Nanomolar Levels Of Pahs In Extracts From Urban Air Induce Mapk Signaling In Hepg2 Cells.

dc.creatorJarvis, I W H
dc.creatorBergvall, C
dc.creatorMorales, D A
dc.creatorKummrow, F
dc.creatorUmbuzeiro, G A
dc.creatorWesterholm, R
dc.creatorStenius, U
dc.creatorDreij, K
dc.date2014-Aug
dc.date2015-11-27T13:42:42Z
dc.date2015-11-27T13:42:42Z
dc.date.accessioned2018-03-29T01:21:00Z
dc.date.available2018-03-29T01:21:00Z
dc.identifierToxicology Letters. v. 229, n. 1, p. 25-32, 2014-Aug.
dc.identifier1879-3169
dc.identifier10.1016/j.toxlet.2014.06.013
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/24910982
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201462
dc.identifier24910982
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1301695
dc.descriptionPolycyclic 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.
dc.description229
dc.description25-32
dc.languageeng
dc.relationToxicology Letters
dc.relationToxicol. Lett.
dc.rightsfechado
dc.rightsCopyright © 2014 Elsevier Ireland Ltd. All rights reserved.
dc.sourcePubMed
dc.subjectAir
dc.subjectAir Pollutants
dc.subjectBenzo(a)pyrene
dc.subjectBlotting, Western
dc.subjectCell Line
dc.subjectEnvironmental Pollutants
dc.subjectExtracellular Signal-regulated Map Kinases
dc.subjectGene Expression
dc.subjectHumans
dc.subjectIndicators And Reagents
dc.subjectMap Kinase Kinase 4
dc.subjectMitogen-activated Protein Kinases
dc.subjectPolycyclic Hydrocarbons, Aromatic
dc.subjectRna Interference
dc.subjectReal-time Polymerase Chain Reaction
dc.subjectSignal Transduction
dc.subjectTranscription Factor Ap-1
dc.subjectTranscriptional Activation
dc.subjectUrban Health
dc.subjectAir Particulate Matter
dc.subjectBenzo[a]pyrene
dc.subjectComplex Mixtures
dc.subjectMapk
dc.subjectPahs
dc.titleNanomolar Levels Of Pahs In Extracts From Urban Air Induce Mapk Signaling In Hepg2 Cells.
dc.typeArtículos de revistas


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