Identifying Health Impacts of Exposure to Copper Using Transcriptomics and Metabolomics in a Fish Model

Abstract

Copper (Cu) is a micronutrient essential for the biochemical functioning of numerous processes in vertebrates but is also often present in the aquatic environment at concentrations able to cause adverse health effects in aquatic organisms. This study investigated the signaling pathways mediating the effects of exposure to Cu using a toxicogenomic approach in a fish model, the stickleback ( Gasterosteus aculeatus ). Freshwater-acclimated male fish were exposed via the water to Cu, including at environmentally relevant concentrations (3.2-128 microg of Cu/L for 4 days), and the biological responses explored through analyses of the hepatic transcriptome and metabolome and phenotypic end points, including assessment of DNA damage in blood cells. The Cu exposures resulted in DNA strand breaks in blood cells at all exposure concentrations and alterations in hepatic gene expression and metabolite concentrations in a concentration-dependent manner (from 10 microg of Cu/L). Genes associated with the cholesterol biosynthesis pathway were significantly over-represented and consistently down-regulated (at 128 microg of Cu/L), similar to that occurring in a mouse model for Wilson's disease. Additionally, inductions in metallothionein and catalase were also observed. The concentrations of NAD(+) and lactate increased significantly with the Cu exposure, consistent with a shift toward anaerobic metabolism, and these aligned closely with changes observed in gene expression. The pathways of Cu toxicity identified in our study support the conserved mechanisms of Cu toxicity from lower vertebrates to mammals, provide novel insights into the deleterious effects of Cu in fish, and further demonstrate the utility of fish as environmental sentinels for chemical impacts on both environmental and human health.

Metabolic responses to metal pollution in shrimp Crangon affinis from the sites along the Laizhou Bay in the Bohai Sea

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Proteomic and metabolomic responses in hepatopancreas of Mytilus galloprovincialis challenged by Micrococcus luteus and Vibrio anguillarum

“…With the emergence and development of system biology techniques, including genomics, transcriptomics, proteomics and metabolomics, have offered great potential in unraveling biological problems and have been successfully employed in multiple areas such as environmental sciences, drug discovery and immunology [11][12][13]. Among these approaches, proteomics can theoretically present all the proteins encoded by the given genome in an organism [14].…”

“…Since proteomics and metabolomics may characterize the perturbations in metabolites and proteins involved in the same metabolic pathway, their combination can better understand the biological effects of stressors in organisms [21]. These perturbed metabolites and proteins are a definite set of molecular biomarkers related to biological effects of stressors [11,12]. Therefore, these two '-omic' techniques provide a great potential in environmental monitoring of environmental stressors, such as pathogens, using corresponding metabolite and protein biomarkers.…”

A metabolomic study on the biological effects of metal pollutions in oysters Crassostrea sikamea

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