Caspase inhibition selectively reduces the apoptotic component of oxygen-glucose deprivation-induced cortical neuronal cell death

Frank J. Gottron, Howard S. Ying, Dennis W. Choi

Research output: Contribution to journalArticlepeer-review

Abstract

Cultured mouse cortical neurons undergo apoptosis when exposed to staurosporine. The cell-permeable caspase inhibitor Z-Val-Ala-Asp fluoromethylketone (Z-VAD.FMK) attenuated this death, without altering overall protein synthesis. Z-VAD.FMK also attenuated cortical neuronal apoptosis induced by removal of serum. However, Z-VAD.FMK did not attenuate the excitotoxic necrosis induced by 5-min exposure to 100 μMNMDA, 24-h exposure to 100 μM kainate, or 90-min exposure to oxygen-glucose deprivation. We have previously shown that blockade of the excitotoxic component of oxygen-glucose deprivationinduced neuronal death with glutamate antagonists unmasks an apoptotic death. Treatment with Z-VAD.FMK, but not the cathepsin-B protease inhibitor Z-Phe-Ala fluoromethylketone (Z-FA.FMK), also attenuated this oxygenglucose deprivation-induced neuronal apoptosis. These data support the idea that brain caspases mediate the apoptotic component of oxygen-glucose deprivation induced neuronal death and raise the possibility that combining caspase inhibitors with glutamate antagonists might attenuate brain damage induced by hypoxicischemic insults in vivo.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalMolecular and Cellular Neurosciences
Volume9
Issue number3
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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