Comparative proteomic characterization of platelet aggregation induced by thrombin and PA-BJ, a serine proteinase from the venom of Bothrops jararaca.

• Grant number: 10/17328-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): February 01, 2011
• Effective date (End): January 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Ana Karina de Oliveira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 98/14307-9 - Center for Applied Toxinology, AP.CEPID

Abstract

PA-BJ is a serine proteinase isolated from Bothrops jararaca venom that induces platelet aggregation in platelet-rich plasma and washed platelets suspensions. This effect of PA-BJ on platelets aggregation is mediated by thrombin receptors PAR1 and PAR4 (Proteinase-Activated Receptors) that are G-protein coupled signaling receptors that require the cleavage of their extracellular N-terminal domain by proteinases such as thrombin, trypsin, and tryptase, generating a new N-terminal. PA-BJ cleaves in vitro the recombinant exodomain of PAR1 at Arg41-Ser42 and Arg46-Asn47 peptides bonds, resulting in the inactivation of the tethered ligand. PA-BJ also promotes calcium mobilization in fibroblasts transfected with PAR4 and desensitizes these cells to the thrombin action. PA-BJ is composed of 232 amino acid residues and contains one N- and one O-glycosidically linked carbohydrate moiety at residues Asn20 and Ser23 respectively. In order to better understand the signaling events caused by cleavage of the PAR1 receptor and following platelet activation we will employ a combination of proteomics and phosphoproteomics profiling and computational analyses to analyze the proteome of platelets activated by PA-BJ and thrombin. The purpose of this study is to provide insights into the mechanism of interaction of serine proteinases with their substrates and to describe new signaling pathways in platelets.

Scientific publications

(5)

(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)

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)

ZELANIS, ANDRE; OLIVEIRA, ANA K.; PRUDOVA, ANNA; HUESGEN, PITTER F.; TASHIMA, ALEXANDRE K.; KIZHAKKEDATHU, JAYACHANDRAN; OVERALL, CHRISTOPHER M.; SERRANO, SOLANGE M. T.. Deep Profiling of the Cleavage Specificity and Human Substrates of Snake Venom Metalloprotease HF3 by Proteomic Identification of Cleavage Site Specificity (PICS) Using Proteome Derived Peptide Libraries and Terminal Amine Isotopic Labeling of Substrates (TAILS) N-Terminomics. JOURNAL OF PROTEOME RESEARCH, v. 18, n. 9, p. 3419-3428, SEP 2019. (13/07467-1, 11/23403-8, 11/08514-8, 10/17328-0)

SERRANO, SOLANGE M. T.; OLIVEIRA, ANA K.; MENEZES, MILENE C.; ZELANIS, ANDRE. The proteinase-rich proteome of Bothrops jararaca venom. Toxin Reviews, v. 33, n. 4, p. 169-184, DEC 2014. (13/07467-1, 10/17328-0)

ZELANIS, ANDRE; HUESGEN, PITTER F.; OLIVEIRA, ANA KARINA; TASHIMA, ALEXANDRE K.; SERRANO, SOLANGE M. T.; OVERALL, CHRISTOPHER M.. Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites. JOURNAL OF PROTEOMICS, v. 113, p. 260-267, JAN 15 2015. (13/07467-1, 10/17328-0, 11/23403-8, 11/08514-8)

ASEGA, AMANDA F.; OLIVEIRA, ANA K.; MENEZES, MILENE C.; NEVES-FERREIRA, ANA GISELE C.; SERRANO, SOLANGE M. T.. Interaction of Bothrops jararaca venom metalloproteinases with protein inhibitors. Toxicon, v. 80, p. 1-8, MAR 15 2014. (98/14307-9, 10/17328-0, 10/00206-0)

Academic Publications

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

OLIVEIRA, Ana Karina de. Comparative proteomic characterization of platelet aggregation induced by thrombin and PA-BJ, a serine proteinase from the venom of Bothrops jararaca. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.