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Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise

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Cell Stress and Chaperones Aims and scope

Abstract

Both protein kinase C (PKC) activation and Hsp70 expression have been shown to be key components for exercise-mediated myocardial protection during ischemia–reperfusion injury. Given that Hsp70 has been shown to undergo inducible phosphorylation in striated muscle and liver, we hypothesized that PKC may regulate myocardial Hsp70 function and subsequent exercise-conferred cardioprotection through this phosphorylation. Hence, acute exercise of male Sprague–Dawley rats (30 m/min for 60 min at 2% grade) was employed to assess the role of PKC and its selected isoforms in phosphorylation of Hsp70 and protection of the myocardium during ischemia–reperfusion injury. It was observed that administration of the PKC inhibitor chelerythrine chloride (5 mg/kg) suppressed the activation of three exercise-induced PKC isoforms (PKCα, PKCδ, and PKCɛ) and attenuated the exercise-mediated reduction of myocardial infarct size during ischemia–reperfusion injury. While this study also demonstrated that exercise led to an alteration in the phosphorylation status of Hsp70, this posttranslational modification appeared to be dissociated from PKC activation, as exercise-induced phosphorylation of Hsp70 was unchanged following inhibition of PKC. Taken together, these results indicate that selected isoforms of PKC play an important role in exercise-mediated protection of the myocardium during ischemia–reperfusion injury. However, exercise-induced phosphorylation of Hsp70 does not appear to be a mechanism by which PKC induces this cardioprotective effect.

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Acknowledgements

This work was supported by grant 8170-05 RGPIN from the National Science and Engineering Research Council of Canada to E.G. Noble and by Ontario Graduate Scholarships for Science and Technology to C.W.J. Melling.

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Authors and Affiliations

  1. School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada, N6A 3K7

    C. W. James Melling, David B. Thorp, Kevin J. Milne & Earl G. Noble

  2. Lawson Health Research Institute, The University of Western Ontario, London, Ontario, Canada, N6A 3K7

    Earl G. Noble

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  1. C. W. James Melling
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Correspondence to Earl G. Noble.

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Melling, C.W.J., Thorp, D.B., Milne, K.J. et al. Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise. Cell Stress and Chaperones 14, 141–150 (2009). https://doi.org/10.1007/s12192-008-0065-x

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  • DOI: https://doi.org/10.1007/s12192-008-0065-x

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