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dc.creatorMoreira, Vanessa
dc.creatorde Castro Souto, Pollyana Cristina Maggio
dc.creatorRamirez Vinolo, Marco Aurélio
dc.creatorLomonte, Bruno
dc.creatorGutiérrez, José María
dc.creatorCuri, Rui
dc.creatorTeixeira, Catarina de Fátima
dc.date.accessioned2018-04-25T17:04:37Z
dc.date.available2018-04-25T17:04:37Z
dc.date.issued2013-05-15
dc.identifier.citationhttps://www.sciencedirect.com/science/article/pii/S0014299913000927es_ES
dc.identifier.issn0014-2999
dc.identifier.urihttp://hdl.handle.net/10669/74504
dc.description.abstractThe effects of a snakevenom Lys-49phospholipaseA2 (PLA2) homolog named MT-II,devoid of enzymatic activity, on the biosynthesis of prostaglandins and protein expression of cyclooxygenase-2(COX-2) and signaling pathways involved were evaluated in mouse macrophages in culture and in peritoneal cells ex vivo. Stimulation of macrophages wit hMT-II leads to production of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) and protein expression of COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1). Inhibition of cytosolic PLA2 (cPLA2), but not Ca2+ independent PLA2 (iPLA2) reduced release of PGD2 and PGE2 and expression of COX-2induced by MT-II. Inhibition of nuclear factor kB (NF-kB) significantly reduced MT-II-induced PGE2, but not PGD2 production and COX-2 expression. Inhibitors of either proteinkinase C (PKC), proteintyrosinekinase (PTK),or extracellular signal-regulated kinase(ERK) pathways abrogated MT-II-induced NF-kB activation and reduced COX-2 expression and PGE2 release, whereas the p38 mitogen-activated protein kinase (MAPK) inhibit or reduced MT-II-induced COX-2 expression and PGD2 production.Inhibition of phosphatidylinositol-3-kinase (PI3K) pathway abrogated MT-II-induced NF-kB activation,but affected neither prostaglandins production nor COX-2expression.MT-II-induced production of PGD2 and PGE2 and COX-2 expression were also observed in vivo after intraperitoneal injection into mice. Collectively,our data demonstrate that a catalytically-inactivePLA2 homolog is capable of inducing prostaglandins biosynthesis and COX-2expression in macrophages in both in vitro and in vivo models,indicating that the enzymatic activity of PLA2 is not necessary to trigger these effects. MT-II-activated NF-kB, cPLA2 and distinct protein kinases are the principal steps involved in these cellular events.es_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo/[02/13863-2]/FAPESP/Brasiles_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo/[07/03336-9]/FAPESP/Brasiles_ES
dc.description.sponsorshipInstituto Nacional de Ciência e Tecnologia em Toxinas/[2008/57898-0]/INCT-TOX/Brasiles_ES
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico/[306099/2008-0]/CNPq/Brasiles_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo/[07/03337-5]/FAPESP/Brasiles_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo/[06/58341-4]/FAPESP/Brasiles_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo/[10/07630-1]/FAPESP/Brasiles_ES
dc.language.isoen_USes_ES
dc.sourceEuropean Journal of Pharmacology 708, 68-79 (2013)es_ES
dc.subjectSnake venom sPLA2 homologes_ES
dc.subjectProstaglandines_ES
dc.subjectCyclooxygenasees_ES
dc.subjectMacrophagees_ES
dc.subjectSignaling pathwayes_ES
dc.subjectNF-kBes_ES
dc.subjectSnake venomes_ES
dc.titleA catalytically-inactive snake venom Lys49 phospholipase A2 homolog induces expression of cyclooxygenase-2 and production of prostaglandins through selected signaling pathways in macrophageses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1016/j.ejphar.2013.01.061
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.pmid23416211


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