Novel therapeutic strategy of the fatal arrhythmia targeting specific domain in the ryanodine receptor molecle
Project/Area Number |
20590868
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Yamaguchi University |
Principal Investigator |
YAMAMOTO Takeshi Yamaguchi University, 大学院・医学系研究科, 助教 (50363122)
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Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Shigeki 山口大学, 医学部附属病院, 助教 (90397993)
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Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 分子心臓病態学 / 致死的不整脈 / リアノジン受容体 / 興奮収縮連関 / 心不全 / 心室性不整脈 |
Research Abstract |
We identified the important RyR2 domain for the stabilization of the RyR2 channel as domain 2114-2149 and its counterpart. The counterpart of domain 2114-2149 is in the central portion of the RyR2. The compound which affect these two domains might be novel medicines for heart failure of fatal arrhythmias.
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Urinary 8-Hydroxy-2' -Deoxyguanosine Reflects Symptomatic Status and Severity of Systolic Dysfunction in Patients with Chronic Heart Failure.2011
Author(s)
Kobayashi S, Susa T, Tanaka T, Wada Y, Okuda S, Doi M, Nao T, Yoshiga Y, Yamada J, Okamura T, Ueyama T, Kawamura S, Yano M, Matsuzaki M.
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Journal Title
Eur J Heart Fail. 13(1)
Pages: 29-36
Related Report
Peer Reviewed
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[Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2 R2474S/+knock-in mouse model.2010
Author(s)
Kobayashi S, Yano M, Uchinoumi H, Suetomi T, Susa T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Yamamoto T, Matsuzaki M.
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Journal Title
Circ J. 74(12)
Pages: 2579-2584
NAID
Related Report
Peer Reviewed
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[Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure.2010
Author(s)
Ono M, Yano M, Hino A, Suetomi T, Xu X, Susa T, Uchinoumi H, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M.
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Journal Title
Cardiovasc Res. 87(4)
Pages: 609-617
Related Report
Peer Reviewed
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[Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction.2010
Author(s)
Xu X, Yano M, Uchinoumi H, Hino A, Suetomi T, Ono M, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, lkeda Y, lkemoto N, Matsuzaki M.
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Journal Title
Biochem Biophys Res Commun. 394(3)
Pages: 660-666
Related Report
Peer Reviewed
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[Journal Article] Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor.2010
Author(s)
Uchinoumi H, Yano M, Suetomi T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, lkeda Y, Ohkusa T, lkemoto N, Matsuzaki M.
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Journal Title
Circ Res. 106(8)
Pages: 1413-1424
Related Report
Peer Reviewed
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[Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor.2009
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, lkemoto N, Matsuzaki M.
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Journal Title
J Am Coll Cardiol. 53(21)
Pages: 1993-2005
Related Report
Peer Reviewed
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[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, 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.
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Journal Title
Cardiovasc Res. 81(3)
Pages: 536-545
Related Report
Peer Reviewed
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[Presentation] Domain2114-2149 Within RyR2 Plays a Key Role for Correcting Channel Disorder in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)2008
Author(s)
Yamamoto, T, Yano, M, Suedomi, T, Ohno, M, Xu, XJ, Tateishi, H, Okuda, S, Kobayashi, S, Ikeda, Y, Matsuzaki, M
Organizer
Scientific Sessions 2008 of American Heart Association
Place of Presentation
NewOrleans, USA
Related Report
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[Presentation] Identification of Target Domains of the Cardiac Ryanodine Receptor to Correct Channel Disorder in Failing Hearts2008
Author(s)
Yamamoto, T, Yano, M, Suedomi, T, Ohno, M, Xu, XJ, Tateishi, H, Okuda, S, Kobayashi, S, Ikeda, Y, Matsuzaki, M
Organizer
Basic Cardiovascular Sciences Annual Conference 2009-Molecular Mechanisms of Cardiovascular Disease.
Place of Presentation
Keystone, USA
Related Report
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