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首页> 外文期刊>Cellular Physiology and Biochemistry >Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production
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Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production

机译：长期口服Theaphenon-E可通过影响Phospholamban磷酸化和ATP的产生来改善心肌细胞力学和钙动力学。

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Background/Aims Dietary polyphenols from green tea have been shown to possess cardio-protective activities in different experimental models of heart diseases and age-related ventricular dysfunction. The present study was aimed at evaluating whether long term in vivo administration of green tea extracts (GTE), can exert positive effects on the normal heart, with focus on the underlying mechanisms. Methods The study population consisted of 20 male adult Wistar rats. Ten animals were given 40 mL/day tap water solution of GTE (concentration 0.3%) for 4 weeks (GTE group). The same volume of water was administered to the 10 remaining control rats (CTRL). Then, in vivo and ex vivo measurements of cardiac function were performed in the same animal, at the organ (hemodynamics) and cellular (cardiomyocyte mechanical properties and intracellular calcium dynamics) levels. On cardiomyocytes and myocardial tissue samples collected from the same in vivo studied animals, we evaluated (1) the intracellular content of ATP, (2) the endogenous mitochondrial respiration, (3) the expression levels of the Sarcoplasmic Reticulum Ca2+-dependent ATPase 2a (SERCA2), the Phospholamban (PLB) and the phosphorylated form of PLB, the L-type Ca2+ channel, the Na+-Ca2+ exchanger, and the ryanodine receptor 2. Results GTE cardiomyocytes exhibited a hyperdynamic contractility compared with CTRL (the rate of shortening and re-lengthening, the fraction of shortening, the amplitude of calcium transient, and the rate of cytosolic calcium removal were significantly increased). A faster isovolumic relaxation was also observed at the organ level. Consistent with functional data, we measured a significant increase in the intracellular ATP content supported by enhanced endogenous mitochondrial respiration in GTE cardiomyocytes, as well as higher values of the ratios phosphorylated-PLB/PLB and SERCA2/PLB. Conclusions Long-term in vivo administration of GTE improves cell mechanical properties and intracellular calcium dynamics in normal cardiomyocytes, by increasing energy availability and removing the inhibitory effect of PLB on SERCA2.
机译：背景/目的在不同的心脏病和年龄相关性心室功能不全的实验模型中，绿茶中的膳食多酚已被证明具有心脏保护作用。本研究旨在评估长期体内施用绿茶提取物（GTE）是否可以对正常心脏产生积极影响，重点在于其潜在机制。方法研究对象为20只成年雄性Wistar大鼠。十只动物接受40 mL /天的GTE自来水溶液（浓度0.3％）治疗4周（GTE组）。向其余10只对照大鼠（CTRL）注入相同体积的水。然后，在同一只动物的器官（血液动力学）和细胞（心肌细胞机械特性和细胞内钙动力学）水平进行体内和体外心脏功能的测量。在从相同的体内研究动物收集的心肌细胞和心肌组织样品上，我们评估了（1）ATP的细胞内含量，（2）内源性线粒体呼吸作用，（3）肌浆网Ca2 +依赖性ATPase 2a（ SERCA2），磷脂酰磷脂（PLB）和磷酸化形式的PLB，L型Ca2 +通道，Na + -Ca2 +交换剂和ryanodine受体2。结果GTE心肌细胞与CTRL相比，表现出高动力收缩性（缩短率和收缩率）。重新加长，缩短的分数，钙瞬变的幅度和胞浆钙的去除率均显着提高）。在器官水平也观察到更快的等容松弛。与功能性数据一致，我们测量了GTE心肌细胞内源性线粒体呼吸增强所支持的细胞内ATP含量的显着增加，以及磷酸化PLB / PLB和SERCA2 / PLB的比率值更高。结论长期体内施用GTE可通过增加能量利用率和消除PLB对SERCA2的抑制作用来改善正常心肌细胞的细胞力学性能和细胞内钙动力学。

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