Antioxidant network expression abrogates oxidative posttranslational modifications in mice.

Mital R, Zhang W, Cai M, Huttinger ZM, Goodman LA, Wheeler DG, Ziolo MT, Dwyer KM, d'Apice AJ, Zweier JL, He G, Cowan PJ, Gumina RJ
Am J Physiol Heart Circ Physiol. 2011 300 (5): H1960-70

PMID: 21335461 · PMCID: PMC3094079 · DOI:10.1152/ajpheart.01285.2010

Antioxidant enzymatic pathways form a critical network that detoxifies ROS in response to myocardial stress or injury. Genetic alteration of the expression levels of individual enzymes has yielded mixed results with regard to attenuating in vivo myocardial ischemia-reperfusion injury, an extreme oxidative stress. We hypothesized that overexpression of an antioxidant network (AON) composed of SOD1, SOD3, and glutathione peroxidase (GSHPx)-1 would reduce myocardial ischemia-reperfusion injury by limiting ROS-mediated lipid peroxidation and oxidative posttranslational modification (OPTM) of proteins. Both ex vivo and in vivo myocardial ischemia models were used to evaluate the effect of AON expression. After ischemia-reperfusion injury, infarct size was significantly reduced both ex vivo and in vivo, ROS formation, measured by dihydroethidium staining, was markedly decreased, ROS-mediated lipid peroxidation, measured by malondialdehyde production, was significantly limited, and OPTM of total myocardial proteins, including fatty acid-binding protein and sarco(endo)plasmic reticulum Ca(²+)-ATPase (SERCA)2a, was markedly reduced in AON mice, which overexpress SOD1, SOD3, and GSHPx-1, compared with wild-type mice. These data demonstrate that concomitant SOD1, SOD3, and GSHPX-1 expression confers marked protection against myocardial ischemia-reperfusion injury, reducing ROS, ROS-mediated lipid peroxidation, and OPTM of critical cardiac proteins, including cardiac fatty acid-binding protein and SERCA2a.

MeSH Terms (16)

Animals Antioxidants Glutathione Peroxidase Lipid Peroxidation Mice Mice, Inbred C57BL Mice, Transgenic Models, Animal Myocardial Reperfusion Injury Myocardium Oxidative Stress Protein Processing, Post-Translational Reactive Oxygen Species Sarcoplasmic Reticulum Calcium-Transporting ATPases Superoxide Dismutase Superoxide Dismutase-1

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