Molecular characterization of the in vivo effects of the hemorrhagic metalloproteinase HF3: insights from the proteomic analysis of mouse plasma and kidney tissue

• Grant number: 17/23871-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 20, 2018
• End date: September 19, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Dilza Trevisan Silva
• Supervisor: Oliver Schilling
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of Freiburg, Germany
• Associated to the scholarship: 17/00715-0 - Proteolytic enzymes from snake venoms trigger cascades of yet unknown molecular events, BP.PD

Abstract

Snake venom metalloproteinases (SVMPs) are among the most abundant enzymes found in viperid venoms and are responsible for several of the pathological effects observed upon envenomation. The structural similarity of SVMPs with ADAMs (A Disintegrin and Metalloproteinase) and ADAMTSs (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) has guided a number of functional assays currently employed in toxinology studies. The study of SVMPs activities in complex biological systems with the use of omics technologies has allowed the evaluation of several aspects of the pathology of the snake envenomation, as well as the in vivo effects triggered by SVMPs. The general aim of this project is to elucidate in vivo effects of HF3, a potent hemorrhagic metalloproteinase from Bothrops jararaca venom, in the plasma and kidneys of mice submitted to injection of HF3 in the thigh muscle. To this end, the following specific aims are proposed: (I) to apply quantitative N-terminomics technologies to identify in the mouse kidney tissue and plasma (both whole and albumin-depleted samples) the in vivo substrates of HF3 and also the substrates of other proteinases possibly activated by HF3 (to be carried out at Albert-Ludwigs-Universität Freiburg during the research internship - BEPE-PD); (II) to analyze the plasma peptidome in order to identify proteins degraded in response to the HF3-treatment (underway at Butantan Institute); (III) to identify mRNAs differentially abundant in the mouse kidney tissue using next generation technology (NGS) for RNA-seq (underway at Butantan Institute). (AU)