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2009 Fiscal Year Final Research Report

Analysis of G protein signaling pathways involved in the development of heart failure and discovery of the novel therapeutic target.

Research Project

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Project/Area Number 19689003
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKyushu University

Principal Investigator

NISHIDA Motohiro  Kyushu University, 大学院・薬学研究院, 准教授 (90342641)

Project Period (FY) 2007 – 2009
Keywords薬理学 / 心不全 / シグナル伝達 / G蛋白質
Research Abstract

We focused on the roles of heterotrimeric G proteins coupling with receptors on the plasma membrane, and found that Gq protein singaling participates in the development of myocardial hypertrophy while G12 protein signaling participates in the development of cardiac fibrosis. In addition, we identified that TRPC channels mediate Gq-induced activation of Ca2+ signaling, and P2Y6 receptor triggers activation of G12 protein signaling. Furthermore, we found that inhibition of these targets improves heart failure in in vivo mouse hearts.

  • Research Products

    (46 results)

All 2010 2009 2008 2007 Other

All Journal Article (25 results) Presentation (20 results) Remarks (1 results)

  • [Journal Article] Ca2+ influx and protein scaffolding via TRPC3 sustain PKCb and ERK activation in B cells.2010

    • Author(s)
      Numaga T, Nishida M, Kiyonaka S, Kato K, Katano M, Mori E, Kurosaki T, Inoue R, Hikida M, Putney JW Jr, Mori Y
    • Journal Title

      J Cell Sci. 123

      Pages: 927-938

  • [Journal Article] Determining the activation of Rho as an index of coupling to G12/13.Chapter for "Receptor Signal Transduction Protocols" as part of the Humana Press2010

    • Author(s)
      Nakaya M, Ohba M, Nishdia M, Kurose H
    • Journal Title

      Methods in Molecular Biology(series) Vol.83

  • [Journal Article] カルシウムシグナリング研究の最前線~電位非依存性カルシウムチャネルの様々な生理・病理機能~2010

    • Author(s)
      西田基宏
    • Journal Title

      YAKUGAKU ZASSHI Vol.130,No.3

      Pages: 279-280

  • [Journal Article] ジアシルグリセロール感受性TRPCチャネルを介した心肥大誘導のメカニズム2010

    • Author(s)
      西田基宏, 渡辺健太, 仲矢道雄, 黒瀬等
    • Journal Title

      YAKUGAKU ZASSHI Vol.130,No.3

      Pages: 295-302

  • [Journal Article] 森泰生TRPCチャネルを標的とした新規Ca2+拮抗薬の創製2010

    • Author(s)
      清中茂樹, 加藤賢太, 西田基宏
    • Journal Title

      YAKUGAKU ZASSHI Vol.130,No.3

      Pages: 303-311

  • [Journal Article] 三量体g蛋白質シグナリングを介した心不全発症の分子機構2010

    • Author(s)
      西田基宏, 大場三奈, 仲矢道雄, 黒瀬等
    • Journal Title

      日本薬理学雑誌 (in press)

  • [Journal Article] Amphotericin B-Induced Renal Tubular Cell Injury is Mediated by Na+ Influx through Ion-Permeable Pores and Subsequent Activation of MAP Kinases and Elevation of Intracellular Ca2+.2009

    • Author(s)
      Yano T, Itoh Y, Kawamura E, Maeda A, Egashira N, Nishida M, Kurose H, Oishi R
    • Journal Title

      Antimicrob Agents Chemother. 53

      Pages: 1420-1426

  • [Journal Article] Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound.2009

    • Author(s)
      Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I, Mori Y
    • Journal Title

      Proc Natl Acad Sci USA. 106

      Pages: 5400-5405

  • [Journal Article] AT1受容体を介する心肥大形成におけるTRPCチャネルの役割2009

    • Author(s)
      黒瀬等、西田基宏
    • Journal Title

      医学のあゆみ Vol.228,No.5

      Pages: 395-399

  • [Journal Article] TRPチャネルタンパク質の新たな機能と病態生理(序文)2009

    • Author(s)
      西田基宏
    • Journal Title

      日薬理誌 Vol.134,No.3

      Pages: 115

  • [Journal Article] Gタンパク質共役型受容体-TRPCチャネルタンパク複合体形成による心肥大シグナル制御2009

    • Author(s)
      西田基宏, 佐藤陽治, 仲矢道雄, 黒瀬等
    • Journal Title

      日本薬理学雑誌 Vol.134,No.3

      Pages: 131-136

  • [Journal Article] Keap1 regulates the constitutive expression of GST A1 during differentiation of Caco-2 cells.2008

    • Author(s)
      Kusano Y, Horie S, Shibata T, Satsu H, Shimizu M, Hitomi E, Nishida M, Kurose H, Itoh K, Kobayashi A, Yamamoto M, Uchida K.
    • Journal Title

      Biochemistry 47

      Pages: 6169-77

  • [Journal Article] A food-derived synergist of NGF signaling: Identification of protein tyrosine phosphatase 1B as a key regulator of NGF receptor-initiated signal transduction.2008

    • Author(s)
      Shibata T, Nakahara H, Kita N, Matsubara Y, Han C, Morimitsu Y, Iwamoto N, Kumagai Y, Nishida M, Kurose H, Aoki N, Ojika M, Uchida K.
    • Journal Title

      J Neurochem. 107

      Pages: 1248-1260

  • [Journal Article] P2Y_6 Receptor-Gα_<12/13> Signaling in Cardiomyocytes Triggers Pressure Overload-induced Cardiac Fibrosis.2008

    • Author(s)
      Nishida M, Sato Y, Uemura A, Narita Y, Tozaki-Saitoh H, Nakaya M, Ide T, Suzuki K, Inoue K, Nagao T, Kurose H.
    • Journal Title

      EMBO J 27

      Pages: 3104-3115

  • [Journal Article] Roles of TRP channels in the development of cardiac hypertrophy.2008

    • Author(s)
      Nishida M, Kurose H
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol. 378

      Pages: 395-406

  • [Journal Article] 機械的伸展刺激により活性化されるGタンパク質共役型受容体の解析2008

    • Author(s)
      西田基宏、上村綾、仲矢道雄、黒瀬等
    • Journal Title

      表面 Vol.46,No.3

  • [Journal Article] 心不全治療の新たな標的としてのTRPCチャネル2008

    • Author(s)
      西田基宏
    • Journal Title

      日本薬理学雑誌 Vol.132,No.8

      Pages: 130-131

  • [Journal Article] Gα_<12/13>-mediated upregulation of TRPC6 negatively regulates endothelin-1-induced cardiac myofibroblast formation and collagen synthesis through NFAT activation.2007

    • Author(s)
      Nishida M, Onohara N, Sato Y, Suda R, Ogushi M, Tanabe S, Inoue R, Mori Y, Kurose H.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 23117-23128

  • [Journal Article] Transient receptor potential channels in Alzheimer's disease.2007

    • Author(s)
      Yamamoto S, Wajima T, Hara Y, Nishida M, Mori Y
    • Journal Title

      Biochim Biophys Acta 1772

      Pages: 958-967

  • [Journal Article] TRPチャネルと心疾患2007

    • Author(s)
      黒瀬等、西田基宏
    • Journal Title

      生化学 Vol.79,No.10

  • [Journal Article] アンジオテンシンIIで誘発される心肥大の分子機構-TRP蛋白質を巡って2007

    • Author(s)
      西田基宏、小野原直哉、井上隆司、森泰生、黒瀬等
    • Journal Title

      日本臨床生理学会雑誌 Vol.37,No.4

  • [Journal Article] イオンチャネルと心疾患-心肥大形成とTRPC-NFATシグナリング2007

    • Author(s)
      黒瀬等、西田基宏
    • Journal Title

      医学のあゆみ Vol.223,No.6

  • [Journal Article] Inoue R and Kurose H. Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition.

    • Author(s)
      Nishida M, Watanabe K, Sato Y, Nakaya M, Kitajima K, Ide T
    • Journal Title

      J. Biol. Chem. (in press)

  • [Journal Article] Pertussis toxin upregulates angiotensin type1 receptors through TLR4-mediated Rac activation.

    • Author(s)
      Nishida M, Suda R, Tanabe S, Onohara N, Nakaya M, Kanaho Y, Sumimoto H, Sato Y, Kurose H.
    • Journal Title

      J. Biol. Chem (in press)

  • [Journal Article] Heterotrimeric G proteins in heart failure.

    • Author(s)
      Nishida M, Ohba M, Nakaya M, Kurose H
    • Journal Title

      Heart Failure: Symptoms, Causes and Treatment Options. (in press.)

  • [Presentation] s-ニトロシル化修飾によるアンジオテンシン受容体シグナリングの調節2010

    • Author(s)
      西田基宏, 仲矢道雄, 黒瀬等
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      20100300
  • [Presentation] 心肥大を仲介するTRPCチャネル2010

    • Author(s)
      西田基宏, 黒瀬等, 渡辺健太, 清中茂樹, 森泰生
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      20100300
  • [Presentation] TRPCチャネルのリン酸化による血管緊張性の制御2010

    • Author(s)
      西田基宏, 西岡絹恵, 有吉麻里奈, 仲矢道雄, 黒瀬等
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      20100300
  • [Presentation] 心不全を制御する三量体g蛋白質2010

    • Author(s)
      西田基宏
    • Organizer
      京都大学先端医工学研究ユニットh21年度研究発表交流会
    • Place of Presentation
      京都
    • Year and Date
      20100300
  • [Presentation] Diacylglycerol-activated TRPC channels as a new therapeutic target of heart failure.2010

    • Author(s)
      Nishida M
    • Organizer
      The 9^<th> International Symposium on 'Recent Trends in Pharmaceutical Sciences'
    • Place of Presentation
      Yeungnam University, Gyeongsan, Korea
    • Year and Date
      2010-02-04
  • [Presentation] P2Y6 receptor-Gα12/13 signaling triggers pressure overload-induced cardiac fibrosis.2009

    • Author(s)
      Nishida M, Sato Y, Uemura A, Tozaki-Saitoh H, Nakaya M, Inoue K, Kurose H
    • Organizer
      Fukuoka Purine 2009 (Joint with JSPS Core-to-Core Program A Satellite Symposium for IUPS2009)
    • Place of Presentation
      Fukuoka
    • Year and Date
      20090700
  • [Presentation] 受容体-TRPCチャネルの機能的共役による心肥大シグナル制御2009

    • Author(s)
      西田基宏、佐藤陽治、仲矢道雄、井上隆司、森泰生、黒瀬等
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20090300
  • [Presentation] 心臓の病的肥大におけるTRPCチャネルの役割2009

    • Author(s)
      西田基宏、佐藤陽治、井上隆司、森泰生、黒瀬等
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      20090300
  • [Presentation] 百日咳毒素によるアンジオテンシン受容体発現増加のメカニズム2009

    • Author(s)
      西田基宏, 仲矢道雄, 黒瀬等
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      20090000
  • [Presentation] Heterologous down-regulation of angiotensin type1 receptor by purinergic P2Y2 receptor stimulation.2009

    • Author(s)
      Nishida M, Ogushi M, Suda R, Nakaya M, Kurose H
    • Organizer
      The 36th Congress of the International Union of Physiological Sciences
    • Place of Presentation
      July, Kyoto
    • Year and Date
      20090000
  • [Presentation] Role of diacylglycerol-activated TRPC channels in the development of heart failure.2009

    • Author(s)
      Nishida M
    • Organizer
      The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists.
    • Place of Presentation
      Huis Ten Bosch, Nagasaki, Japan
    • Year and Date
      2009-11-25
  • [Presentation] Purinergic P2Y6 Receptor in Cardiomyocytes Initiates Pressure Overload-induced Cardiac Fibrosis.2009

    • Author(s)
      Nishida M, Uemura A, Nakaya M, Kurose H.
    • Organizer
      2009' International Symposium for Pharmaceutical Sciences.
    • Place of Presentation
      Fukuoka
    • Year and Date
      2009-11-05
  • [Presentation] Down-regulation of angiotensin receptors by S-nitrosylation of NF-κB. Society for Free Radical Research (SFRR) International.2009

    • Author(s)
      Nishida M
    • Organizer
      Free Radical School in Japan 2009
    • Place of Presentation
      Nagano
    • Year and Date
      2009-09-03
  • [Presentation] TRPC channels as a new therapeutic target for heart failure.2009

    • Author(s)
      Nishida M
    • Organizer
      The 36th Congress of the International Union of Physiological Sciences
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-07-29
  • [Presentation] S-ニトロシル化修飾によるアンジオテンシン受容体の調節機構2008

    • Author(s)
      西田基宏、大串真理子、須田玲子、仲矢道雄、黒瀬等
    • Organizer
      生化学会・分子生物学会合同大会BMB2008
    • Place of Presentation
      神戸
    • Year and Date
      20081200
  • [Presentation] Extracellular nucleotides trigger pressure overload-induced cardiac fibrosis through P2Y_6R-Gα_<12/13> signaling pathways.2008

    • Author(s)
      Nishida M
    • Organizer
      KUSCR Japan/Korea Conference on Cellular Signaling 2008.
    • Place of Presentation
      Fukuoka
    • Year and Date
      20080000
  • [Presentation] 心不全治療の新たな標的としてのTRPCチャネル2007

    • Author(s)
      西田基宏
    • Organizer
      第279回情報計算化学生物(CBI)学会研究講演会
    • Year and Date
      20071100
  • [Presentation] Gα_<13>-TRPC6-NFAT signaling pathway negatively regulates cardiac myofibroblast formation.2007

    • Author(s)
      Nishida M, Onohara N, Kurose H
    • Organizer
      XIX World Congress of the ISHR Bologna
    • Place of Presentation
      Italy
    • Year and Date
      20070600
  • [Presentation] Role of TRPC channels in agonist-induced cardiac hypertrophy.2007

    • Author(s)
      Nishida M, Nakaya M, Kurose H
    • Organizer
      2007' International Symposium for Pharmaceutical Sciences.
    • Place of Presentation
      Nagasaki
    • Year and Date
      20070000
  • [Presentation] アンジオテンシンIIによる心筋細胞の肥大応答におけるTRPC3/TRPC6チャネルの関与2007

    • Author(s)
      西田基宏、小野原直哉、井上隆司、住本英樹、佐藤陽治、森泰生、長尾拓、黒瀬等
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      20070000
  • [Remarks]

    • URL

      http://210.233.60.66/~chudoku/

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Published: 2011-06-18   Modified: 2016-04-21  

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