Coordinated Regulation of Murine Cardiomyocyte Contractility by Nanomolar (-)-Epigallocatechin-3-Gallate, the Major Green Tea Catechin
Coordinated Regulation of Murine Cardiomyocyte Contractility by Nanomolar (-)-Epigallocatechin-3-Gallate, the Major Green Tea Catechin
复制标题
DOI：
10.1124/mol.112.079707
复制
发表时间：
2012-11-01
影响因子：
3.6
通讯作者：
Knollmann, Bjoern C.
中科院分区：
文献类型：
--
作者：
Feng, Wei;Hwang, Hyun Seok;Knollmann, Bjoern C.
绿色茶多酚儿茶素在多种细胞类型中表现出生物活性。尽管非专业和科学文献中的报告表明了改善心血管健康的治疗潜力，但其潜在的分子作用机制仍不清楚。先前的研究已经暗示了主要的绿色茶儿茶素（-）-表没食子儿茶素-3-没食子酸酯（EGCG）在心肌中的广泛分子靶点，但是仅在临床相关性不清楚的微摩尔浓度下观察到效果。在这里，我们报告说，纳摩尔浓度的表没食子儿茶素没食子酸酯显着增强完整的小鼠心肌细胞的收缩性，通过增加电诱发的钙瞬变，肌浆网（SR）钙含量，和兰尼碱受体2型（RyR 2）通道开放的概率。电压钳实验表明，10 nM EGCG显着抑制Na+-Ca 2+交换。重要的是，其它Na+和Ca 2+处理蛋白如Ca 2 +-ATP酶、Na+-H+交换器和Na+-K+-ATP酶不受1 μ M EGCG的影响。这些新认识到的行动纳摩尔和微摩尔的表没食子儿茶素没食子酸酯应考虑时，绿色茶补充剂的治疗和毒理学潜力进行评估，并可能提供一种新的治疗策略，改善收缩功能的心力衰竭。
Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltage-clamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na+-Ca2+ exchanger. Of importance, other Na+ and Ca2+ handling proteins such as Ca2+-ATPase, Na+-H+ exchanger, and Na+-K+-ATPase were not affected by EGCG 1 mu M. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.