Menadione mimics the infarct-limiting effect of preconditioning in isolated rat hearts
Departments of 1 Cell Biology and Neuroscience, 2 Physiology, and 3 Medicine, University of South Alabama, College of Medicine, Mobile, Alabama 36688 The role of mitochondrial free radicals in the cardioprotective effect of ischemic preconditioning was examined in isolated buffer-perfused rat hea...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 281; no. 2; pp. H590 - H595 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.08.2001
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Subjects | |
Online Access | Get full text |
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Summary: | Departments of 1 Cell Biology and Neuroscience,
2 Physiology, and 3 Medicine, University of South
Alabama, College of Medicine, Mobile, Alabama 36688
The role of mitochondrial free radicals
in the cardioprotective effect of ischemic preconditioning was
examined in isolated buffer-perfused rat hearts. Infarct size in
control rat hearts subjected to 30 min of regional ischemia and
120 min of reperfusion was 32.6 ± 3.4% of the risk zone.
Ischemic preconditioning (3 cycles of 5-min global
ischemia/5-min reperfusion) before the same regional
ischemia and reperfusion protocol significantly reduced infarct
size to 2.6 ± 0.8% of the risk zone. Perfusion with menadione
(3.0 µM), a generator of mitochondrial free radicals, in lieu of
preconditioning ischemia significantly reduced infarction to
10.9 ± 2.7%. N -2-mercaptopropionylglycine (1.0 mM), a
free radical scavenger, blocked the protection of menadione,
significantly increasing infarction to 23.5 ± 1.1%. Myxothiazol
(0.6 µM), a site III mitochondrial inhibitor, blocked the protection
of menadione and significantly increased infarction to 25.2 ± 3.8%. The infarct-limiting effect of menadione was attenuated to
19.7 ± 1.5% of the risk zone by 10 µM SB203580, a p38
mitogen-activated protein kinase (MAPK) inhibitor. Furthermore,
menadione significantly increased p38 MAPK phosphorylation to a level
5.6-fold over basal. These results indicate that free radicals that
originate within mitochondria can activate p38 MAPK and protect hearts
against infarction.
myocardial infarction; ischemia; mitochondria; p38
MAPK |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.2001.281.2.h590 |