title: Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.
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.
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: Elliott M
authors: EM
authors: McMillan
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: Marie-France
authors: MF
authors: Paré
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: Brittany L
authors: BL
authors: Baechler
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: Drew A
authors: DA
authors: Graham
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: James W E
authors: JW
authors: Rush
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: Joe
authors: J
authors: Quadrilatero
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D001794:Blood Pressure; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
chemical_list: C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D055372:AMP-Activated Protein Kinases; D010447:Peptide Hydrolases