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Tyrosine nitration of mitochondrial proteins during myocardial ischemia and reperfusion

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Abstract

Myocardial ischemia reperfusion is associated with mitochondrial dysfunction and increased formation of reactive oxygen/nitrogen species. The main purpose of this study was to assess the role of tyrosine nitration of mitochondrial proteins in postischemic contractile dysfunction known as myocardial stunning. Isolated Langendorff-perfused rat hearts were subjected to 20-min global ischemia followed by 30-min reperfusion. The reperfused hearts showed marked decline in left ventricular developed pressure, maximal rate of contraction (+dP/dt), and maximal rate of relaxation (−dP/dt). Immunofluorescence and ELISA assays demonstrated enhanced protein tyrosine nitration in reperfused hearts. Using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry, eight mitochondrial proteins were identified to be nitrated after ischemia reperfusion. These proteins are crucial in mitochondrial electron transport, fatty acid oxidation, tricarboxylic acid cycle, ATP synthesis, and control of high-energy phosphates. The proteome data also indicated reduced abundance in several of nitrated proteins. The results suggest that these changes may contribute to inhibition of aconitase activity but are unlikely to affect electron transport chain activity. Whether tyrosine nitration of mitochondrial proteins can be considered the contributing factor of postischemic contractile dysfunction remains to be explored.

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Funding

This work was partially supported by grant VEGA 1/0004/19, project “Biomedical Center Martin,” ITMS code: 26220220187 co-financed from EU sources and project “Competence Center for research and development in the field of diagnostics and therapy of oncological diseases,” ITMS: 26220220153, co-financed from EU sources.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia

    Zuzana Tatarkova, Monika Kmetova Sivonova, Peter Racay, Jan Lehotsky & Peter Kaplan

  2. Department of Histology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovakia

    Maria Kovalska

  3. Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia

    Peter Racay, Jan Lehotsky & Peter Kaplan

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  1. Zuzana Tatarkova
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  2. Maria Kovalska
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  3. Monika Kmetova Sivonova
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  4. Peter Racay
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  5. Jan Lehotsky
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  6. Peter Kaplan
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Correspondence to Peter Kaplan.

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All experiments were conducted in accordance with the European Community guidelines and were approved by the Ethical Committee of the Jessenius Faculty of Medicine.

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Tatarkova, Z., Kovalska, M., Sivonova, M.K. et al. Tyrosine nitration of mitochondrial proteins during myocardial ischemia and reperfusion. J Physiol Biochem 75, 217–227 (2019). https://doi.org/10.1007/s13105-019-00683-7

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  • DOI: https://doi.org/10.1007/s13105-019-00683-7

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