Actions of the Kunitz-type serine protease inhibitor Amblyomin-X on VEGF-A-induced angiogenesis

Autor(es)

Drewes, C. C. ; Dias, R. Y. S. ; Hebeda, C. B. ; Simons, S. M. ^[1] ; Barreto, S. A. ^[1] ; Ferreira Junior, J. M. ^[2] ; Chudzinski-Tavassi, A. M. ^{[1, 3]} ; Farsky, S. H. P. ^[4]

Afiliação do(s) autor(es)

^[1] Butantan Inst, Biochem & Biophys Lab, BR-05503000 Sao Paulo - Brazil

^[2] Butantan Inst, Lab Immunochem, BR-05503000 Sao Paulo - Brazil

^[3] Butantan Inst, Ctr Appl Toxinol CEPID, BR-05503000 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 60, n. 3, p. 333-340, SEP 1 2012.
• Citações Web of Science: 15

Resumo

Amblyomin-X is a Kunitz-type serine protease inhibitor (Kunitz-type SPI) designed from the cDNA library of the Amblyomma cajennense tick, which displays in vivo anti-tumor activities. Here, the mechanisms of actions of Amblyomin-X in vascular endothelial growth factor A (VEGF-A)-induced angiogenesis were characterized. Topical application of Amblyomin-X (10 or 100 ng/10 mu l; each 48 h) inhibited VEGF-A-induced (10 ng/10 mu l; each 48 h) angiogenesis in the dorsal subcutaneous tissue in male Swiss mice. Moreover, similar effect was observed in the VEGF-A-induced angiogenesis in the chicken chorioallantoic membrane (CAM). Additional in vitro assays in t-End cells showed that Amblyomin-X treatment delayed the cell cycle, by maintaining them in G0/G1 phase, and inhibited cell proliferation and adhesion, tube formation and membrane expression of the adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-I), regardless of mRNA synthesis. Together, results herein reveal the role of Kunitz-type SPI on in vivo VEGF-A-induced angiogenesis, by exerting modulatory actions on endothelial cell proliferation and adhesion, especially on membrane expression of PECAM-1. These data provide further mechanisms of actions of Kunitz-type SPI, corroborating their relevance as scientific tools in the design of therapeutic molecules. (C) 2012 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 08/57850-8 - Caracterizacao dos efeitos do amblyomin-x sobre a angiogenese e sobre a funcao de macrofagos.
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/52669-3 - Avaliação do mecanismo de ação pró-apoptótica do Amblyomin-X
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Regular