Calcium overload is essential for the acceleration of staurosporine-induced cell death following neuronal differentiation in PC12 cells

Differentiation of neuronal cells has been shown to accelerate stress-induced cell death, but the underlying mechanisms are not completely understood. Here, we find that early and sustained increase in cytosolic ([Ca²⁺]_c) and mitochondrial Ca²⁺ levels ([Ca²⁺]_m) is essential for the increased sensitivity to staurosporine-induced cell death following neuronal differentiation in PC12 cells. Consistently, pretreatment of differentiated PC12 cells with the intracellular Ca²⁺-chelator EGTA-AM diminished staurosporine-induced PARP cleavage and cell death. Furthermore, Ca²⁺ overload and enhanced vulnerability to staurosporine in differentiated cells were prevented by Bcl-X_L overexpression. Our data reveal a new regulatory role for differentiation-dependent alteration of Ca²⁺ signaling in cell death in response to staurosporine.