Registro completo |
Provedor de dados: |
J. Venom. Anim. Toxins incl. Trop. Dis.
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País: |
Brazil
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Título: |
Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom
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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.
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Data: |
2018-01-01
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Ano: |
2018
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Palavras-chave: |
Snake venom
Bothrops jararaca
Phospholipase A2
Inflammation
Cytotoxicity
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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.
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Tipo: |
Info:eu-repo/semantics/article
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Idioma: |
Inglês
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Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992018000100324
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Editor: |
Centro de Estudos de Venenos e Animais Peçonhentos
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Relação: |
10.1186/s40409-018-0170-y
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Formato: |
text/html
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Fonte: |
Journal of Venomous Animals and Toxins including Tropical Diseases v.24 2018
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Direitos: |
info:eu-repo/semantics/openAccess
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