RESUMO
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.
Assuntos
Poluentes Atmosféricos/toxicidade , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Ar/análise , Poluentes Atmosféricos/análise , Benzo(a)pireno/toxicidade , Western Blotting , Linhagem Celular , Poluentes Ambientais/toxicidade , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Indicadores e Reagentes , MAP Quinase Quinase 4/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição AP-1/efeitos dos fármacos , Fator de Transcrição AP-1/genética , Ativação Transcricional/efeitos dos fármacos , Saúde da População UrbanaRESUMO
Time-resolved emissions of particulate polycyclic aromatic hydrocarbons (PAHs) and total organic particulate matter (OA) from a wood log stove and an adjusted pellet stove were investigated with high-resolution time-of-flight aerosol mass spectrometry (AMS). The highest OA emissions were found during the addition of log wood on glowing embers, that is, slow burning pyrolysis conditions. These emissions contained about 1% PAHs (of OA). The highest PAH emissions were found during fast burning under hot air starved combustion conditions, in both stoves. In the latter case, PAHs contributed up to 40% of OA, likely due to thermal degradation of other condensable species. The distribution of PAHs was also shifted toward larger molecules in these emissions. AMS signals attributed to PAHs were found at molecular weights up to 600 Da. The vacuum aerodynamic size distribution was found to be bimodal with a smaller mode (Dva â¼ 200 nm) dominating under hot air starved combustion and a larger sized mode dominating under slow burning pyrolysis (Dva â¼ 600 nm). Simultaneous reduction of PAHs, OA and total particulate matter from residential biomass combustion may prove to be a challenge for environmental legislation efforts as these classes of emissions are elevated at different combustion conditions.