Quantitative analysis of the polar cod (Boreogadus saida) hepatic proteome highlights interconnected responses in cellular adaptation and defence mechanisms after dietary benzo[a]pyrene exposure.

Increased industrial offshore activities in northern waters raise the question of impact of polycyclic aromatic hydrocarbons (PAHs) on key Arctic marine species. One of these is the ecologically important polar cod (Boreogadus saida), which is the primary food source for Arctic marine mammals and seabirds. In the present work, we have conducted the first comprehensive proteomics study with this species by exploring the effects of dietary PAH exposure on the hepatic proteome, using benzo[a]pyrene (BaP) as a PAH model-compound. Functional annotation and pathway analyses of the proteins affected by BaP revealed a concerted cellular response for handling and adopting to its exposure, involving numerous interconnected signalling pathways and metabolic processes. In accordance with BaP being a strong aryl hydrocarbon receptor (Ahr) agonist, a prominent activation of the canonical Ahr signalling pathway was observed, including upregulation of Ahr target proteins like cytochrome P450 enzymes and microsomal glutathione transferase. Furthermore, cellular pathways for handling oxidative stress, protein misfolding and degradation, as well as endoplasmic reticulum stress and calcium homeostasis, were also activated by BaP, possibly as a result of the formation of harmful and redox reactive BaP metabolites via phase I metabolism. Activation of proteins that participate in the acute-phase response was also observed, suggesting prevalent tissue- and cellular damage that triggers the immune system and inflammatory responses. Our results at the protein level aligns well with previous analyses on the effects of BaP on the polar cod liver transcriptome and support that exposure to BaP and structural similar PAHs can cause adverse effects on polar cod physiology. Although more data is required for demonstrating how these molecular responses propagate to higher levels of biological organisation, increased knowledge about the initial cellular and molecular mechanisms that induce toxicity is a key-step towards a mechanistically informed impact assessment of PAH pollutants in the Arctic.