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Fructose-1,6-bisphosphate attenuates induction of nitric oxide synthase in microglia stimulated with lipopolysaccharide

Authors
Kim, YC; Park, TY; Baik, E; Lee, SH
Citation
Life sciences, 90(9-10):365-372, 2012
Journal Title
Life sciences
ISSN
0024-32051879-0631
Abstract
AIMS: Fructose-1,6-bisphosphate (FBP) is a glycolytic intermediate with neuroprotective action in various brain injury models. However, the mechanism underlying the neuroprotection of FBP has not been fully defined. In this study, we investigated whether FBP inhibits endotoxin-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in microglial cells and explored the possible mechanisms of the effects of FBP.



MAIN METHODS: Murine microglial cell line BV2 and primary cultured murine microglial cells were used. NO production and iNOS expression were determined by Griess reaction, RT-PCR and Western blot. Luciferase assay using iNOS promoter-luciferase (iNOS-Luc) construct was adopted for measuring transcriptional activity.



KEY FINDINGS: FBP dose-dependently suppressed lipopolysaccharide (LPS)-induced NO production, along with reducing the expression of iNOS at both the protein and mRNA level in primary cultured murine microglia and BV2 cells. FBP significantly inhibited iNOS promoter activity but stabilized iNOS mRNA. Among transcription factors known to be related to iNOS expression, activator protein (AP-1) activation was significantly blocked by FBP. FBP suppressed LPS-induced phosphorylation of three MAPK subtypes-p38 MAPK, JNK and ERK. FBP inhibited LPS-induced production of reactive oxygen species (ROS) and decreased intracellular GSSG/GSH ratio.



SIGNIFICANCE: Our findings suggest that FBP attenuates the LPS-induced iNOS expression through inhibition of JNK and p38 MAPK, which might be related to ROS downregulation.
MeSH terms
AnimalsAnimals, NewbornCells, Cultured*CytoprotectionFructosediphosphates/*pharmacologyLipopolysaccharides/pharmacologyMAP Kinase Kinase 4/antagonists & inhibitors/metabolismMAP Kinase Signaling System/drug effectsMiceMicroglia/cytology/*drug effects/enzymologyNeuroprotective Agents/*pharmacologyNitric Oxide/antagonists & inhibitors/metabolismNitric Oxide Synthase Type II/*antagonists & inhibitors/metabolismPhosphorylationRNA, Messenger/biosynthesisReactive Oxygen Species/*metabolismTranscription Factor AP-1/antagonists & inhibitors/metabolismp38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
DOI
10.1016/j.lfs.2011.12.011
PMID
22227475
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
백, 은주이, 수환
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