Modulation of astroglial energy metabolism by nitric oxide.
Activated astroglial cells produce large amounts of nitric oxide (NO) which, through the binding to soluble guanylyl cyclase, rapidly increases cyclic GMP concentrations. In addition, through the binding with the a-a (3) binuclear center of cytochrome c oxidase, NO rapidly decreases the affinity of this complex for O(2), hence reversibly inhibiting the mitochondrial electron flux and ATP synthesis. Despite promoting a profound degree of mitochondrial inhibition, astrocytes show remarkable resistance to NO and peroxynitrite, whereas neurons are highly vulnerable. Recent evidence suggests that the inhibition of mitochondrial respiration by these nitrogen-derived reactive species leads to the modulation of key regulatory steps of glucose metabolism. Thus, upregulation of glucose uptake, the stimulation of glycolysis and the activation of pentose-phosphate pathway appear to be important sites of action. The stimulation of these glucose-metabolizing pathways by NO would represent a transient attempt by the glial cells to compensate for energy impairment and oxidative stress, and thus to emerge from an otherwise pathological outcome.
Bolaños
Juan P
JP
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca/Instituto de Neurociencias de Castilla y León, Centro Nacional de Investigaciones Cardiovasculares, Campus Miguel de Unamuno, Salamanca, Spain. jbolanos@usal.es
Almeida
Angeles
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D016923:Cell Death; D002952:Citric Acid Cycle / Q000502:physiology; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000502:physiology; D030421:Peroxynitrous Acid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D005947:Glucose