Edema induced by a crotalus durissus terrificus venom serine protease (Cdtsp 2) involves the PAR pathway and PKC and PLC activation

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dc.contributorLaboratório de Herpetologiapt_BR
dc.contributor.authorCosta, Caroline R.C.pt_BR
dc.contributor.authorBelchor, Mariana Novopt_BR
dc.contributor.authorFabri, Carolinept_BR
dc.contributor.authorToyama, Daniela de Oliveirapt_BR
dc.contributor.authorde Oliveira, Marcos Antoniopt_BR
dc.contributor.authorNovaes, Danielle P.pt_BR
dc.contributor.authorToyama, Marcos Hikaript_BR
dc.date.accessioned2020-07-09T21:21:20Z-
dc.date.available2020-07-09T21:21:20Z-
dc.date.issued2018-
dc.identifier.citationCosta CR.C., Belchor MN, Fabri C, Toyama DO, de Oliveira MA, Novaes DP., et al. Edema induced by a crotalus durissus terrificus venom serine protease (Cdtsp 2) involves the PAR pathway and PKC and PLC activation. Int. J. Mol. Sci.. 2018 Aug;19(8):2405. doi:10.3390/ijms19082405.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2563-
dc.description.abstractSnake venom serine proteases (SVSPs) represent an essential group of enzymatic toxins involved in several pathophysiological effects on blood homeostasis. Some findings suggest the involvement of this class of enzymatic toxins in inflammation. In this paper, we purified and isolated a new gyroxin isoform from the Crotalus durissus terrificus (Cdt) venom, designated as Cdtsp 2, which showed significant proinflammatory effects in a murine model. In addition, we performed several studies to elucidate the main pathway underlying the edematogenic effect induced by Cdtsp 2. Enzymatic assays and structural analysis (primary structure analysis and three-dimensional modeling) were closely performed with pharmacological assays. The determination of edematogenic activity was performed using Cdtsp 2 isolated from snake venom, and was applied to mice treated with protein kinase C (PKC) inhibitor, phospholipase C (PLC) inhibitor, dexamethasone (Dexa), antagonists for protease-activated receptors (PARs), or saline (negative control). Additionally, we measured the levels of cyclooxygenase 2 (COX-2), malondialdehyde (MDA), and prostaglandin E2 (PGE2). Cdtsp 2 is characterized by an approximate molecular mass of 27 kDa, an isoelectric point (pI) of 4.5, and significant fibrinolytic activity, as well as the ability to hydrolyze Na-benzoyl-L-arginine 4-nitroanilide (BAPNA). Its primary and three-dimensional structures revealed Cdtsp 2 as a typical snake venom serine protease that induces significant edema via the metabolism of arachidonic acid (AA), involving PARs, PKC, PLC, and COX-2 receptors, as well as inducing a significant increase in MDA levels. Our results showed that Cdtsp 2 is a serine protease with significant enzymatic activity, and it may be involved in the degradation of PAR1 and PAR2, which activate PLC and PKC to mobilize AA, while increasing oxidative stress. In this article, we provide a new perspective for the role of SVSPs beyond their effects on blood homeostasis. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.format.extent2405pt_BR
dc.languageengpt_BR
dc.relation.ispartofInternational Journal of Molecular Sciencespt_BR
dc.rightsOpen Accesspt_BR
dc.titleEdema induced by a crotalus durissus terrificus venom serine protease (Cdtsp 2) involves the PAR pathway and PKC and PLC activationpt_BR
dc.typeArticlept_BR
dc.identifier.doi10.3390/ijms19082405pt_BR
dc.identifier.urlhttp://dx.doi.org/10.3390/ijms19082405pt_BR
dc.contributor.externalUniversidade Estadual Paulista Júlio de Mesquita Filho (UNESP)¦¦Brasilpt_BR
dc.identifier.citationvolume19pt_BR
dc.identifier.citationissue8pt_BR
dc.subject.keywordsnake venom serine proteasept_BR
dc.subject.keywordCrotalus durissus terrificus (Cdt)pt_BR
dc.subject.keywordedemapt_BR
dc.subject.keywordinflammationpt_BR
dc.subject.keywordoxidative stresspt_BR
dc.subject.keywordprotease-activated receptorpt_BR
dc.subject.keywordCOX-2pt_BR
dc.subject.keywordMDApt_BR
dc.relation.ispartofabbreviatedInt. J. Mol. Sci.pt_BR
dc.identifier.citationabntv. 19, n. 8, 2405, ago. 2018pt_BR
dc.identifier.citationvancouver2018 Aug;19(8):2405pt_BR
dc.contributor.butantanFabri, Caroline|:Aluno|:Laboratório de Herpetologia|:pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2017/20291-0pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦p2017/19942-7pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
item.openairetypeArticle-
item.fulltextCom Texto completo-
item.grantfulltextembargo_29990101-
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