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Type: Artigo de periódico
Title: Nanomolar Levels Of Pahs In Extracts From Urban Air Induce Mapk Signaling In Hepg2 Cells.
Author: Jarvis, I W H
Bergvall, C
Morales, D A
Kummrow, F
Umbuzeiro, G A
Westerholm, R
Stenius, U
Dreij, K
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.
Subject: Air
Air Pollutants
Blotting, Western
Cell Line
Environmental Pollutants
Extracellular Signal-regulated Map Kinases
Gene Expression
Indicators And Reagents
Map Kinase Kinase 4
Mitogen-activated Protein Kinases
Polycyclic Hydrocarbons, Aromatic
Rna Interference
Real-time Polymerase Chain Reaction
Signal Transduction
Transcription Factor Ap-1
Transcriptional Activation
Urban Health
Air Particulate Matter
Complex Mixtures
Rights: fechado
Identifier DOI: 10.1016/j.toxlet.2014.06.013
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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