title: The effect of inflammatory stimuli on NMDA-related activation of glutamine synthase in human cultured astroglial cells.
abstract: Removal of glutamate from the synaptic cleft by astroglial glutamine synthase (GS) is a crucial step in the regulation of glutamate turnover and metabolism, thus participating in endogenous neuroprotective processes occurring within brain tissues. Here we investigated on the effect of inflammatory cytokines on GS activity in astroglial cells undergoing NMDA receptors stimulation. Incubation of human cultured astroglial cells with NMDA (100 microM) enhanced GS expression, an effect driven by the generation of nitric oxide (NO) since l-NAME (500 microM), an inhibitor of NO synthase, reversed this effect. NMDA-related increase of GS activity and glutamine concentration was antagonised by previous incubation of astroglial cells with a mixture of LPS plus gammaIFN, an effect counteracted by dexamethasone, the latter effect being accompanied by inhibition of inducible NO synthase. These results show that LPS plus gammaIFN inhibit elevation of GS activity subsequent to NMDA receptor stimulation in astroglial cells via enhancement of inducible NO synthase, and this may represent the site of interaction between pro-inflammatory and excitotoxic stimuli in the brain.
authors.affiliation: Faculty of Pharmacy, Magna Graecia University of Catanzaro, Complesso Nini' Barbieri, Roccelletta di Borgia, 88100 Catanzaro, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Muscoli
authors.forename: Valeria
authors.initials: V
authors.lastname: Visalli
authors.forename: Carmen
authors.initials: C
authors.lastname: Colica
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.forename: Ernesto
authors.initials: E
authors.lastname: Palma
authors.forename: Nicola
authors.initials: N
authors.lastname: Costa
authors.forename: Domenicantonio
authors.initials: D
authors.lastname: Rotiroti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nisticò
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D016202:N-Methylaspartate / Q000494:pharmacology*
chemical_list: D016202:N-Methylaspartate; D005974:Glutamate-Ammonia Ligase