Effect of a six week exercise training program on proteolytic enzyme activity, ROS generation and autophagy in the white gastrocnemius and left ventricle of normotensive and hypertensive rats

Abstract

Hypertension is a cardiovascular disease associated with increased cell death and proteolytic activity in both skeletal and cardiac muscle. Autophagy is a degradative system that plays an essential role in muscle health and can influence cell death processes. Little is known about the effects of exercise training on autophagy in healthy or diseased states. The purpose of this study was to investigate the effects of exercise training on markers of autophagy, proteolytic activity, and ROS levels in white gastrocnemius (WG) and left ventricle (LV) of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Male WKY and SHR were assigned to a sedentary condition or exercise consisting of treadmill running for 6 wks. In the WG muscle of SHR, greater LC3I protein (p<0.01) and a lower LC3II/I protein ratio (p<0.05) was observed compared to WKY rats. Exercise training did not alter the WG LC3II/I protein ratio; however, exercise training upregulated Beclin (p<0.02), LC3 (p<0.05), and p62 (p<0.04) mRNA and reduced ATG7 (p<0.04) and Beclin (p<0.01) protein levels. Following exercise training, lower caspase‐3 (p<0.001) and cathepsin (p<0.001) activity as well as a trend towards lower ROS production (p<0.08) was observed in the WG. In the LV, SHR had a lower LC3II/I protein ratio (p<0.05) and a greater accumulation of p62 protein (p<0.01) compared to WKY rats. Training increased both Beclin and p62 mRNA levels (p<0.05) in the LV; however, no change in the LC3II/I protein ratio was observed. Exercise training lowered LV caspase‐3 (p<0.001) and calpain (p<0.001) activity, as well as tended to reduce cathepsin activity and ROS production (p<0.07). Together, these results suggest that autophagy is altered in the SHR muscle and heart, and exercise training can alter upstream regulators of autophagy, attenuate ROS production and proteolytic enzyme activity in WG and LV of normotensive and hypertensive rats.