Inhibition of autophagy and glycolysis by nitric oxide during hypoxia-reoxygenation impairs cellular bioenergetics and promotes cell death in primary neurons

摘要: Excessive nitric oxide (NO) production is known to damage mitochondrial proteins and the autophagy repair pathway so can potentially contribute neurotoxicity. Accordingly, we hypothesized that protection against protein from reactive oxygen nitrogen species under conditions of low by in neurons would be impaired NO enhance bioenergetic dysfunction. Rat primary cortical had same basal cellular respiration hypoxia as normoxia, whereas NO-exposed cells exhibited a gradual decrease hypoxia. Upon reoxygenation, NO-treated did not recover prehypoxic levels. Hypoxia-reoxygenation presence was associated with inhibition autophagy, inability during reoxygenation exacerbated an inhibitor 3-methyladenine. The effects could recapitulated inhibiting glycolytic flux normoxic conditions. Under both hypoxic exposure induced immediate stimulation glycolysis, but prolonged exposure, irreversible hypoxia, inhibited glycolysis. Importantly, found only when glucose absent medium or glycolysis 2-deoxy-d-glucose, revealing novel NO-dependent mechanism for modulated Taken together these data suggest oxygen-dependent interaction between respiration, protecting neuronal exposed NO. they indicate dysfunction intimately linked failure In addition, studies provide new insights into understanding how may play interactive roles neuroinflammation-induced damage, which pertinent our pathology neurodegenerative diseases excessive generated.