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.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology