TY - JOUR
T1 - The effect of inflammatory stimuli on NMDA-related activation of glutamine synthase in human cultured astroglial cells
AU - Muscoli, Carolina
AU - Visalli, Valeria
AU - Colica, Carmen
AU - Nisticò, Robert
AU - Palma, Ernesto
AU - Costa, Nicola
AU - Rotiroti, Domenicantonio
AU - Nisticò, Giuseppe
AU - Mollace, Vincenzo
PY - 2005/1/20
Y1 - 2005/1/20
N2 - 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 μM) enhanced GS expression, an effect driven by the generation of nitric oxide (NO) since L-NAME (500 μM), 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 γIFN, an effect counteracted by dexamethasone, the latter effect being accompanied by inhibition of inducible NO synthase. These results show that LPS plus γIFN 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.
AB - 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 μM) enhanced GS expression, an effect driven by the generation of nitric oxide (NO) since L-NAME (500 μM), 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 γIFN, an effect counteracted by dexamethasone, the latter effect being accompanied by inhibition of inducible NO synthase. These results show that LPS plus γIFN 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.
KW - Cytokine
KW - Inflammation
KW - Lipopolysaccaride
KW - Nitric oxide
KW - NMDA
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U2 - 10.1016/j.neulet.2004.09.079
DO - 10.1016/j.neulet.2004.09.079
M3 - Article
C2 - 15619540
AN - SCOPUS:16644388273
VL - 373
SP - 184
EP - 188
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -