Characterization of polypeptide modulators of angiogenesis derived from the degradation of kininogen and fibrinogen by Bothropasin

• Grant number: 14/02788-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2014
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fernanda Calheta Vieira Portaro
• Grantee: Cristiane Castilho Fernandes da Silva
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

For angiogenesis to occur from previously existing capillary beds the basal membrane must be degraded by proteolytic enzymes which are secreted by the endothelial cells involved in the process and their migration and proliferation must occur in an ordered way. This tipically happens as a shift towards a positive balance in the molecular components of the angiogenic cocktail. In adults normal physiology angiogenesis is kept suppressed but can activated either transiently, as it occurs under menstrual cycle and tissue repair, or constitutively as is the case in some pathologies i.e. reumathoid arthrites, tumor vascularization. In the past ten years many criptical fragments (i.e. Tunstatin E Endostatin) generated by the proteolysis of basal membrane componentes (i.e. Colagen IV E XVIII) have been characterized as angiogenic modulators. The present project aims to explore the well known action of SVMPs from Bothrops jararaca on ECM molecules as substrates, as a tool for the generation of new endothelial cells migration, proliferation and adhesion modulators. We shall use bothropasin for the digestion of plasm and extracellular matrix structural componentes, kininogen and fibrinogen. The resulting polipeptides will be recovered for the following procedures: mass spectrometry analysis, functional assays of cell proliferation, migration and adhesion, as the experimental steps that recapitulate the process of angiogenesis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES SILVA, CRISTIANE CASTILHO; MENEZES, MILENE CRISTINA; PALOMINO, MIRYAM; OLIVEIRA, ANA KARINA; IWAI, LEO KEI; FARIA, MARCELLA; PORTARO, FERNANDA VIEIRA. Peptides derived from plasma proteins released by bothropasin, a metalloprotease present in the Bothrops jararaca venom. Toxicon, v. 137, p. 65-72, OCT 2017. (14/02788-7, 13/07467-1, 15/15364-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Cristiane Castilho Fernandes da. Search for bioactive derived degradation polypeptides of kininogen, fibrinogen and fibronectin by bothropasin and Bothrops protease A.. 2017. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.