| Cells can lose viability through two mechanisms, apoptosis, which consists of a series of pre-programmed events that require energy and take hours to days to complete, and necrosis, which is thought to be much less regulated, requires no energy and occurs suddenly. A recent report (Eur. J. Pharmacol. 516:187) detailed the differential effect of calcium on two hematopoietic cell lines (CEM and HL-60), inducing apoptosis in one and necrosis in the other. Moreover, this work supported the contention that there are controlled molecular and cellular mechanisms that control necrosis. To determine how general these findings are, the effects of variable amounts of intra- and extra-cellular calcium on these cell lines plus other hematopoietic (Jurkat) and non-hematopoietic (HeLa and PC3) cell lines were assessed. Apoptotic induction was detected by monitoring 1) the amount of phosphatidyl serine in the outer leaflet of the plasma membrane; 2) the loss of mitochondrial membrane potential; and 3) the induction of caspases. Necrosis was detected by monitoring cell morphology and loss of viability in the absence of apoptotic markers. The cell lines exhibited complex and discrepant responses to various apoptotic inducers including the calcium ionophore A23187, which were further modulated by changes in calcium levels. We conclude that apoptosis is the “default” mode of death, but in cases of high-level insult or severe compromise of mitochondrial and/or cellular functions, necrosis ensues. |
