inositol-1-4-5-trisphosphate and Parotid-Neoplasms

The effects of radiation on the Ca2+ signaling system in HSY cells transfected with the Bcl-2 or Bcl-XL gene were studied. Bcl-2 overexpression did not alter carbachol (CCh)-elicited initial increase in cytosolic free Ca2+ concentrations ([Ca2+]i), but Bcl-XL overexpression dramatically reduced this 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 response to CCh at 4-h post-irradiation was decreased in wild-type and control-transfected cells, but not in Bcl-2 and Bcl-XL transfectants. The capacity of the IP3-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-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 Bcl-XL partially protects cells from radiation-induced inhibition of Ca2+ signaling.

Topics: Adenocarcinoma; bcl-X Protein; Calcium; Calcium Signaling; Carbachol; Cholinergic Agonists; Epithelial Cells; Humans; Inositol 1,4,5-Trisphosphate; Parotid Gland; Parotid Neoplasms; Proto-Oncogene Proteins c-bcl-2; Statistics, Nonparametric; Transfection; Tumor Cells, Cultured