Interleukin-1β Enhances NMDA Receptor-Mediated Intracellular Calcium Increase through Activation of the Src Family of Kinases
| Autor: | M. Di Luca, M. Margarita Behrens, Annamaria Vezzani, Stefano Bartesaghi, Barbara Viviani, Marina Marinovich, C. L. Galli, M. Binaglia, Fabrizio Gardoni, Tamas Bartfai, Emanuela Corsini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Intracellular Fluid
medicine.medical_specialty N-Methylaspartate medicine.drug_class Sialoglycoproteins Excitotoxicity Biology medicine.disease_cause Receptors N-Methyl-D-Aspartate chemistry.chemical_compound Internal medicine medicine Excitatory Amino Acid Agonists Animals Enzyme Inhibitors Phosphorylation Cells Cultured Neurons Cell Death Dose-Response Relationship Drug Kinase General Neuroscience Tyrosine phosphorylation Drug Synergism Receptor antagonist Molecular biology Rats Enzyme Activation Interleukin 1 Receptor Antagonist Protein Endocrinology src-Family Kinases chemistry nervous system NMDA receptor Calcium Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src Cellular/Molecular Interleukin-1 |
| Zdroj: | Scopus-Elsevier |
| Popis: | Interleukin (IL)-1β is a proinflammatory cytokine implicated in various pathophysiological conditions of the CNS involving NMDA receptor activation. Circumstantial evidence suggests that IL-1β and NMDA receptors can functionally interact. Using primary cultures of rat hippocampal neurons, we investigated whether IL-1β affects NMDA receptor function(s) by studying (1) NMDA receptor-induced [Ca2+]iincrease and (2) NMDA-mediated neurotoxicity. IL1β (0.01-0.1 ng/ml) dose-dependently enhances NMDA-induced [Ca2+]iincreases with a maximal effect of ∼45%. This effect occurred only when neurons were pretreated with IL-1β, whereas it was absent if IL-1β and NMDA were applied simultaneously, and it was abolished by IL-1 receptor antagonist (50 ng/ml). Facilitation of NMDA-induced [Ca2+]iincrease by IL-1β was prevented by both lavendustin (LAV) A (500 nm) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) (1 μm), suggesting an involvement of tyrosine kinases. Increased tyrosine phosphorylation of NMDA receptor subunits 2A and 2B and coimmunoprecipitation of activated Src tyrosine kinase with these subunits was observed after exposure of hippocampal neurons to 0.05 ng/ml IL-1β. Finally, 0.05 ng/ml IL-1β increased by ∼30% neuronal cell death induced by NMDA, and this effect was blocked by both lavendustin A and PP2.These data suggest that IL-1β increases NMDA receptor function through activation of tyrosine kinases and subsequent NR2A/B subunit phosphorylation. These effects may contribute to glutamate-mediated neurodegeneration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|