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 α (TNF-α) and interleukin 1β (IL-1β) 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-α 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-α as well as exercise-induced increase in TNF-α and IL-1β. The production of reactive oxygen species and endogenous TNF-α and IL-1β 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.
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7 June 1999
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June 07 1999
Exercise Provides Direct Biphasic Cardioprotection via Manganese Superoxide Dismutase Activation
Nobushige Yamashita,
Nobushige Yamashita
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
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Shiro Hoshida,
Shiro Hoshida
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
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Kinya Otsu,
Kinya Otsu
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
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Michio Asahi,
Michio Asahi
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
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Tsunehiko Kuzuya,
Tsunehiko Kuzuya
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
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Masatsugu Hori
Masatsugu Hori
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
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Nobushige Yamashita
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Shiro Hoshida
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Kinya Otsu
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Michio Asahi
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Tsunehiko Kuzuya
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Masatsugu Hori
From the *Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan; and the ‡Cardiovascular Division, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Address correspondence to Shiro Hoshida, Cardiovascular Division, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Osaka 591-8025, Japan. Phone: 81-722-52-3561; Fax: 81-722-50-5492; E-mail: [email protected]
Received:
December 08 1998
Revision Received:
March 23 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (11): 1699–1706.
Article history
Received:
December 08 1998
Revision Received:
March 23 1999
Citation
Nobushige Yamashita, Shiro Hoshida, Kinya Otsu, Michio Asahi, Tsunehiko Kuzuya, Masatsugu Hori; Exercise Provides Direct Biphasic Cardioprotection via Manganese Superoxide Dismutase Activation . J Exp Med 7 June 1999; 189 (11): 1699–1706. doi: https://doi.org/10.1084/jem.189.11.1699
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