Reconfiguration of the cardiac proteome mediated by endogenous proteases in response to Bothropic envenomation

• Grant number: 25/14321-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Bianca Carla Silva Campitelli de Barros
• Grantee: Isabella Soares Marques Barcelos
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil

Abstract

In Brazil, approximately 90% of snakebite accidents are attributed to snakes of the Bothrops genus. Bothrops jararaca is among the species with the greatest clinical impact and is predominantly found in the southern and southeastern regions of the country. In cases of Bothrops envenomation, victims typically develop local effects such as edema and pain, as well as systemic manifestations including coagulation disorders, renal failure, and cardiovascular shock. These effects are primarily caused by thediverse array of proteases present in B. jararaca venom, including metalloproteases, serine proteases, and phospholipases. Although the systemic effects of envenomation are well documented in theliterature, the molecular mechanisms underlying cardiovascular shock remain poorly explored and understood. In this context, proteomic analysis by mass spectrometry emerges as a powerful tool to map the alterations induced by envenomation in the host proteome. Therefore, the present project aims to characterize the proteome and the response of cardiac tissue in mice subjected to intramuscular administration of B. jararaca venom, as well as to investigate the effects of Bothrops antivenom and protease inhibitors (meprin and cathepsin inhibitors) on the hearts of envenomed animals. To this end, soluble proteins will be extracted from previously collected cardiac tissue, and the samples will be processed for proteomic analysis using the SP3 protocol. When appropriate, the peptide fraction of the samples will also be collected for peptidomic analysis by mass spectrometry, and cardiac tissue histopathology will be assessed by brightfield microscopy and hematoxylin and eosin staining.