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Elucidation of the molecular components and regulatory mechanism of anion channels controlling the cell homeostasis and death

Research Project

Project/Area Number 15K15029
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionUniversity of Toyama

Principal Investigator

SAKAI Hideki  富山大学, 大学院医学薬学研究部(薬学), 教授 (60242509)

Co-Investigator(Kenkyū-buntansha) 清水 貴浩  富山大学, 大学院医学薬学研究部(薬学), 准教授 (40353437)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords生理学 / 細胞・組織 / イオンチャネル / 生体膜 / 細胞容積
Outline of Final Research Achievements

Volume-sensitive outward rectifying (VSOR) anion channel contributes to keep cell homeostasis and to trigger cell death such as apoptosis. In this study, we tried to elucidate the molecular components of the VSOR anion channel by using cellular physiological and molecular physiological techniques.
Here, we found that SSNK-1 (tentative name) is one of essential components of the VSOR channel. SSNK-1 may be associated with LRRC8A in the membrane microdomain of plasma membrane, where they elicit the channel activity for the cell volume regulation. In contrast, SSNK-2 and SSNK-3 were not involved in formation of the VSOR anion channel.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (21 results) (of which Int'l Joint Research: 5 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Hypotonic stress-induced down-regulation of claudin-1 and -2 mediated by dephosphorylation and clathrin-dependent endocytosis in renal tubular epithelial cells2016

    • Author(s)
      Fujii N, Matsuo Y, Matsunaga T, Endo S, Sakai H, Yamaguchi M, Yamazaki Y, Sugatani J, Ikari A
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 47 Pages: 24787-24799

    • DOI

      10.1074/jbc.m116.728196

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 胃酸分泌における塩素イオントランスポーター複合体の関与2016

    • Author(s)
      酒井秀紀,藤井拓人
    • Journal Title

      日本臨牀

      Volume: 74 Pages: 1401-1405

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Positive regulation of the enzymatic activity of gastric H+,K+-ATPase by sialylation of its β-subunit.2016

    • Author(s)
      Fujii T, Watanabe M, Shimizu T, Takeshima H, Kushiro K, Takai M, Sakai H.
    • Journal Title

      Biochim. Biophys. Acta.

      Volume: 1858 Issue: 6 Pages: 1228-1235

    • DOI

      10.1016/j.bbamem.2016.02.029

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inhibition of gastric H+,K+-ATPase by 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)oxybutyric acid (DCPIB), an inhibitor of volume-regulated anion channel.2015

    • Author(s)
      Fujii T, Takahashi Y, Takeshima H, Saitoh C, Shimizu T, Takeguchi N, Sakai H.
    • Journal Title

      Eur. J. Pharmacol.

      Volume: 765 Pages: 34-41

    • DOI

      10.1016/j.ejphar.2015.08.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clathrin-dependent endocytosis of claudin-2 by DFYSP peptide causes lysosomal damage in lung adenocarcinoma A549 cells.2015

    • Author(s)
      Ikari A, Taga S, Watanabe R, Sato T, Shimobaba S, Sonoki H, Endo S, Matsunaga T, Sakai H, Yamaguchi M, Yamazaki Y, Sugatani J.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1848 Issue: 10 Pages: 2326-2336

    • DOI

      10.1016/j.bbamem.2015.07.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] The outer pore region of the mouse PKD2L1 channel contributes to voltage-dependent inactivation2017

    • Author(s)
      清水貴浩,樋口大河,藤井拓人,Bernd Nilius,酒井秀紀
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウスATP13A4のカチオン輸送機能の解析.2017

    • Author(s)
      藤井拓人, 斎藤祐輝, 清水貴浩, 永森收志, 金井好克, 酒井秀紀
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] SLC26A7 Cl- チャネルは胃酸分泌細胞の細胞防御機構に関与する2016

    • Author(s)
      井上貴斗,阿波加隼也,藤田恭輔,清水貴浩,藤井拓人,田渕圭章,Ursula Seidler,酒井秀紀
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] PKD2L1チャネルに対する香辛料成分の効果2016

    • Author(s)
      鳥羽俊弘,清水貴浩,藤井拓人,酒井秀紀
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] TMEM16F におけるイオンチャネル機能とリン脂質スクランブラーゼ機能の相関性2016

    • Author(s)
      清水貴浩,鍋島彰太,藤井拓人,小澤茂喜,家原貴大,酒井秀紀
    • Organizer
      生理研研究会「上皮膜輸送調節蛋白の異常と病態生理学の融合」
    • Place of Presentation
      自然科学研究機構 岡崎統合バイオサイエンスセンター(愛知県岡崎市)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 容積感受性アニオンチャネル阻害剤DCPIBによる胃プロトンポンプ活性阻害2016

    • Author(s)
      大野智恵,藤井拓人,竹島浩,齋藤知里,清水貴浩,酒井秀紀
    • Organizer
      第38回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      名古屋市立大学(愛知県名古屋市)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] TMEM16F が有するイオンチャネル機能/リン脂質スクランブラーゼ機能2016

    • Author(s)
      清水貴浩,鍋島彰太,藤井拓人,小澤茂喜,家原貴大,酒井秀紀
    • Organizer
      第63回中部日本生理学会大会
    • Place of Presentation
      自然科学研究機構 岡崎コンファレンスセンター(愛知県岡崎市)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胃プロトンポンプβ鎖のシアル酸修飾によるポンプ活性制御2016

    • Author(s)
      藤井拓人,清水貴浩,竹島浩,久代京一郎,高井まどか,酒井秀紀
    • Organizer
      第63回中部日本生理学会大会
    • Place of Presentation
      自然科学研究機構 岡崎コンファレンスセンター(愛知県岡崎市)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Butyrate induces apoptosis via activation of volume-sensitive outwardly rectifying anion chanels in mouse colonic epithelial MCE301 cells2016

    • Author(s)
      Shimizu T, Ohtake H, Fujii T, Tabuchi Y, Sakai H
    • Organizer
      The First International Symposium on Toyama-Asia-Africa Pharmaceutical Network (1st TAA-Pharm Symposium)
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cardiac glycoside ouabain exerts anti-cancer activity by activation of volume-regulated anion channel2016

    • Author(s)
      Fujii T, Shimizu T, Takeshima H, Sakai H.
    • Organizer
      The First International Symposium on Toyama-Asia-Africa Pharmaceutical Network (1st TAA-Pharm Symposium)
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胃酸分泌細胞の頂端膜界面の構造と機能2016

    • Author(s)
      藤井拓人,清水貴浩,高井まどか,高橋康史,酒井秀紀
    • Organizer
      生理研研究会「生体界面研究会」
    • Place of Presentation
      自然科学研究機構 生理学研究所(愛知県岡崎市)
    • Year and Date
      2016-07-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞骨格による容積感受性アニオンチャネルの制御が抗癌剤耐性に寄与する2016

    • Author(s)
      清水貴浩,大竹宏尚,藤井拓人,岡田泰伸,酒井秀紀
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 胃酸分泌細胞の生体界面においてH,K-ATPase β鎖のシアル化はプロトンポンプ活性を正に調節する2016

    • Author(s)
      酒井秀紀,藤井拓人,久代京一郎,高井まどか
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 胃壁細胞分泌膜界面において糖鎖末端のシアル酸はプロトンポンプ活性を正に調節する2016

    • Author(s)
      藤井拓人,酒井秀紀
    • Organizer
      第4回生体界面研究会
    • Place of Presentation
      新潟大学(新潟県新潟市)
    • Year and Date
      2016-02-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Activation of volume-regulated anion channel by nanomolar concentrations of ouabain in human cancer cells.2015

    • Author(s)
      Fujii T, Shimizu T, Takeshima H, Sakai H.
    • Organizer
      8th Federation of the Asian and Oceanian Physiological Societies (FAOPS) Congress
    • Place of Presentation
      Centra Grand and Bangkok Convention Centre at Central World (Bangkok, Thailand)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Properties of volume-sensitive anion channel in butyrate-triggered apoptosis of murine colonic epithelial cells.2015

    • Author(s)
      Shimizu T, Ohtake H, Fujii T, Tabuchi Y, Sakai H.
    • Organizer
      8th Federation of the Asian and Oceanian Physiological Societies (FAOPS) Congress
    • Place of Presentation
      Centra Grand and Bangkok Convention Centre at Central World (Bangkok, Thailand)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Properties of chloride-transporting proteins in gastric parietal cells.2015

    • Author(s)
      Sakai H, Fujii T, Shimizu T.
    • Organizer
      The 21st Kyung Hee Ease-West Pharmaceutical Research Institute Symposium
    • Place of Presentation
      Kyung HeeUniversity (Seoul, Korea)
    • Year and Date
      2015-11-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ナトリウムポンプと容積感受性アニオンチャネルによる癌細胞増殖抑制機構2015

    • Author(s)
      山本翔太,藤井拓人,清水貴浩,田渕圭章,竹島浩,酒井秀紀
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山大学杉谷キャンパス(富山県富山市)
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] PKD2L1カチオンチャネルの電位依存的不活性化機構の解析2015

    • Author(s)
      大野智恵,樋口大河,清水貴浩,藤井拓人,Bernd Nilius,酒井秀紀
    • Organizer
      第62回中部日本生理学会大会
    • Place of Presentation
      富山大学五福キャンパス(富山県富山市)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
  • [Presentation] TMEM16Fが有するリン脂質スクランブラーゼ機能2015

    • Author(s)
      鍋島彰太,清水貴浩,藤井拓人,小澤茂喜,家原貴大,岡田泰伸,酒井秀紀
    • Organizer
      第62回中部日本生理学会大会
    • Place of Presentation
      富山大学五福キャンパス(富山県富山市)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
  • [Presentation] 胃細胞の分泌膜界面の構成と機能2015

    • Author(s)
      酒井秀紀,藤井拓人,清水貴浩
    • Organizer
      生理研研究会「第3回生体界面研究会」
    • Place of Presentation
      自然科学研究機構 生理学研究所(愛知県岡崎市)
    • Year and Date
      2015-07-16
    • Related Report
      2015 Research-status Report
  • [Book] 「疾病と病態生理」改訂第4版.1消化器疾患 A. 消化器系2016

    • Author(s)
      酒井秀紀
    • Publisher
      南江堂
    • Related Report
      2016 Annual Research Report
  • [Book] Met. Ions Life Sci. (Proton-Potassium (H+/K+) ATPases: Properties and Roles in Health and Diseases.)2016

    • Author(s)
      Sakai H, Fujii T, Takeguchi N.
    • Total Pages
      628
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report
  • [Remarks] 所属研究室Webページ

    • URL

      http://www.pha.u-toyama.ac.jp/phaphy1/index-j.html

    • Related Report
      2016 Annual Research Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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