Post-transcriptional control of Amblyomin-X on secretion of vascular endothelial growth factor and expression of adhesion molecules in endothelial cells

Author(s)

Drewes, C. C. ^[1] ; Dias, R. Y. ^[1] ; Branco, V. G. ^[2] ; Cavalcante, M. F. ^[3] ; Souza, J. G. ^[2] ; Abdalla, D. S. P. ^[3] ; Chudzinski-Tavassi, A. M. ^[2] ; Farsky, S. H. P. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Analyses, Lab Expt Toxicol, BR-05503900 Sao Paulo, SP - Brazil

^[2] Butantan Inst, Biochem & Biophys Lab, BR-05503900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Biochem Lab, BR-05503900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Toxicon; v. 101, p. 1-10, JUL 2015.
• Web of Science Citations: 7

Abstract

Angiogenesis is a pivotal process of homeostasis and tissue repair, but it also favours neovascularisation syndromes and cancer nutrition. The chemical mediation of angiogenesis is complex, involving a balance between serine proteases and their inhibitors. We addressed the mechanisms of action of a Kunitz serine protease inhibitor (KPI) on spontaneous angiogenesis, using Amblyomin-X, a KPI designed from the cDNA library of the Amblyomma cajennense tick. Amblyomin-X treatment (10-1000 ng/10 mu l.; each 48 h; 3 times) reduced the number of vessels in the subcutaneous dorsal tissue of male Swiss mice, as measured by intravital microscopy, haematoxylin-eosin staining, and PECAM-1 immunofluorescence labeling. Incubation of Amblyomin-X with t-End endothelial cells, a murine endothelial microvascular lineage, did not alter cell proliferation, cell-cycle phases, necrosis and apoptosis, and the production of nitric oxide and prostaglandin E2. Nevertheless, Amblyomin-X treatment reduced t-End migration and adhesion to Matrigel (R), and inhibited the VEGF-A secretion and VCAM-1 and beta(3) integrin expressions by posttranscriptional pathways. Together, data herein outline novel posttranscriptional mechanisms of KPIs on endothelial cells during angiogenesis and point out the possible application of Amblyomin-X as a local inhibitor to undesired neovascularisation process. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 09/08584-6 - Supramolecular chemistry and nanotechnology
• Grantee: Henrique Eisi Toma
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/06944-8 - Effect of Amblyomin-X at interface of the immune system and hemostasis during progression RENCA tumor (murine renal cell carcinoma): in vivo and in vitro
• Grantee: Jean Gabriel de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/19802-1 - Effects of lipid-core nanocapsules with acetyleugenol in melanomas: in vivo and in vitro studies
• Grantee: Carine Cristiane Drewes
• Support Opportunities: Scholarships in Brazil - Doctorate