In this study we determined whether caspase-3 is required in mouse cortical neurons for sodium azide-mediated apoptosis. Primary cortical neuronal cultures were treated with a cell permeable caspase-3 inhibitor, DEVD (1 nM-100 fM), prior to sodium azide-induced hypoxia. Treatment with the caspase-3 inhibitor resulted in a dose-dependent decrease in apoptosis, suggesting that sodium azide-induced apoptosis is mediated through a caspase-3 dependent pathway. Levels of cytochrome-c release and caspase-3 cleavage were assayed by Western analysis. Cytochrome-c release and caspase-3 cleavage were observed at 5h (85.3 ± 5.8%) and 8h (53.4 ± 14.9%), respectively. We have previously reported that angiotensin II, acting through the AT2 receptor subtype, protects cultured mouse cortical neurons from sodium azide-induced apoptosis. We also examined whether the protective effect of angiotensin II is mediated through modulation of caspase-3. Pre-treatment of cells with angiotensin II and the AT1 receptor antagonist, losartan, reduced levels of sodium azide-induced caspase-3 cleavage by 95.0 ± 4.0%. Cells pre-treated with the AT2 receptor antagonist, PD123319 showed a smaller reduction of caspase-3 cleavage (53.8 ± 3.4%). Our findings indicate that sodium azide-induced apoptosis is caspase-3 dependent and that angiotensin II protects cortical neurons from chemical-induced apoptosis by reducing caspase-3 cleavage.
|Original language||English (US)|
|Number of pages||7|
|Journal||Brain Research Bulletin|
|State||Published - Jan 15 2004|
- Sodium azide
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