Expression of CONNEXIN43 is highly sensitive to ionizing radiation: implications for the radiation-induced bystander effect

Full text: In order to gain a greater understanding of the mechanisms underlying the cellular responses to low-dose ionizing radiation, gene expression profiles were examined by microarray analysis of cDNA from confluent human diploid fibroblast cultures exposed to very low fluences of α-particles. The data, supported by northern and western analyses, indicate that radiation induces a significant up-regulation of CONNEXIN43 expression. This phenomenon was observed in a variety of irradiated cell types. These findings are consistent with our previous observations that connexin43 mediated gap-junction intercellular communication is involved in the bystander response observed in cell cultures exposed to fluences of α-particles by which only a very small fraction of the cell nuclei is traversed by a particle track (Proc. Natl. Acad. Sci. 98: 473, 2001). Increased mRNA levels in cells from irradiated cultures correlated with increased connexin43 protein levels by about 4 h after irradiation. The induction of connexin43 was observed by mean-α-particle doses as low as 0.16 cGy, and also in cells exposed to γ-rays, t-butyl hydroperoxide and hyperthermia. Exposure to these stresses also resulted in post-translational modification of connexin43; increased phosphorylation and hyperphosphorylation of the protein was observed. Up-regulation of connexin43 expression in ionizing radiation exposed cells correlated with functional communication through gap-junctions between irradiated and non-irradiated cells. In contrast, the response following ultraviolet radiation varied and was cell type dependent. Overall, these data suggest a critical role for genes involved in intercellular communication in mediating the cellular responses to a variety of stresses