Biological actions of green tea catechins on cardiac troponin C |
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Authors: | Tadano Naoto Du Cheng-Kun Yumoto Fumiaki Morimoto Sachio Ohta Mika Xie Ming-Fang Nagata Koji Zhan Dong-Yun Lu Qun-Wei Miwa Yoshikazu Takahashi-Yanaga Fumi Tanokura Masaru Ohtsuki Iwao Sasaguri Toshiyuki |
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Affiliation: | Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. |
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Abstract: | BACKGROUND AND PURPOSECatechins, biologically active polyphenols in green tea, are known to have a protective effect against cardiovascular diseases. In this study, we investigated direct actions of green tea catechins on cardiac muscle function to explore their uses as potential drugs for cardiac muscle disease.EXPERIMENTAL APPROACHThe effects of catechins were systematically investigated on the force-pCa relationship in skinned cardiac muscle fibres to determine their direct effects on cardiac myofilament contractility. The mechanisms of action of effective catechins were investigated using troponin exchange techniques, quartz crystal microbalance, nuclear magnetic resonance and a transgenic mouse model.KEY RESULTS(-)-Epicatechin-3-gallate (ECg) and (-)-epigallocatechin-3-gallate (EGCg), but not their stereoismers (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate, decreased cardiac myofilament Ca2+ sensitivity probably through its interaction with cardiac troponin C. EGCg restored cardiac output in isolated working hearts by improving diastolic dysfunction caused by increased myofilament Ca2+ sensitivity in a mouse model of hypertrophic cardiomyopathy.CONCLUSIONS AND IMPLICATIONSThe green tea catechins, ECg and EGCg, are Ca2+ desensitizers acting through binding to cardiac troponin C. These compounds might be useful compounds for the development of therapeutic agents to treat the hypertrophic cardiomyopathy caused by increased Ca2+ sensitivity of cardiac myofilaments. |
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Keywords: | catechin gallate troponin calcium sensitivity cardiomyopathy |
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