Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan 430072, China.
University of Chinese Academy of Sciences , Beijing 100049, China.
Environ Sci Technol. 2017 Jan 3;51(1):596-607. doi: 10.1021/acs.est.6b03990. Epub 2016 Dec 22.
In this study, for the first time, changes in expressions of proteins and profiles of metabolites in liver of the small, freshwater fish [Formula: see text] (zebrafish) were investigated after long-term exposure to environmentally relevant concentrations of microcystin-LR (MC-LR). Male zebrafish were exposed via water to 1 or 10 μg MC-LR/L for 90 days, and iTRAQ-based proteomics and H NMR-based metabolomics were employed. Histopathological observations showed that MC-LR caused damage to liver, and the effects were more pronounced in fish exposed to 10 μg MC-LR/L. Metabolomic analysis also showed alterations of hepatic function, which included changes in a number of metabolic pathways, including small molecules involved in energy, glucose, lipids, and amino acids metabolism. Concentrations of lactate were significantly greater in individuals exposed to MC-LR than in unexposed controls. This indicated a shift toward anaerobic metabolism, which was confirmed by impaired respiration in mitochondria. Proteomics revealed that MC-LR significantly influenced multiple proteins, including those involved in folding of proteins and metabolism. Endoplasmic reticulum stress contributed to disturbance of metabolism of lipids in liver of zebrafish exposed to MC-LR. Identification of proteins and metabolites in liver of zebrafish responsive to MC-LR provides insights into mechanisms of chronic toxicity of MCs.
在这项研究中，首次研究了长期暴露于环境相关浓度的微囊藻毒素-LR（MC-LR）后，小型淡水鱼[化学式：见文本]（斑马鱼）肝脏中蛋白质表达的变化和代谢物谱。雄性斑马鱼通过水暴露于 1 或 10μg MC-LR/L 90 天，并采用 iTRAQ 基于蛋白质组学和 H NMR 基于代谢组学进行研究。组织病理学观察表明，MC-LR 导致肝脏损伤，并且在暴露于 10μg MC-LR/L 的鱼类中更为明显。代谢组学分析还显示肝脏功能发生改变，包括涉及能量、葡萄糖、脂质和氨基酸代谢的小分子的许多代谢途径的改变。暴露于 MC-LR 的个体中的乳酸浓度明显高于未暴露对照。这表明向厌氧代谢转变，这通过线粒体呼吸受损得到证实。蛋白质组学显示，MC-LR 显著影响多种蛋白质，包括参与蛋白质折叠和代谢的蛋白质。内质网应激导致 MC-LR 暴露的斑马鱼肝中脂质代谢紊乱。鉴定对 MC-LR 有反应的斑马鱼肝中的蛋白质和代谢物，为 MC 慢性毒性的机制提供了深入的了解。
