Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve, Belgium.
Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve, Belgium; Irstea, UR RiverLy, Centre de Lyon-Villeurbanne, 5, 69625 Villeurbanne, France.
Aquat Toxicol. 2018 Jun;199:174-187. doi: 10.1016/j.aquatox.2018.03.025. Epub 2018 Mar 22.
Lipids, and their constitutive fatty acids, are key nutrients for fish health as they provide energy, maintain cell structure, are precursors of signalling molecules and act as nuclear receptor ligands. These specific roles may be of crucial importance in a context of exposure to pollutants. We recently showed that the fatty acid profile of rainbow trout liver cell phospholipids modulates sensitivity to an acute methylmercury challenge. In order to investigate mechanisms of effects, we herein tested whether specific polyunsaturated fatty acids (PUFAs) may protect cells from methylmercury through decreasing intracellular mercury accumulation and/or enhancing cellular defences (e.g. via modulation of gene expression patterns). We also investigated the inverse relationship and assessed the impact of methylmercury on cellular fatty acid metabolism. To do so, the fatty acid composition of rainbow trout liver cell phospholipids was first modified by incubating them in a medium enriched in a specific PUFA from either the n-3 family (alpha-linolenic acid, ALA; eicosapentaenoic acid, EPA) or the n-6 family (linoleic acid, LA; arachidonic acid, AA). Cells were then exposed to methylmercury (0.15 or 0.50 μM) for 24 h and sampled thereafter for assessing phospholipid fatty acid profile, intracellular total mercury burden, and expression pattern of genes involved in fatty acid metabolism, synthesis of PUFA-derived signalling molecules and stress response. We observed that cells incorporated the given PUFA and some biotransformation products in their phospholipids. Methylmercury had few impacts on this cellular phospholipid composition. None of the PUFA enrichments affected the cellular mercury burden, suggesting that the previously observed cytoprotection conferred by ALA and EPA was not linked to a global decrease in cellular accumulation of mercury. Fatty acid enrichments and methylmercury exposure both modulated gene expression patterns. Genes involved in the synthesis of PUFA-derived signalling molecules, in stress response and the orphan cytochrome P450 20A1 were identified as possible sites of interaction between fatty acids and methylmercury in rainbow trout liver cells.
脂质及其组成脂肪酸是鱼类健康的关键营养素，因为它们提供能量、维持细胞结构、是信号分子的前体，并作为核受体配体发挥作用。在暴露于污染物的情况下，这些特定的作用可能至关重要。我们最近表明，虹鳟鱼肝细胞磷脂的脂肪酸谱调节了对急性甲基汞挑战的敏感性。为了研究作用机制，我们在此测试了特定的多不饱和脂肪酸 (PUFA) 是否可以通过减少细胞内汞积累和/或增强细胞防御（例如通过调节基因表达模式）来保护细胞免受甲基汞的侵害。我们还研究了相反的关系，并评估了甲基汞对细胞脂肪酸代谢的影响。为此，首先通过在富含来自 n-3 家族（α-亚麻酸，ALA；二十碳五烯酸，EPA）或 n-6 家族（亚油酸，LA；花生四烯酸，AA）的特定 PUFA 的培养基中孵育虹鳟鱼肝细胞来改变其脂肪酸组成。然后将细胞暴露于甲基汞（0.15 或 0.50 μM）24 小时，此后取样以评估磷脂脂肪酸谱、细胞内总汞负担以及参与脂肪酸代谢、PUFA 衍生信号分子合成和应激反应的基因的表达模式。我们观察到细胞将给定的 PUFA 和一些生物转化产物纳入其磷脂中。甲基汞对这种细胞磷脂组成几乎没有影响。PUFA 的富集都没有影响细胞内的汞负担，这表明之前观察到的 ALA 和 EPA 赋予的细胞保护作用与细胞内汞积累的总体减少无关。脂肪酸富集和甲基汞暴露都调节了基因表达模式。参与 PUFA 衍生信号分子合成、应激反应和孤儿细胞色素 P450 20A1 的基因被确定为脂肪酸和甲基汞在虹鳟鱼肝细胞中相互作用的可能位点。
