dc.creator | Moreira, Vanessa | |
dc.creator | de Castro Souto, Pollyana Cristina Maggio | |
dc.creator | Ramirez Vinolo, Marco Aurélio | |
dc.creator | Lomonte, Bruno | |
dc.creator | Gutiérrez, José María | |
dc.creator | Curi, Rui | |
dc.creator | Teixeira, Catarina de Fátima | |
dc.date.accessioned | 2018-04-25T17:04:37Z | |
dc.date.available | 2018-04-25T17:04:37Z | |
dc.date.issued | 2013-05-15 | |
dc.identifier.citation | https://www.sciencedirect.com/science/article/pii/S0014299913000927 | |
dc.identifier.issn | 0014-2999 | |
dc.identifier.uri | https://hdl.handle.net/10669/74504 | |
dc.description.abstract | The 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.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo/[02/13863-2]/FAPESP/Brasil | es_ES |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo/[07/03336-9]/FAPESP/Brasil | es_ES |
dc.description.sponsorship | Instituto Nacional de Ciência e Tecnologia em Toxinas/[2008/57898-0]/INCT-TOX/Brasil | es_ES |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico/[306099/2008-0]/CNPq/Brasil | es_ES |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo/[07/03337-5]/FAPESP/Brasil | es_ES |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo/[06/58341-4]/FAPESP/Brasil | es_ES |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo/[10/07630-1]/FAPESP/Brasil | es_ES |
dc.language.iso | en_US | es_ES |
dc.source | European Journal of Pharmacology 708, 68-79 (2013) | es_ES |
dc.subject | Snake venom sPLA2 homolog | es_ES |
dc.subject | Prostaglandin | es_ES |
dc.subject | Cyclooxygenase | es_ES |
dc.subject | Macrophage | es_ES |
dc.subject | Signaling pathway | es_ES |
dc.subject | NF-kB | es_ES |
dc.subject | Snake venom | es_ES |
dc.title | A catalytically-inactive snake venom Lys49 phospholipase A2 homolog induces expression of cyclooxygenase-2 and production of prostaglandins through selected signaling pathways in macrophages | es_ES |
dc.type | artículo original | |
dc.identifier.doi | 10.1016/j.ejphar.2013.01.061 | |
dc.description.procedence | UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) | es_ES |
dc.identifier.pmid | 23416211 | |