Overexpression of Myosin Phosphatase Reduces Ca2+ Sensitivity of Contraction and Impairs Cardiac Function
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- Konishi Katsuhisa
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Mizutani Hideo
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Okamoto Ryuji
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Moriki Nobuyuki
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Taniguchi Masaya
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Fujita Satoshi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Dohi Kaoru
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Onishi Katsuya
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Suzuki Noboru
- Functional Genomics Institutes, Life Science Research Center, Mie University
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- Makino Naoki
- Division of Molecular and Clinical Gerontology, Medical Institute of Bioregulation, Kyushu university
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- Itoh Takeo
- Department of Cellular and Molecular Pharmacology, Graduate School of Medical Sciences, Nagoya City University
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- Hartshorne David J.
- Muscle Biology Group, University of Arizona
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- Ito Masaaki
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
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- Satoh Shinji
- Department of Cardiology, National Hospital Organization Kyushu Medical Center
書誌事項
- 公開日
- 2010
- DOI
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- 10.1253/circj.cj-09-0462
- 公開者
- 一般社団法人 日本循環器学会
この論文をさがす
説明
Background: Phosphorylation of the regulatory light chain of myosin (MLC) has roles in cardiac function. In vitro, myosin phosphatase target subunit 2 (MYPT2) is a strongly suspected regulatory subunit of cardiac myosin phosphatase (MP), but there is no in-vivo evidence regarding the functions of MYPT2 in the heart. Methods and Results: Transgenic mice (Tg) overexpressing MYPT2 were generated using the α-MHC promoter. Tg hearts showed an increased expression of MYPT2 and concomitant increase of the endogenous catalytic subunit of type 1 phosphatase (PP1cδ), resulting in an increase of the MP holoenzyme. The level of phosphorylation of ventricular MLC was reduced. The pCa-tension relationship, using β-escin permeabilized fibers, revealed decreased Ca2+ sensitization of contraction in the Tg heart. LV enlargement with associated impairment of function was observed in the Tg heart and ultrastructural examination showed cardiomyocyte degeneration. Conclusions: Overexpression of MYPT2 and the increase in PP1cδ resulted in an increase of the MP holoenzyme and a decrease in the level of MLC phosphorylation. The latter induced Ca2+ desensitization of contraction and decreased LV contractility, resulting in LV enlargement. Thus, MYPT2 is truly the regulatory subunit of cardiac MP in-vivo and plays a significant role in modulating cardiac function. (Circ J 2010; 74: 120 - 128)<br>
収録刊行物
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- Circulation Journal
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Circulation Journal 74 (1), 120-128, 2010
一般社団法人 日本循環器学会
