Cytotoxic and genotoxic effects on human keratinocytes triggered by sphingomyelinase D from Loxosceles venom

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dc.contributorLCC - Laboratório de Ciclo Celularpt_BR
dc.contributorLab. Imunoquímicapt_BR
dc.contributor.authorSilva, Marcelo Santos dapt_BR
dc.contributor.authorLopes, Priscila Hesspt_BR
dc.contributor.authorElias, Maria Carolinapt_BR
dc.contributor.authorTambourgi, Denise Vilarinhopt_BR
dc.date.accessioned2020-07-09T21:28:18Z-
dc.date.available2020-07-09T21:28:18Z-
dc.date.issued2020pt_BR
dc.identifier.citationSilva MS, Lopes PH, Elias MC, Tambourgi DV. Cytotoxic and genotoxic effects on human keratinocytes triggered by sphingomyelinase D from Loxosceles venom. Arch. Toxicol.. 2020 jun.. doi:10.1007/s00204-020-02830-2.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3082-
dc.description.abstractThe spiders of the Loxosceles genus (called brown or violin spiders) are of medical relevance in several countries due to the many human envenomation cases reported. The main component of Loxosceles venom is the enzyme sphingomyelinase D (SMase D), which is responsible for the local and systemic effects induced by the whole venom. Here, we investigated the cytotoxic and genotoxic effects caused by Loxosceles laeta venom and SMase D on human keratinocytes to better understand the dermonecrosis development mechanism. Our findings indicate that whole venom, as well as SMase D, increases intracellular superoxide levels, leading to DNA damage. These effects appear to be dependent on the binding of SMase D to the cell surface, although the complete pathway triggered as a result of the binding still needs to be elucidated. Moreover, after SMase D treatment, we observed the presence of histone ?H2AX, suggesting that the cells are undergoing DNA repair. Moreover, when ATR kinase was inhibited, the cell viability of human keratinocytes was decreased. Together, our findings strongly suggest that L. laeta venom, as well as SMase D, increases intracellular superoxide levels, leading to DNA damage in human keratinocytes. Additionally, the induced DNA damage is repaired through the activation of an apparent ATR-mediated DNA-damage response. This knowledge may contribute to a better understanding of the behaviour of human keratinocytes during cutaneous loxoscelism, a condition that affects thousands of people around the world.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.format.extent3563-3577pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofArchives of Toxicologypt_BR
dc.rightsRestricted Accesspt_BR
dc.titleCytotoxic and genotoxic effects on human keratinocytes triggered by sphingomyelinase D from Loxosceles venompt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1007/s00204-020-02830-2pt_BR
dc.identifier.urlhttps://doi.org/10.1007/s00204-020-02830-2pt_BR
dc.identifier.citationvolume94pt_BR
dc.subject.keywordLoxosceles venompt_BR
dc.subject.keywordSphingomyelinase Dpt_BR
dc.subject.keywordReactive oxygen speciespt_BR
dc.subject.keywordDNA damagept_BR
dc.subject.keywordDNA-damage responsept_BR
dc.relation.ispartofabbreviatedArch Toxicolpt_BR
dc.identifier.citationabntv. 94, p. 3563-3577, jun. 2020pt_BR
dc.identifier.citationvancouver2020 jun;94:3563-3577pt_BR
dc.contributor.butantanSilva, Marcelo Santos da|:Aluno|:LCC - Laboratório de Ciclo Celular|:PrimeiroAutorpt_BR
dc.contributor.butantanLopes, Priscila Hess|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanElias, Maria Carolina|:Pesquisador|:LCC - Laboratório de Ciclo Celularpt_BR
dc.contributor.butantan|Tambourgi, Denise Vilarinho|:Pesquisador:Docente Permanente PPGTOX|:Lab. Imunoquímica|:Autor de correspondênciapt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦301358/2017-6pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦306199/2018-1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07467-1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2014/24170-5pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/17053-5pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
item.fulltextCom Texto completo-
item.grantfulltextembargo_29990101-
item.languageiso639-1English-
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crisitem.author.orcid0000-0003-1896-9074-
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