Decreased DNA fragmentation and apoptotic signaling in soleus muscle of hypertensive rats following 6 weeks of treadmill training

Abstract

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.

High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension

“…This finding was unexpected; however, these data clearly suggest that typical exercise adaptations are compromised in a model of disease. Nevertheless, previous work has demonstrated inconsistencies in the response of CS activity after exercise training in spontaneously hypertensive rats (22,32,45). While both ET and HIIT increased markers of the electron transport chain, these adaptations suggest the absence of a coordinated increase in the oxidative capacity within the WG following both ET and HIIT in a model of hypertension.…”

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death

“…14, 15). TEX cells were treated with avocatin B or a vehicle control for 1 hour, as performed for the Seahorse Bioanalyzer experiments (i.e., assessment of fatty acid oxidation), and cytosolic and mitochondrial fractions were then isolated, as previously described (16). Fraction purity was determined by Western blot analysis for the mitochondrial-specific protein ND1 (i.e., complex 1).…”

Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats

“…Furthermore, markers of cellular stress as well as apoptotic signalling are elevated in skeletal muscle of SHR (Quadrilatero & Rush , , McMillan et al . ).…”