2010 Fiscal Year Final Research Report
Novel molecular mechanisms for cardiotonic action, their involvement in diseases and application for treatment
| Project/Area Number |
19390211
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Mie University |
|---|
Principal Investigator |
ITO Masaaki Mie University, 大学院・医学系研究科, 教授 (00223181)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Ryuji 三重大学, 大学院・医学系研究科, 助教 (60378346)
ONISHI Katsuya 三重大学, 大学院・医学系研究科, 助教 (40343222)
|
|---|
| Project Period (FY) |
2007 – 2010
|
| Keywords | 心筋ミオシン / リン酸化 / ミオシン軽鎖キナーゼ / ミオシンホスファターゼ / 心不全 |
|---|
| Research Abstract |
The regulatory mechanism, function and the involvement in pathologic conditions of cardiac myosin light chain (MLC2) phosphorylation were investigated. Cardiac MLC2 was found to be phosphorylated by cardiac myosin light chain kinase (cMLCK), but not by smooth MLCK nor ZIP-kinase. However, cMLCK was not detected in several animal species, suggesting the existence of another (iso)forms of cardiac MLCK. Biochemical characteristics of cMLCK were different from those of smMLCK including the enzyme kinetics and the sensitivity for antagonists. The overexpression of cardiac myosin phosphatase in heart induced a reduction of MLC2 phosphorylation levels concomitant with a Ca^<2+> desensitization of contraction and decreased LV contractility, resulting in LV enlargement. Thus the phosphorylation of cardiac MLC2 plays a significant role in maintaining normal cardiac function. Agonist stimulation including endothelin-1 induced the expression of cMLCK and increased the phosphorylation level of MLC2. In addition, the expression of cMLCK and the phosphorylation levels of MLC2 were varied in several animal models, suggesting the phosphorylation of MLC2 might be involved in the several pathologic conditions in heart.
|
-
-
-
-
[Journal Article] Overexpression of myosin phosphatase reduced Ca2+ sensitivity of contraction and impairs cardiac function.2010
Author(s)
Mizutani H, Okamoto R, Moriki N, Konishi K, Taniguchi M, Fujita S, Dohi K, Onishi K, Suzuki M, Satoh S, Makino N, Itoh T, Hartshorne DJ, Ito M.
-
Journal Title
Circ.J. 74
Pages: 120-128
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Impaired myocardial perfusion reserve in patients with fatty liver disease assessed by quantitative myocardial perfusion MRI.2010
Author(s)
Nakamori S, Onishi K, Nakajima H, Kato S, Yoon YE, Kitagawa K, Dohi K, Nakamura M, Sakuma H, Ito M
Organizer
American Heart Association 2010 Scientifc Sessions.
Place of Presentation
Chicago, U.S.A.
Year and Date
20101113-20101117
-
-
[Presentation] Role of hemodialytic therapy on left venatirular mechanical dyssynchrony in patients with end-stage renal failure quantified by speckle-tracking strain imaging.2010
Author(s)
Dohi K, Murata T, Onishi K, Sugiura E, Sugimoto T, Yamada N, Nomura S, Miyahara M, Nakamura M, Ito M
Organizer
European Society of Cardiology Congress 2010.
Place of Presentation
Stockholm, Sweden
Year and Date
20100828-20100901
-
[Presentation] Diagnostic utility of serum intact parathyroid hormone in predicting impaired cardiac hemodynamics combined with brain natriuretic peptide in patients with heart failure.2010
Author(s)
Sugimoto T, Dohi K, Nakajima H, Ichikawa K, Nakamori S, Tanabe M, Onishi K, Miyahara M, Nakamura M, Ito M
Organizer
European Society of Cardiology Congress 2010.
Place of Presentation
Stockholm, Sweden
Year and Date
20100828-20100901
-
-
-
[Presentation] Long term prognostic value of stress perfusion CMR study for the prediction of cardiovascular death and nonfatal acute myocardial infarction in 1009 asian patients.2009
Author(s)
Kurita T, Sakuma H, Nakajima H, Kato S, Miyagi H, Nakamori S, Kitagawa K, Onishi K, Nakamura M, Ito M
Organizer
American Heart Association 2009 Scientifc Sessions.
Place of Presentation
Orlando, U.S.A.
Year and Date
20091114-20091118
-
[Presentation] Human atrial natriuretic peptide preserved infract-related myocardial blood flow quantified by perfusion MRI in patients with acute myocardial infarction.2009
Author(s)
Kurita T, Tanigawa T, Sakuma H, Sato K, Nakajima H, Nakamori S, Ichikawa Y, Kitagawa K, Matsuoka K, Onishi K, Nakamura T, Ito M
Organizer
American Heart Association 2009 Scientifc Sessions.
Place of Presentation
Orlando, U.S.A.
Year and Date
20091114-20091118
-
[Presentation] Coupling of systolic and diastolic function and regional synchrony in normal, hypertrophic, and failing myocardium quantified by speckle-tracking echocardiography.2009
Author(s)
Dohi K, Onishi K, Takamura T, Sugiura E, Nakajima H, Ichikawa K, Tanabe M, Miyahara M, Nakamura M, Ito M
Organizer
European Society of Cardiology Congress 2009.
Place of Presentation
Barcelona, Spain
Year and Date
20090829-20090902
-
[Presentation] Presence of myocardial scar is strongly associated with abnormal regional myocardial blood flow in hypertrophic cardiomyopathy.2009
Author(s)
Nakajima H, Onishi K, Kurita T, Ishida M, Nagata M, Kitagawa K, Dohi K, Nakamura M, Sakuma H, Ito M
Organizer
European Society of Cardiology Congress 2009.
Place of Presentation
Barcelona, Spain
Year and Date
20090829-20090902
-
[Presentation] Quantification of left ventricular contraction and relaxation in patients with diastolic heart failure by speckle-tracking strain and strain rateechocardiography.2009
Author(s)
Ogawa E, Dohi K, Onishi K, Takamura T, Nakajima H, IchikawaK, Tanabe M, Tamada H, Miyahara M, Nakamura M, Ito M
Organizer
第73回日本循環器学会総会・学術集会
Place of Presentation
大阪
Year and Date
20090320-20090323
-
[Presentation] Quantification of left ventricular mechanical dyssynchrony in normal, hypertrophied, and dilated myocardium quantified by speckle-tracking strain echocardiography.2009
Author(s)
Dohi K, Onishi K, Takamura T, Ogawa E, Nakajima H, Ichikawa K, Tanabe M, Tamada H, Miyahara M, Nakamura M, Ito M
Organizer
第73回日本循環器学会総会・学術集会
Place of Presentation
大阪
Year and Date
20090320-20090323
-
[Presentation] Subendmyocardial perfusion reserve correlated with left ventricular diastolic function in patients with various types of left ventricular hypertrophy.2008
Author(s)
Kurita T, Onishi K, Sakuma H, Takamura T, Nagata M, Nakajima H, Ishida M, Fujimoto N, Dohi K, Takeda K, Ito M
Organizer
American Heart Association 2008 Scientifc Sessions.
Place of Presentation
New Orleans, U.S.A.
Year and Date
20081108-20081112
-
[Presentation] Hypertension plays an important role on the impairment of myocardial perfusion reserve determined by quantitative analysis of myocardial perfusion MRI.2008
Author(s)
Nakajima H, Onishi K, Kurita T, Ishida M, Takamura T, Ishida N, Dohi K, Nakamura M, Sakuma H, Ito M
Organizer
American Heart Association 2008 Scientifc Sessions.
Place of Presentation
New Orleans, U.S.A.
Year and Date
20081108-20081112
-
[Presentation] 心筋ミオシンホスファターゼの分子性状とその機能2008
Author(s)
水谷英夫, 森木宣行, 岡本隆二, 井阪直樹,中野赳, 伊藤正明, 大西勝也, 鈴木昇, 佐藤真司, 牧野直樹, David Hartshorne.
Organizer
第37回日本心脈管作動物質学会
Place of Presentation
仙台
Year and Date
2008-02-02
-
