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

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

Author Jarvis, I. W. H. Google Scholar
Bergvall, C. Google Scholar
Morales, D. A. Google Scholar
Kummrow, F. Autor UNIFESP Google Scholar
Umbuzeiro, G. A. Google Scholar
Westerholm, R. Google Scholar
Stenius, U. Google Scholar
Dreij, K. Google Scholar
Institution Karolinska Inst
Stockholm Univ
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Polycyclic 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.
Keywords PAHs
Air particulate matter
Complex mixtures
Benzo[a]pyrene
MAPK
Language English
Sponsor Swedish Research Council Formas, Cancer- och Allergifonden, Stockholm University
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
EU/FP7 Marie Curie IRG
Date 2014-08-17
Published in Toxicology Letters. Clare: Elsevier B.V., v. 229, n. 1, p. 25-32, 2014.
ISSN 0378-4274 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 25-32
Origin http://dx.doi.org/10.1016/j.toxlet.2014.06.013
Access rights Closed access
Type Article
Web of Science ID WOS:000340044800004
URI http://repositorio.unifesp.br/handle/11600/38096

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