Quantitative proteomic analysis reveals the mode-of-action for chronic mercury hepatotoxicity to marine medaka (Oryzias melastigma)

Mercury (Hg) is a widespread persistent pollutant in aquatic ecosystems. We investigated the protein profiles of medaka (Oryzias melastigrna) liver chronically exposed to different mercuric chloride (HgCl2) concentrations (1 or 10 mu.g/L) for 60 d using two-dimensional difference gel electrophoresis (2D-DIGE), as well as cell ultrastructure and Hg content analysis of the hepatic tissue. The results showed that Hg exposure significantly increased metal accumulation in the liver, and subsequently damaged liver ultrastructure. Comparison of the 2D-DIGE protein profiles of the exposed and control groups revealed that the abundance of 45 protein spots was remarkably altered in response to Hg treatment. The altered spots were subjected to matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis, with the resultant identification of 33 spots. These proteins were mainly involved in cytoskeleton assembly, oxidative stress, and energy production. Among them, several proteins related to mitochondrial function (e.g. respiratory metabolism) were significantly altered in the treated hepatocytes, implying that this organelle might be the primary target for Hg attack in the cells. This study provided new insights into the molecular mechanisms and/or toxic pathways by which chronic Hg hepatotoxicity affects aquatic organisms, and also provided basic information for screening potential biomarkers for aquatic Hg monitoring. (C) 2013 Elsevier B.V. All rights reserved.