Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation.
Epidemiologic investigations have shown that exercise reduces morbidity and mortality from coronary artery disease. In this study, using a rat model, we attempted to determine whether exercise can reduce ischemic injury to the heart and elucidate a mechanism for the cardioprotective effect of exercise. Results showed that exercise significantly reduced the magnitude of a myocardial infarction in biphasic manner. The time course for cardioprotection resembled that of the change in manganese superoxide dismutase (Mn-SOD) activity. The administration of the antisense oligodeoxyribonucleotide to Mn-SOD abolished the expected decrease in infarct size. We showed that the level of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) increased after exercise. The simultaneous administration of the neutralizing antibodies to the cytokines abolished the exercise-induced cardioprotection and the activation of Mn-SOD. Furthermore, TNF-alpha can mimic the biphasic pattern of cardioprotection and activation of Mn-SOD. An antioxidant completely abolished cardioprotection and the activation of Mn-SOD by exercise or the injection of TNF-alpha as well as exercise-induced increase in TNF-alpha and IL-1beta. The production of reactive oxygen species and endogenous TNF-alpha and IL-1beta induced by exercise leads to the activation of Mn-SOD, which plays major roles in the acquisition of biphasic cardioprotection against ischemia/reperfusion injury in rats.
Yamashita
N
N
Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
Hoshida
S
S
Otsu
K
K
Asahi
M
M
Kuzuya
T
T
Hori
M
M
D000818:Animals; D001483:Base Sequence; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D020319:Oligodeoxyribonucleotides, Antisense; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase