Alternagin-C, a disintegrin-like protein, induces vascular endothelial cell growth factor (VEGF) expression and endothelial cell proliferation in vitro

Autor(es)

Cominetti, Márcia R. ^[1] ; Terruggi, Cristina H. B. ; Ramos, Oscar H. P. ; Fox, Jay W. ; Mariano-Oliveira, Andrea ; Freitas, Marta S. de ; Figueiredo, Camila C. ; Morandi, Veronica ; Selistre-de-Araujo, Heloisa S.

Afiliação do(s) autor(es)

^[1] Universidade Federal de São Carlos (UFSCAR). Centro de Ciências Biológicas e da Saúde - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Biological Chemistry; v. 279, n. 18, p. 18247-18255, Apr. 2004.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Assunto(s): Venenos de origem animal Serpentes Bothrops Proteínas Fibroblastos

Resumo

Alternagin-C (ALT-C), a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, interacts with the major collagen I receptor, the alpha(2)beta(1) integrin, inhibiting collagen binding. Here we show that ALT-C also inhibits the adhesion of a mouse fibroblast cell line (NIH-3T3) to collagen I (IC50 2.2 muM). In addition, when immobilized on plate wells, ALT-C supports the adhesion of this cell line as well as of human vein endothelial cell (HUVEC). ALT-C (3 muM) does not detach cells that were previously bound to collagen I. ALT-C (5 nM) induces HUVEC proliferation in vitro, and it inhibits the positive effect of vascular endothelial growth factor (VEGF) or FGF-2 on the proliferation of these cells, thus suggesting a common mechanism for these proteins. Gene expression analysis of human fibroblasts growing on ALT-C- or collagen-coated plates showed that ALT-C and collagen I induce a very similar pattern of gene expression. When compared with cells growing on plastic only, ALT-C up-regulates the expression of 45 genes including the VEGF gene and downregulates the expression of 30 genes. Fibroblast VEGF expression was confirmed by RT-PCR and ELISA assay. Up-regulation of the VEGF gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates Akt/PKB phosphorylation, a signaling event involved in endothelial survival and angiogenesis. In conclusion, ALT-C acts as a survival factor, promoting adhesion and endothelial cell proliferation. (AU)

• Processo FAPESP: 00/05520-2 - Isolamento, caracterização química e biológica de novas disintegrinas de venenos de serpente e estudo de seus precursores
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 00/09495-2 - Estudo do efeito da "alternagin-c" uma desintegrina do veneno de "bothrops alternatus", sobre a adesao de celulas normais e tumorais avaliacao do seu potencial como agente anti-metastatico.
• Beneficiário: Cristina Helena Bruno Terruggi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 98/14138-2 - Center for Structural Molecular Biotechnology
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs