Pathological roles of ion transporter/channel as therapeutic targets in muscle degenerative disease

• Project/Area Number: 19390080
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: WAKABAYASHI Shigeo National Cardiovascular Center Research Institute, 循環分子生理部, 部長 (70158583)
• Co-Investigator(Kenkyū-buntansha): IWATA Yuko 国立循環器病センター研究所, 循環分子生理部, 室長 (80171908) ; NISHITANI Tomoe 国立循環器病センター研究所, 循環分子生理部, 室長 (50393244) ; HISAMITSU Takashi 国立循環器病センター研究所, 循環分子生理部, 室員 (50327946) ; KOBAYASHI Soushi 国立循環器病センター研究所, 循環分子生理部, 流動研究員 (50511531)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 循環器・高血圧 / 生体分子 / 蛋白質 / トランスレーショナルリサーチ / バイオテクノロジー

Research Abstract

We conclude that Ca^<2+>-permeable channel TRPV2 and Na^+/H^+ exchanger NHE1 play important pathological roles in abnormal Ca^<2+>-handling commonly occurring in dilated cardiomyopathy, heart failure and muscular dystrophy.

Research Products

• [Journal Article] Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models (2009)
  • Author(s): Iwata, Y., Katanosaka, Y., Arai, Y., Shigekawa, M., Wakabayashi, S
  • Journal Title: Hum. Mol. Gen Vol.18,No.5 Pages: 824-834
  • Peer Reviewed
• [Journal Article] Essential role of TRPV2 ion channel in the sensitivity of dystrophic muscle to eccentric contractions (2009)
  • Author(s): Zanou,N., et al.
  • Journal Title: FEBS Lett. 583 Pages: 3600-3604
  • Peer Reviewed
• [Journal Article] A Model of Na^+/H^+ Exchanger and Its Central Role in Regulation of pH and Na^+ in Cardiac Myocytes (2009)
  • Author(s): Cha,C.Y., et al.
  • Journal Title: Biophys.J. 97 Pages: 2674-2683
  • Peer Reviewed
• [Journal Article] Dominant-negative inhibition of Ca^<2+> influx via TRPV2 ameliorates muscular dystrophy in animal models (2009)
  • Author(s): Iwata, Y., et al.
  • Journal Title: Hum. Mol. Gen 18(5) Pages: 824-834
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 中村(西谷)友重, 他
  • Journal Title: 創薬研究者必見!-最新トランスポーター研究2009“遺伝子医学MOOK 12"(株式会社メディカル ドゥ) Pages: 255-261
• [Journal Article] Activation of Na+/H+ exchanger 1 is sufficient to generate Ca2+ signals that induce cardiac hypertrophy and heart failure (2008)
  • Author(s): Nakamura, T.Y., Iwata, Y., Arai, Y., Komamura, K., Wakabayashi, S
  • Journal Title: Circ. Res Vol.103/No.8 Pages: 891-899
  • Peer Reviewed
• [Journal Article] Down-regulation of P-glycoprotein expression by sustained intracellular acidification in K562/DOX cells (2008)
  • Author(s): Lu, Y., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 377(2) Pages: 441-446
  • Peer Reviewed
• [Journal Article] Activation of Na^+/H^+ exchanger 1 is sufficient to generate Ca^<2+> signals that induce cardiac hypertrophy and heart failure (2008)
  • Author(s): Nakamura, T. Y., et al.
  • Journal Title: Circ. Res. 103(8) Pages: 891-899
  • Peer Reviewed
• [Journal Article] Enhanced Na+/H+ exchange activity contributes to the pathogenesis of muscular dystrophy via involvement of P2 receptors (2007)
  • Author(s): Iwata, Y., Katanosaka, Y., Hisamitsu, T., Wakabayashi, S
  • Journal Title: Am. J. Pathol Vol.171/No.5 Pages: 1576-1587
  • Peer Reviewed
• [Journal Article] Enhanced Na^+/H^+ exchange activity contributes to the pathogenesis of muscular dystrophy via involvement of P2 receptors. (2007)
  • Author(s): Iwata, Y., et. al.
  • Journal Title: Am. J. Pathol. 171/5 Pages: 1576-1587
  • Peer Reviewed
• [Journal Article] Functional Importance of Charged Residues within the Putative Intracellular Loops in pH regulation by Na^+/H^+ Exchanger NHE1. (2007)
  • Author(s): Hisamitsu, T., et. al.
  • Journal Title: FEBS J. 274/16 Pages: 4326-4336
  • Peer Reviewed
• [Presentation] 心筋症モデル動物におけるCa^<2+>透過チャネルTRPV2の活性阻害は筋変性を軽減する (2010)
  • Author(s): 岩田裕子、若林繁夫
  • Organizer: 日本薬理学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-03-18
• [Presentation] 拡張型心筋症発症におけるCa^<2+>透過チャネルTRPV2の病態的役割 (2009)
  • Author(s): 岩田裕子、若林繁夫
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2009-10-24
• [Presentation] 心筋細胞におけるCa^<2+>結合蛋白質CHP3の生理機能の解析 (2009)
  • Author(s): 古林創史、若林繁夫
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2009-10-24
• [Presentation] Molecular and functional aspects of Na+/H+ exchanger 1: Relevance in cardiac hypertrophy and heart failure (2009)
  • Author(s): Wakabayshi, S., Nakamura-Nishitani, T.Y., Iwata, Y
  • Organizer: 第36回国際生理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-07-30
• [Presentation] Amelioration of muscular dystrophy by dominant-negative inhibition of Ca2+ influx via TRPV2 (2009)
  • Author(s): Iwata, Y., Wakabayashi, S
  • Organizer: 第36回国際生理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-07-30
• [Presentation] Amelioration of muscular dystrophy by dominant-negative inhibition of Ca^<2+> influx via TRPV2 (2009)
  • Author(s): Iwata,Y., Wakabayashi,S.
  • Organizer: 国際生理学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-07-30
• [Presentation] Ca^<2+>-permeable channel TRPV2 as a promising therapeutic target for muscular dystrophy (2009)
  • Author(s): Iwata,Y., Wakabayashi,S.
  • Organizer: 日仏筋ジストロフィーシンポジウム
  • Place of Presentation: パリ、心筋研究所
  • Year and Date: 2009-07-03
• [Presentation] Ca^<2+>透過チャネルTRPV2阻害による筋変性疾患最善効果 (2009)
  • Author(s): 岩田裕子、若林繁夫
  • Organizer: TRPチャネル研究会
  • Place of Presentation: 岡崎カンファレンスセンター
  • Year and Date: 2009-06-04
• [Presentation] SF9細胞からのNa^+/H^+交換輸送体/CHP複合体の発現と精製 (2008)
  • Author(s): 若林繁夫, 他
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2008-12-10
• [Presentation] Ca^<2+>透過性チャネルTRPV2のドミナントネガティブ変異体による筋ジストロフィーの病態改善効果 (2008)
  • Author(s): 岩田裕子, 他
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2008-12-10
• [Presentation] Activation of Na^+/H^+ exchange is sufficient to induce hypertrophy and failure (2008)
  • Author(s): Iwata, Y., et al.
  • Organizer: 国際心臓研究学会日本部会
  • Place of Presentation: 横浜市開港記念会館
  • Year and Date: 2008-12-05
• [Presentation] Enhanced Na^+/H^+ exchange activity participates in pathogenesis of Muscular dystrophy and cardiomyopathy (2008)
  • Author(s): Iwata, Y., et al.
  • Organizer: 心筋代謝研究会
  • Place of Presentation: 東京慈恵会医科大学
  • Year and Date: 2008-07-13
• [Presentation] Na+/H+交換輸送体の活性化は心肥大・心不全を引き起こす:細胞内イオン代謝と分子機構の解析 (2008)
  • Author(s): 中村(西谷)友重、岩田裕子、若林繁夫
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 京王プラザホテル東京
  • Year and Date: 2008-03-26
• [Presentation] Na^+/H^+交換輸送体の活性化は心肥大・心不全を引き起こす:細胞内イオン代謝と分子機構の解析 (2008)
  • Author(s): 西谷 友重, 他
  • Organizer: 日本生理学会
  • Place of Presentation: 京王プラザホテル東京
  • Year and Date: 2008-03-26
• [Book] 創薬研究者必見!-最新トランスポーター研究2009“遺伝子医学MOOK 12" (2009)
  • Author(s): 中村(西谷)友重、古林創史、久光隆、岩田裕子、若林繁夫
• [Book] Na+/H+交換輸送体の構造・機能と病態的意義循環器病研究の進歩 (2007)
  • Author(s): 若林繁夫、岩田裕子、中村(西谷)友重、久光隆、ベンアマー・ヨセフ
• [Book] Na^+/H^+交換輸送体の構造・機能と病態的意義(循環器病研究の進歩 通巻47号) (2007)
  • Author(s): 若林繁夫, 他
  • Total Pages: 10
  • Publisher: 協和企画
• [Book] 動物細胞Na^+/H^+交換輸送体:分子から疾患まで (生化学 79/6) (2007)
  • Author(s): 若林繁夫, 他
  • Total Pages: 9
  • Publisher: (社)日本生化学会
• [Book] 動物細胞Na+/H+交換輸送体:分子から疾患まで生化学
  • Author(s): 若林繁夫、久光隆、ユセフ・ベンアマー、中村(西谷)友重、岩田裕子
• [Patent(Industrial Property Rights)] 抗TRPV2抗体 (2010)
  • Inventor(s): 岩田裕子、若林繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-001676
  • Filing Date: 2010-01-28
• [Patent(Industrial Property Rights)] 抗TRPV2抗体 (2010)
  • Inventor(s): 岩田裕子, 若林繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-016760
  • Filing Date: 2010-01-28
• [Patent(Industrial Property Rights)] TRPV2の部分ペプチド (2009)
  • Inventor(s): 岩田裕子、若林繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2009-186219
  • Filing Date: 2009-08-11
• [Patent(Industrial Property Rights)] TRPV2の部分ペプチド (2009)
  • Inventor(s): 岩田裕子, 若林繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2009-186219
  • Filing Date: 2009-08-11
• [Patent(Industrial Property Rights)] 目的物質精製用タグおよび精製用タグを用いた目的物質の精製方法 (2007)
  • Inventor(s): 若林繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2007-130239
  • Filing Date: 2007-05-16
• [Patent(Industrial Property Rights)] トランスジェニック非ヒト動物 (2007)
  • Inventor(s): 岩田裕子、西谷友重、若林繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2007-123514
  • Filing Date: 2007-05-08
• [Patent(Industrial Property Rights)] トランスジェニック非ヒト動物 (2007)
  • Inventor(s): 岩田 裕子,西谷 友重,若林 繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2007-123514
  • Filing Date: 2007-05-08
• [Patent(Industrial Property Rights)] 目的物質精製用タグおよび精製用タグを用いた目的物資の精製方法 (2007)
  • Inventor(s): 若林 繁夫
  • Industrial Property Rights Holder: (財)ヒューマンサイエンス振興財団
  • Industrial Property Number: 2007-130239
  • Filing Date: 2007-05-16