Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress.
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-2H-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.
Vexler
Zinaida S
ZS
Department of Neurology, University of California San Francisco, Box 0114, 521 Parnassus Ave, San Francisco, CA, USA. zinaida@itsa.ucsf.edu
Wong
Arthur
A
Francisco
Carla
C
Manabat
Catherine
C
Christen
Stephan
S
Täuber
Martin
M
Ferriero
Donna M
DM
Gregory
George
G
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000494:pharmacology; D005635:Fructosediphosphates / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
D004791:Enzyme Inhibitors; D005609:Free Radicals; D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; C002385:linsidomine; D008981:Molsidomine; D005980:Glutathione Reductase; C022616:thiazolyl blue; D005978:Glutathione; C029063:fructose-1,6-diphosphate; D002330:Carmustine