Protein kinase C epsilon is involved in ionizing radiation induced bystander response in human cells

Our earlier study demonstrated the induction of PKC isoforms (betaII, PKC-alpha/beta, PKC-theta) by ionizing radiation induced bystander response in human cells. In this study, we extended our investigation to yet another important member of PKC family, PKC epsilon (PKCepsilon). PKCepsilon functions both as an anti-apoptotic and pro-apoptotic protein and it is the only PKC isozyme implicated in oncogenesis. Given the importance of PKCepsilon in oncogenesis, we wished to determine whether or not PKCepsilon is involved in bystander response. Gene expression array analysis demonstrated a 2-3-fold increase in PKCepsilon expression in the bystander human primary fibroblast cells that were co-cultured in double-sided Mylar dishes for 3h with human primary fibroblast cells irradiated with 5Gy of alpha-particles. The elevated PKCepsilon expression in bystander cells was verified by quantitative real time PCR. Suppression of PKCepsilon expression by small molecule inhibitor Bisindolylmaleimide IX (Ro 31-8220) considerably reduced the frequency of micronuclei (MN) induced both by 5Gy of gamma-rays (low LET) and alpha-particles (high LET) in bystander cells. Similar cytoprotective effects were observed in bystander cells after siRNA mediated silencing of PKCepsilon suggestive of its critical role in mediating some of the bystander effects (BE). Our novel study suggests the possibility that PKC signaling pathway may be a critical molecular target for suppression of ionizing radiation induced biological effects in bystander cells.