Jararhagin, a snake venom metalloproteinase-disintegrin, stimulates epithelial cell migration in an in vitro restitution model

Autor(es)

Costa, Érica Pereira ^[1] ; Santos, Marinilce Fagundes

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo (USP). Instituto de Ciências Biomédicas. Departamento de Biologia Celular e do Desenvolvimento - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 44, n. 8, p. 861-870, Oct. 2004.
• Área do conhecimento: Ciências Biológicas - Morfologia
• Assunto(s): Metaloproteinases Integrinas Movimento celular Venenos de origem animal

Resumo

The snake venom metalloproteinase-disintegrin jararhagin (JG) has no chemotactic activity but stimulates the migration of neutrophils in vivo through a mechanism still unclear. In this study we investigated the effects of jararhagin on epithelial cell adhesion and migration in vitro. F-actin arrangement and the distribution of laminin, fibronectin, several integrins and phosphorylated Focal Adhesion Kinase (FAK) were studied using rhodamine-phalloidin and immunofluorescence. Maximum stimulation of migration (about 100%) was obtained with 5 µg/ml JG, with about 38% inhibition of cellular adhesion. In migratory cells the toxin stimulated the formation of filopodia, lamellipodia and stress fibers. The pericellular fibronectin matrix was lost in migrating cells, while laminin was less affected. The toxin stimulated FAK phosphorylation and the recruitment of av-containing integrins to focal contacts, whereas integrins containing the a2 subunit were reduced in these junctions. Inactivation of the toxin with 1,10 phenanthroline showed that the catalytic activity is important for the effect of jararhagin on cell migration, FAK phosphorylation and for the recruitment of av, but not as much for the anti-adhesive effect. In conclusion, jararhagin stimulates the migration of epithelial cells in vitro through a mechanism that involves its proteolytic activity, qualitative changes in cellular adhesion and the formation of actin-rich cellular processes. (AU)

• Processo FAPESP: 97/09507-6 - Estudo da expressao de diferentes receptores para matriz extracelular durante a morfogenese e diferenciacao da glandula submandibular de ratos.
• Beneficiário: Marinilce Fagundes dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/09047-2 - Desenvolvimento e degeneração da retina de vertebrados: aspectos celulares e moleculares
• Beneficiário: Dania Emi Hamassaki
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 00/12769-7 - Efeitos da toxina jararagina de (Bothrops jararaca) sobre a adesão e migração celulares
• Beneficiário: Érica Pereira da Costa
• Modalidade de apoio: Bolsas no Brasil - Doutorado