Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive Ca(2+) release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of Ca(2+) homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular Ca(2+) metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (γ)-irradiation. In irradiated RKO cells, Ca(2+) influx via activation of NCX reverse mode was enhanced and a decline of [Ca(2+)]i via forward mode was accelerated. The amount of Ca(2+) released from the ER in RKO cells by the activation of IP3 receptor was also enhanced by irradiation. An increase in [Ca(2+)]i via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that γ-irradiation elicits enhancement of cellular Ca(2+) metabolism in radiation-sensitive RKO cells yielding programmed cell death.
Keywords: A549 cells; Inositol-1,4,5-triphosphate receptors; Na+-Ca2+ exchanger; RKO cells; Store-operated Ca2+ influx.