Amyloid beta-protein induces necrotic cell death mediated by ICE cascade in PC12 cells

Exp Cell Res. 1997 Aug 1;234(2):507-11. doi: 10.1006/excr.1997.3639.


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.

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Caspase 1
  • Caspase 3
  • Caspases*
  • Cell Nucleus / drug effects
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Enzyme Activation
  • Necrosis*
  • Nerve Growth Factors / pharmacology
  • Oligopeptides / pharmacology
  • PC12 Cells
  • Rats


  • Amyloid beta-Peptides
  • Cysteine Proteinase Inhibitors
  • Nerve Growth Factors
  • Oligopeptides
  • acetyl-aspartyl-glutamyl-valyl-aspartal
  • L 709049
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Caspase 1