Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim

Detalhes bibliográficos
Autor(a) principal: Cedro, Rafhaella C. A.
Data de Publicação: 2018
Outros Autores: Menaldo, Danilo L., Costa, Tássia R., Zoccal, Karina F., Sartim, Marco A., Santos-Filho, Norival A. [UNESP], Faccioli, Lúcia H., Sampaio, Suely V.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1186/s40409-018-0170-y
http://hdl.handle.net/11449/188420
Resumo: 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-1β 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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spelling Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. SartimBothrops jararacaCytotoxicityInflammationPhospholipase A2Snake venomBackground: 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-1β 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.Departamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo (FCFRP-USP), Avenida do Café, s/n, B. Monte AlegreCampus Experimental de Registro Universidade Estadual Paulista (UNESP)Campus Experimental de Registro Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Cedro, Rafhaella C. A.Menaldo, Danilo L.Costa, Tássia R.Zoccal, Karina F.Sartim, Marco A.Santos-Filho, Norival A. [UNESP]Faccioli, Lúcia H.Sampaio, Suely V.2019-10-06T16:07:30Z2019-10-06T16:07:30Z2018-11-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/s40409-018-0170-yJournal of Venomous Animals and Toxins Including Tropical Diseases, v. 24, n. 1, 2018.1678-91991678-9180http://hdl.handle.net/11449/18842010.1186/s40409-018-0170-yS1678-919920180001003242-s2.0-85057309005S1678-91992018000100324.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Venomous Animals and Toxins Including Tropical Diseasesinfo:eu-repo/semantics/openAccess2024-05-03T13:20:08Zoai:repositorio.unesp.br:11449/188420Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:42:41.372533Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
title Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
spellingShingle Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
Cedro, Rafhaella C. A.
Bothrops jararaca
Cytotoxicity
Inflammation
Phospholipase A2
Snake venom
title_short Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
title_full Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
title_fullStr Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
title_full_unstemmed Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
title_sort Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
author Cedro, Rafhaella C. A.
author_facet Cedro, Rafhaella C. A.
Menaldo, Danilo L.
Costa, Tássia R.
Zoccal, Karina F.
Sartim, Marco A.
Santos-Filho, Norival A. [UNESP]
Faccioli, Lúcia H.
Sampaio, Suely V.
author_role author
author2 Menaldo, Danilo L.
Costa, Tássia R.
Zoccal, Karina F.
Sartim, Marco A.
Santos-Filho, Norival A. [UNESP]
Faccioli, Lúcia H.
Sampaio, Suely V.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Cedro, Rafhaella C. A.
Menaldo, Danilo L.
Costa, Tássia R.
Zoccal, Karina F.
Sartim, Marco A.
Santos-Filho, Norival A. [UNESP]
Faccioli, Lúcia H.
Sampaio, Suely V.
dc.subject.por.fl_str_mv Bothrops jararaca
Cytotoxicity
Inflammation
Phospholipase A2
Snake venom
topic Bothrops jararaca
Cytotoxicity
Inflammation
Phospholipase A2
Snake venom
description 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-1β 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.
publishDate 2018
dc.date.none.fl_str_mv 2018-11-23
2019-10-06T16:07:30Z
2019-10-06T16:07:30Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/s40409-018-0170-y
Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 24, n. 1, 2018.
1678-9199
1678-9180
http://hdl.handle.net/11449/188420
10.1186/s40409-018-0170-y
S1678-91992018000100324
2-s2.0-85057309005
S1678-91992018000100324.pdf
url http://dx.doi.org/10.1186/s40409-018-0170-y
http://hdl.handle.net/11449/188420
identifier_str_mv Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 24, n. 1, 2018.
1678-9199
1678-9180
10.1186/s40409-018-0170-y
S1678-91992018000100324
2-s2.0-85057309005
S1678-91992018000100324.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Venomous Animals and Toxins Including Tropical Diseases
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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