Effects of radiation on Ca²⁺ signaling in salivary epithelial cell lines transfected with Bcl-2 and Bcl-XL

The effects of radiation on the Ca²⁺ signaling system in HSY cells transfected with the Bcl-2 or Bel-XL gene were studied. Bcl-2 overexpression did not alter carbachol (CCh)-elicited initial increase in cytosolic free Ca²⁺ concentrations ([Ca²⁺]_i), but Bel-XL overexpression dramatically reduced this response. Exposure to 10 Gy γ-ray did not alter basal [Ca²⁺]_i. By contrast, the CCh-stimulated initial [Ca²⁺]ⁱ increase was reduced at 0.5 and 4 h post-irradiation in all cell types and remained decreased at 24 h in wild-type and control-transfected cells, but recovered in Bcl-2- and Bcl-XL-transfectants. The formation of inositol 1,4,5-trisphosphate (IP₃) in response to CCh at 4-h post-irradiation was decreased in wild-type and control-transfected cells, but not in Bcl-2 and Bel-XL transfectants. The capacity of the IP₃-sensitive Ca²⁺ store was significantly reduced by radiation in all cells except Bel-XL transfectants. Ca²⁺ influx after stimulation with CCh was suppressed by exposure to radiation in wild-type and control-transfected cells, but not in Bcl-2- and Bcl-XL-transfectants. However, radiation enhanced Ca²⁺ influx activated by thapsigargin in all cell types. These results suggest that 1) radiation diminishes IP₃ formation and Ca²⁺ release in response to CCh, but potentiates the store-operated Ca²⁺ influx; and 2) overexpression of Bcl-2 or Bel-XL partially protects cells from radiation-induced inhibition of Ca²⁺ signaling.