Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion.
Reactive oxygen species induce myocardial damage after ischemia and reperfusion in experimental animal models. Numerous studies have investigated the deleterious effects of ischemia-reperfusion (I/R)-induced oxidant production using various pharmacological interventions. More recently, in vitro studies have incorporated gene-targeted mice to decipher the role of antioxidant enzymes in myocardial reperfusion injury. We examined the role of cellular antioxidant enzymes in the pathogenesis of myocardial I/R (MI/R) injury in vivo in gene-targeted mice. Neither deficiency nor overexpression of Cu-Zn superoxide dismutase (SOD) altered the extent of myocardial necrosis. Overexpression of glutathione peroxidase did not affect the degree of myocardial injury. Conversely, overexpression of manganese (Mn)SOD significantly attenuated myocardial necrosis after MI/R. Transthoracic echocardiography was performed on MnSOD-overexpressing and wild-type mice that were subjected to a more prolonged period of reperfusion. Cardiac output was significantly depressed in the nontransgenic but not the transgenic MnSOD-treated mice. Anterior wall motion was significantly impaired in the nontransgenic mice. These findings demonstrate an important role for MnSOD but not Cu/ZnSOD or glutathione peroxidase in mice after in vivo MI/R.
Jones
Steven P
SP
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130, USA.
Hoffmeyer
Michaela R
MR
Sharp
Brent R
BR
Ho
Ye-Shih
YS
Lefer
David J
DJ
D000818:Animals; D004452:Echocardiography; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007425:Intracellular Membranes / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D017202:Myocardial Ischemia / Q000201:enzymology*; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left
D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase