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Transient anoxia and oxyradicals induce a region-specific activation of MAPKs in the embryonic heart

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Abstract

We have previously reported in the early septating embryonic heart that electromechanical disturbances induced by anoxia-reoxygenation are distinct in atria, ventricle, and outflow tract, and are attenuated in ventricle by opening of mitochondrial KATP (mitoKATP) channels. Here, we assessed the regional activation of mitogen-activated protein kinases (MAPKs) ERK, p38, and JNK in response to anoxia-reoxygenation and H2O2. Hearts isolated from 4-day-old chick embryos were subjected to 30-min anoxia and 60-min reoxygenation or exposed to H2O2 (50 μM–1 mM). The temporal pattern of activation of ERK, p38, and JNK in atria, ventricle, and outflow tract was determined using immunoblotting and/or kinase assay. The effect of the mitoKATP channel opener diazoxide (50 μM) on JNK phosphorylation was also analyzed. Under basal conditions, total ERK and JNK were homogeneously distributed within the heart, whereas total p38 was the lowest in outflow tract. The phosphorylated/total form ratio of each MAPK was similar in all regions. Phosphorylation of ERK increased in atria and ventricle at the end of reoxygenation without change in outflow tract. Phosphorylation of p38 was augmented by anoxia in the three regions, and returned to basal level at the end of reoxygenation except in the outflow tract. JNK activity was not altered by anoxia-reoxygenation in atria and outflow tract. In ventricle, however, the diazoxide-inhibitable peak of JNK activity known to occur during reoxygenation was not accompanied by a change in phosphorylation level. H2O2 over 500 μM impaired cardiac function, phosphorylated ERK in all the regions and p38 in atria and outflow tract, but did not affect JNK phosphorylation. At a critical stage of early cardiogenesis, anoxia, reoxygenation, exogenous H2O2 and opening of mitoKATP channels can subtly modulate ERK, p38, and JNK pathways in a region-specific manner.

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Acknowledgments

The collaboration of Fabienne Maurer, Christophe Bonny, and Miguel Van Bemmelen, is gratefully acknowledged. We thank Anne-Catherine Thomas for her skillful technical assistance. This work was supported by the Swiss National Science Foundation n°3100A0-105901.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

    Stephany Gardier, Sarah Pedretti, Alexandre Sarre & Eric Raddatz

  2. Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 1211, Geneve 4, Switzerland

    Stephany Gardier

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  1. Stephany Gardier
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Correspondence to Stephany Gardier.

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Gardier, S., Pedretti, S., Sarre, A. et al. Transient anoxia and oxyradicals induce a region-specific activation of MAPKs in the embryonic heart. Mol Cell Biochem 340, 239–247 (2010). https://doi.org/10.1007/s11010-010-0423-8

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  • DOI: https://doi.org/10.1007/s11010-010-0423-8

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