Agradecimentos: The authors would like to thank Professor Bengt Jernström for valuable comments on the manuscript and helpful discussions throughout. This work was supported by the Swedish Research Council Formas, Cancer- och Allergifonden, Stockholm University, CAPES – Coodernação de...

Agradecimentos: The authors would like to thank Professor Bengt Jernström for valuable comments on the manuscript and helpful discussions throughout. This work was supported by the Swedish Research Council Formas, Cancer- och Allergifonden, Stockholm University, CAPES – Coodernação de Aperfeiçoamento de Pessoal de Nível Superior (to D.A.M) and EU/FP7 Marie Curie IRG (to K.D). The authors declare no competing financial interests

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...

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

COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES

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