Apoptotic cell death and CPP32-like activation induced by thapsigargin and their prevention by nerve growth factor in PC12 cells

Biochim Biophys Acta. 1998 Jan 2;1401(1):63-71. doi: 10.1016/s0167-4889(97)00116-x.

Abstract

Thapsigargin, an endoplasmic reticular Ca2+-ATPase inhibitor, induced apoptotic cell death (chromatin condensation and DNA fragmentation) accompanied by the activation of CPP32-like protease, a member of the interleukin-1beta converting enzyme protease (ICE) family, but not the activation of ICE-like protease. Nerve growth factor (NGF) completely inhibited the cell death and CPP32-like activation induced by thapsigargin while Ac-Asp-Glu-Val-Asp-CHO, an inhibitor of CPP32-like protease, reduced the cell death. PD98059, a specific inhibitor of Map kinase kinase, did not reduce the protective effect of NGF on thapsigargin-induced cell death. These results suggest that calcium ion-induced apoptotic cell death was mediated by CPP32-like, but not ICE-like, protease and was regulated by a neurotrophic factor possibly, through the Map kinase cascade independent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Calcium / analysis
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Caspase 1
  • Caspase 3
  • Caspases*
  • Cycloheximide / pharmacology
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Mitogen-Activated Protein Kinase Kinases
  • Nerve Growth Factors / pharmacology*
  • Neurons
  • Oligopeptides / pharmacology
  • PC12 Cells
  • Protein Kinase Inhibitors
  • Protein Synthesis Inhibitors / pharmacology
  • Rats
  • Thapsigargin / pharmacology*

Substances

  • Cysteine Proteinase Inhibitors
  • Enzyme Inhibitors
  • Flavonoids
  • Nerve Growth Factors
  • Oligopeptides
  • Protein Kinase Inhibitors
  • Protein Synthesis Inhibitors
  • acetyl-aspartyl-glutamyl-valyl-aspartal
  • Thapsigargin
  • Cycloheximide
  • L-Lactate Dehydrogenase
  • Mitogen-Activated Protein Kinase Kinases
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Caspase 1
  • Calcium-Transporting ATPases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Calcium