Pregnane X receptor (PXR) signaling in seabream primary hepatocytes exposed to extracts of seawater samples collected from polycyclic aromatic hydrocarbons (PAHs)-contaminated coastal areas

- Seabream hepatocytes were exposed to seawater extracts from PAH-polluted sites.
- Exposure produced increased expression of both PXR and its target CYP3A.
- Seawater extracts induced LXRα gene transcription in parallel to that of SREBP-1c.
- Samples with relevant PAH levels have the potential to affect multiple pathways.

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants damaging to the marine environment and the wildlife. Herein, we investigated the effects of extracts from coastal seawaters (central Adriatic sea, Italy), showing high concentrations of PAHs, on pregnane X receptor (PXR)-transcriptional regulation of the cytochrome P450 3A (CYP3A) gene using seabream primary hepatocytes. The results show that concentrated extracts of seawater with original ΣPAH concentrations above the putative threshold of 30 ng L−1 increased expression of PXR and its main target gene, CYP3A. Similar results were observed for LXR and its target gene SREBP-1c suggesting pathway cross-talk. These data are further supported by the finding of multiple PXR and LXR response elements in the putative promoters of their target genes. Overall, our data indicate the capacity of seawater extracts, containing environmentally relevant levels of PAHs, to affect multiple pathways, including lipid and cholesterol metabolism.