| 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) | |
| FAPESP's process: | 08/57850-8 - Caracterizacao dos efeitos do amblyomin-x sobre a angiogenese e sobre a funcao de macrofagos. |
| Grantee: | Sandra Helena Poliselli Farsky |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 10/52669-3 - Avaliação do mecanismo de ação pró-apoptótica do Amblyomin-X |
| Grantee: | Ana Marisa Chudzinski-Tavassi |
| Support Opportunities: | Regular Research Grants |