Leucurogin, a new recombinant disintegrin cloned from Bothrops leucurus (white-tailed-jararaca) with potent activity upon platelet aggregation and tumor growth

• Autor(a) principal: Higuchi, D. A.
• Data de Publicação: 2011
• Outros Autores: Almeida, M. C., Barros, C. C., Sanchez, E. F., Pesquero, P. R., Lang, E. A. S., Samaan, M., Araujo, Ronaldo Carvalho [UNIFESP], Pesquero, João Bosco [UNIFESP], Pesquero, J. L.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1016/j.toxicon.2011.05.013; http://repositorio.unifesp.br/handle/11600/33821
• topic: Disintegrins; Bothrops leucurus; Platelet aggregation; Tumor growth

Disintegrins and disintegrins-like proteins are able to inhibit platelet aggregation and integrin-mediated cell adhesion. the aim of this study was to produce one disintegrin-like cloned from Bothrops leucurus venom gland and to characterize it regarding biological activity. the recombinant protein was purified by one step procedure involving anion-exchange chromatography (DEAE-cellulose) and presented a molecular mass of 10.4 kDa. the purified protein was able to inhibit platelet aggregation induced by collagen (IC(50) = 0.65 mu M) and to inhibit growth of Ehrlich tumor implanted in mice by more than 50% after 7 days administration of 10 mu g/day. No effects were observed upon adenosine 5'diphosphate (ADP)-and arachidonic acid (AA)-induced platelet aggregation. the recombinant protein was recognized by an antibody specific for jararhagin one metalloproteinase isolated from Bothrops jararaca venom, and therefore it was named leucurogin. Anti-angiogenesis effect of leucurogin was evaluated by the sponge implant model. After 7 days administration leucurogin inhibited, in a dose dependent way, the vascularization process in the sponge. Leucurogin represents a new biotechnological tool to understand biological processes where disintegrins-like are involved and may help to characterize integrins that can be involved in development and progression of malignant cells. (C) 2011 Elsevier B.V. All rights reserved.