Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom Suely V. Sampaio, Eliane C. Arantes, Marco A. Sartim
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
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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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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1808128689865490432 |