Coordination of changes in expression and phosphorylation of eukaryotic elongation factor 2 (eEF2) and eEF2 kinase in hypertrophied cardiomyocytes

•eEF2 kinase (eEF2K) is a unique Ca2+/calmodulin-dependent protein kinase.•eEF2K expression increased but phosphorylation decreased in cardiac hypertrophy.•eEF2 phosphorylation increased in cardiac hypertrophy.•Expression and phosphorylation state of eEF2K/eEF2 was common to hypertrophy model.•eEF2K/eEF2 signaling might affect the pathogenesis of cardiac hypertrophy.

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is one of the Ca2+/calmodulin-dependent protein kinases. Activated eEF2K phosphorylates its specific substrate, eEF2, which results in inhibition of protein translation. We have recently shown that protein expression of eEF2K was specifically increased in hypertrophied left ventricles (LV) from spontaneously hypertensive rats (SHR). However, phosphorylation state of eEF2K and eEF2 in hypertrophied LV is not determined. In the present study, we examined expression and phosphorylation of eEF2K and eEF2 in LV from SHR as well as the pressure overload (transverse aortic constriction: TAC)- and isoproterenol (ISO)-induced cardiac hypertrophy model. In LV from TAC mice, eEF2K expression was increased as determined by Western blotting. In LV from TAC mice and SHR, eEF2K phosphorylation at Ser366 (inactive site) was decreased. Consistently, eEF2 phosphorylation at Thr56 was increased. In LV from ISO rats, while eEF2K phosphorylation was decreased, eEF2K expression and eEF2 phosphorylation were not different as determined by Western blotting. In the results obtained from immunohistochemistry, however, total eEF2K and phosphorylated eEF2 (at Thr56) localized to cardiomyocytes were increased in LV cardiomyocytes from ISO rats. Accordingly, the increased expression and the decreased phosphorylation of eEF2K and the increased phosphorylation of eEF2 in hypertrophied LV were common to all models in this study. The present results thus suggest that cardiac hypertrophy may be regulated at least partly via eEF2K-eEF2 signaling pathway.

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