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

• Grant number: 17/00715-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2017
• End date: May 25, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Dilza Trevisan Silva
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID
• Associated scholarship(s): 17/23871-8 - Molecular characterization of the in vivo effects of the hemorrhagic metalloproteinase HF3: insights from the proteomic analysis of mouse plasma and kidney tissue, BE.EP.PD

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 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 in vivo molecular characterization of the effects of 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)

TREVISAN-SILVA, DILZA; COSENZA-CONTRERAS, MIGUEL; OLIVEIRA, URSULA C.; DA ROS, NANCY; ANDRADE-SILVA, DEBORA; MENEZES, MILENE C.; OLIVEIRA, ANA KARINA; ROSA, JAQUELINE G.; SACHETTO, ANA T. A.; BINIOSSEK, MARTIN L.; et al. Systemic toxicity of snake venom metalloproteinases: Multi-omics analyses of kidney and blood plasma disturbances in a mouse model. International Journal of Biological Macromolecules, v. 253, p. 17-pg., 2023-10-24. (13/07467-1, 17/23871-8, 13/13548-4, 17/00715-0)

SILVA, DILZA TREVISAN; ANDRARE-SILVA, DEBORA; NISHIYAMA-, MILTON Y., JR.; OLIVEIRA, URSULA C.; JUNQUEIRA-DE-AZEVEDO, INACIO L. M.; SCHILLING, OLIVER; SERRANO, SOLANGE M. T.. OMICS APPROACHES REVEALED SYSTEMIC EFFECTS OF HF3 FROM BOTHROPS JARARACA VENOM IN THE MOUSE KIDNEY. Toxicon, v. 168, p. 2-pg., 2019-10-05. (17/00715-0)

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)