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Modulation of the c-Jun N-terminal kinase activity in the embryonic heart in response to anoxia-reoxygenation: involvement of the Ca2+ and mitoKATP channels

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Abstract

Whether the response of the fetal heart to ischemia-reperfusion is associated with activation of the c-Jun N-terminal kinase (JNK) pathway is not known. In contrast, involvement of the sarcolemmal L-type Ca2+ channel (LCC) and the mitochondrial KATP (mitoKATP) channel has been established. This work aimed at investigating the profile of JNK activity during anoxia-reoxygenation and its modulation by LCC and mitoKATP channel. Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30 min) and reoxygenation (60 min). Using the kinase assay method, the profile of JNK activity in the ventricle was determined every 10 min throughout anoxia-reoxygenation. Effects on JNK activity of the LCC blocker verapamil (10 nM), the mitoKATP channel opener diazoxide (50 μM) and the blocker 5-hydroxydecanoate (5-HD, 500 μM), the mitochondrial Ca2+ uniporter (MCU) inhibitor Ru360 (10 μM), and the antioxidant N-(2-mercaptopropionyl) glycine (MPG, 1 mM) were determined. In untreated hearts, JNK activity was increased by 40% during anoxia and peaked fivefold relative to basal level after 30–40 min reoxygenation. This peak value was reduced by half by diazoxide and was tripled by 5-HD. Furthermore, the 5-HD-mediated stimulation of JNK activity during reoxygenation was abolished by diazoxide, verapamil or Ru360. MPG had no effect on JNK activity, whatever the conditions. None of the tested pharmacological agents altered JNK activity under basal normoxic conditions. Thus, in the embryonic heart, JNK activity exhibits a characteristic pattern during anoxia and reoxygenation and the respective open-state of LCC, MCU and mitoKATP channel can be a major determinant of JNK activity in a ROS-independent manner.

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Acknowledgements

We thank Anne-Catherine Thomas for her skilful 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, 7 rue du Bugnon, 1005, Lausanne, Switzerland

    Alexandre Sarre, Stéphany Gardier & Eric Raddatz

  2. Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    Fabienne Maurer & Christophe Bonny

Authors
  1. Alexandre Sarre
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  2. Stéphany Gardier
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  3. Fabienne Maurer
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  4. Christophe Bonny
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  5. Eric Raddatz
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Corresponding author

Correspondence to Eric Raddatz.

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A. Sarre and S. Gardier contributed equally to this work.

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Sarre, A., Gardier, S., Maurer, F. et al. Modulation of the c-Jun N-terminal kinase activity in the embryonic heart in response to anoxia-reoxygenation: involvement of the Ca2+ and mitoKATP channels. Mol Cell Biochem 313, 133–138 (2008). https://doi.org/10.1007/s11010-008-9750-4

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  • DOI: https://doi.org/10.1007/s11010-008-9750-4

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