PKCε-dependent signalling in cardiac differentiation

Abstract

The Protein kinase C (PKC) family, composed by 12 different isoforms, plays a pivotal role in many biological contexts such as cell differentiation, proliferation and survival. PKCe has been demonstrated to be relevant for cardio-protection as well as in ischemia-reperfusion injury (Budas et al. 2010). Transgenic mice over-expressing a constitutively active PKCε show concentric hypertrophy (Takeishi et al. 2000) suggesting negative effects of a permanently active PKCε in cardiac cells. Although the effects of PKCε over-expression have been analyzed both from the physiological and morphological points of view, molecular studies of its consequences on early cardiac marker gene expression are still lacking. On the other side Bone Marrow Mesenchymal Stem Cells (BMMSCs) can be induced to acquire a cardiac fate by treatment with 5-azacytidine (5-AZ) (Wakitani et al. 1995), representing a good in vitro model for cardiac differentiation studies. We addressed the role of in vivo PKCε over-expression on early cardiac genes (namely, nkx2.5 and gata4) regulation. Our results suggest a negative role of PKCε, mediated by ERK1/2, on expression of these two genes both in vivo and in ex-vivo rat BMMSCs, showing that this protein is a fine tuner of precursor cardiac cells.