Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated activation of murine N9 microglial cell line.

摘要: Lipopolysaccharide, the main component of cell wall Gram-negative bacteria, is known to activate microglial cells following its interaction with CD14/Toll-like receptor complex (TLR-4). The activation pathway triggered by lipopolysaccharide in microglia involves enhanced basal levels intracellular calcium ([Ca2+]i) and terminates increased generation cytokines/chemokines nitric oxide. Here we demonstrate that lipopolysaccharide-stimulated murine N9 cells, cyclic ADP-ribose, a universal potent Ca2+ mobiliser generated from NAD+ ADP-ribosyl cyclases (ADPRC), behaves as second messenger pathway. Lipopolysaccharide induced phosphorylation, mediated multiple protein kinases, mammalian ADPRC CD38, which resulted significantly activity 1.7-fold increase concentration ADP-ribose. This event was paralleled doubling [Ca2+]i levels, largely prevented ADP-ribose antagonists 8-Br-cyclic ryanodine (by 75% 88%, respectively). Both inhibited, although incompletely, functional events downstream lipopolysaccharide-induced microglia-activating pathway, i.e. expression inducible oxide synthase, overproduction release tumor necrosis factor alpha. identification key signal metabolite cascade eventually leading pro-inflammatory molecules may suggest new therapeutic target for treatment neurodegenerative diseases related activation.