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Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation.

Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M - J. Exp. Med. (1999)

Bottom Line: The administration of the antisense oligodeoxyribonucleotide to Mn-SOD abolished the expected decrease in infarct size.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan.

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.

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Effects of ASODN to Mn-SOD on the size of the myocardial infarct (top) and the activity (center) and content (bottom) of MnSOD. SODN, ASODN, or scrambled ODN to Mn-SOD were injected  intraperitoneally into rats just after exercise (EX). In 48 h, rats were subjected to occlusion of the LCA for 20 min, followed by reperfusion for 48 h.  The size of the myocardial infarct was measured after reperfusion (n =  6–10). The activity and content of Mn-SOD (n = 4–5) was evaluated 48 h  after exercise. C 48h, sham-treated control 48 h after sham treatment.  Data are expressed as mean ± SEM; *P < 0.05 vs. sham-treated control;  +P < 0.05 vs. without ASODN by one-way ANOVA with the Bonferroni's post hoc test for multiple comparisons.
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Figure 2: Effects of ASODN to Mn-SOD on the size of the myocardial infarct (top) and the activity (center) and content (bottom) of MnSOD. SODN, ASODN, or scrambled ODN to Mn-SOD were injected intraperitoneally into rats just after exercise (EX). In 48 h, rats were subjected to occlusion of the LCA for 20 min, followed by reperfusion for 48 h. The size of the myocardial infarct was measured after reperfusion (n = 6–10). The activity and content of Mn-SOD (n = 4–5) was evaluated 48 h after exercise. C 48h, sham-treated control 48 h after sham treatment. Data are expressed as mean ± SEM; *P < 0.05 vs. sham-treated control; +P < 0.05 vs. without ASODN by one-way ANOVA with the Bonferroni's post hoc test for multiple comparisons.

Mentions: We examined the relationship between the acquisition of tolerance to ischemia/reperfusion and the induction of Mn-SOD in the myocardium 48 h after exercise. We manipulated the level of expression of Mn-SOD using ASODN. The administration of ASODN completely inhibited the increases in Mn-SOD activity and content 48 h after exercise (Fig. 2, center and bottom). However, SODN did not attenuate the increases in Mn-SOD activity and content induced by exercise. As shown in Fig. 2 (top), the expected decrease in infarct size induced by exercise was also abolished in rats treated with ASODN to Mn-SOD, in which the induction of Mn-SOD was specifically inhibited. SODN, which did not attenuate the induction of Mn-SOD in the myocardium after exercise, did not abolish the protective effect of exercise. Administration of the scrambled oligonucleotide had no effect on infarct size or on Mn-SOD activity as seen with SODN. Administration of ASODN decreased the activity and content of Mn-SOD and increased the infarct size after reperfusion in sham-treated control rats.


Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation.

Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M - J. Exp. Med. (1999)

Effects of ASODN to Mn-SOD on the size of the myocardial infarct (top) and the activity (center) and content (bottom) of MnSOD. SODN, ASODN, or scrambled ODN to Mn-SOD were injected  intraperitoneally into rats just after exercise (EX). In 48 h, rats were subjected to occlusion of the LCA for 20 min, followed by reperfusion for 48 h.  The size of the myocardial infarct was measured after reperfusion (n =  6–10). The activity and content of Mn-SOD (n = 4–5) was evaluated 48 h  after exercise. C 48h, sham-treated control 48 h after sham treatment.  Data are expressed as mean ± SEM; *P < 0.05 vs. sham-treated control;  +P < 0.05 vs. without ASODN by one-way ANOVA with the Bonferroni's post hoc test for multiple comparisons.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193084&req=5

Figure 2: Effects of ASODN to Mn-SOD on the size of the myocardial infarct (top) and the activity (center) and content (bottom) of MnSOD. SODN, ASODN, or scrambled ODN to Mn-SOD were injected intraperitoneally into rats just after exercise (EX). In 48 h, rats were subjected to occlusion of the LCA for 20 min, followed by reperfusion for 48 h. The size of the myocardial infarct was measured after reperfusion (n = 6–10). The activity and content of Mn-SOD (n = 4–5) was evaluated 48 h after exercise. C 48h, sham-treated control 48 h after sham treatment. Data are expressed as mean ± SEM; *P < 0.05 vs. sham-treated control; +P < 0.05 vs. without ASODN by one-way ANOVA with the Bonferroni's post hoc test for multiple comparisons.
Mentions: We examined the relationship between the acquisition of tolerance to ischemia/reperfusion and the induction of Mn-SOD in the myocardium 48 h after exercise. We manipulated the level of expression of Mn-SOD using ASODN. The administration of ASODN completely inhibited the increases in Mn-SOD activity and content 48 h after exercise (Fig. 2, center and bottom). However, SODN did not attenuate the increases in Mn-SOD activity and content induced by exercise. As shown in Fig. 2 (top), the expected decrease in infarct size induced by exercise was also abolished in rats treated with ASODN to Mn-SOD, in which the induction of Mn-SOD was specifically inhibited. SODN, which did not attenuate the induction of Mn-SOD in the myocardium after exercise, did not abolish the protective effect of exercise. Administration of the scrambled oligonucleotide had no effect on infarct size or on Mn-SOD activity as seen with SODN. Administration of ASODN decreased the activity and content of Mn-SOD and increased the infarct size after reperfusion in sham-treated control rats.

Bottom Line: The administration of the antisense oligodeoxyribonucleotide to Mn-SOD abolished the expected decrease in infarct size.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, The First Department of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan.

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.

Show MeSH
Related in: MedlinePlus