Responses of the Proteome and Metabolome in Livers of Zebrafish Exposed Chronically to Environmentally Relevant Concentrations of Microcystin-LR

Authors: Chen, Liang; Hu, Yufei; He, Jun; Chen, Jun; Giesy, John P.; Xie, Ping

In this study, for the first time, changes in expressions of proteins and profiles of metabolites in liver of the small, freshwater fish Danio rerio (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 mu g MC-LR/L for 90 days, and iTRAQ-based proteomics and H-1 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 mu g 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.

Volume: 51
Issue: 12
Pages: 596 - 607
Published Online: 2016
Full Text Link: http://dx.doi.org/10.1021/acs.est.6b03990