• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Exploration into the Development of New Therapy for Heart Failure by Modifying Sarcoplasmic Reticulum Nanodomain Function

Research Project

Project/Area Number 19209030
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionYamaguchi University

Principal Investigator

MATSUZAKI Masunori  Yamaguchi University, 大学院・医学系研究科, 教授 (60116754)

Co-Investigator(Kenkyū-buntansha) IKEDA Yasuhiro  山口大学, 医学部, 講師 (00260349)
YANO Masafumi  山口大学, 医学部・附属病院, 講師 (90294628)
AOKI Hiroki  山口大学, 医学部, 准教授 (60322244)
YAMAMOTO Takeshi  山口大学, 大学院・医学系研究科, 助教 (50363122)
IZUMI Tomonori  山口大学, 大学院・医学系研究科, 准教授 (00261694)
MAEKAWA Tsuyoshi  山口大学, 大学院・医学系研究科, 教授 (60034972)
Research Collaborator 青山 英和  山口大学, 大学院・医学系研究科, 大学院生
宮崎 要介  山口大学, 大学院・医学系研究科, 大学院生
藤本 静香  山口大学, 大学院・医学系研究科, 技術補佐員
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥50,700,000 (Direct Cost: ¥39,000,000、Indirect Cost: ¥11,700,000)
Fiscal Year 2008: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2007: ¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000)
Keywordssarcoplasmic reticulum(SR) / shotgun proteomics / junctional SR / longitudinal SR / calcium / protein phosphatase / ryanodine receptor / protein phosphatase 1β
Research Abstract

重症心不全の心筋細胞でみられるCa^<2+>循環制御蛋白のリン酸化異常を惹起する分子機構を解明し、治療応用するための基盤的研究である。心筋から精製した筋小胞体(SR)再分画を使って、各ドメイン蛋白群(Ca^<2+>放出SR : Junctional SR、Ca^<2+>取り込みSR : Longitudinal SR)をそれぞれ同定し、リン酸化制御に関する主要蛋白の蛋白相互作用・機能解析を行った。また、その中でも最も重要な蛋白でCa^<2+>放出チャネルあるリアノジン受容体(RyR)について、機能安定化作用を有するアミノ酸配列を同定した。さらに筋小胞体表面の脱リン酸化調節をおこなう蛋白ホスファターゼ1の最も重要なアイソフォームを同定した。これら発見は心不全に対する分子標的療法を確立していくうえで重要な知見になると考えられた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (47 results)

All 2009 2008 2007 Other

All Journal Article (23 results) (of which Peer Reviewed: 11 results) Presentation (16 results) Book (3 results) Remarks (5 results)

  • [Journal Article] Inhibitor-1 is Potential Target for Enhancing2009

    • Author(s)
      Ikeda Y, Yano M.
    • Journal Title

      SarcoplasmicReticulum Ca(2+) Loading in Failing Hearts. Circ J. 73(6)(Editorial)

      Pages: 1018-9

    • Related Report
      2008 Final Research Report
  • [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia2009

    • Author(s)
      Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M.
    • Journal Title

      markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor. J Am Coll Cardiol 53(21)

      Pages: 1993-2005

    • Related Report
      2008 Final Research Report
  • [Journal Article] Role of ryanodine receptor as a Ca(2+) regulatory center in normal and failing hearts2009

    • Author(s)
      Yano M, Yamamoto T, Kobayashi S, Matsuzaki M.
    • Journal Title

      J Cardiol 53(1)

      Pages: 1-7

    • NAID

      10025182309

    • Related Report
      2008 Final Research Report
  • [Journal Article] Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca2+ leak in failing hearts.2009

    • Author(s)
      Tateishi H
    • Journal Title

      Cardiovascular Research 81

      Pages: 536-545

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca^<2+> leak in failing hearts2008

    • Author(s)
      Tateishi H, Yano M, Mochizuki M, Suetomi T, Ono M, Xu X, Uchinoumi H, Okuda S, Oda T, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
    • Journal Title

      Cardiovasc Res

    • Related Report
      2008 Final Research Report
  • [Journal Article] Identification of target domains of the cardiac ryanodine receptor to correct channel disorder in failing hearts2008

    • Author(s)
      Yamamoto T, Yano M, Xu X, Uchinoumi H, Tateishi H, Mochizuki M, Oda T, Kobayashi S, Ikemoto N, Matsuzaki M.
    • Journal Title

      Circulation 117(6)(PubMed PMID : 18227387)

      Pages: 762-72

    • Related Report
      2008 Final Research Report
  • [Journal Article] Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel2008

    • Author(s)
      Maturana AD, Walchli S, Iwata M, Ryser S, Van Lint J, Hoshijima M, Schlegel W, Ikeda Y, Tanizawa K, Kuroda S.
    • Journal Title

      Cardiovasc Res 78(3)

      Pages: 458-65

    • Related Report
      2008 Final Research Report
  • [Journal Article] Identification and physiological activity of survival factor released from cardiomyocytes during ischaemia and reperfusion2008

    • Author(s)
      Mizukami Y, Ono K, Du CK, Aki T, Hatano N, Okamoto Y, Ikeda Y, Ito H, Hamano K, Morimoto S.
    • Journal Title

      Cardiovasc Res 79(4)

      Pages: 589-99

    • Related Report
      2008 Final Research Report
  • [Journal Article] Lentiviral Vector-mediated SERCA2 Gene Transfer Protects Against Heart Failure and Left Ventricular Remodeling After Myocardial Infarction in Rats2008

    • Author(s)
      Niwano K, Arai M, Koitabashi N, Watanabe A, Ikeda Y, Miyoshi H, Kurabayashi M.
    • Journal Title

      Mol Ther (Epub ahead of print)

    • Related Report
      2008 Final Research Report
  • [Journal Article] Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects2008

    • Author(s)
      Briggs LE, Takeda M, Cuadra AE, Wakimoto H, Marks MH, Walker AJ, Seki T, Oh SP, Lu JT, Sumners C, Raizada MK, Horikoshi N, Weinberg EO, Yasui K, Ikeda Y, Chien KR, Kasahara H.
    • Journal Title

      Circ Res 103(6)

      Pages: 580-90

    • Related Report
      2008 Final Research Report
  • [Journal Article] Role of ryanodine receptor as a Ca(2+) regulatory center in normal and failing hearts.2008

    • Author(s)
      Yano M
    • Journal Title

      J Cardiol 53

      Pages: 1-7

    • NAID

      10025182309

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of target domains of the cardiac ryanodine receptor to correct channel disorder in failing hearts.2008

    • Author(s)
      Yamamoto T
    • Journal Title

      Circulation 117

      Pages: 762-72

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects.2008

    • Author(s)
      Briggs LE
    • Journal Title

      Circulation Research 103

      Pages: 580-590

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and physiological activity of survival factor released from cardiomyocytes during ischaemia and reperfusion.2008

    • Author(s)
      Mizukami Y
    • Journal Title

      Cardiovascular Research 73

      Pages: 589-599

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lentiviral vector-mediated SERCA2 gene transfer protects against heart failure and left ventricular remodeling after myocardial infarction in rats.2008

    • Author(s)
      Niwano K
    • Journal Title

      Mol Ther. 16

      Pages: 1026-32

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Toward biologically targeted therapy of calcium cycling defects in heart failure.2008

    • Author(s)
      Ikeda Y
    • Journal Title

      Physiology 23

      Pages: 6-16

    • Related Report
      2008 Annual Research Report 2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of target domains of the cardiac ryanodine receptor to correctchannel disorder in failing hearts.2008

    • Author(s)
      Yamamoto T
    • Journal Title

      Circulation 117

      Pages: 762-72

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of cell therapy and cytokine therapy for functional repair in ischemic and nonischemic heart failure2007

    • Author(s)
      Li TS, Mikamo A, Takahashi M, Suzuki R, Ueda K, Ikeda Y, Matsuzaki M, Hamano K.
    • Journal Title

      Cell Transplant 16(4)

      Pages: 365-74

    • Related Report
      2008 Final Research Report
  • [Journal Article] Progression of heart failure was suppressed by inhibition of apoptosis-signal regulating kinase2007

    • Author(s)
      Hikoso M, Ikeda Y, Yamaguchi O, Takeda T, Higuchi Y, Hirotani S, Kashiwase K, Yamada M, Asahi M, Matsumura Y, Nishida K, Matsuzaki M, Hori M, Otsu K.
    • Journal Title

      1(ASK-1) via transcoronary gene transferJ Am Coll Cardiol 50(5)(co-first author)

      Pages: 453-462

    • Related Report
      2008 Final Research Report
  • [Journal Article] Scavenging free radicals by low-dose carvedilol prevents redox-dependent Ca2+ leak via stabilization of ryanodine receptor in heart failure2007

    • Author(s)
      Mochizuki M, Yano M, Oda T, Tateishi H, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
    • Journal Title

      J Am Coll Cardiol 49(16)

      Pages: 1722-32

    • Related Report
      2008 Final Research Report
  • [Journal Article] Progression of heart failure was suppressed by inhibition of apoptosis signal-regulating kinase 1 via transcoronary gene transfer.2007

    • Author(s)
      Hikoso S
    • Journal Title

      J Am Coll Cardiol. 50

      Pages: 453-62

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of cell therapy and cytokine therapy for functional repair in ischemicand nonischemic heart failure.2007

    • Author(s)
      Li TS
    • Journal Title

      Cell Transplant. 16

      Pages: 365-374

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scavenging free radicals by low-dose carvedilol prevents redox-dependent Ca2+ leak via stabilization of ryanodine receptor in heart failure.2007

    • Author(s)
      Mochizuki M
    • Journal Title

      J Am Coll Cardiol. 49

      Pages: 1722-32

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Abstract 1533 : Protein Phosphatase 1 Beta is Most Abundan2008

    • Author(s)
      Aoyama H, Ikeda Y, Miyazaki Y, Ono M, Yoshimura K, Yamamoto T, Aoki H, Inui M, and Matsuzaki M
    • Organizer
      Isoform in the Longitudinal Sarcoplasmic Reticulum and Regulates Phospholamban Phosphorylation in Cardiomyocytes Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_345-c-346S_-c)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 1355 : The Vascular Smooth Muscle Cell-Autonomous Role of Id2 in Phenotypic Modulation In Vitro And2008

    • Author(s)
      Aoki H, Yoshimura K, Ikeda Y, and Matsuzaki M
    • Organizer
      Atherogenesis In Vivo Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_312-a)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 427 : c-Jun N-terminal Kinase 2 Translates Mechanical Stress to2008

    • Author(s)
      Yoshimura K, Aoki H, Kimura K, Ikeda Y, Aoyama H, Miyazaki Y, Morikage N, Furutani A, Hamano H, and Matsuzaki M
    • Organizer
      Inflammatory Signal in Macrophages and Promotes Progression of Abdominal Aortic Aneurysm In Vivo Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_303-b)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 5251 : Defective Inter-domain Interaction May Cause Spontaneous Ca^<2+> Release Via2008

    • Author(s)
      Ono M, Yano M, Suetomi T, Xu X, Uchinoumi H, Tateishi H, Okuda S, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, and Matsuzaki M
    • Organizer
      Reduced Affinity of Calmodulin Binding to RyR2 in Failing Hearts Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_513-d-514S_ -d)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 5272 : Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction Defects2008

    • Author(s)
      Briggs LE, Takeda M, Cuadra AE, Wakimoto H, Lu JT, Yasui K, Ikeda Y, Chien KR, and Kasahara H
    • Organizer
      Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_517-a)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 5289 : Abnormally Tight Domain-Domain Interaction at Mutation Site Could be a Primary Cause of Catecholaminergic Polymorphic Ventricular Tachycardia : Insight from RyR2^<S2246L/+> Knock-In Mouse2008

    • Author(s)
      Suetomi T, Yano M, Xu X, Ono M, Uchinoumi H, Tateishi H, Okuda S, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, and Matsuzaki M
    • Organizer
      Model Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_520-b)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 5303 : Decreased Affinity of Calmodulin Binding to RyR2 May Cause Leaky Channel in CPVT-Associated Mutation : Insight from RyR2^<R2474s/+> Knock-In Mouse Model2008

    • Author(s)
      Xu X, Yano M, Suetomi T, Ono M, Uchinoumi H, Tateishi H, Okuda S, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, and Matsuzaki M
    • Organizer
      Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_523-a)
    • Related Report
      2008 Final Research Report
  • [Presentation] Abstract 5322 : Mutation-Linked, Defective Inter-Domain Interaction within the Cardiac Ryanodine Receptor as a Critical Cause of2008

    • Author(s)
      Uchinoumi H, Yano M, Suetomi T, Xu Z, Ono M, Tateishi H, Okuda S, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, and Matsuzaki M
    • Organizer
      Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Circulation
    • Place of Presentation
      New Orleans、USA(118 : S_526-b)
    • Related Report
      2008 Final Research Report
  • [Presentation] Protein Phosphatase 1 Beta is Most Abundant Isoform in the Longitudinal Sarcoplasmic Reticulum and Regulates Phospholamban Phosphorylation in Cardiomyocytes2008

    • Author(s)
      Aoyama H
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mutation-Linked, Defective Inter-Domain Interaction within the Cardiac Ryanodine Receptor as a Critical Cause of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)2008

    • Author(s)
      Uchinoumi H
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Decreased Affinity of Calmodulin Binding to RyR2 May Cause Leaky Channel in CPVT-Associated Mutation : Insight from RyR2^<R2474s/+> Knock-In Mouse Model2008

    • Author(s)
      Xu X
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Abnormally Tight Domain-Domain Interaction at Mutation Site Could be a Primary Cause of Catecholaminergic Polymorphic Ventricular Tachycardia : Insight from RyR2^<S2246L/+> Knock-In Mouse Model2008

    • Author(s)
      Suetomi T
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Defective Inter-domain Interaction May Cause Spontaneous Ca^<2+> Release Via Reduced Affinity of Calmodulin Binding to RyR2 in Failing Hearts2008

    • Author(s)
      Ono M
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] c-Jun N-terminal Kinase 2 Translates Mechanical Stress to Inflammatory Signal in Macrophages and Promotes Progression of Abdominal Aortic Aneurysm In Vivo2008

    • Author(s)
      Yoshimura K
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] The Vascular Smooth Muscle Cell-Autonomous Role of Id2 in Phenotypic Modulation In Vitro And Atherogenesis In Vivo2008

    • Author(s)
      Aoki H
    • Organizer
      AHA Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Protein phosphatase 1β is the major phospholamban phosphatase that regulates cardiac contractility in adult rat cardiomyocytes.2007

    • Author(s)
      Aoyama Hidekazu
    • Organizer
      American Heart Association Annual Meeting
    • Place of Presentation
      Orlando Convention Center,Florida,USA
    • Year and Date
      2007-11-06
    • Related Report
      2007 Annual Research Report
  • [Book] Oxford University Press2008

    • Author(s)
      Ikeda Y, Yamamoto T, Yano M, Matsuzaki M.
    • Publisher
      Heart Failure Pathophyiology in Supportive Care for Cardiac Patient
    • Related Report
      2008 Final Research Report
  • [Book] Supportive Care in Heart Failure2008

    • Author(s)
      Ikeda Y
    • Total Pages
      489
    • Publisher
      Oxford University Press
    • Related Report
      2008 Annual Research Report
  • [Book] Heart Failure Pathophysiology in Supportive Care for Cardiac Patient2008

    • Author(s)
      Ikeda Y
    • Publisher
      Oxford University Press(In print)
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~ninai/ninai.htm

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~ninai/ninai.htm

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.crm.med.yamaguchi-u.ac.jp/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~ninai/ninai.html

    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.crm.med.yamaguchi-u.ac.jp/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi