Interactions between marine n-3 fatty acids and methylmercury in Atlantic salmon (Salmo salar)
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Methylmercury (MeHg) is an environmental contaminant widely distributed in the aquatic environment. MeHg toxicity is characterized by a broad range of molecular cellular effects, often, if not always, induced through the strong affinity MeHg has for thiol groups. Through epidemiological and experimental studies, it has been concluded that dietary status can beneficially affect the severity of MeHg toxicity. However, discrepancies observed in symptomatology after MeHg exposure under different dietary regimes have not yet been elucidated at the molecular level. In the present study, the molecular interactions between the marine n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with MeHg was sought investigated. Additionally, whether each specific n-3 marine fatty acids could affect MeHg toxicity in an ameliorating or detrimental manner, were investigated. MeHg toxicity in the kidney of Atlantic salmon (Salmo salar) was investigated both in vivo and in vitro, with subsequent investigation of the marine n-3 fatty acids impact on MeHg toxicity in vitro. An in vivo study was undertaken to explore how MeHg toxicity, at a sub-lethal level, is manifested in the proteome of the Atlantic salmon kidney. For in vitro studies, Atlantic Salmon Kidney (ASK) and Human Embryonic Kidney 293 (HEK293) cells were pre-incubated with DHA or EPA, before exposure to MeHg. These cells were subsequently analyzed for accumulation of MeHg, apoptosis, oxidative stress, and transcriptomic and proteomic differential regulation. MeHg toxicity in the kidney, and in kidney-derived cells, of the Atlantic salmon was characterized by differential regulation of protein markers related to apoptosis, oxidative stress, structural degeneration, disrupted calcium homeostasis, immunological effects, and effects on cell signalling. When cells were pre-incubated with DHA an increase in MeHg-induced apoptosis was observed, and DHA alone also increased the oxidative stress in HEK293 cells. When cells were pre-incubated with EPA, a decrease in apoptosis was observed. Both DHA and EPA affected several transcriptomic and proteomic markers concomitantly affected by MeHg. These included markers involved in apoptosis, calcium homeostasis, cell signalling, and structural degeneration. In conclusion, marine n-3 fatty acids affected the toxicity of MeHg. EPA may prove to be remedial, whereas DHA can be potentially augmenting, to the toxicity of MeHg. This finding underlines the importance of considering interaction effects between nutrient and contaminants when assessing the toxicity of environmental toxicants.
Paper I: Nøstbakken, O.J., Martin, S.A.M., Cash, P., Torstensen, B.E., Amlund, H., & Olsvik, P.A. (2011): “Dietary methylmercury alters the proteome in Atlantic salmon (Salmo salar) kidney”. In press. Aquatic Toxicology. The article is available at: http://hdl.handle.net/1956/51430Paper II: Nøstbakken, O.J., Bredal, I.L., Olsvik, P.A., Huang, T.S., & Torstensen, B.E.(2011): "Effect of marine omega 3 fatty acids on methylmercury-induced toxicity in fish and mammalian cells in vitro". Full text not available in BORA.Paper III: Nøstbakken, O.J., Goksøyr, A., Martin, S.A.M., Cash, P., & Torstensen, B.E. (2011): "Marine n-3 fatty acids alter the proteomic response to MeHg in Atlantic salmon kidney (ASK) cells". Full text not available in BORA.