Proteolytic enzymes from snake venoms trigger cascades of yet unknown molecular events

• Grant number: 15/01234-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2015
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Eric Conrad Kyle Gren
• 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

The proteinase domain of hemorrhagic snake venom metalloproteinases (SVMPs) is believed to function to degrade capillary basement membranes, endothelial cell surfaces, and stromal matrix ultimately causing extravasation of capillary contents into the surrounding stroma. Hemorrhagic factor 3 (HF3) is a glycosylated P-III SVMP isolated from Bothrops jararaca venom. HF3 is an extremely active toxin that shows a minimum hemorrhagic dose of 240 fmol on the rabbit skin. Previous studies have shown that HF3 degrades plasma and extracellular matrix (ECM) proteins such as fibronectin, vitronectin, fibrinogen, von Willebrand factor, and collagens IV and VI. Analysis of HF3 effects on the mice dermis analyzed by proteomic approaches revealed a decrease of proteins related to cytoskeleton and extracellular matrix. The aims of this project are to improve the molecular characterization of the hemorrhage induced by HF3 and to characterize the hemorrhagic tissue regeneration. To tackle the challenge of uncovering putative molecular cascades triggered by HF3 we have adopted a systemic approach by proteomics based on mass spectrometry. (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)

GREN, ERIC C. K.; KITANO, EDUARDO S.; ANDRADE-SILVA, DEBORA; IWAI, LEO KEI; REIS, MARCELO S.; MENEZES, MILENE C.; SERRANO, SOLANGE M. T.. Comparative analysis of the high molecular mass subproteomes of eight Bothrops snake venoms. Comparative Biochemistry and Physiology D-Genomics & Proteomics, v. 30, p. 113-121, JUN 2019. (13/07467-1, 15/01234-0, 13/13548-4)