Exposure to astrocyte-derived nitric oxide for 24 hours caused reversible damage to neuronal mitochondrial complexes II/III and IV, whereas 48-hour exposure caused irreversible damage to complex IV.
Astrocyte-derived NO causes duration-dependent damage to neuronal mitochondrial respiratory chain complexes, with prolonged exposure leading to irreversible complex IV dysfunction.
Cytokine-stimulated astrocytes produce nitric oxide (NO), which, along with its metabolite peroxynitrite (ONOO(-)), can inhibit components of the mitochondrial respiratory chain. We used astrocytes as a source of NO/ONOO(-) and monitored the effects on neurons in coculture. We previously demonstrated that astrocytic NO/ONOO(-) causes significant damage to the activities of complexes II/III and IV of neighbouring neurons after a 24-h coculture. Under these conditions, no neuronal death was observed. Using polytetrafluoroethane filters, which are permeable to gases such as NO but impermeable to NO derivatives, we have now demonstrated that astrocyte-derived NO is responsible for the damage observed in our coculture system. Expanding on these observations, we have now shown that 24 h after removal of NO-producing astrocytes, neurons exhibit complete recovery of complex II/III and IV activities. Furthermore, extending the period of exposure of neurons to NO-producing astrocytes does not cause further damage to the neuronal mitochondrial respiratory chain. However, whereas the activity of complex II/III recovers with time, the damage to complex IV caused by a 48-h coculture with NO-producing astrocytes is irreversible. Therefore, it appears that neurons can recover from short-term damage to mitochondrial complex II/III and IV, whereas exposure to astrocytic-derived NO for longer periods causes permanent damage to neuronal complex IV.
Stewart et al. (Tue,) reported a other. Astrocyte-derived nitric oxide was evaluated on Damage to neuronal mitochondrial respiratory chain complexes II/III and IV. Exposure to astrocyte-derived nitric oxide for 24 hours caused reversible damage to neuronal mitochondrial complexes II/III and IV, whereas 48-hour exposure caused irreversible damage to complex IV.