Catalytically active phospholipase A2 myotoxin from Crotalus durissus terrificus induces proliferation and differentiation of myoblasts dependent on prostaglandins produced by both COX-1 and COX-2 pathways

2021 ◽  
Author(s):  
Nadine C. Silva ◽  
Angela M. Alvarez ◽  
Carlos DeOcesano-Pereira ◽  
Consuelo L. Fortes-Dias ◽  
Vanessa Moreira
Keyword(s):  
Phospholipase A2 ◽  
Crotalus Durissus Terrificus ◽  
Proliferation And Differentiation ◽  
Catalytically Active ◽  
Cox 2 ◽  
Crotalus Durissus ◽  
Cox 1

scholarly journals Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation

2018 ◽  
Vol 19 (8) ◽  
pp. 2405 ◽  
Author(s):  
Caroline Costa ◽  
Mariana Belchor ◽  
Caroline Rodrigues ◽  
Daniela Toyama ◽  
Marcos de Oliveira ◽  
...  
Keyword(s):  
Serine Protease ◽  
Snake Venom ◽  
Serine Proteases ◽  
Three Dimensional ◽  
Negative Control ◽  
Protease Activated Receptors ◽  
Crotalus Durissus Terrificus ◽  
Three Dimensional Modeling ◽  
Cox 2 ◽  
Crotalus Durissus

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 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.

Fast and efficient procedure for purification of secretory phospholipase A2 (SPLA2) from Crotalus durissus terrificus venom using a solid phase extraction

Toxicon ◽  
2020 ◽  
Vol 177 ◽  
pp. S49
Author(s):  
Airam Roggero dos Santos Silva ◽  
Laila Lucyane Ferreira de Moraes ◽  
Mariana Novo Belchor ◽  
Caroline R.C. Costa ◽  
Danielle P. Novaes ◽  
...  
Keyword(s):  
Solid Phase Extraction ◽  
Phospholipase A2 ◽  
Solid Phase ◽  
Phase Extraction ◽  
Secretory Phospholipase A2 ◽  
Efficient Procedure ◽  
Crotalus Durissus Terrificus ◽  
Secretory Phospholipase ◽  
Crotalus Durissus

Phospholipase A2 injection in mice induces immunity against the lethal effects of Crotalus durissus terrificus venom

Toxicon ◽  
1988 ◽  
Vol 26 (2) ◽  
pp. 207-213 ◽  
Author(s):  
M.C. dos Santos ◽  
C.R. Diniz ◽  
M.A. Whitaker Pacheco ◽  
W. Dias da Silva
Keyword(s):  
Phospholipase A2 ◽  
Lethal Effects ◽  
Crotalus Durissus Terrificus ◽  
Crotalus Durissus

scholarly journals Crotalus durissus ruruima Snake Venom and a Phospholipase A2 Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ana Eduarda Zulim de Carvalho ◽  
Karina Giannotti ◽  
Elbio Leiguez Junior ◽  
Márcio Matsubara ◽  
Maria Cristina Dos Santos ◽  
...  
Keyword(s):  
Snake Venom ◽  
Inflammatory Mediators ◽  
Lipid Droplets ◽  
Lipid Mediators ◽  
Immunological Responses ◽  
Inflammatory Stimuli ◽  
Cox 2 ◽  
Crotalus Durissus ◽  
Cox 1

Viper snake Crotalus durissus ruruima (Cdr) is a subspecies found in northern area of Brazil. Among the snakes of Crotalus genus subspecies, the venom of Cdr presents highest level of crotoxin, which is the major component of Crotalus snake venoms, formed by two subunits (crotapotin and a phospholipase A2 named CBr) and presents potent neurotoxic activity. Curiously, the venom of C. d. ruruima (CdrV) is better neutralized by antibothropic than by anticrotalic serum, strongly suggesting that this venom has similarities with venom of Bothrops genus snakes with regard to the ability to induce inflammation. Macrophages are cells with a central role in inflammatory and immunological responses. Upon inflammatory stimuli, these cells exhibit increased numbers of lipid droplets, which are key organelles in the synthesis and release of inflammatory mediators. However, the effects of CdrV and CBr in macrophage functions are unknown. We herein investigated the ability of CdrV and CBr to activate macrophages with focus on the formation of lipid droplets (LDs), synthesis of lipid mediators, and mechanisms involved in these effects. The involvement of LDs in PGE2 biosynthesis was also assessed. Stimulation of murine macrophages with CdrV and CBr induced an increased number of LDs and release of prostanoids (PGE2, PGD2, and TXB2). Neither CdrV nor CBr induced the expression of COX-1 and COX-2 by macrophages. LDs induced by both CdrV and CBr are associated to PLIN2 recruitment and expression and were shown to be dependent on COX-1, but not COX-2 activity. Moreover, PGE2 colocalized to CdrV- and CBr-induced LDs, revealing the role of these organelles as sites for the synthesis of prostanoids. These results evidence, for the first time, the ability of a whole snake venom to induce formation of LDs and the potential role of these organelles for the production of inflammatory mediators during envenomation by Crotalus snakes.

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