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Type: Artigo
Title: Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: a role for alpha-actinin nitration
Author: Marcondes, S.
Cardoso, M.H.M.
Antunes, E.
Morganti, R.P.
Thomazzi, S.M.
De Nucci, G.
Lilla, S.
Murad, F.
Abstract: The nitric oxide-mediated actions are mostly due to cyclic GMP (cGMP) formation, but cGMP-independent mechanisms, such as tyrosine nitration, have been suggested as potential signaling pathways modulating the NO-induced responses. However, the mechanisms that lead to tyrosine nitration in platelets are poorly studied, and the protein targets of nitration have not been identified in these cells. Therefore, we have used the model of platelet adhesion to fibrinogen-coated plates to investigate the cGMP-independent mechanisms of the NO-donor sodium nitroprusside (SNP) that leads to inhibition of platelet adhesion. SNP concentration-dependently inhibited platelet adhesion, as observed at 15-min and 60-min adhesion. Additionally, SNP markedly increased the cGMP levels, and the soluble guanylate inhibitor ODQ nearly abolished the SNP-mediated cGMP elevations in all experimental conditions used. Nevertheless, ODQ failed to affect the adhesion inhibition obtained with 1.0 mM SNP at 15 min. On the other hand, superoxide dismutase or peroxynitrite (ONOO-) scavenger epigallocatechin gallate significantly reversed the inhibition of platelet adhesion by SNP (11 mM, 15 min). Western blot analysis in SNP (1 mM, 15 min)-treated platelets showed a single tyrosine-nitrated protein with an apparent mass of approximate to 105 kDa. Nanospray LC-MS/MS identified the human alpha-actinin 1 cytoskeletal isoform (P12814) as the protein contained in the nitrated SIDS gel band. Thus, tyrosine nitration of alpha-actinin, through ONOO- formation, may be a key modulatory mechanism to control platelet adhesion
Subject: Nitroprussiato
Ácido peroxinitroso
Country: Estados Unidos
Editor: National Academy of Sciences
Citation: Proceedings Of The National Academy Of Sciences Of The United States Of America. Natl Acad Sciences, v. 103, n. 9, n. 3434, n. 3439, 2006.
Rights: fechado
Identifier DOI: 10.1073/pnas.0509397103
Date Issue: 2006
Appears in Collections:FCM - Artigos e Outros Documentos

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