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Rhomb-I, a P-I metalloproteinase from Lachesis muta rhombeata venom degrades vessel extra cellular matrix components and impairs platelet aggregation.
de Alvarenga, Valéria Gonçalves; Oliveira, Luciana S; Santos, Gustavo O; Vivas-Ruiz, Dan E; Borges, Márcia Helena; de Souza, Rodrigo C G; Eble, Johannes A; Moura-da-Silva, Ana Maria; Sanchez, Eladio F.
Afiliação
  • de Alvarenga VG; Laboratório de Bioquímica de Proteínas de Venenos Animais, Fundação Ezequiel Dias, Belo Horizonte, Brazil.
  • Oliveira LS; Laboratório de Bioquímica de Proteínas de Venenos Animais, Fundação Ezequiel Dias, Belo Horizonte, Brazil.
  • Santos GO; Laboratório de Bioquímica de Proteínas de Venenos Animais, Fundação Ezequiel Dias, Belo Horizonte, Brazil.
  • Vivas-Ruiz DE; Laboratório de Biologia Molecular, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • Borges MH; Laboratório de Proteômica e Aracnídeos, Fundação Ezequiel Dias, Belo Horizonte, Brazil.
  • de Souza RCG; Serra Grande Center, Itacaré, Bahia, Brazil.
  • Eble JA; Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Germany.
  • Moura-da-Silva AM; Laboratório de Imunopatologia, Instituto Butantan, São Paulo, Brazil.
  • Sanchez EF; Laboratório de Bioquímica de Proteínas de Venenos Animais, Fundação Ezequiel Dias, Belo Horizonte, Brazil. Electronic address: eladio.flores@funed.mg.gov.br.
Toxicon ; 228: 107097, 2023 Jun 01.
Article em En | MEDLINE | ID: mdl-37028563
ABSTRACT
Rhomb-I, a 23-kDa metalloproteinase was isolated from L. m. rhombeata venom. Its dimethylcasein proteolysis was abolished by metal chelators, and slightly enhanced by Ca2+ and Mg2+ ions, but inhibited by Co2+, Zn2+ and α2-macroglobulin. In aqueous solution, rhomb-I autoproteolyzed to a 20- and 11-kDa fragments at 37 °C. The amino acid sequence showed high homology with other snake venom metalloproteinases. Rhomb-I causes hemorrhage that may be ascribed to hydrolysis of essential basement membrane, extracellular matrix and plasma proteins. It preferentially cleaves the α-chains of fibrin (ogen). Rhomb-I inhibited convulxin- and von Willebrand factor (vWF)-induced aggregation on human platelets without significant effect on collagen-stimulated aggregation or other effectors. It digests vWF into a low-molecular-mass multimers of vWF and a rvWF-A1 domain to a 27-kDa fragment as revealed by western blotting with mouse anti-rvWF A1-domain IgG. Incubation of platelets with rhomb-I resulted in adhesion to and cleavage of platelet receptors glycoprotein (GP)Ibα and GPVI to release a 55-kDa soluble form. Both membrane glycoproteins GPIbα that binds vWF, together with GPVI which binds collagen, play a key role in mediating platelet adhesion/activation and can initiate (patho)physiological thrombus formation.

Conclusions:

rhomb-I is implicated in the pathophysiology of Lachesis envenoming by disrupting vasculature, hemostasis and platelet aggregation through impairing vWF-GPIb axis and blocking GPVI-collagen binding.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de von Willebrand / Agregação Plaquetária Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de von Willebrand / Agregação Plaquetária Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article