Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation
| العنوان: | 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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| المؤلفون: | Danielle P. Novaes, Caroline Fabri Bittencourt Rodrigues, Marcos Antonio de Oliveira, Caroline R. C. Costa, Marcos H. Toyama, Daniela de Oliveira Toyama, Mariana Novo Belchor |
| المساهمون: | Universidade Estadual Paulista (Unesp), Instituto Butantan |
| المصدر: | International Journal of Molecular Sciences, Vol 19, Iss 8, p 2405 (2018) Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP International Journal of Molecular Sciences Volume 19 Issue 8 |
| بيانات النشر: | MDPI AG, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, protease-activated receptor, Proteases, Protease-activated receptor, MDA, Venom, Pharmacology, Crotalus durissus terrificus (Cdt), Catalysis, Inorganic Chemistry, Serine, lcsh:Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Edema, oxidative stress, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Protein kinase C, Serine protease, Inflammation, Phospholipase C, biology, Chemistry, Organic Chemistry, Snake venom serine protease, General Medicine, snake venom serine protease, COX-2, Computer Science Applications, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Snake venom, Oxidative stress, inflammation, biology.protein, Arachidonic acid, edema |
| الوصف: | Snake 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 N&alpha 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62aee9457e7544dcd2abd6bd093ada96 http://www.mdpi.com/1422-0067/19/8/2405 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....62aee9457e7544dcd2abd6bd093ada96 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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