Effects of ICE-like protease and calpain inhibitors on neuronal apoptosis

Neuroreport. 1996 Dec 20;8(1):249-55. doi: 10.1097/00001756-199612200-00050.


Both ice-like protease and calpain have been shown to be involved in apoptosis in non-neuronal cells. Cultured rat cerebellar granule neurons undergo apoptosis when exposed to low potassium-containing medium. Calpain inhibitors 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and N-acetyl-Leu-Leu-Met-CHO (calpain inhibitor II) as well as interleukin-beta 1 converting enzyme (ICE)-like protease inhibitor Z-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB) protect against such apoptotic death. They also reduce DNA laddering and the number of apoptotic nuclei. Staurosporine treatment also evokes apoptosis in human neuroblastoma SH-SY5Y. While Z-D-DCB is again anti-apoptotic, calpain inhibitors only provide modest effects in this model. Our results suggest that ICE-like protease plays a critical role in neuronal apoptosis whereas the contributions of calpain are more cell-type dependent.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / pathology
  • Calpain / antagonists & inhibitors*
  • Caspase 1
  • Coloring Agents
  • Cysteine Endopeptidases / metabolism*
  • DNA Fragmentation / drug effects
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Neuroblastoma / enzymology
  • Neuroblastoma / pathology
  • Neurons / drug effects*
  • Protease Inhibitors / pharmacology*
  • Rats
  • Tumor Cells, Cultured


  • Coloring Agents
  • Protease Inhibitors
  • L-Lactate Dehydrogenase
  • Calpain
  • Cysteine Endopeptidases
  • Caspase 1