Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109901
DC Field | Value | Language |
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dc.contributor.author | Simões, Ana Patrícia | - |
dc.contributor.author | Duarte, João A | - |
dc.contributor.author | Agasse, Fabienne | - |
dc.contributor.author | Canas, Paula M. | - |
dc.contributor.author | Tomé, Ângelo R. | - |
dc.contributor.author | Agostinho, Paula | - |
dc.contributor.author | Cunha, Rodrigo A. | - |
dc.date.accessioned | 2023-11-06T10:02:14Z | - |
dc.date.available | 2023-11-06T10:02:14Z | - |
dc.date.issued | 2012-08-20 | - |
dc.identifier.issn | 1742-2094 | pt |
dc.identifier.uri | http://hdl.handle.net/10316/109901 | - |
dc.description.abstract | Background and purpose: Blockade of adenosine A2A receptors (A2AR) affords robust neuroprotection in a number of brain conditions, although the mechanisms are still unknown. A likely candidate mechanism for this neuroprotection is the control of neuroinflammation, which contributes to the amplification of neurodegeneration, mainly through the abnormal release of pro-inflammatory cytokines such as interleukin(IL)-1β. We investigated whether A2AR controls the signaling of IL-1β and its deleterious effects in cultured hippocampal neurons. Methods: Hippocampal neuronal cultures were treated with IL-1β and/or glutamate in the presence or absence of the selective A2AR antagonist, SCH58261 (50 nmol/l). The effect of SCH58261 on the IL-1β-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK) and p38 was evaluated by western blotting and immunocytochemistry. The effect of SCH58261 on glutamate-induced neurodegeneration in the presence or absence of IL-1β was evaluated by nucleic acid and by propidium iodide staining, and by lactate dehydrogenase assay. Finally, the effect of A2AR blockade on glutamate-induced intracellular calcium, in the presence or absence of IL-1β, was studied using single-cell calcium imaging. Results: IL-1β (10 to 100 ng/ml) enhanced both JNK and p38 phosphorylation, and these effects were prevented by the IL-1 type 1 receptor antagonist IL-1Ra (5 μg/ml), in accordance with the neuronal localization of IL-1 type 1 receptors, including pre-synaptically and post-synaptically. At 100 ng/ml, IL-1β failed to affect neuronal viability but exacerbated the neurotoxicity induced by treatment with 100 μmol/l glutamate for 25 minutes (evaluated after 24 hours). It is likely that this resulted from the ability of IL-1β to enhance glutamate-induced calcium entry and late calcium deregulation, both of which were unaffected by IL-1β alone. The selective A2AR antagonist, SCH58261 (50 nmol/l), prevented both the IL-1β-induced phosphorylation of JNK and p38, as well as the IL-1β-induced deregulation of calcium and the consequent enhanced neurotoxicity, whereas it had no effect on glutamate actions. Conclusions: These results prompt the hypothesis that the neuroprotection afforded by A2AR blockade might result from this particular ability of A2AR to control IL-1β-induced exacerbation of excitotoxic neuronal damage, through the control of MAPK activation and late calcium deregulation. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | POCTI/BIA-BCM-59980/2004 | pt |
dc.relation | PTDC/SAU-NEU-108668/2008 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Adenosine | pt |
dc.subject | A2A receptor | pt |
dc.subject | Interleukin 1β | pt |
dc.subject | Neurodegeneration | pt |
dc.subject | p38 MAPK | pt |
dc.subject | Calcium | pt |
dc.subject.mesh | Adenosine A2 Receptor Antagonists | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Cells, Cultured | pt |
dc.subject.mesh | Female | pt |
dc.subject.mesh | Interleukin-1beta | pt |
dc.subject.mesh | MAP Kinase Signaling System | pt |
dc.subject.mesh | Male | pt |
dc.subject.mesh | Neurons | pt |
dc.subject.mesh | Pregnancy | pt |
dc.subject.mesh | Pyrimidines | pt |
dc.subject.mesh | Rats | pt |
dc.subject.mesh | Rats, Wistar | pt |
dc.subject.mesh | Receptor, Adenosine A2A | pt |
dc.subject.mesh | Triazoles | pt |
dc.subject.mesh | p38 Mitogen-Activated Protein Kinases | pt |
dc.title | Blockade of adenosine A2A receptors prevents interleukin-1β-induced exacerbation of neuronal toxicity through a p38 mitogen-activated protein kinase pathway | pt |
dc.type | article | - |
degois.publication.firstPage | 204 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Journal of Neuroinflammation | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1186/1742-2094-9-204 | pt |
degois.publication.volume | 9 | pt |
dc.date.embargo | 2012-08-20 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-8671-989X | - |
crisitem.author.orcid | 0000-0001-5523-4945 | - |
crisitem.author.orcid | 0000-0003-2550-6422 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FCTUC Ciências da Vida - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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Blockade of adenosine A2A receptors prevents interleukin-1β-induced exacerbation of neuronal toxicity through a p38 mitogen-activated protein kinase pathway.pdf | 1.85 MB | Adobe PDF | View/Open |
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