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Studies on temperature sensitivity and molecular identity of the acid-sensitive outwardly rectifying anion channel (ASOR) in neurons in relation to the mechanism of hypothermic neuroprotection

Research Project

Project/Area Number 25670112
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionThe Graduate University for Advanced Studies (2014)
National Institute for Physiological Sciences (2013)

Principal Investigator

OKADA Yasunobu  総合研究大学院大学, 学長 (10025661)

Co-Investigator(Kenkyū-buntansha) NUMATA Kaori (SATO Kaori)  生理学研究所, 細胞器官研究系, 研究員 (60614196)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsアニオンチャネル / 温度感受性 / 酸毒性 / ニューロン / 低体温療法 / 酸毒性死
Outline of Final Research Achievements

In the brain, strong acidosis is a common feature of ischemia, seizure, trauma and hyperglycemia, and it contributes to neuronal injury. On the other hand, the acid-sensitive outwardly rectifying anion channel (ASOR) has been found in non-neuronal cell types and to be involved in acidotoxic cell death. In the present study, we found that ASOR is expressed in mouse cortical neurons and involved in acidotoxic neuronal cell death. Also, it was found that the neuronal ASOR exhibits strong sensitiviry to temperature and that acidotoxic neuronal necrosis is largely protected by reduction of temperature to 25℃. Thus, it is suggested that this high temperature sensitivity provides a basis for hypothermic neuroprotection under acidotoxic conditions. Furthermore, we tried to identify the ASOR molecule. Using the gene-silencing technique, a number of the candidates were excluded from the molecular entity of ASOR.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (6 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Temperature sensitivity of acid-sensitive outwardly rectifying (ASOR) anion channels in cortical neurons is involved in hypothermic neuroprotection against acidotoxic necrosis.2014

    • Author(s)
      Sato-Numata K, Numata T, Okada Y
    • Journal Title

      Channels (Austin)

      Volume: 8 Issue: 3 Pages: 278-283

    • DOI

      10.4161/chan.27748

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A newly cloned ClC-3 isoform, ClC-3d, as well as ClC-3a mediates Cd^<2+>-sensitive outwardly rectifying anion currents.2014

    • Author(s)
      岡田俊昭、秋田天平、佐藤(沼田)かお理、Md. Rafiqul Islam、岡田泰伸
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 33 Issue: 3 Pages: 539-556

    • DOI

      10.1159/000358633

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR) anion channel in the central nervous system.2014

    • Author(s)
      T. Akita & Y. Okada
    • Journal Title

      Neuroscience

      Volume: 275 Pages: 211-231

    • DOI

      10.1016/j.neuroscience.2014.06.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 生から死へ、死から生への生理学 -統合科学序説-.2014

    • Author(s)
      岡田泰伸
    • Journal Title

      総合研究大学院大学葉山彙報

      Volume: 5 Pages: 31-51

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Acid-sensitive outwardly rectifying (ASOR) anion channels in human epithelial cells are highly sensitive to temperature and independent of ClC-3.2013

    • Author(s)
      Sato-Numata K, Numata T, Okada T, Okada Y.
    • Journal Title

      Pflugers Arch

      Volume: 465 Issue: 11 Pages: 1535-1543

    • DOI

      10.1007/s00424-013-1296-y

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Annexin A2 is a modulator of maxi-anion channel (Maxi-Cl) in mouse mammary C127 cells.2015

    • Author(s)
      Islam Md R, Okada T, Merzlyak PG, Sabirov RZ, Okada Y
    • Organizer
      第92回 日本生理学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Exploration of temperature sensitivity and new antagonists of acid-sensitive outwardly rectifying anion channel (ASOR).2015

    • Author(s)
      Sato-Numata K, Numata T, Okada Y
    • Organizer
      第92回 日本生理学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Examination of the role of LRRC8A in the function of volume-sensitive outwardly rectifying anion channel (VSOR).2015

    • Author(s)
      Okada T, Sato-Numata K, Islam Md R, Sabirov RZ, Okada Y
    • Organizer
      第92回 日本生理学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Volume-sensitive anion channels in melanoma cells before and after tumor formation.2015

    • Author(s)
      Sabirov RZ, Tsiferova NA, Merzlyak PG, Okada Y
    • Organizer
      第92回 日本生理学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Volume-related ion channels involved in cell survival-death switching.

    • Author(s)
      岡田泰伸
    • Organizer
      10th International Congress:Cell Volume Regulation: Novel Therapeutic Targets & Pharmacological Approaches (CVR2013)
    • Place of Presentation
      モスクワ大学(モスクワ、ロシア)
    • Related Report
      2013 Research-status Report
  • [Presentation] 細胞生死スイッチに関与する細胞容積関連性イオンチャネル.

    • Author(s)
      岡田泰伸
    • Organizer
      第22回 日本Cell Death学会学術集会
    • Place of Presentation
      京都大学医学部 芝蘭会館(京都府)
    • Related Report
      2013 Research-status Report
  • [Book] “ギャノング 生理学”(原書24版)2014

    • Author(s)
      岡田泰伸(監訳者)
    • Total Pages
      838
    • Publisher
      丸善
    • Related Report
      2014 Annual Research Report
  • [Remarks] 生理学研究所 岡田研究室ホームページ

    • URL

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

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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