Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
J Appl Physiol (1985). 2012 Oct;113(7):1048-57. doi: 10.1152/japplphysiol.00290.2012. Epub 2012 Aug 2.
Cardiovascular diseases such as hypertension are associated with a generalized skeletal myopathy including a proapoptotic phenotype. Current evidence suggests that exercise may alter apoptosis-related signaling in skeletal muscle; however, the effect of exercise on skeletal muscle DNA fragmentation and apoptotic signaling is unclear in hypertensive animals. Male normotensive Wistar Kyoto (WKY; n = 24) and spontaneously hypertensive rats (SHR; n = 24) were assigned to a sedentary (SED) condition or exercise (EX) consisting of progressive treadmill running 5 days/wk for 6 wks. Consistent with our previous work we found that soleus muscle of hypertensive animals had significantly higher DNA fragmentation (a hallmark of apoptosis), elevated proapoptotic factors (Bax, caspase-3 activity), and lower antiapoptotic proteins (apoptosis repressor with caspase recruitment domain, Bcl-2, X-linked inhibitor of apoptosis protein) compared with normotensive rats. In addition, soleus muscle of hypertensive animals displayed myosin accumulation and fragmentation, had elevated cytosolic cytochrome c, second mitochondrial-derived activator of caspase (Smac), apoptosis inducing factor (AIF), and endonuclease G protein levels, higher nuclear AIF content, and greater muscle reactive oxygen species generation compared with normotensive animals. Interestingly, exercise training significantly lowered DNA fragmentation and myosin accumulation/fragmentation in soleus muscle of hypertensive rats. Furthermore, exercise training significantly reduced cytosolic levels of cytochrome c as well as cytosolic and nuclear AIF in soleus muscle of hypertensive animals. This beneficial response is likely due to exercise-mediated elevations in Bcl-2, heat shock protein 70, and manganese superoxide dismutase protein content, as well as reductions in Bax protein levels and the Bax-to-Bcl-2 ratio. These results suggest that regular exercise training provides protection against skeletal muscle apoptosis by altering a number of apoptosis regulatory proteins and by influencing mitochondrial-mediated apoptotic signaling mechanisms.
心血管疾病如高血压与包括促凋亡表型在内的全身性骨骼肌病有关。目前的证据表明，运动可能改变骨骼肌中与细胞凋亡相关的信号转导；然而，运动对高血压动物骨骼肌 DNA 片段化和凋亡信号的影响尚不清楚。雄性正常血压 Wistar Kyoto（WKY；n = 24）和自发性高血压大鼠（SHR；n = 24）被分配到安静（SED）或运动（EX）条件下，运动包括 5 天/周进行渐进式跑步机跑步 6 周。与我们之前的工作一致，我们发现高血压动物的比目鱼肌的 DNA 片段化（凋亡的标志）明显更高，促凋亡因子（Bax、caspase-3 活性）升高，抗凋亡蛋白（含 caspase 募集域的凋亡抑制剂、Bcl-2、X 连锁凋亡抑制剂蛋白）降低与正常血压大鼠相比。此外，高血压动物的比目鱼肌显示肌球蛋白积累和片段化，细胞质细胞色素 c、第二线粒体衍生的半胱天冬酶激活剂（Smac）、凋亡诱导因子（AIF）和内切核酸酶 G 蛋白水平升高，核 AIF 含量升高，肌肉活性氧生成增加与正常血压动物相比。有趣的是，运动训练显著降低了高血压大鼠比目鱼肌的 DNA 片段化和肌球蛋白积累/片段化。此外，运动训练显著降低了高血压动物比目鱼肌细胞质细胞色素 c 以及细胞质和核 AIF 的水平。这种有益的反应可能是由于运动介导的 Bcl-2、热休克蛋白 70 和锰超氧化物歧化酶蛋白含量的升高，以及 Bax 蛋白水平和 Bax-to-Bcl-2 比值的降低。这些结果表明，有规律的运动训练通过改变许多凋亡调节蛋白和影响线粒体介导的凋亡信号机制，为骨骼肌凋亡提供保护。
