| Texto completo | |
| Autor(es): |
Martins, Antonio H.
[1, 2]
;
Alves, Janaina M.
[3]
;
Perez, Dinely
[2]
;
Carrasco, Marimee
[2]
;
Torres-Rivera, Wilmarie
[2]
;
Eterovic, Vesna A.
[2]
;
Ferchmin, Pedro A.
[2]
;
Ulrich, Henning
[1]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo - Brazil
[2] Univ Cent Caribe, Dept Biochem, Bayamon, PR - USA
[3] Univ Fed Sao Paulo, Dept Neurol Neurocirurgia, Sao Paulo - Brazil
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PLoS One; v. 7, n. 2 FEB 10 2012. |
| Citações Web of Science: | 22 |
| Resumo | |
Background: Kinins, with bradykinin and des-Arg(9)-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg(9)-bradykinin as well as Lys-des-Arg(9)-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-Daspartate (NMDA)-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. Principal Findings: Bradykinin at 10 nM and 1 mu M concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg(9)-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spike recovery. The inhibition of population spikes recovery was reversed by PD98059,showing that MEK/MAPK was involved in the induction of apoptosis mediated by the B1 receptor. Conclusions: Bradykinin exerted protection against NMDA-induced excitotoxicity which is reversed in the presence of a kinin-B1 receptor agonist. As bradykinin is converted to the kinin-B1 receptor metabolite des-Arg(9)-bradykinin by carboxypeptidases, present in different areas including in brain, our results provide a mechanism for the neuroprotective effect in vitro despite of the deleterious effect observed in vivo. (AU) | |
| Processo FAPESP: | 06/61285-9 - Bases moleculares da diferenciação de células-tronco e progenitoras neurais |
| Beneficiário: | Alexander Henning Ulrich |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |