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Elucidation of mechanisms underlying regulation of inflammatory cellular responses by redox-sensitive TRP channels.

Research Project

Project/Area Number 24249017
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKyoto University

Principal Investigator

Mori Yasuo  京都大学, 地球環境学堂, 教授 (80212265)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
Fiscal Year 2015: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2013: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2012: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Keywordsカルシウム / TRP / チャネル / レドックス / 活性酸素種 / 炎症 / 生理学 / イオンチャネル / シグナル伝達 / ストレス / 癌
Outline of Final Research Achievements

Reactive oxygen species (ROS) and electrophiles, known to exert stress on organisms, are emerging as mediators of cellular signals. Transient Receptor Potential (TRP) Ca2+-permeable cation channels are activated by various triggers from outside and inside the cell. We and others have revealed that multiple redox-sensitive TRPs sense ROS to induce diverse physiological/pathological responses, such as cell death, chemotaxis, and pain transduction. TRPs sense ROS/electrophiles either indirectly through second messengers or directly via oxidative modification of cysteine residues. In this project, I clarified roles of redox-sensitive TRPs in inflammation. In particular, TRPM2 turned out to be a key signal regulator for diverse inflammatory cellular responses. Also, TRPA1 showed a unique, high sensitivity to oxidants including O2. Understanding the physiological significance of redox-sensitive TRPs will lead us to consider these TRP channels as viable therapeutic targets.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (19 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (2 results) Remarks (1 results)

  • [Int'l Joint Research] トロント大学/ウェスタン大学(カナダ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] TRPC3 amplifies B cell receptor-induced ERK signaling via protein kinase D-dependent Rap1 activation2016

    • Author(s)
      T. Numaga-Tomita, M. Nishida, J.W. Jr. Putney and Y. Mori
    • Journal Title

      Biochem J

      Volume: 473(2) Issue: 2 Pages: 201-210

    • DOI

      10.1042/bj20150596

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds2016

    • Author(s)
      S. Sawamura, M. Hatano, Y. Takada, K. Hino, T. Kawamura, J. Tanikawa, H. Nakagawa, H. Hase, A. Nakao, M. Hirano, R. Rotrattanadumrong, S. Kiyonaka, M.X. Mori, M. Nishida, Y. Hu, R. Inoue, R. Nagata and Y. Mori
    • Journal Title

      Mol Pharmacol

      Volume: 89(3) Issue: 3 Pages: 348-363

    • DOI

      10.1124/mol.115.102863

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line2016

    • Author(s)
      Badr H, Kozai D, Sakaguchi R, Numata T, Mori Y
    • Journal Title

      Front. Pharmacol.

      Volume: 7 Pages: 19-19

    • DOI

      10.3389/fphar.2016.00019

    • NAID

      120005848247

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] TRPM2 channels in alveolar epithelial cells mediate bleomycin-induced lung inflammation2016

    • Author(s)
      Yonezawa R, Yamamoto S, Takenaka M, Kage Y, Negoro T, Toda T, Ohbayashi M, Numata T, Nakano Y, Yamamoto T, Mori Y, Ishii M, Shimizu S
    • Journal Title

      Free Radic Biol Med

      Volume: 90 Pages: 101-113

    • DOI

      10.1016/j.freeradbiomed.2015.11.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment2015

    • Author(s)
      Ostapchenko VG, Chen M, Guzman MS, Xie YF, Lavine N, Fan J, Beraldo FH, Martyn AC, Belrose JC, Mori Y, MacDonald JF, Prado VF, Prado MA, Jackson MF
    • Journal Title

      J. Neurosci.

      Volume: 35, Issue: 45 Pages: 15157-15169

    • DOI

      10.1523/jneurosci.4081-14.2015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transient receptor potential melastatin 2 protects mice against polymicrobial sepsis by enhancing bacterial clearance.2014

    • Author(s)
      Qian X, Numata T, Zhang K, Li C, Hou J, Mori Y & Fang X
    • Journal Title

      Anesthesiology

      Volume: 121 Issue: 2 Pages: 336-351

    • DOI

      10.1097/aln.0000000000000275

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRPM2 mediates the lysophosphatidic acid-induced neurite retraction in the developing brain.2014

    • Author(s)
      Jang Y, Lee MH, Lee J, Jung J, Lee SH, Yang DJ, Kim BW, Son H, Lee B, Chang S, Mori Y & Oh U
    • Journal Title

      Pflugers Arch.

      Volume: 466 Issue: 10 Pages: 1987-1998

    • DOI

      10.1007/s00424-013-1436-4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P22014

    • Author(s)
      Nobuaki Takahashi, Sayaka Hamada-Nakahara, Yuzuru Itoh, Kazuhiro Takemura, Atsushi Shimada,Yoshifumi Ueda, Manabu Kitamata, Rei Matsuoka, Kyoko Hanawa-Suetsugu, Yosuke Senju, Masayuki X. Mori, Shigeki Kiyonaka, Daisuke Kohda, Akio Kitao, Yasuo Mori and Shiro Suetsugu
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 4994-4994

    • DOI

      10.1038/ncomms5994

    • NAID

      130005100825

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transnitrosylation directs TRPA1 selectivity in N-nitrosamine activators.2014

    • Author(s)
      Kozai D, Kabasawa Y, Ebert M, Kiyonaka S ; Finnan, Otani Y, Numata T, Takahashi N, Mori Y, Ohwada T.
    • Journal Title

      Molecular Pharmacology

      Volume: 85 Issue: 1 Pages: 175-185

    • DOI

      10.1124/mol.113.088864

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells2013

    • Author(s)
      Shigeki Kiyonaka, Taketoshi Kajimoto, Reiko Sakaguchi, Daisuke Shinmi, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Hiromi Imamura, Takenao Yoshizaki, Itaru Hamachi, Takashi Morii, Yasuo Mori
    • Journal Title

      Nature Methods

      Volume: 10 Issue: 12 Pages: 1232-1238

    • DOI

      10.1038/nmeth.2690

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRP channels as sensors of oxygen availability.2013

    • Author(s)
      Numata T, Ogawa N, Takahashi N, Mori Y
    • Journal Title

      Pflügers Archiv – European Journal of Physiology

      Volume: 465 Issue: 8 Pages: 1075-1085

    • DOI

      10.1007/s00424-013-1237-9

    • NAID

      120005474466

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial ischaemia/reperfusion injury2013

    • Author(s)
      Hiroi T, Wajima T, Negoro T, Ishii M, Yasuko Nakano, Kiuchi K, Mori Y, and Shimizu S
    • Journal Title

      Cardiovasc Res

      Volume: vol.97 Issue: 2 Pages: 271-281

    • DOI

      10.1093/cvr/cvs332

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of TRPM2 function protects against irradiation-induced salivary gland dysfunction.2013

    • Author(s)
      Liu X, Cotrim A, Teos L, Zheng C, Swaim W, Mitchell J, Mori Y, Ambudkar I
    • Journal Title

      Nature Communication

      Volume: 4 Issue: 1 Pages: 1515-1515

    • DOI

      10.1038/ncomms2526

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRPM2 links oxidative stress to NLRP3 inflammasome activation.2013

    • Author(s)
      Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L
    • Journal Title

      Nature Communication

      Volume: 4 Issue: 1 Pages: 1611-1611

    • DOI

      10.1038/ncomms2608

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells2014

    • Author(s)
      Kiyonaka S, Kajimoto T, ○Sakaguchi R, Shinmi D, Omatsu-Kanbe M, Matsuura H, Imamura H, Yoshizaki T, Hamachi I, Morii T, Mori Y
    • Organizer
      58th Annual Meeting of the Biophysical Society
    • Place of Presentation
      California, USA
    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
  • [Presentation] 心臓TRPM2は、虚血・再灌流障害を増悪させる2014

    • Author(s)
      沼田朋大、清水俊一、森泰生
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島県、鹿児島市
    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
  • [Remarks] 【森研究室】京都大学大学院工学研究科 合成・生物化学専攻 分子生物化学分野 森研究室

    • URL

      http://www.sbchem.kyoto-u.ac.jp/mori-lab/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-15   Modified: 2022-01-28  

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