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PMID: 10359573 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation.

The Journal of experimental medicine ·Vol. 189 ·No. 11 ·1999-06-07 ·Pages 1699-706

Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M

Abstract

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.

MeSH Terms
Animals Base Sequence Enzyme Activation Humans Interleukin-1/biosynthesis Male Myocardial Infarction/enzymology,physiopathology,prevention & control Myocardial Reperfusion Injury/enzymology,physiopathology,prevention & control Oligodeoxyribonucleotides, Antisense/genetics,pharmacology Physical Exertion/physiology Rats Rats, Wistar Reactive Oxygen Species/metabolism Signal Transduction Superoxide Dismutase/antagonists & inhibitors,genetics,metabolism Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
Interleukin-1 Oligodeoxyribonucleotides, Antisense Reactive Oxygen Species Tumor Necrosis Factor-alpha Superoxide Dismutase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yamashita N
Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
Hoshida S
Otsu K
Asahi M
Kuzuya T
Hori M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.189.11.1699
Published
1999-06-07
Pages
1699-706
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193084
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.189.11.1699 PMC Full Text View journal details
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