Abstract
Graphene oxide (GO) is an engineered nanomaterial which was demonstrated to have outstanding capacity for adsorption of organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), the ligands and activators of the aryl hydrocarbon receptor (AhR). Due to the partially overlapping ligand capacity of AhR and pregnane X receptor (PXR), we tested the impact of GO particles on their signalling. While reporter gene assay revealed potentiating effect of GO on ligand-activated AhR-dependent luciferase activity, there was no effect for PXR. However, inducible target genes for AhR (CYP1A1) or PXR (ABCB1) were decreased at mRNA as well as protein levels by the presence of GO in HepG2 (for AhR), LS180 (for PXR) or primary human hepatocytes (both receptors). Moreover, the presence of GO diminished PXR and AhR protein levels in primary cultures of human hepatocytes. This was partially reversed by proteasome inhibitor MG132 for AhR but not for PXR. In conclusion, GO decreases ligand-stimulated activities of AhR and PXR in human cells.
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