Nitric oxide protects astrocytes from oxidative stress

Oxidative stress in astrocytes has been observed in a number of pathological conditions, however the effect of nitric oxide on oxidatively stressed astrocytes remains unclear. The goal of this research was to determine how nitric oxide influences the mechanism of peroxide-induced oxidative stress in astrocytes. We used enriched mouse-astrocyte cultures and tertiarybutyl hydroperoxide to study astrocyte oxidative stress. Cellular integrity was measured at the ultrastructural level by electron microscopy and plasma membrane integrity measured by lactate dehydrogenase release. Mitochondrial swelling and disruption of cristae were observed by electron microscopy in the absence of damage to other organelles. Astrocytes exposed to peroxide eventually succumbed to necrotic loss of plasma membrane integrity. However, when astrocytes were subjected to oxidative stress in the presence of nitric oxide, mitochondrial integrity was preserved and cell death delayed. This protection of nitric oxide resembled that of iron chelation and nitric oxide reduced susceptibility usually associated with iron-loaded astrocytes exposed to oxidative stress. Taken together, these data suggest that nitric oxide can act as a powerful antioxidant for astrocytes preserving mitochondrial and cellular integrity during oxidative stress.