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 transfec ted with the Bcl-2 or Bcl-XL gene were studied. Bcl-2 overexpression did no t alter carbachol (CCh)-elicited initial increase in cytosolic free Ca2+ co ncentrations ([Ca2+](i)), but Bcl-XL overexpression dramatically reduced th is response. Exposure to 10 Gy gamma -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 r esponse to CCh at 4-h post-irradiation was decreased in wild-type and contr ol transfected cells, but not in Bcl-2 and Bcl-XL transfectants. The capaci ty of the IP sensitive Ca2+ store was significantly reduced by radiation in all cells except Bcl-XL transfectants. Ca2+ influx after stimulation with CCh was suppressed by exposure to radiation in wild-type and control-transf ected cells, but not in Bcl-2- and Bcl-XL-transfectants. However. radiation enhanced Ca2+ influx activated by thapsigargin in all cell types. These re sults suggest that 1) radiation diminishes IP3 formation and Ca2+ release i n response to CCh, but potentiates the store-operated Ca2+ influx, and 2) o verexpression of Bcl-2 or Bcl-XL partially protects cells from radiation-in duced inhibition of Ca2+ signaling.