Biological actions of green tea catechins on cardiac troponin C
Biological actions of green tea catechins on cardiac troponin C
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DOI：
10.1111/j.1476-5381.2010.00942.x
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发表时间：
2010-11-01
影响因子：
7.3
通讯作者：
Sasaguri, Toshiyuki
中科院分区：
文献类型：
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作者：
Tadano, Naoto;Du, Cheng-Kun;Sasaguri, Toshiyuki
背景和目的儿茶素是绿茶中具有生物活性的多酚，已知对心血管疾病具有保护作用。在这项研究中，我们研究了绿茶儿茶素对心肌功能的直接作用，以探索它们作为治疗心肌疾病的潜在药物的用途。实验方法系统地研究了儿茶素对带皮心肌纤维中力-pCa关系的影响，以确定它们对心肌丝收缩力的直接影响。使用肌钙蛋白交换技术、石英晶体微天平、核磁共振和转基因小鼠模型研究了有效儿茶素的作用机制。 主要结果 (-)-表儿茶素-3-没食子酸酯 (ECg) 和 (-)-表没食子儿茶素-3-没食子酸酯 (EGCg)，但不是它们的立体异构体 (-)-儿茶素-3-没食子酸酯和 (-)-没食子儿茶素-3-没食子酸酯，减少了心肌丝Ca2+ 敏感性可能是通过其与心肌肌钙蛋白 C 的相互作用而实现的。EGCg 通过改善肥厚型心肌病小鼠模型中肌丝 Ca2+ 敏感性增加引起的舒张功能障碍，从而恢复离体工作心脏的心输出量。结论和意义绿茶儿茶素、ECg 和 EGCg 是通过与心肌肌钙蛋白 C 结合发挥作用的 Ca2+ 脱敏剂。这些化合物可能是用于开发治疗药物的有用化合物，以治疗肥厚型心肌病。心肌肌丝 Ca2+ 敏感性增加引起的肥厚型心肌病。
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.