Environmental Chemistry Department, IDAEA -CSIC-, C/ Jordi Girona 18-26, 08034 Barcelona, Spain.
Environmental Chemistry Department, IDAEA -CSIC-, C/ Jordi Girona 18-26, 08034 Barcelona, Spain.
Aquat Toxicol. 2021 Feb;231:105733. doi: 10.1016/j.aquatox.2020.105733. Epub 2020 Dec 24.
There is increasing awareness that exposure to endocrine disrupters interferes with lipid homeostasis in vertebrates, including fish. Many of these compounds exert their action by binding to nuclear receptors, such as peroxisome proliferator-activated receptors and retinoid X receptor. This work investigates the use of fish liver cells (PLHC-1 and ZFL cells) for the screening of metabolic and lipid disrupters in the aquatic environment by assessing changes in the cell's lipidome after exposure to the model compounds, tributyltin chloride and all-trans retinoic acid. Lipid extracts, analyzed by FIA-ESI (+/-) Orbitrap, evidenced the intracellular accumulation of triglycerides and diglycerides in both cell models after exposure to 100 and 200 nM tributyltin chloride for 24 h. Exposure to 1 μM all-trans retinoic acid led to a significant accumulation of triglycerides in PLHC-1 cells, while few triglycerides were accumulated in ZFL cells. Retinoic acid (cyp26b1, cyp3a65, lrata) and lipid metabolism (fasn, scd, elovl6) related genes were up-regulated by tributyltin chloride and all-trans retinoic acid, while only all-trans retinoic acid down-regulated the expression of dgat1a. The two cell models show sensitivity and responses to tributyltin chloride and all-trans retinoic acid comparable to those previously reported in mammalian cells. These results support the use of fish liver cells as alternative models for the detection of contaminants that act as lipid disrupters in the aquatic environment.
人们越来越意识到，内分泌干扰物的暴露会干扰脊椎动物（包括鱼类）的脂质动态平衡。许多此类化合物通过与核受体（如过氧化物酶体增殖物激活受体和视黄酸 X 受体）结合来发挥作用。本研究通过评估暴露于模型化合物三丁基锡氯化物和全反式视黄酸后细胞脂质组的变化，利用鱼类肝细胞（PLHC-1 和 ZFL 细胞）来筛选水生环境中的代谢和脂质干扰物。通过 FIA-ESI（+/-）轨道阱分析脂质提取物，发现在暴露于 100 和 200 nM 三丁基锡氯化物 24 小时后，两种细胞模型中都有甘油三酯和二甘油酯在细胞内积累。暴露于 1 μM 全反式视黄酸会导致 PLHC-1 细胞中甘油三酯的大量积累，而 ZFL 细胞中积累的甘油三酯很少。视黄酸（cyp26b1、cyp3a65、lrata）和脂质代谢（fasn、scd、elovl6）相关基因被三丁基锡氯化物和全反式视黄酸上调，而只有全反式视黄酸下调了 dgat1a 的表达。这两种细胞模型对三丁基锡氯化物和全反式视黄酸的敏感性和反应与以前在哺乳动物细胞中报道的相似。这些结果支持使用鱼类肝细胞作为检测水生环境中作为脂质干扰物的污染物的替代模型。
