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 (beta AP) showed the cytolytic activity to rat pheochromocytoma PC12 cells. Nuclear morphological study revealed that beta AP-induced cytolytic activity is due to necrotic cell death, rather than apoptotic cell death. To examine the molecular machinery of beta AP-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), beta AP-induced necrotic cell death was prevented. In addition, the interleukin-1 beta converting enzyme (ICE) subfamily activation preceded CPP32 subfamily activation during beta AP-induced necrotic cell death. On the basis of these findings, I suggest that beta AP induces necrotic cell death mediated by the ICE cascade and that the ICE cascade may possibly be involved in Alzheimer's disease. (C) 1997 Academic Press.