title: Modulation of astroglial energy metabolism by nitric oxide.
abstract: 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.
authors.affiliation: 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
authors.forename: Juan P
authors.initials: JP
authors.lastname: Bolaños
authors.forename: Angeles
authors.initials: A
authors.lastname: Almeida
mesh_terms: 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
chemical_list: D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D005947:Glucose