title: Menadione mimics the infarct-limiting effect of preconditioning in isolated rat hearts.
abstract: 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 microM), 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 microM), 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 microM 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.
authors.affiliation: Department of Cell Biology and Neuroscience, University of South Alabama, College of Medicine, Mobile, Alabama 36688, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yue
authors.forename: M
authors.initials: M
authors.lastname: Krenz
authors.forename: M V
authors.initials: MV
authors.lastname: Cohen
authors.forename: J M
authors.initials: JM
authors.lastname: Downey
authors.forename: S D
authors.initials: SD
authors.lastname: Critz
mesh_terms: D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D014812:Vitamin K / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D005609:Free Radicals; D014812:Vitamin K