Calcium ionophore-induced degradation of neurofilament and cell death in MSN neuroblastoma cells.
Extensive necrotic death of MSN neuroblastoma cells could be induced after incubation with the calcium ionophore, A23187. The reaction was concentration-dependent and time course-dependent. Levels of the 66 kd/alpha-internexin neurofilament protein (NF-66) and the cognate heat shock protein 70 (Hsc 70) decreased during the Ca2+-activated cell death. Addition of the calcium chelator, ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) restored the normal level of NF-66 and partially that of the Hsc 70. Use of either calpain I or calpain II inhibitor could alleviate the reduction of 66 kd protein during the ionophore treatment whereas only calpain I inhibitor treatment was effective in restoring the normal level of the Hsc 70. Neither of these calpain inhibitors could block the ionophore triggered cell death. EGTA was toxic to cells in a wide range of concentration suggesting a calcium-independent activation of cell death mechanism.
Chan
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Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Runko
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Anyane-Yeboa
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Chiu
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D000001:Calcimycin / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D009454:Neurofibrils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D007381:Intermediate Filament Proteins; D007976:Leupeptins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; C046643:alpha-internexin; C063261:acetylleucyl-leucyl-norleucinal; C069861:calpain inhibitor 2; D000001:Calcimycin; D002154:Calpain