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Gangliosides activate cultured rat brain microglia.

Authors
Pyo, H; Joe, E; Jung, S; Lee, SH; Jou, I
Citation
The Journal of biological chemistry, 274(49):34584-34589, 1999
Journal Title
The Journal of biological chemistry
ISSN
0021-92581083-351X
Abstract
Microglia, brain resident macrophages, are activated in brain injuries and several neurodegenerative diseases. However, microglial activators that are produced in the brain are not yet defined. In this study, we showed that gangliosides, sialic acid-containing glycosphingolipids, could be a microglial activator. Gangliosides induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) and expression of cyclooxygenase-2 (COX-2). The effect of gangliosides on NO release increased dose-dependently in the range of 10-100 microgram/ml; however, the effect decreased at concentrations higher than 200 microgram/ml. Specific types of gangliosides showed differential effects on microglial activation. Similar to gangliosides, GT1b induced production of NO and TNF-alpha and expression of COX-2. However, GM1 and GD1a induced expression of COX-2 but had little effect on NO and TNF-alpha release. The effect of gangliosides and GT1b on NO release was reduced in the presence of neuraminidase, which removes sialic acid residues from gangliosides and GT1b. Gangliosides activated extracellular signal-regulated kinase significantly but activated c-jun N-terminal kinase/stress-activated protein kinase and p38 relatively weakly. The inhibition of extracellular signal-regulated kinase by PD98059 reduced NO release from both gangliosides- and GT1b-treated microglia whereas inhibition of p38 by SB203580 increased it rather slightly. Gangliosides activated NF-kappaB, and N-acetyl cystein, an inhibitor of NF-kappaB, reduced NO release. These results suggest that gangliosides could be a microglial activator that functions via activation of mitogen-activated protein kinase and NF-kappaB.
MeSH terms
Acetylcysteine/metabolismAmyloid beta-Peptides/metabolismAnimalsBrain/drug effects*Brain/metabolismCulture TechniquesCyclooxygenase 2Enzyme Inhibitors/pharmacologyFlavonoids/pharmacologyGangliosides/pharmacology*Imidazoles/pharmacologyIsoenzymes/metabolismLipopolysaccharides/metabolismMAP Kinase Signaling System*Microglia/drug effects*Microglia/metabolismMitogen-Activated Protein Kinases/metabolismNF-kappa B/metabolismNeuraminidase/pharmacologyNitric Oxide/metabolismNitric Oxide Synthase/metabolismNitric Oxide Synthase Type IIProstaglandin-Endoperoxide Synthases/metabolismPyridines/pharmacologyRatsRats, Sprague-DawleySignal TransductionTime FactorsTumor Necrosis Factor-alpha/metabolism
PMID
10574921
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
표, 한경조, 은혜이, 수환주, 일로
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