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Study on the regulation of cardiac homeostasis by formation of TRPC3/6 channel protein complex

Research Project

Project/Area Number 25293018
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionOkazaki Research Facilities, National Institutes of Natural Sciences

Principal Investigator

Nishida Motohiro  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 (90342641)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords心血管疾患 / チャネル / 恒常性 / 活性酸素 / 創薬 / レジリエンス / 心血管リモデリング / TRPチャネル / 血管成熟 / 線維化 / 心血管 / カルシウムチャネル / TRPC / 再生・修復 / 心血管病 / カルシウム / イオンチャネル / 薬理学 / 生理学
Outline of Final Research Achievements

Human living activity is maintained by systemic and pulmonary blood circulation, and muscular cells, including cardiomyocytes, vascular smooth muscle cells, and skeltal muscle cells, predominantly support this system. We focused on transient receptor potential canonical 3 and 6 heterotetramer channels (TRPC3/6), a non-selective cation-permeable channel that regualtes resting membrane potential in cells, and found that inhibition of TRPC3/6 channel activities in muscular cells will be a new strategy for the prevention of our cardiovascular system from ischemic and hypertensive stresses, using mouse models for human cardiovascular diseases.

Report

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

    (37 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (19 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 7 results,  Acknowledgement Compliant: 3 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Mahidol University(タイ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Sabah University(マレーシア)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The purinergic P2Y6 receptor heterodimerizes with the angiotensin AT1 receptor to promote angiotensin II-induced hypertension2016

    • Author(s)
      A. Nishimura, C. Sunggip, H. Tozaki-Saitoh, T. Shimauchi, T. Numaga-Tomita, K. Hirano, T. Ide, J-M. Boeynaems, H. Kurose, M. Tsuda, B. Robaye, K. Inoue and M. Nishida
    • Journal Title

      Science Signaling

      Volume: Jan 19;9(411) Issue: 411

    • DOI

      10.1126/scisignal.aac9187

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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] Sustained betaAR stimulation mediates cardiac insulin resistance in a PKA-dependent manner2016

    • Author(s)
      S. Mangmool, T. Denkaew, S. Phosri, D. Pinthong, W. Parichatikanond, T. Shimauchi and M. Nishida
    • Journal Title

      Mol. Endocrinol.

      Volume: 30(1) Issue: 1 Pages: 118-132

    • DOI

      10.1210/me.2015-1201

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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] Redox signaling regulated by electrophiles and reactive sulfur species.2016

    • Author(s)
      Nishida M, Kumagai Y, Ihara H, Fujii S, Motohashi H, Akaike T.
    • Journal Title

      J. Clin. Biochem. Nutr.

      Volume: in press

    • NAID

      130005132519

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Divergent Roles of CAAX Motif-signaled Posttranslational Modifications in the Regulation and Subcellular Localization of Ral GTPases2015

    • Author(s)
      LR Gentry, A. Nishimura, A.D. Cox, T.D. Martin, D. Tsygankov, M. Nishida, T.C. Elston and C.J. Der
    • Journal Title

      J Biol Chem.

      Volume: 290(37) Issue: 37 Pages: 22851-22861

    • DOI

      10.1074/jbc.m115.656710

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reactive sulfur species-mediated activation of the Keap1-Nrf2 pathway by 1,2-napthoquinone through sulfenic acids formation under oxidative stress.2015

    • Author(s)
      Shinkai Y, Abiko Y, Ida T, Miura T, Kakehashi H, Ishii I, Nishida M, Sawa T, Akaike T, Kumagai Y.
    • Journal Title

      Chem Res Toxicol.

      Volume: 印刷中 Issue: 5 Pages: 838-847

    • DOI

      10.1021/tx500416y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TRP Channels: Their Function and Potentiality as Drug Targets2015

    • Author(s)
      Nishida M, Kuwahara K, Kozai D, Sakaguchi R, Mori Y.
    • Journal Title

      Innovative Medicine: Basic Research and Development (Springer Open, edited by Nakao K, Minato N and Uemoto S)

      Volume: 978-4-431-55651-0 (eBook) Pages: 195-218

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] カルシウムシグナルの基本機構とその可能性2015

    • Author(s)
      森泰生、森誠之、西田基宏
    • Journal Title

      Clinical Calcium

      Volume: 25(1) Pages: 47-58

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.2014

    • Author(s)
      Yamada Y, Kinoshita H, Kuwahara K, Nakagawa Y, Kuwabara Y, Minami T, Yamada C, Shibata J, Nakao K, Cho K, Arai Y, Yasuno S, Nishikimi T, Ueshima K, Kamakura S, Nishida M, Kiyonaka S, Mori Y, Kimura T, Kangawa K, Nakao K.
    • Journal Title

      Cardiovas Res

      Volume: 104 Pages: 183-193

    • NAID

      120005619790

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 心臓におけるTRPチャネルの多様な役割2014

    • Author(s)
      北島直幸、西田基宏
    • Journal Title

      実験医学

      Volume: 32 Pages: 527-533

    • Related Report
      2013 Annual Research Report
  • [Journal Article] β-arrestin2 in infiltrated macrephages iihibits excessive inflammation aftermyocardial infarction2013

    • Author(s)
      Watari K, Nakaya M, Nishida M, Kim KM, Kurose H
    • Journal Title

      PLOSONE

      Volume: 8 Issue: 7 Pages: e68351-e68351

    • DOI

      10.1371/journal.pone.0068351

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance2013

    • Author(s)
      Nakaya M, Tajima M, Kosako H, Nakaya T, Hashimoto A, Watari K, Nishihara H, Ohba M, Komiya S, Tani N, Nishida M, Taniguchi H, Sato Y, Matsumoto M, Tsuda M, Kuroda M, Inoue K, Kurose H
    • Journal Title

      Nature Commun

      Volume: 4 Issue: 1 Pages: 1532-1532

    • DOI

      10.1038/ncomms2540

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice.2013

    • Author(s)
      Nishida M, Ishikawa T, Saiki S, Sunggip C, Aritomi S, Harada E, Kuwahara K, Hirano K, Mori Y, Kim-Mitsuyama S
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 434 Issue: 2 Pages: 210-216

    • DOI

      10.1016/j.bbrc.2013.03.040

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atrial natriuretic peptide-mediated inhibition of microcirculatory endothelial Ca2+ and permeability response to histamine involves cGMP-dependent protein kinase I and TRPC6 channels.2013

    • Author(s)
      Chen W, Oberwinkler H, Werner F, Gaßner B, Nakagawa H, Feil R, Hofmann F, Schlossmann J, Dietrich A, Gudermann T, Nishida M, Del Galdo S, Wieland T, Kuhn M.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 33 Issue: 9 Pages: 2121-2129

    • DOI

      10.1161/atvbaha.113.001974

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide.2013

    • Author(s)
      Sawa T, Ihara H, Ida T, Fujii S, Nishida M and Akaike T.
    • Journal Title

      Nitric Oxide

      Volume: 34 Pages: 10-18

    • DOI

      10.1016/j.niox.2013.04.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of redox signaling by an electrophilic cyclic nucleotide.2013

    • Author(s)
      Akaike T, Nishida M and Fujii S.
    • Journal Title

      J. Biochem.

      Volume: 153 Issue: 2 Pages: 131-138

    • DOI

      10.1093/jb/mvs145

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox control of cardiovascular homeostasis by Angiotensin II.2013

    • Author(s)
      Sunggip C, Kitajima N & Nishida M
    • Journal Title

      Curr. Pharm. Des.

      Volume: 19 Pages: 3022-3032

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRPチャネルの生理機能と病態生理2013

    • Author(s)
      西田基宏,角田将明,北島直幸
    • Journal Title

      Clinical Calcium

      Volume: 23 Pages: 561-568

    • Related Report
      2013 Annual Research Report
  • [Presentation] 運動療法を模倣する循環器疾患治療薬の開発2016

    • Author(s)
      西田基宏
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜 会議センター(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Imitation of kinesitherapy by inhibition of TRPC6 channel activities.2015

    • Author(s)
      Nishida M, Numaga-Tomita T, Shimauchi T, Matsukane R, Nishimura A.
    • Organizer
      International Symposium on Chronic Inflammatory Diseases, Kumamoto (ISCIDK2015).
    • Place of Presentation
      熊本大学(熊本県熊本市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Negative regulation of cardiac remodeling by S-polythiolation of G proteins.2015

    • Author(s)
      Nishida M.
    • Organizer
      2nd Symposium of SPU Innovative Project for Pharmaceutical Analyses of Covalent Modification in Biomolecule.
    • Place of Presentation
      昭和薬科大学(東京都町田市)
    • Year and Date
      2015-08-31
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心血管リスク軽減の新たなストラテジー ~Ca2+拮抗薬のエコファーマ~2015

    • Author(s)
      西田基宏
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫県 神戸学院大学
    • Year and Date
      2015-03-25 – 2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 心臓の繊維化におけるTRPC3チャネルの役割2015

    • Author(s)
      西田基宏
    • Organizer
      第120回日本解剖学会・第92回日本生理学会大会
    • Place of Presentation
      兵庫県 神戸国際会議場
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] ROS-generating TRPC channels in cardiac remodeling2015

    • Author(s)
      Motohiro Nishida
    • Organizer
      The 88th Annual Meeting of The Japanese Pharmacological Society
    • Place of Presentation
      愛知県 名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of TRPC3 channels in mechano-chemo transduction in hearts.2014

    • Author(s)
      Nishida M
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学郡元キャンパス(鹿児島)
    • Related Report
      2013 Annual Research Report
  • [Presentation] TRPCチャネルを標的とした新規末梢循環改善薬の探索2014

    • Author(s)
      西田基宏、冨田拓郎、島内司、松金良祐、武吉恭子
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市鶴屋百貨店東館(熊本)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of TRPC channels in mechano-chemo transduction in the heart.2013

    • Author(s)
      Nishida M.
    • Organizer
      6th International Workshop on Cardiac Mechano-Erectric Coupling and Arrhythmias (MEC2013)
    • Place of Presentation
      University of Oxford (Oxford, UK)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Role of TRPC3 channels in mechanical stress-induced cardiac fibrosis.2013

    • Author(s)
      Kitajima N, Numaga-Tomita T, Nishida M.
    • Organizer
      6th International Workshop on Cardiac Mechano-Erectric Coupling and Arrhythmias (MEC2013)
    • Place of Presentation
      University of Oxford (Oxford, UK)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 創薬研究から見えてきたTRPCチャネルの新たな生理機能2013

    • Author(s)
      西田基宏
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Annual Research Report
  • [Presentation] TRPC3/6チャネルによる心臓リモデリング制御2013

    • Author(s)
      西田基宏、北島直幸、外山喬士、冨田拓郎
    • Organizer
      第60回中部日本生理学会
    • Place of Presentation
      岐阜大学医学部記念会館ホール(岐阜)
    • Related Report
      2013 Annual Research Report
  • [Remarks] 生理学研究所心循環シグナル研究部門

    • URL

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

    • Related Report
      2015 Annual Research Report
  • [Remarks] 心循環シグナル研究部門

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] Drp1重合阻害剤2015

    • Inventor(s)
      西田基宏、石川達也
    • Industrial Property Rights Holder
      味の素株式会社、自然科学研究機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-11-20
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Drp1重合阻害剤2014

    • Inventor(s)
      西田基宏、石川達也
    • Industrial Property Rights Holder
      西田基宏、石川達也
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-11-24
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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