Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: Toxicon; v. 60, n. 3, p. 333-340, SEP 1 2012.
Web of Science Citations: 15
Abstract

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)