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 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.
Sun
X
X
Department of Pediatrics, University of Texas Health Science Center, San Antonio, USA.
Liu
X B
XB
Martinez
J R
JR
Dang
H
H
Zhang
G H
GH
D000230:Adenocarcinoma; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000528:radiation effects*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000528:radiation effects; D010306:Parotid Gland / Q000166:cytology / Q000528:radiation effects; D010307:Parotid Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D018709:Statistics, Nonparametric; D014162:Transfection; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D018679:Cholinergic Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D002118:Calcium