The role of PKC[epsilon]-dependent signaling for cardiac differentiation

Protein kinase Cepsilon (PKC[straight epsilon]) exerts a well-known cardio-protective activity in ischemia-reperfusion injury and plays a pivotal role in stem cell proliferation and differentiation. Although many studies have been performed on physiological and morphological effects of PKC[straight epsilon] mis-expression in cardiomyocytes, molecular information on the role of PKC[straight epsilon] on early cardiac gene expression are still lacking. We addressed the molecular role of PKC[straight epsilon] in cardiac cells using mouse cardiomyocytes and rat bone marrow mesenchymal stem cells. We show that PKC[straight epsilon] is modulated in cardiac differentiation producing an opposite regulation of the cardiac genes NK2 transcription factor related, locus 5 (nkx2.5) and GATA binding protein 4 (gata4) both in vivo and in vitro. Phospho-extracellular regulated mitogen-activated protein kinase 1/2 (p-ERK1/2) levels increase in PKC[straight epsilon] over-expressing cells, while pkc[straight epsilon] siRNAs produce a decrease in p-ERK1/2. Indeed, pharmacological inhibition of ERK1/2 rescues the expression levels of both nkx2.5 and gata4, suggesting that a reinforced (mitogen-activated protein kinase) MAPK signaling is at the basis of the observed inhibition of cardiac gene expression in the PKC[straight epsilon] over-expressing hearts. We demonstrate that PKC[straight epsilon] is critical for cardiac cell early gene expression evidencing that this protein is a regulator that has to be fine tuned in precursor cardiac cells.[PUBLICATION ABSTRACT]