Amyloid beta-protein induces necrotic cell death mediated by ICE cascade in PC12 cells.
A major component of Alzheimer's disease plaque amyloid beta protein (betaAP) showed the cytolytic activity to rat pheochromocytoma PC 12 cells. Nuclear morphological study revealed that betaAP-induced cytolytic activity is due to necrotic cell death, rather than apoptotic cell death. To examine the molecular machinery of betaAP-induced necrotic cell death in detail, I investigated the direct involvement of caspase. When nerve growth factor-treated and -untreated PC12 cells were incubated with the synthesized tetrapeptide inhibitors of caspase, YVAD-CHO (Ac-Tyr-Val-Ala-Asp-CHO) or DEVD-CHO (Ac-Asp-Glu-Val-Asp-CHO), betaAP-induced necrotic cell death was prevented. In addition, the interleukin-1beta converting enzyme (ICE) subfamily activation preceded CPP32 subfamily activation during betaAP-induced necrotic cell death. On the basis of these findings, I suggest that betaAP induces necrotic cell death mediated by the ICE cascade and that the ICE cascade may possibly be involved in Alzheimer's disease.
Suzuki
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Drug Safety Research Lab., Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, Edogawa-ku, Japan. LEB00373@niftyserve.or.jp
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002467:Cell Nucleus / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D009336:Necrosis; D009414:Nerve Growth Factors / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats
D016229:Amyloid beta-Peptides; D015853:Cysteine Proteinase Inhibitors; D009414:Nerve Growth Factors; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C096429:L 709049; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1