Proteomics and life-history variability of Endogenous Phospholipases A2 Inhibitors (PLIs) in Bothrops jararaca plasma

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Serino-Silva, Caroline ; Bittencourt Rodrigues, Caroline Fabri ; Miyamoto, Jackson Gabriel ; Hatakeyama, Daniela Miki ; Kavazoi, Victor Koiti ; Da Rocha, Marisa Maria Teixeira ; Tanaka, Aparecida Sadae ; Tashima, Alexandre Keiji ; de Morais-Zani, Karen ; Grego, Kathleen Fernandes ; Tanaka-Azevedo, Anita Mitico

• Document type: Journal article
• Source: PLoS One; v. 19, n. 2, p. 19-pg., 2024-02-06.

Abstract

In Brazil, the genus Bothrops is responsible for most ophidian accidents. Snake venoms have a wide variety of proteins and peptides exhibiting a broad repertoire of pharmacological and toxic effects that elicit systemic injury and characteristic local effects. The snakes' natural resistance to envenomation caused by the presence of inhibitory compounds on their plasma have been extensively studied. However, the presence of these inhibitors in different developmental stages is yet to be further discussed. The aim of this study was to evaluate the ontogeny of Bothrops jararaca plasma inhibitor composition and, to this end, plasma samples of B. jararaca were obtained from different developmental stages (neonates, youngs, and adults) and sexes (female and male). SDS-PAGE, Western blotting, affinity chromatography, and mass spectrometry were performed to analyze the protein profile and interaction between B. jararaca plasma and venom proteins. In addition, the presence of gamma BjPLI, a PLA(2) inhibitor previously identified and characterized in B. jararaca serum, was confirmed by Western blotting. According to our results, 9-17% of plasma proteins were capable of binding to venom proteins in the three developmental stages. The presence of different endogenous inhibitors and, more specifically, different PLA(2) inhibitor (PLI) classes and antihemorrhagic factors were confirmed in specimens of B. jararaca from newborn by mass spectrometry. For the first time, the alpha PLI and beta PLI were detected in B. jararaca plasma, although low or no ontogenetic and sexual correlation were found. The gamma PLI were more abundant in adult female, than in neonate and young female, but similar to neonate, young and adult male according to the results of mass spectrometry analysis. Our results suggest that there are proteins in the plasma of these animals that can help counteract the effects of self-envenomation from birth. (AU)

• FAPESP's process: 21/11707-4 - Evaluation of alternative in vitro methods to the use of animals for in vivo tests in the study of snake venoms: principle of the 3R's
• Grantee: Anita Mitico Tanaka-Azevedo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/25786-0 - Phospholipase A2 inhibitors (PLIs) present in venomous and non-venomous snake plasmas and evaluation of the neutralizing activity of these inhibitors on the phospholipase A2 (PLA2) activities of snake venoms
• Grantee: Anita Mitico Tanaka-Azevedo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/03779-5 - Use of phage display as a tool in the diagnosis and control of diseases transmitted by hematophagous vectors
• Grantee: Aparecida Sadae Tanaka
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/03657-8 - Inhibitor and proteases of ectoparasites: relationship of structure-function and identification of the role of these molecules in the interaction of diseases vector e their etiological agents
• Grantee: Aparecida Sadae Tanaka
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/20106-9 - Peptidomics of Brazilian snake and spider venoms
• Grantee: Alexandre Keiji Tashima
• Support Opportunities: Regular Research Grants