Apoptotic cell death and caspase 3 (CPP32) activation induced by calcium ionophore at low concentrations and their prevention by nerve growth factor in PC12 cells.
A23187 (a calcium ionophore) at low concentration (0.1 microM) induced apoptotic cell death (chromatin condensation and DNA fragmentation) accompanied by the activation of caspase-3 (CPP32), a member of the interleukin-1beta-converting enzyme protease. On the other hand, A23187 at high concentration (2 microM) induced necrotic cell death not accompanied by the activation of CPP32. Nerve growth factor inhibited the cell death and CPP32 activation induced by 0.1 microM A23187, but not the cell death induced by 2 microM A23187. Acylaspartyl-glutamyl-valyl-aspartyl-aldehyde, an inhibitor of CPP32, reduced the cell death induced by 0.1 microM A23187. These results suggest that calcium-ion-induced apoptotic cell death was mediated by CPP32 activation in PC12 cells.
Takadera
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Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Ohyashiki
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000001:Calcimycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007476:Ionophores / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats
D015853:Cysteine Proteinase Inhibitors; D007476:Ionophores; D009414:Nerve Growth Factors; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D000001:Calcimycin; D007770:L-Lactate Dehydrogenase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases