Elevated extracellular calcium can prevent apoptosis via the calcium-sensing receptor

KI Lin, N Chattopadhyay, M Bai, R Alvarez… - Biochemical and …, 1998 - Elsevier
KI Lin, N Chattopadhyay, M Bai, R Alvarez, CV Dang, JM Baraban, EM Brown, RR Ratan
Biochemical and biophysical research communications, 1998Elsevier
The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor
present on parathyroid cells which monitors the level of extracellular calcium (Ca2+ o) 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 (Ca2+ o) may act as a first messenger to regulate diverse
cellular functions. To test this hypothesis, we examined the effect of increasing Ca2+ oon …
The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (Ca2+o) 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 (Ca2+o) may act as a first messenger to regulate diverse cellular functions. To test this hypothesis, we examined the effect of increasing Ca2+oon 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 Ca2+o(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 Ca2+o. In addition to preventing SV-induced death, elevated Ca2+oalso 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 Ca2+ocan act with the CaR to prevent apoptosis and define a novel mechanism by which calcium ions can regulate cell survival.
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