Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes

Autor(es):Mostrar menos -

Sartim, Marco A. ^[1] ; Costa, Tassia R. ^[1] ; Laure, Helen J. ^{[2, 3]} ; Espindola, Milena S. ^[1] ; Frantz, Fabiani G. ^[1] ; Sorgi, Carlos A. ^[1] ; Cintra, Adelia C. O. ^[1] ; Arantes, Eliane C. ^[4] ; Faccioli, Lucia H. ^[1] ; Rosa, Jose C. ^{[2, 3]} ; Sampaio, Suely V. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ctr Quim Prot, Fac Med Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Fis & Quim, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF TOXICOLOGY; v. 90, n. 5, p. 1261-1278, MAY 2016.
• Citações Web of Science: 8

Resumo

Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated alpha-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-alpha, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders. (AU)

• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático