Antioxidant network expression abrogates oxidative posttranslational modifications in mice

R. Mital, W. Zhang, M. Cai, Z. M. Huttinger, L. A. Goodman, D. G. Wheeler, M. T. Ziolo, K. M. Dwyer, A. J.F. d'Apice, J. L. Zweier, G. He, P. J. Cowan, Richard J Gumina

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 Ca2+-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number5
DOIs
StatePublished - May 1 2011

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Post Translational Protein Processing
Reperfusion Injury
Myocardial Reperfusion Injury
Myocardial Ischemia
Antioxidants
Lipid Peroxidation
Fatty Acid-Binding Proteins
Reticulum
Proteins
Calcium-Transporting ATPases
Malondialdehyde
Oxidative Stress
Staining and Labeling
Wounds and Injuries
Enzymes

Keywords

  • Myocardial ischemia
  • Reactive oxygen species
  • Reperfusion injury
  • Sarco(endo)plasmic reticulum ca-atpase 2a
  • Superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Antioxidant network expression abrogates oxidative posttranslational modifications in mice. / Mital, R.; Zhang, W.; Cai, M.; Huttinger, Z. M.; Goodman, L. A.; Wheeler, D. G.; Ziolo, M. T.; Dwyer, K. M.; d'Apice, A. J.F.; Zweier, J. L.; He, G.; Cowan, P. J.; Gumina, Richard J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 300, No. 5, 01.05.2011.

Research output: Contribution to journalArticle

Mital, R, Zhang, W, Cai, M, Huttinger, ZM, Goodman, LA, Wheeler, DG, Ziolo, MT, Dwyer, KM, d'Apice, AJF, Zweier, JL, He, G, Cowan, PJ & Gumina, RJ 2011, 'Antioxidant network expression abrogates oxidative posttranslational modifications in mice', American Journal of Physiology - Heart and Circulatory Physiology, vol. 300, no. 5. https://doi.org/10.1152/ajpheart.01285.2010
Mital, R. ; Zhang, W. ; Cai, M. ; Huttinger, Z. M. ; Goodman, L. A. ; Wheeler, D. G. ; Ziolo, M. T. ; Dwyer, K. M. ; d'Apice, A. J.F. ; Zweier, J. L. ; He, G. ; Cowan, P. J. ; Gumina, Richard J. / Antioxidant network expression abrogates oxidative posttranslational modifications in mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2011 ; Vol. 300, No. 5.
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