究部門

    • URL

      http://www.nips.ac.jp/cs/

    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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