Potentiated glucose deprivation-induced death of astrocytes after induction of iNOS

Astrocytes play an essential role in the maintenance of normal neuronal function. Here we report that pre-treatment of interferon-γ (IFN-γ) and lipopolysaccharides (LPS) made murine astrocytes highly vulnerable to glucose deprivation-induced death. Neither 12-hr glucose deprivation nor 2-day treatment with IFN-γ (100 U/ml) and LPS (1 μg/ml) altered the viability of astrocytes. However, significant death of IFN-γ/LPS-treated astrocytes was observed after 4-hr glucose deprivation. This augmented death was mimicked by the nitric oxide releasing reagent 3-morpholinosydnonimine and was in part prevented by the nitric oxide synthase inhibitor N(G)-nitroarginine. The data indicate that immunostimulated astrocytes can undergo suicidal death during glucose deprivation through the expression of inducible nitric oxide synthase.