Abstract
Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG) of hypertensive rats had higher (p<0.05) caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05) ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05) Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05) Beclin-1 and ATG7 protein, as well as decreased (p<0.05) caspase-3, calpain, and cathepsin activity. Left ventricle (LV) of hypertensive rats had reduced (p<0.05) AMPKα and LC3II protein, as well as elevated (p<0.05) p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05) proteasome activity but reduced (p<0.05) caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats.
Highlights
Hypertension is a cardiovascular disease most commonly associated with pathology of blood vessels and heart, and skeletal muscle
T-test analysis revealed that calpain activity was significantly (p
In the Left ventricle (LV), cathepsin activity was elevated (p
Summary
Hypertension is a cardiovascular disease most commonly associated with pathology of blood vessels and heart, and skeletal muscle. Underlying a number of skeletal and cardiac muscle pathologies are alterations to autophagic signaling and flux. Macroautophagy ( referred to as autophagy) is a catabolic process responsible for the bulk and selective degradation of aggregated or damaged proteins and organelles [1]. In terminally differentiated cells such as skeletal and cardiac myocytes, basal autophagy is essential to prevent the accumulation of damaged/dysfunctional proteins and organelles which can be detrimental to the cell [2,3]; increased autophagy can contribute to pathological tissue remodeling [4,5]. Modification of autophagic proteins such as Beclin-1 and ATG5 by apoptosis-related enzymes can promote cell death [6,7]. The literature supports that a fine regulation of autophagy is important for proper tissue function and cellular homeostasis
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