Role of calpain- and interleukin-1 beta converting enzyme-like proteases in the beta-amyloid-induced death of rat hippocampal neurons in culture

J Neurochem. 1997 Apr;68(4):1612-21. doi: 10.1046/j.1471-4159.1997.68041612.x.


We investigated the potential role of different proteases in the death of cultured rat hippocampal pyramidal neurons induced by beta-amyloid (A beta) (25-35). Both A beta(25-35)- and staurosporine-induced death of these neurons appeared to involve apoptosis, as indicated using Hoechst 33342 and terminal dUDP nick end labeling staining, whereas NMDA-induced death appeared more complex. Two irreversible inhibitors of the interleukin-1 beta converting enzyme (ICE) and related proteases, Z-Val-Ala-Asp-CH2F and acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone, blocked neuronal death produced by A beta(25-35), staurosporine, and NMDA to differing extents. Furthermore, MDL 28,170, a selective inhibitor of the calcium-regulated protease calpain, also inhibited death induced by all agents. A beta(25-35) and staurosporine stimulated the breakdown of the protein spectrin, a calpain substrate. Spectrin breakdown was inhibited by MDL 28,170 but not by ICE inhibitors. Leupeptin was only effective in preventing NMDA-induced death. These results support the role of apoptosis in neuronal death due to A beta(25-35) treatment and also suggest a role for calcium-regulated proteases in this process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Calcium / physiology
  • Calpain / metabolism*
  • Caspase 1
  • Cell Death / drug effects
  • Cells, Cultured / drug effects
  • Cells, Cultured / enzymology
  • Cysteine Endopeptidases / metabolism*
  • DNA Fragmentation
  • Endopeptidases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Female
  • Interleukin-1 / metabolism
  • N-Methylaspartate / pharmacology
  • Neurotoxins / pharmacology
  • Peptide Fragments / pharmacology
  • Pregnancy
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / enzymology
  • Rats
  • Staurosporine / pharmacology


  • Amyloid beta-Peptides
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Interleukin-1
  • Neurotoxins
  • Peptide Fragments
  • N-Methylaspartate
  • Endopeptidases
  • Calpain
  • Cysteine Endopeptidases
  • Caspase 1
  • Staurosporine
  • Calcium