Data/hora: 08/06/2024 06:53:22

Provedor de dados: | Journal of Venomous Animals and Toxins Including Tropical Diseases
País: | Brazil
Título: | Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom
Autores: | Cedro,Rafhaella C. A.; Menaldo,Danilo L.; Costa,Tássia R.; Zoccal,Karina F.; Sartim,Marco A.; Santos-Filho,Norival A.; Faccioli,Lúcia H.; Sampaio,Suely V.
Data: | 2018-01-01
Ano: | 2018
Palavras-chave: | Snake venom; Bothrops jararaca; Phospholipase A2; Inflammation; Cytotoxicity.
Resumo: | Abstract  Background: Snake venom phospholipases A2 (PLA2s) have been reported to induce myotoxic, neurotoxic, hemolytic, edematogenic, cytotoxic and proinflammatory effects. This work aimed at the isolation and functional characterization of a PLA2 isolated from Bothrops jararaca venom, named BJ-PLA2-I.  Methods and Results: For its purification, three consecutive chromatographic steps were used (Sephacryl S-200, Source 15Q and Mono Q 5/50 GL). BJ-PLA2-I showed acidic characteristics, with pI~4.4 and molecular mass of 14. 2 kDa. Sequencing resulted in 60 amino acid residues that showed high similarity to other Bothrops PLA2s, including 100% identity with BJ-PLA2, an Asp49 PLA2 previously isolated from B. jararaca venom. Being an Asp49 PLA2, BJ-PLA2-I showed high catalytic activity, and also inhibitory effects on the ADP-induced platelet aggregation. Its inflammatory characterization showed that BJ-PLA2-I was able to promote leukocyte migration in mice at different concentrations (5, 10 and 20 μg/mL) and also at different response periods (2, 4 and 24 h), mainly by stimulating neutrophil infiltration. Furthermore, increased levels of total proteins, IL-6, IL-1 β and PGE2 were observed in the inflammatory exudate induced by BJ-PLA2-I, while nitric oxide, TNF-α, IL-10 and LTB4 levels were not significantly altered. This toxin was also evaluated for its cytotoxic potential on normal (PBMC) and tumor cell lines (HL-60 and HepG2). Overall, BJ-PLA2-I (2.5-160 μg/mL) promoted low cytotoxicity, with cell viabilities mostly varying between 70 and 80% and significant values obtained for HL-60 and PBMC only at the highest concentrations of the toxin evaluated.  Conclusions: BJ-PLA2-I was characterized as an acidic Asp49 PLA2 that induces acute local inflammation and low cytotoxicity. These results should contribute to elucidate the action mechanisms of snake venom PLA2s.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992018000100324
Editor: | Centro de Estudos de Venenos e Animais Peçonhentos
Relação: | 10.1186/s40409-018-0170-y
Formato: | text/html
Fonte: | Journal of Venomous Animals and Toxins including Tropical Diseases  v.24 2018
Fonte: | info:eu-repo/semantics/openAccess