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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 101, p. 1-10, JUL 2015.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 09/08584-6 - Química e nanotecnologia molecular
• Beneficiário: Henrique Eisi Toma
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 08/56072-1 - Caracterizacao dos efeitos do amblyomn-x sobre a angiogenese
• Beneficiário: Carine Cristiane Drewes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• 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: 12/06944-8 - Efeito do Amblyomin-X na interface do sistema imune e hemostático durante a progressão do tumor RENCA ( carcinoma renal murino): in vivo e in vitro
• Beneficiário: Jean Gabriel de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/19802-1 - Efeitos das nanocápsulas de núcleo lipídico contendo acetileugenol em melanomas: estudos in vivo e in vitro
• Beneficiário: Carine Cristiane Drewes
• Modalidade de apoio: Bolsas no Brasil - Doutorado