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

Our earlier study demonstrated the induction of PKC isoforms (beta II, 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 (PKC epsilon). PKC epsilon functions both as an anti-apoptotic and proapoptotic protein and it is the only PKC isozyme implicated in oncogenesis. Given the importance of PKC epsilon in oncogenesis, we wished to determine whether or not PKCe is involved in bystander response. Gene expression array analysis demonstrated a 2-3-fold increase in PKC epsilon expression in the bystander human primary fibroblast cells that were co-cultured in double-sided Mylar dishes for 3 h with human primary fibroblast cells irradiated with 5 Gy of alpha-particles. The elevated PKC epsilon expression in bystander cells was verified by quantitative real time PCR. Suppression of PKC epsilon expression by small molecule inhibitor Bisindolylmaleimide IX (Ro 31-8220) considerably reduced the frequency of micronuclei (MN) induced both by 5 Gy 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 PKC epsilon 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. (C) 2009 Elsevier Ltd. All rights reserved.