Details

Autor(en) / Beteiligte

• Cominetti, Márcia R
• Terruggi, Cristina H B
• Ramos, Oscar H P
• Fox, Jay W
• Mariano-Oliveira, Andrea
• De Freitas, Marta S
• Figueiredo, Camila C
• Morandi, Veronica
• Selistre-de-Araujo, Heloisa S

Titel

Alternagin-C, a Disintegrin-like Protein, Induces Vascular Endothelial Cell Growth Factor (VEGF) Expression and Endothelial Cell Proliferation in Vitro

Ist Teil von

• The Journal of biological chemistry, 2004-04, Vol.279 (18), p.18247-18255

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2004

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 α 2 β 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 (IC 50 2.2 μ m ). 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 μ m ) does not detach cells that were previously bound to collagen I. ALT-C (5 n m ) 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 down-regulates 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.