Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary.
Rev Cardiovasc Med. 2021 Dec 22;22(4):1079-1085. doi: 10.31083/j.rcm2204119.
Although the knowledge of sports cardiology advanced significantly in the recent years, the molecular mechanisms by which exercise training augments cardiac performance is poorly understood. Here we aimed at determining left ventricular (LV) myocardial sarcomeric protein modifications in a rat model of exercise training and detraining. Young male Wistar rats were divided into exercised (Ex) and control (Co) groups. Trained rats swam 200 min/day for 12 weeks. Detrained (DEx) and control (DCo) rats remained sedentary for 8 weeks after completion of the 12-week-long protocol. Ca-regulated active force production (F), its Ca-sensitivity (pCa) and Ca-independent passive tension (F) were determined in isolated permeabilized cardiomyocytes and phosphorylation levels of sarcomeric proteins were assayed by biochemical methods. Means of maximal Ca-activated isometric force (F) and pCa50 values were higher ( < 0.05) in the Ex group (28.0 ± 1.4 kN/m and 5.91 ± 0.03, respectively, mean ± SEM) than those in the Co group (15.8 ± 0.8 kN/m and 5.81 ± 0.03, respectively). F did not differ between these two groups. The level of cardiac troponin I (cTnI) phosphorylation decreased upon exercise (from 1.00 ± 0.02 to 0.66 ± 0.06, < 0.05; in relative units). Site specific phosphorylation assays revealed cTnI hypophosphorylations at the protein kinase A (PKA)-specific Ser-22/23 sites and at the protein kinase C (PKC)-specific Thr-143 site. Mechanical and biochemical parameters of the DEx and DCo groups did not differ from each other following the detraining period. Exercise-induced hypertrophy is associated with reversible increases in Ca-dependent force production and its Ca-sensitivity in LV cardiomyocytes, which can be associated with changes in cTnI phosphorylation.
尽管近年来运动心脏病学的知识有了显著的进步，但运动训练增强心脏功能的分子机制仍知之甚少。在这里，我们旨在确定运动训练和停训大鼠模型左心室（LV）心肌肌节蛋白的修饰。年轻雄性 Wistar 大鼠被分为运动（Ex）和对照组（Co）。训练组大鼠每天游泳 200 分钟，持续 12 周。停训（DEx）和对照组（DCo）大鼠在完成 12 周长的方案后 8 周内保持不运动。在分离的通透化心肌细胞中测定 Ca 调节的主动力产生（F）、其 Ca 敏感性（pCa）和 Ca 非依赖性被动张力（F），并通过生化方法测定肌节蛋白的磷酸化水平。Ex 组的最大 Ca 激活等长力（F）和 pCa50 值更高（<0.05）（分别为 28.0 ± 1.4 kN/m 和 5.91 ± 0.03，平均值±SEM），高于 Co 组（分别为 15.8 ± 0.8 kN/m 和 5.81 ± 0.03）。这两组之间的 F 没有差异。肌钙蛋白 I（cTnI）磷酸化水平在运动后降低（从 1.00 ± 0.02 降至 0.66 ± 0.06，<0.05；以相对单位表示）。特异性磷酸化测定显示 cTnI 在蛋白激酶 A（PKA）特异性 Ser-22/23 位点和蛋白激酶 C（PKC）特异性 Thr-143 位点的低磷酸化。停训后，DEx 和 DCo 组的力学和生化参数彼此之间没有差异。LV 心肌细胞中与运动诱导的肥大相关的 Ca 依赖性力产生和其 Ca 敏感性可逆增加，可能与 cTnI 磷酸化的变化有关。
