CALCIUM IONOPHORE-INDUCED DEGRADATION OF NEUROFILAMENT AND CELL-DEATHIN MSN NEUROBLASTOMA-CELLS

Extensive necrotic death of MSN neuroblastoma cells could be induced a fter incubation with the calcium ionophore, A23187. The reaction was c oncentration-dependent and time course-dependent. Levels of the 66 kd/ alpha-internexin neurofilament protein (NF-66) and the cognate heal sh ock protein 70 (Hsc 70) decreased during the Ca2+-activated cell death . Addition of the calcium chelator, ethylene glycol-bis(beta-aminoethy l ether) N,N,N',N'-tetraacetic acid (EGTA) restored the normal level o f NF-66 and partially that of the Hsc 70. Use of either calpain I or c alpain II inhibitor could alleviate the reduction of 66 kd protein dur ing the ionophore treatment whereas only calpain I inhibitor treatment was effective in restoring the normal level of the Hse 70. Neither of these calpain inhibitors could block the ionophore triggered cell dea th. EGTA was toxic to cells in a wide range of concentration suggestin g a calcium-independent activation of cell death mechanism.