TY - JOUR
T1 - Elevated extracellular calcium can prevent apoptosis via the calcium-sensing receptor
AU - Lin, Kuo I.
AU - Chattopadhyay, Naibedya
AU - Bai, Mei
AU - Alvarez, Rene
AU - Dang, Chi V.
AU - Baraban, Jay M.
AU - Brown, Edward M.
AU - Ratan, Rajiv R.
N1 - Funding Information:
We thank Rosalind Segal and Stephen Soltoff for their review of the manuscript. This work was supported by grants from the NIH [DK48330, DK41415, and DK52005 to E.M.B.; DK09436 to M.B.; and NS34473 to J.M.B. and R.R.], the St. Giles Foundation (to E.M.B.), and NPS Pharmaceuticals, Inc. (to E.M.B.).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1998/8/19
Y1 - 1998/8/19
N2 - The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (Ca(o)2+) and transduces signals involved in serum calcium regulation. Expression of CaR protein in tissues with functions unrelated to systemic calcium homeostasis, including the brain, suggests that extracellular calcium (Ca(o)2+) may act as a first messenger to regulate diverse cellular functions. To test this hypothesis, we examined the effect of increasing Ca(o)2+ on apoptosis induced by Sindbis Virus in AT-3 prostate carcinoma cells. We found a steep increase in cell survival with between 5 and 7 mM added Ca(o)2+ (EC50 = 6.1 mM). Magnesium, a less potent agonist of the calcium sensing receptor, was also protective (EC50 = 23.4 mM). Northern and immunocytochemical analyses confirmed the presence of the CaR message and protein in AT-3 prostate carcinoma cells. Enforced expression of CaR protein by stable transfection in human embryonic kidney (HEK)-293 cells, which normally don't express the receptor, resulted in resistance to SV-induced apoptosis in the presence of elevated Ca(o)2+. In addition to preventing SV-induced death, elevated Ca(o)2+ also abrogated apoptosis induced by c-Myc overexpression/serum deprivation in rat 1A fibroblasts, and these fibroblasts were shown to express CaR message and protein. Altogether, these observations suggest that Ca(o)2+ can act with the CaR to prevent apoptosis and define a novel mechanism by which calcium ions can regulate cell survival.
AB - The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (Ca(o)2+) and transduces signals involved in serum calcium regulation. Expression of CaR protein in tissues with functions unrelated to systemic calcium homeostasis, including the brain, suggests that extracellular calcium (Ca(o)2+) may act as a first messenger to regulate diverse cellular functions. To test this hypothesis, we examined the effect of increasing Ca(o)2+ on apoptosis induced by Sindbis Virus in AT-3 prostate carcinoma cells. We found a steep increase in cell survival with between 5 and 7 mM added Ca(o)2+ (EC50 = 6.1 mM). Magnesium, a less potent agonist of the calcium sensing receptor, was also protective (EC50 = 23.4 mM). Northern and immunocytochemical analyses confirmed the presence of the CaR message and protein in AT-3 prostate carcinoma cells. Enforced expression of CaR protein by stable transfection in human embryonic kidney (HEK)-293 cells, which normally don't express the receptor, resulted in resistance to SV-induced apoptosis in the presence of elevated Ca(o)2+. In addition to preventing SV-induced death, elevated Ca(o)2+ also abrogated apoptosis induced by c-Myc overexpression/serum deprivation in rat 1A fibroblasts, and these fibroblasts were shown to express CaR message and protein. Altogether, these observations suggest that Ca(o)2+ can act with the CaR to prevent apoptosis and define a novel mechanism by which calcium ions can regulate cell survival.
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U2 - 10.1006/bbrc.1998.9124
DO - 10.1006/bbrc.1998.9124
M3 - Article
C2 - 9712695
AN - SCOPUS:0032547239
VL - 249
SP - 325
EP - 331
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -