The role of superoxide anion in the inhibitory effect of SIN-1 in thrombin-activated human platelet adhesion

dc.creatorCardoso, MHM
dc.creatorMorganti, RP
dc.creatorLilla, S
dc.creatorMurad, F
dc.creatorDe Nucci, G
dc.creatorAntunes, E
dc.creatorMarcondes, S
dc.date2010
dc.dateFEB 10
dc.date2014-11-16T06:49:50Z
dc.date2015-11-26T16:20:46Z
dc.date2014-11-16T06:49:50Z
dc.date2015-11-26T16:20:46Z
dc.date.accessioned2018-03-28T23:03:05Z
dc.date.available2018-03-28T23:03:05Z
dc.identifierEuropean Journal Of Pharmacology. Elsevier Science Bv, v. 627, n. 41699, n. 229, n. 234, 2010.
dc.identifier0014-2999
dc.identifierWOS:000274093800034
dc.identifier10.1016/j.ejphar.2009.10.060
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/72404
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/72404
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/72404
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1267864
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionReactive oxygen species have an important role in the control of platelet activity. Superoxide anion (O(2)(-)) is a free radical that can be converted into other reactive oxygen species such as peroxynitrite (ONOO(-)) that is formed from the reaction between O(2)(-) and nitric oxide (NO). There are conflicting data on ONOO(-) effects in platelets because it presents pro- or anti-aggregatory actions. 3-morpholinosydnonimine (SIN-1) co-generates NO and O(2)(-), yielding ONOO(-). Therefore, the present study aimed to investigate the mechanisms involved in the inhibition of human platelet adhesion by SIN-1. Microtiter plates were coated with human fibrinogen, after which washed platelets (6 x 10(8) platelets/ml) were added to adhere. Exposure of non-activated and thrombin-activated platelets to SIN-1 (0.001-100 mu M) concentration-dependently inhibited adhesion, which was accompanied by marked increases in the cyclic GMP levels. In non-activated platelets, the soluble guanylate cyclase inhibitor ODQ prevented the SIN-1 -induced cGMP elevations and adhesion inhibition. In thrombin-activated platelets, ODQ fully prevented the SIN-1-induced cGMP elevations, but only partly prevented the adhesion inhibition. The O(2)(-) and ONOO(-) scavengers superoxide dismutase (SOD) and -(-)epigallocatechin gallate, respectively, had minimal effects in non-activated platelets. The inhibition of activated platelets by SIN-1 1 was reversed by SOD and partly reduced by ECG. Western blot analysis of SIN-1-treated platelets showed a single 105 kDa-nitrated band. Nanospray LC-MS-MS identified the protein containing 3-nitrotyrosine residues as human alpha-actinin-1-cytoskeletal isoform. Our data show that platelet adhesion inhibition by SIN-1 in activated platelets involves cGMP-independent mechanism through O(2)(-) generation. Superoxide anion signaling pathway includes ONOO(-) formation and alpha-actinin nitration. Published by Elsevier B.V.
dc.description627
dc.description41699
dc.description229
dc.description234
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageen
dc.publisherElsevier Science Bv
dc.publisherAmsterdam
dc.publisherHolanda
dc.relationEuropean Journal Of Pharmacology
dc.relationEur. J. Pharmacol.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subject3-Morpholinosydnonimine (SIN-1)
dc.subjectNitration
dc.subjectPeroxynitrite
dc.subjectPlatelets
dc.subjectSuperoxide anion
dc.subjectCgmp-independent Mechanisms
dc.subjectSensitive Guanylyl Cyclase
dc.subjectNitric-oxide Donor
dc.subjectAlpha-actinin
dc.subjectTyrosine Nitration
dc.subjectCytoplasmic Domain
dc.subjectBlood-platelets
dc.subjectPeroxynitrite
dc.subjectAggregation
dc.subjectRelease
dc.titleThe role of superoxide anion in the inhibitory effect of SIN-1 in thrombin-activated human platelet adhesion
dc.typeArtículos de revistas


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