Bothrops jararaca venom metalloproteinases are essential for coagulopathy and incr...
| Full text | |
| Author(s): |
Sartim, Marco A.
;
Cezarette, Gabriel N.
;
Jacob-Ferreira, Anna L.
;
Frantz, Fabiani G.
;
Faccioli, Lucia H.
;
Sampaio, Suely V.
Total Authors: 6
|
| Document type: | Journal article |
| Source: | International Journal of Biological Macromolecules; v. 103, p. 1077-1086, OCT 2017. |
| Web of Science Citations: | 3 |
| Abstract | |
Snake venom toxins that activate coagulation factors are key players in the process of venom-induced coagulopathy, and account for severe clinical manifestations. The present study applies a variety of biochemical, hematological, and histopathological approaches to broadly investigate the intravascular and systemic effects of moojenactivase (MooA), the first described Mild subclass metalloprotease isolated from Bothrops sp. venom that activates coagulation factors. MooA induced consumption coagulopathy with high toxic potency, characterized by prolongation of prothrombin and activated partial thromboplastin time, consumption of fibrinogen and the plasma coagulation factors X and II, and thrombocytopenia. MooA promoted leukocytosis and expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, accompanied by tissue factor-dependent procoagulant activity in peripheral blood mononuclear cells. This metalloprotease also caused intravascular hemolysis, elevated plasma levels of creatine kinase-MB, aspartate transaminase, and urea/creatinine, and induced morphopathological alterations in erythrocytes, heart, kidney, and lungs associated with thrombosis and hemorrhage. Diagnosis of MooA-induced disseminated intravascular coagulation represents an important approach to better understand the pathophysiology of Bothrops envenomation and develop novel therapeutic strategies targeting hemostatic disturbances. (C) 2017 Published by Elsevier B.V. (AU) | |
| FAPESP's process: | 15/06290-6 - Evaluation of anti-inflammatory potential of crotoxin, a phospholipase A2 isolated from Crotalus durissus terrificus venom, in a disseminated intravascular coagulation model induced by endotoxemia |
| Grantee: | Marco Aurélio Sartim |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| FAPESP's process: | 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis |
| Grantee: | Suely Vilela |
| Support type: | Research Projects - Thematic Grants |