Molecular characterization of the in vivo effects of the hemorrhagic metalloproteinase HF3: analyses of the proteome of mice muscle tissue

• Grant number: 18/06751-1
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): January 01, 2019
• Effective date (End): February 29, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Eric Junqueira Brito Pereira
• 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

Envenomation due to snakebite is a major concern, given the severity of accidents and the high number of deaths occurring each year. In Brazil, Bothrops snakes account for more than 70% of snakebite accidents, and envenomation caused by these snakes often promotes intense pain, edema, hemorrhage, necrosis, disturbances in blood coagulation, cardiovascular disorders, and renal failure. These symptoms are related to the composition of their venoms, which are rich in peptides and enzymes, including metalloproteinases (Snake Venom Metalloproteinases; SVMPs), that play a critical role in the envenomation process. SVMPs exhibit zinc-dependent catalytic activity and are often associated with local and systemic hemorrhagic events due to their ability to degrade basement membrane components of capillaries and to alter hemostasis in mammals. Hemorrhagic factor 3 (HF3) is a potent hemorrhagic and myotoxic SVMP, isolated from the venom of Bothrops jararaca. Studies with this toxin have shown that it can degrade components of the extracellular matrix, cytoskeleton, and plasma proteins. It has also been shown that HF3 promotes pro-inflammatory events, such as phagocytic macrophage activity and leukocyte rolling. In this context, the present project aims to expand the molecular characterization of hemorrhage and myotoxicity induced by HF3, which are important aspects to better understand the molecular events that take place in snake envenomation. Hence, the muscle tissue of mice injected with HF3 will be evaluated to: (1) Characterize the proteome and the peptidome; (2) Analyze the abundance of proteins involved in inflammation and cell death; (3) Analyze the activation of collagenases; (4) Evaluate DNA damage related to the generation of reactive oxygen species. The aim is to increase the knowledge about the molecular targets of HF3 and the signaling pathways involved in the generation of hemorrhage and myotoxicity. (AU)