Mouse skin peptidomic analysis of the hemorrhage induced by a snake venom metalloprotease

Author(s)

Asega, Amanda F. ; Barros, Bianca C. S. C. ; Chaves, Alison F. A. ; Oliveira, Ana K. ; Bertholim, Luciana ; Kitano, Eduardo S. ; Serrano, Solange M. T.

• Document type: Journal article
• Source: Amino Acids; v. 55, n. 9, p. 17-pg., 2023-06-30.

Abstract

Hemorrhage induced by snake venom metalloproteases (SVMPs) results from proteolysis, capillary disruption, and blood extravasation. HF3, a potent SVMP of Bothrops jararaca, induces hemorrhage at pmol doses in the mouse skin. To gain insight into the hemorrhagic process, the main goal of this study was to analyze changes in the skin peptidome generated by injection of HF3, using approaches of mass spectrometry-based untargeted peptidomics. The results revealed that the sets of peptides found in the control and HF3-treated skin samples were distinct and derived from the cleavage of different proteins. Peptide bond cleavage site identification in the HF3-treated skin showed compatibility with trypsin-like serine proteases and cathepsins, suggesting the activation of host proteinases. Acetylated peptides, which originated from the cleavage at positions in the N-terminal region of proteins in both samples, were identified for the first time in the mouse skin peptidome. The number of peptides acetylated at the residue after the first Met residue, mostly Ser and Ala, was higher than that of peptides acetylated at the initial Met. Proteins cleaved in the hemorrhagic skin participate in cholesterol metabolism, PPAR signaling, and in the complement and coagulation cascades, indicating the impairment of these biological processes. The peptidomic analysis also indicated the emergence of peptides with potential biological activities, including pheromone, cell penetrating, quorum sensing, defense, and cell-cell communication in the mouse skin. Interestingly, peptides generated in the hemorrhagic skin promoted the inhibition of collagen-induced platelet aggregation and could act synergistically in the local tissue damage induced by HF3. (AU)

• FAPESP's process: 21/10570-5 - Molecular characterization of the in vivo effects of Bothrops jararaca venom: analysis of mouse muscle tissue and plasma, by proteomic and immunohistochemical approaches
• Grantee: Bianca Carla Silva Campitelli de Barros
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/12317-2 - Proteomic analysis of the systemic effects of Bothrops jararaca venom in a murine model
• Grantee: Alison Felipe Alencar Chaves
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/17328-0 - Comparative proteomic characterization of platelet aggregation induced by thrombin and PA-BJ, a serine proteinase from the venom of Bothrops jararaca.
• Grantee: Ana Karina de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/11308-0 - Proteomic analysis of leaves of sugarcane cultivars and genotypes
• Grantee: Eduardo Shigueo Kitano
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 11/16623-1 - Proteomic analysis of the proteolytic activity of HF3, a metalloproteinase from the venom of Bothrops jararaca, upon human and snake plasma.
• Grantee: Luciana Bertholim Nasciben
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 10/00206-0 - Molecular characterization of the hemorrhage induced by the metalloproteinase HF3: analysis of its interaction with extracellular matrix components and of the hemorrhagic tissue regeneration.
• Grantee: Amanda Francine Asega
• Support Opportunities: Scholarships in Brazil - Post-Doctoral