Proteomic analysis of the effects of PA-BJ, a serine proteinase of Bothrops jararaca venom, upon peripheral blood endothelial cell culture

• Grant number: 17/19252-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2017
• End date: March 21, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Daniela Cajado de Oliveira Souza Carvalho
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

PA-BJ is a Bothrops jararaca venom serine proteinase that triggers platelet-aggregation in a thrombin-like fashion by cleaving the protease-activated receptors PAR-1 and PAR-4 on platelets. We recently carried out a study to comparatively analyze the aggregation of platelets activated by thrombin, one of the most important platelet agonists, and PA-BJ. For this purpose, approaches of mass spectrometry and bioinformatics were used to characterize changes in the proteome of non-activated and activated platelets, and also to analyze proteins and peptides present in the supernatant of aggregated platelets. Our findings revealed that although both PA-BJ and thrombin induce platelet aggregation via PAR-1 and PAR-4, these enzymes activate different pathways to cause platelet secretion and aggregation. Endothelial cells express various types of protein receptors, which upon activation by their specific ligands, initiate a signaling network that links extracellular signals in circulation to various biological processes in cells of the vascular system. Thrombin and vitamin K-dependent coagulation proteinases are able to selectively activate cell surface PARs on the vasculature. The aim of the present project is to characterize the molecular effects of PA-BJ upon endothelial cells. To tackle the challenge of uncovering putative molecular cascades triggered by PA-BJ we use degradomics approaches based on mass spectrometry.

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)

DE OLIVEIRA SOUZA CARVALHO, DANIELA CAJADO; SILVA, DEBORA ANDRADE; SILVA, DILZA TREVISAN; DE TOLEDO SERRANO, SOLANGE MARIA. EVALUATION OF SUB-CYTOTOXIC EFFECTS OF PA-BJ UPON ENDOTHELIAL CELLS USING PROTEOMICS APPROACHES.. Toxicon, v. 168, p. 2-pg., 2019-10-05. (17/19252-0)

ASEGA, AMANDA F. .; MENEZES, MILENE C.; TREVISAN-SILVA, DILZA; CAJADO-CARVALHO, DANIELA; BERTHOLIM, LUCIANA; OLIVEIRA, ANA K.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T.. Cleavage of proteoglycans, plasma proteins and the platelet-derived growth factor receptor in the hemorrhagic process induced by snake venom metalloproteinases. SCIENTIFIC REPORTS, v. 10, n. 1, JUL 31 2020. (17/00715-0, 10/00206-0, 17/19252-0, 10/17328-0, 11/08514-8, 13/07467-1)