Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153.
Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153.
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DOI：
10.1016/j.aquatox.2017.01.014
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发表时间：
2017-04
影响因子：
4.5
通讯作者：
F. Yadetie;E. Oveland;A. Døskeland;F. Berven;Anders Goksøyr;O. Karlsen
中科院分区：
文献类型：
--
作者：
F. Yadetie;E. Oveland;A. Døskeland;F. Berven;Anders Goksøyr;O. Karlsen
PCB 153 是生物样品中检测到的最丰富的 PCB 同系物之一。尽管 20 世纪 70 年代末禁止生产和使用多氯联苯，但它是一种持久性化合物，仍然存在于环境中。它在生物群中具有强烈的生物累积和生物放大倾向，研究表明它是一种内分泌和代谢干扰物。为了研究毒性机制，我们将大西洋鳕鱼 (Gadus morhua) 暴露于不同剂量的 PCB 153（0、0.5、2 和 8 mg/kg 体重）两周，并使用无标记定量蛋白质组学检查对肝脏蛋白表达的影响。对肝脏蛋白质组进行无标记液相色谱-质谱分析，定量了 1272 种蛋白质，其中 78 种蛋白质在 PCB 153 处理剂量组中与对照组相比受到差异性调节。功能富集分析表明，受到显着影响的途径与脂质代谢、细胞骨架重塑、细胞周期和细胞粘附有关。重要的是，主要影响似乎是对脂质代谢的影响，新脂肪酸合成途径中酶的上调，与之前的转录组学结果一致。在 PCB 153 处理的鱼中也观察到血浆甘油三酯水平升高，这与脂肪生成基因和蛋白质的诱导一致。结果表明 PCB 153 会扰乱大西洋鳕鱼肝脏中的脂质代谢。脂肪生成酶和血浆甘油三酯水平升高进一步表明脂肪酸和甘油三酯的合成增加。
PCB 153 is one of the most abundant PCB congeners detected in biological samples. It is a persistent compound that is still present in the environment despite the ban on production and use of PCBs in the late 1970s. It has strong tendencies to bioaccumulate and biomagnify in biota, and studies have suggested that it is an endocrine and metabolic disruptor. In order to study mechanisms of toxicity, we exposed Atlantic cod (Gadus morhua) to various doses of PCB 153 (0, 0.5, 2 and 8 mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using label-free quantitative proteomics. Label-free liquid chromatography-mass spectrometry analysis of the liver proteome resulted in the quantification of 1272 proteins, of which 78 proteins were differentially regulated in the PCB 153-treated dose groups compared to the control group. Functional enrichment analysis showed that pathways significantly affected are related to lipid metabolism, cytoskeletal remodeling, cell cycle and cell adhesion. Importantly, the main effects appear to be on lipid metabolism, with up-regulation of enzymes in thede novofatty acid synthesis pathway, consistent with previous transcriptomics results. Increased plasma triglyceride levels were also observed in the PCB 153 treated fish, in agreement with the induction of the lipogenic genes and proteins. The results suggest that PCB 153 perturbs lipid metabolism in the Atlantic cod liver. Elevated levels of lipogenic enzymes and plasma triglycerides further suggest increased synthesis of fatty acids and triglycerides.