Involvement of caspase 3 in apoptotic death of cortical neurons evoked by DNA damage

Mol Cell Neurosci. 2000 Apr;15(4):368-79. doi: 10.1006/mcne.2000.0838.


Previous reports have shown that DNA-damage-evoked death of embryonic cortical neurons is delayed by general caspase inhibitors and is accompanied by an increase in DEVD-AFC cleavage activity. We show here that this cleavage activity is lacking in camptothecin-treated caspase 3-deficient neurons. Moreover, we report that death of camptothecin-treated caspase 3-deficient neurons cultured from E16 embryos is delayed and that no significant increase in survival is observed with cotreatment with the general caspase inhibitor BAF. These results indicate that caspase-dependent death of camptothecin-treated cortical neurons requires caspase 3 activity. The delay in death is accompanied by impairment of DNA fragmentation. However, Bax-dependent cytochrome c release still occurs in camptothecin-treated caspase 3-deficient cortical neurons. Accordingly, we hypothesize that the delayed death which occurs in the absence of caspase 3 activity may be due to mitochondrial dysfunction. Finally, we show that the delay in death observed with E16 caspase 3-deficient neurons does not occur in neurons cultured from E19 embryos. This suggests that the requirement for caspase 3 in death of neurons evoked by DNA damage may differ depending upon the developmental state of the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Brain / cytology
  • Brain / embryology
  • Camptothecin / pharmacology
  • Caspase 3
  • Caspases / genetics*
  • Caspases / metabolism
  • Coumarins / pharmacology
  • Cytochrome c Group / metabolism
  • DNA Damage / physiology*
  • DNA Fragmentation / physiology
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Knockout
  • Neurons / cytology*
  • Neurons / enzymology*
  • Oligopeptides / pharmacology


  • Coumarins
  • Cytochrome c Group
  • Enzyme Inhibitors
  • Oligopeptides
  • aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • Camptothecin