β-micrustoxin (Mlx-9), a PLA2 from Micrurus lemniscatus snake venom: biochemical characterization and anti-proliferative effect mediated by p53

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dc.contributorLab. Farmacologiapt_BR
dc.contributorPrograma de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributorLab. Bioquímicapt_BR
dc.contributor(LDI) Laboratório de Desenvolvimento e Inovação Industrialpt_BR
dc.contributor(LEDS) Laboratório de Dor e Sinalizaçãopt_BR
dc.contributor.authorSantos, Natália Fernanda Teixeira dospt_BR
dc.contributor.authorSouza-Imberg, Andreiapt_BR
dc.contributor.authorMariano, Douglas Oscar Ceolinpt_BR
dc.contributor.authorMoraes, Angelina Cirelli dept_BR
dc.contributor.authorAndrade-Silva, Jessicapt_BR
dc.contributor.authorFernandes, Cristina Mariapt_BR
dc.contributor.authorSobral, Ana Cláudiapt_BR
dc.contributor.authorGiannotti, Karina Cristinapt_BR
dc.contributor.authorKuwabara, Wilson M. Tatagibapt_BR
dc.contributor.authorPimenta, Daniel Carvalhopt_BR
dc.contributor.authorMaria, Durvanei Augustopt_BR
dc.contributor.authorSandoval, Maria Regina Lopespt_BR
dc.contributor.authorAfeche, Solange Castropt_BR
dc.date.accessioned2022-04-19T17:06:45Z-
dc.date.available2022-04-19T17:06:45Z-
dc.date.issued2022pt_BR
dc.identifier.citationSantos NFT, Souza-Imberg A, Mariano DOC, Moraes AC, Andrade-Silva J, Fernandes CM, et al. β-micrustoxin (Mlx-9), a PLA2 from Micrurus lemniscatus snake venom: biochemical characterization and anti-proliferative effect mediated by p53. J. Venom. Anim. Toxins Trop. Dis. 2022 Apr;28:e20210094. doi:10.1590/1678-9199-JVATITD-2021-0094.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/4301-
dc.description.abstractBackground: Endogenous phospholipases A2 (PLA2) play a fundamental role in inflammation, neurodegenerative diseases, apoptosis and cellular senescence. Neurotoxins with PLA2 activity are found in snake venoms from the Elapidae and Viperidae families. The mechanism of action of these neurotoxins have been studied using hippocampal and cerebellar neuronal cultures showing [Ca2+]i increase, mitochondrial depolarization and cell death. Astrocytes are rarely used as a model, despite being modulators at the synapses and responsible for homeostasis and defense in the central nervous system. Preserving the cell division ability, they can be utilized to study the cell proliferation process. In the present work cultured astrocytes and glioblastoma cells were employed to characterize the action of β-micrustoxin (previously named Mlx-9), a PLA2 isolated from Micrurus lemniscatus snake venom. The β-micrustoxin structure was determined and the cell proliferation, cell cycle phases and the regulatory proteins p53, p21 and p27 were investigated. Methods: β-micrustoxin was characterized biochemically by a proteomic approach. Astrocytes were obtained by dissociation of pineal glands from Wistar rats; glioblastoma tumor cells were purchased from ATCC and Sigma and cultured in DMEM medium. Cell viability was evaluated by MTT assay; cell proliferation and cell cycle phases were analyzed by flow cytometry; p53, p21 and p27 proteins were studied by western blotting and immunocytochemistry. Results: Proteomic analysis revealed fragments on β-micrustoxin that aligned with a PLA2 from Micrurus lemniscatus lemniscatus previously identified as transcript ID DN112835_C3_g9_i1/m.9019. β-micrustoxin impaired the viability of astrocytes and glioblastoma tumor cells. There was a reduction in cell proliferation, an increase in G2/M phase and activation of p53, p21 and p27 proteins in astrocytes. Conclusion: These findings indicate that β-micrustoxin from Micrurus lemniscatus venom could inhibit cell proliferation through p53, p21 and p27 activation thus imposing cell cycle arrest at the checkpoint G2/M.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(FINEP) Financiadora de Estudos e Projetospt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.format.extente20210094pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofJournal of Venomous Animals and Toxins Including Tropical Diseasespt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleβ-micrustoxin (Mlx-9), a PLA2 from Micrurus lemniscatus snake venom: biochemical characterization and anti-proliferative effect mediated by p53pt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.1590/1678-9199-JVATITD-2021-0094pt_BR
dc.identifier.urlhttps://doi.org/10.1590/1678-9199-JVATITD-2021-0094pt_BR
dc.identifier.citationvolume28pt_BR
dc.subject.keywordAstrocytespt_BR
dc.subject.keywordGlioblastomapt_BR
dc.subject.keywordβ-micrustoxinpt_BR
dc.subject.keywordMlx-9pt_BR
dc.subject.keywordPLA2pt_BR
dc.subject.keywordMicrurus lemniscatus venompt_BR
dc.subject.keywordp53 proteinpt_BR
dc.relation.ispartofabbreviatedJ. Venom. Anim. Toxins Trop. Dispt_BR
dc.identifier.citationabntv. 28, e20210094, abr. 2022pt_BR
dc.identifier.citationvancouver2022 Apr;28:e20210094pt_BR
dc.contributor.butantanSantos, Natália Fernanda Teixeira dos|:Aluno Egresso|:Lab. Farmacologia:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)|:PrimeiroAutorpt_BR
dc.contributor.butantanSouza-Imberg, Andreia|:Aluno Egresso|:Lab. Farmacologia:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributor.butantanMariano, Douglas Oscar Ceolin|:Outros|:Lab. Bioquímicapt_BR
dc.contributor.butantanMoraes, Angelina Cirelli de|:Desvinculado|:Lab. Biologia Molecularpt_BR
dc.contributor.butantanFernandes, Cristina Maria|:Técnico|:Lab. Farmacologiapt_BR
dc.contributor.butantanGiannotti, Karina Cristina|:Aluno Egresso|:Laboratório de Dor e Sinalização:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributor.butantanPimenta, Daniel Carvalho|:Pesquisador:Docente permanente PPGTox|:Lab. Bioquímicapt_BR
dc.contributor.butantanMaria, Durvanei Augusto|:Pesquisador|:Lab. Biologia Molecularpt_BR
dc.contributor.butantanSandoval, Maria Regina Lopes|:Pesquisador|:Lab. Farmacologiapt_BR
dc.contributor.butantanAfeche, Solange Castro|:Pesquisador:Docente Permanente PPGTox|:Lab. Farmacologia|:Autor de correspondênciapt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2015/04504-9pt_BR
dc.sponsorship.butantan(FINEP) Financiadora de Estudos e Projetos¦¦01.09.0278.04pt_BR
dc.sponsorship.butantan(FINEP) Financiadora de Estudos e Projetos¦¦01.12.0450.03pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦406385/2018-1pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.languageiso639-1English-
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