Brain proteome alterations of Atlantic cod ( Gadus morhua) exposed to PCB 153

Abstract

Polychlorinated biphenyls (PCBs) are still widespread environmental pollutants that bioaccumulate and biomagnify in the aquatic food chains despite the ban on their production. They constitute a class of 209 possible congeners with different chlorination pattern of the biphenyl ring structure resulting in many different toxicities and mechanisms of toxicity. The neurotoxicity of PCBs is relatively poorly understood, and biomarkers for their neurotoxic effects are lacking. We have carried out a proteomic analysis of brain tissue from Atlantic cod ( Gadus morhua) exposed to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153, ortho-substituted and non-coplanar), a previously demonstrated neurotoxic congener and the most prevalent congener in biological samples. The fish received 0, 0.5, 2 and 8 mg/kg PCB 153 by intraperitoneal injection, half of the dose on the first day and the second half after one week, and were exposed for two weeks in total. Using a 2-DE approach we found 56 protein spots to be 20% or more (≤0.8-fold or ≥1.2-fold) significantly different between at least one of the three PCB 153-exposed groups and the control group, and 27 of these were identified by MALDI-TOF MS and MS/MS. Approximately 80% of the differentially regulated proteins may be associated with a non stressor-specific response and/or have previously been classified as notoriously differentially regulated in 2-DE/MS based proteomics studies, such as alterations/responses in energy metabolism, cytoskeleton, protein synthesis, protein degradation (ubiquitin-proteasome system), cellular growth, cycle and death (14-3-3 protein), and (surprisingly) axon guidance (dihydropyrimidinase-like 2 (=collapsin response mediator protein 2, CRMP-2)). The six remaining affected proteins include the strongest up-regulated protein, pyridoxal kinase (essential for synthesis of neurotransmitters such as dopamine, serotonin and GABA), nicotinamide phosphoribosyl-transferase (involved in protection against axonal degeneration) and protein phosphatase 1 (controls brain recovery by synaptic plasticity). The last three of these six proteins (deltex, Rab14 and sorting nexin 6) may preliminarily identify involvement of the Notch signaling pathway and endosomal function in PCB 153-induced neurotoxicity. Our findings constitute novel clues for further research on PCB 153 mode of action in brain, and a proper selection of proteins may, following validation, be applicable in a panel of biomarkers for aquatic environmental monitoring.