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.contributor.authorCosta, Caroline R. C. [UNESP]
dc.contributor.authorBelchor, Mariana Novo [UNESP]
dc.contributor.authorRodrigues, Caroline F. B.
dc.contributor.authorToyama, Daniela de Oliveira [UNESP]
dc.contributor.authorde Oliveira, Marcos A. [UNESP]
dc.contributor.authorNovaes, Danielle P. [UNESP]
dc.contributor.authorToyama, Marcos Hikari [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionInstituto Butantan
dc.date.accessioned2018-12-11T17:38:15Z
dc.date.available2018-12-11T17:38:15Z
dc.date.issued2018-08-15
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 Nα-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.en
dc.description.affiliationInstitute of Biosciences Coastal Campus BIOMOLPEP São Paulo State University (UNESP)
dc.description.affiliationInstituto Butantan
dc.description.affiliationInstitute of Biosciences Coastal Campus LABIMES São Paulo State University (UNESP)
dc.description.affiliationUnespInstitute of Biosciences Coastal Campus BIOMOLPEP São Paulo State University (UNESP)
dc.description.affiliationUnespInstitute of Biosciences Coastal Campus LABIMES São Paulo State University (UNESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipUniversidade Estadual Paulista
dc.description.sponsorshipIdFAPESP: 2017/20291-0
dc.description.sponsorshipIdFAPESP: p2017/19942-7
dc.identifierhttp://dx.doi.org/10.3390/ijms19082405
dc.identifier.citationInternational Journal of Molecular Sciences, v. 19, n. 8, 2018.
dc.identifier.doi10.3390/ijms19082405
dc.identifier.file2-s2.0-85052097829.pdf
dc.identifier.issn1422-0067
dc.identifier.issn1661-6596
dc.identifier.lattes8573195327542061
dc.identifier.scopus2-s2.0-85052097829
dc.identifier.urihttp://hdl.handle.net/11449/180122
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.ispartofsjr1,260
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectCOX-2
dc.subjectCrotalus durissus terrificus (Cdt)
dc.subjectEdema
dc.subjectInflammation
dc.subjectMDA
dc.subjectOxidative stress
dc.subjectProtease-activated receptor
dc.subjectSnake venom serine protease
dc.titleEdema induced by a crotalus durissus terrificus venom serine protease (Cdtsp 2) involves the PAR pathway and PKC and PLC activationen
dc.typeArtigo
unesp.advisor.lattes8573195327542061

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Artigos - Ciências Biológicas - São Vicente