Mitochondrial hydrogen peroxide generation by NADH-oxidase activity following regional myocardial ischemia in the dog.
Recently, an exogenous NADH-oxidase has been shown to be a source of oxygen derived toxic species in heart mitochondria. This enzyme uses NADH and oxygen to form superoxide radicals and hydrogen peroxide. Growing evidence suggests that oxygen radicals and hydrogen peroxide may contribute to cardiac damage during ischemia or hypoxia. The activity of the enzyme NADH-oxidase could play an important role in the damage caused by oxygen derived toxic species, especially since cellular defense mechanisms against free radicals are depleted under ischemic conditions. In this study, a cytochemical method was used to visualize hydrogen peroxide, the reaction product of NADH-oxidase activity, in normal and ischemic dog myocardium. The NADH-oxidase reaction product was present in weak amounts in mitochondria from normoxic myocardium. In viable ischemic areas a high degree of activity was observed in the mitochondria. In infarcted tissue mitochondria contained few or no reaction product at all. The results support the hypothesis that hydrogen peroxide and oxygen radicals produced in the mitochondria by a high NADH-oxidase activity may contribute to the mitochondrial damage observed during ischemia when NADH is no longer oxidized by the respiratory chain and cellular defense mechanisms are impaired.
Vandeplassche
G
G
Department of Cardiovascular Pathophysiology, Janssen Research Foundation, Beerse, Belgium.
Hermans
C
C
Thoné
F
F
Borgers
M
M
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009097:Multienzyme Complexes / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*
D009097:Multienzyme Complexes; D006861:Hydrogen Peroxide; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases