Cd-induced apoptosis was mediated by the release of Ca2+ from intracellular Ca storage.

Previous studies found that cadmium (Cd) could induce apoptosis via interfering with the intracellular calcium (Ca) ions homeostasis. But the detailed mechanisms remain poorly understood. In the present study two cell lines (normal human liver cell HL-7702, and tumor cell Raji cell) were exposed to Cd along or co-incubated with ethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA) and 1,2-bis (2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA-AM), respectively. After the incubation, the apoptosis and intracellular Ca2+ ([Ca2+]i) were measured. Excessive apoptosis was observed both in HL-7702 and Raji cells treated with Cd. Significant elevation of [Ca2+]i was also detected in the cells with higher levels of apoptosis. EGTA (the extracellular Ca2+ chelator) decreased Cd-elicited [Ca2+]i (22% in HL-7702 and 41% in Raji cells; p<0.05) significantly except for apoptosis. However, BAMTA-AM (the [Ca2+]i chelator) attenuated the Cd-elevated [Ca2+]i (78% in HL-7702 and 59% in Raji cells; p<0.05) and inhibited Cd-induced apoptosis significantly (p<0.05). These results suggest that (1) Ca2+ was primarily generated intracellularly and only a small portion was generated extracellularly; (2) Cd-induced apoptosis was mediated by the release of Ca2+ from intracellular Ca storage but not an influx of extracellular Ca2+.