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Differential activation of mitogen-activated protein kinases in ischemic and nitroglycerin-induced preconditioning

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Abstract

Previous studies have shown that the cardioprotective effect of ischemic preconditioning (IPC) can be mimicked pharmacologically with clinically relevant agents, including nitric oxide (NO) donors. However, whether pharmacological preconditioning shares the same molecular mechanism with IPC is not fully elucidated. The present study aimed to determine the activation of mitogen-activated protein kinases (MAPKs) (ERK1/2, p38 MAPK and p46/p54 JNKs) during ischemia and at reperfusion in nitroglycerin-induced preconditioning as compared to IPC and to correlate this with the conferred cardioprotection in anesthetized rabbits. Sixty minutes of intravenous administration of nitroglycerin was capable of inducing both early and late phase preconditioning in anesthetized rabbits, as it was expressed by the reduction of infarct size. Despite the cardioprotective effect conferred by both ischemic and nitroglycerin-induced preconditioning, there was a differential phosphorylation of MAPKs between the studied groups. p38 MAPK was activated early in ischemia in both ischemic and the early nitroglycerin-induced preconditioning while JNKs were markedly increased only after IPC. Furthermore, in these groups, ERK1/2 were activated during reperfusion. A different profile was observed in the late preconditioning induced by nitroglycerin with increased p38 MAPK and ERK1/2 phosphorylation during late ischemia. No activation of JNKs was observed at any time point in this group. It seems that activation of individual MAPK subfamilies depends on the nature of preconditioning stimulus.

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Acknowledgement

This work was supported in part by a grant from the Greek Ministry of Education (PYTHAGORAS, 70/3/7399).

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Authors and Affiliations

  1. 2nd University Department of Cardiology Medical School Attikon General Hospital, University of Athens, Athens, 12462, Greece

    Efstathios K. Iliodromitis, Vassilios Gizas, Elias Bofilis, Anastasia Zoga & Dimitrios Th. Kremastinos

  2. Department of Animal and Human Physiology School of Biology, University of Athens, Athens, 15784, Greece

    Catherine Gaitanaki & Ioanna-Katerina Aggeli

  3. Laboratory of Animal Physiology Department of Zoology School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece

    Antigone Lazou & Isidoros Beis

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  1. Efstathios K. Iliodromitis
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  2. Catherine Gaitanaki
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  9. Dimitrios Th. Kremastinos
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Correspondence to Antigone Lazou.

Additional information

Returned for 1st revision: 18 November 2005 1st revision received: 3 January 2006

Returned for 2nd revision: 19 January 2006 2nd revision received: 6 February 2006

Returned for 3rd revision: 22 February 2006 3rd revision received: 1 March 2006

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Iliodromitis, E.K., Gaitanaki, C., Lazou, A. et al. Differential activation of mitogen-activated protein kinases in ischemic and nitroglycerin-induced preconditioning. Basic Res Cardiol 101, 327–335 (2006). https://doi.org/10.1007/s00395-006-0594-3

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