Figure 1.

Activation of Nrf2 and AhR signaling pathways. Inorganic components of PM, such as metals, cross the cell membrane by facilitated diffusion/membrane transport proteins, where they then induce oxidative stress. Organic components such as PAHs are able to span the cells’ membrane due to their lipophilic characteristics and can also act as AhR ligands. Nrf2 is bound to KEAP-1 in the cytosol; a change in redox homeostasis leads to conformational changes, leading to translocation of Nrf2 to the nucleus. Activation of the Nrf2 pathway is mediated by the ARE enhancer sequence in target genes. AhR can be directly activated by PAHs or naturally occurring compounds and endogenous ligands, which bind to AhR and facilitate AhR translocation to the nucleus, where it binds to XRE and activates phase I/II enzyme genes. Activation of the AhR leads to oxidative stress due to metabolism of the ligand and induction of CYP enzymes.