Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2 cells

Página do item simplificado
dc.contributor.authorJarvis, I. W. H.
dc.contributor.authorBergvall, C.
dc.contributor.authorMorales, D. A.
dc.contributor.authorKummrow, F. [UNIFESP]
dc.contributor.authorUmbuzeiro, G. A.
dc.contributor.authorWesterholm, R.
dc.contributor.authorStenius, U.
dc.contributor.authorDreij, K.
dc.contributor.institutionKarolinska Inst
dc.contributor.institutionStockholm Univ
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:37:44Z
dc.date.available2016-01-24T14:37:44Z
dc.date.issued2014-08-17
dc.description.abstractPolycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that occur naturally in complex mixtures. Many of the adverse health effects of PAHs including cancer are linked to the activation of intracellular stress response signaling. This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira, Brazil, in comparison to BP in HepG2 cells. Nanomolar concentrations of PAHs in the extracts induced activation of MEK4 signaling with down-stream increased gene expression of several important stress response mediators. Involvement of the MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling resulting in significantly reduced MAPK signaling transactivated by the AP-1 transcription factors ATF2 and c-Jun. ATF2 was also identified as a sensitive stress responsive protein with activation observed at extract concentrations equivalent to 0.1 nM BP. We show that exposure to low levels of environmental PAH mixtures more strongly activates these signaling pathways compared to BP alone suggesting effects due to interactions. Taken together, this is the first study showing the involvement of MEK4/JNK/AP-1 pathway in regulating the intracellular stress response after exposure to nanomolar levels of PAHs in environmental mixtures. (C) 2014 Elsevier Ireland Ltd. All rights reserved.en
dc.description.affiliationKarolinska Inst, Inst Environm Med, SE-17177 Stockholm, Sweden
dc.description.affiliationStockholm Univ, Dept Analyt Chem, SE-10691 Stockholm, Sweden
dc.description.affiliationUniv Estadual Campinas, UNICAMP, Fac Technol, BR-13484332 São Paulo, Brazil
dc.description.affiliationFed Univ São Paulo UNIFESP, Inst Environm Chem & Pharmaceut Sci, BR-09972270 São Paulo, Brazil
dc.description.affiliationUnifespFed Univ São Paulo UNIFESP, Inst Environm Chem & Pharmaceut Sci, BR-09972270 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSwedish Research Council Formas, Cancer- och Allergifonden, Stockholm University
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipEU/FP7 Marie Curie IRG
dc.format.extent25-32
dc.identifierhttp://dx.doi.org/10.1016/j.toxlet.2014.06.013
dc.identifier.citationToxicology Letters. Clare: Elsevier B.V., v. 229, n. 1, p. 25-32, 2014.
dc.identifier.doi10.1016/j.toxlet.2014.06.013
dc.identifier.issn0378-4274
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38096
dc.identifier.wosWOS:000340044800004
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofToxicology Letters
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectPAHsen
dc.subjectAir particulate matteren
dc.subjectComplex mixturesen
dc.subjectBenzo[a]pyreneen
dc.subjectMAPKen
dc.titleNanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2 cellsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
Em verificação - Geral