Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress

• Published in: Brain research Vol. 960; no. 1; pp. 90 - 98
• Main Authors: Vexler, Zinaida S., Wong, Arthur, Francisco, Carla, Manabat, Catherine, Christen, Stephan, Täuber, Martin, Ferriero, Donna M., Gregory, George
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 17-01-2003; Amsterdam Elsevier; New York, NY
• Subjects: 6-Bisphosphate; Animals; Biological and medical sciences; Buthionine Sulfoximine - pharmacology; Carmustine - pharmacology; Cell Hypoxia; Cell Survival - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Enzyme Inhibitors - pharmacology; Free Radicals - pharmacology; Fructose-1; Fructosediphosphates - pharmacology; Glutathione; Glutathione - metabolism; Glutathione Reductase - metabolism; Hypoxia; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; Medical sciences; Mice; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents; Nitric Oxide - pharmacology; Oxidation-Reduction; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Reactive oxygen species; Tetrazolium Salts; Thiazoles; Disorders of the nervous system; Hypoxia; Reactive oxygen species; 6-Bisphosphate; Fructose-1; Glutathione; Oxidative stress; Oxygen; Cerebral cortex; Rodentia; Central nervous system; Environmental factor; Neuroprotective agent; Vertebrata; Mammalia; Mouse; Animal; Intracellular; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(02)03777-0

Fructose-1,6-bisphosphate (FBP), an endogenous intermediate of glycolysis, protects the brain against ischemia–reperfusion injury. The mechanisms of FBP protection after cerebral ischemia are not well understood. The current study was undertaken to determine whether FBP protects primary neurons against hypoxia and oxidative stress by preserving reduced glutathione (GSH). Cultures of pure cortical neurons were subjected to oxygen deprivation, a donor of nitric oxide and superoxide radicals (3-morpholinosydnonimine), an inhibitor of glutathione synthesis (
l-buthionine-sulfoximine) or glutathione reductase (1,3-bis(2-chloroethyl)-1-nitrosourea) in the presence or absence of FBP (3.5 mM). Neuronal viability was determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2
H-tetrazolium bromide assay. FBP protected neurons against hypoxia–reoxygenation and oxidative stress under conditions of compromised GSH metabolism. The efficacy of FBP depended on duration of hypoxia and was associated with higher intracellular GSH concentration, an effect partly mediated via increased glutathione reductase activity.