{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:01:46Z","timestamp":1757700106999},"reference-count":74,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:p> 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. <\/jats:p>","DOI":"10.1152\/japplphysiol.00290.2012","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T04:38:00Z","timestamp":1343968680000},"page":"1048-1057","source":"Crossref","is-referenced-by-count":27,"title":["Decreased DNA fragmentation and apoptotic signaling in soleus muscle of hypertensive rats following 6 weeks of treadmill training"],"prefix":"10.1152","volume":"113","author":[{"given":"Elliott M.","family":"McMillan","sequence":"first","affiliation":[{"name":"Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drew A.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W. 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