Diffee Gary M, Seversen Eric A, Stein Thor D, Johnson Jeffrey A
Department of Kinesiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Am J Physiol Heart Circ Physiol. 2003 Mar;284(3):H830-7. doi: 10.1152/ajpheart.00761.2002. Epub 2002 Nov 7.
Previous studies have shown that endurance exercise training increases myocardial contractility. We have previously described training-induced alterations in myocardial contractile function at the cellular level, including an increase in the Ca(2+) sensitivity of tension. To determine the molecular mechanism(s) of these changes, oligonucleotide microarrays were used to analyze the gene expression profile in ventricles from endurance-trained rats. We used an 11-wk treadmill training protocol that we have previously shown results in increased contractility in cardiac myocytes. After the training, the hearts were removed and RNA was isolated from the ventricles of nine trained and nine control rats. With the use of an Affymetrix Rat Genome U34A Array, we detected altered expression of 27 genes. Several genes previously found to have increased expression in hypertrophied myocardium, such as atrial natriuretic factor and skeletal alpha-actin, were decreased with training in this study. From the standpoint of altered contractile performance, the most significant finding was an increase in the expression of atrial myosin light chain 1 (aMLC-1) in the trained ventricular tissue. We confirmed microarray results for aMLC-1 using RT-PCR and also confirmed a training-induced increase in aMLC-1 protein using two-dimensional gel electrophoresis. aMLC-1 content has been previously shown to be increased in human cardiac hypertrophy and has been associated with increased Ca(2+) sensitivity of tension and increased power output. These results suggest that increased expression of aMLC-1 in response to training may be responsible, at least in part, for previously observed training-induced enhancement of contractile function.
先前的研究表明，耐力运动训练可增强心肌收缩力。我们之前曾描述过训练诱导的心肌收缩功能在细胞水平上的改变，包括张力的Ca(2+)敏感性增加。为了确定这些变化的分子机制，我们使用寡核苷酸微阵列分析耐力训练大鼠心室中的基因表达谱。我们采用了一种11周的跑步机训练方案，我们之前已证明该方案可使心肌细胞的收缩力增强。训练后，取出心脏，从9只训练大鼠和9只对照大鼠的心室中分离RNA。使用Affymetrix大鼠基因组U34A阵列，我们检测到27个基因的表达发生了改变。在这项研究中，一些先前发现在肥厚心肌中表达增加的基因，如心钠素和骨骼肌α-肌动蛋白，在训练后表达降低。从收缩性能改变的角度来看，最显著的发现是训练后的心室组织中房性肌球蛋白轻链1（aMLC-1）的表达增加。我们使用RT-PCR证实了aMLC-1的微阵列结果，并使用二维凝胶电泳证实了训练诱导的aMLC-1蛋白增加。先前已表明，aMLC-1含量在人类心肌肥大中增加，并与张力的Ca(2+)敏感性增加和功率输出增加有关。这些结果表明，训练后aMLC-1表达增加可能至少部分地是先前观察到的训练诱导的收缩功能增强的原因。
