title: Responses of the Proteome and Metabolome in Livers of Zebrafish Exposed Chronically to Environmentally Relevant Concentrations of Microcystin-LR.
abstract: 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 and1H 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.
authors.affiliation: 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.
authors.forename: Liang
authors.identifier: 0000-0001-6548-5000
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan 430072, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan 430072, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan , Saskatoon, Saskatchewan S7N 5B3, Canada.|School of Biological Sciences, University of Hong Kong , Hong Kong SAR, China.|State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, 210089, China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan 430072, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D052998:Microcystins / Q000633:toxicity; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D052998:Microcystins; D020543:Proteome