Comparative Effects of Dietary Methylmercury on Gene Expression in Liver, Skeletal Muscle, and Brain of the Zebrafish ( Danio rerio )

Université Bordeaux 1, Talence, Aquitaine, France
Environmental Science and Technology (Impact Factor: 5.33). 07/2005; 39(11):3972-80. DOI: 10.1021/es0483490
Source: PubMed

ABSTRACT

Effects of dietary methylmercury (MeHg) on gene expression were examined in three organs (liver, skeletal muscle, and brain) of the zebrafish (Danio rerio). Adult male fish were fed over 7, 21, and 63 days on three different diets: one control diet (C0: 0.08 microg of Hg g(-1), dry wt) and two diets (C1 and C2) contaminated by MeHg at 5 and 13.5 microg of Hg g(-1), dry wt. Total Hg and MeHg concentrations were determined in the three organs after each exposure duration, and a demethylation process was evidenced only in the liver. Thirteen genes known to be involved in antioxidant defenses, metal chelation, active efflux of organic compounds, mitochondrial metabolism, DNA repair, and apoptosis were investigated by quantitative real-time RT-PCR and normalized according to actin gene expression. Surprisingly, no change in the expression levels of these genes was observed in contaminated brain samples, although this organ accumulated the highest mercury concentration (63.5 +/- 4.4 microg g(-1), dry wt after 63 days). This lack of genetic response could explain the high neurotoxicity of MeHg. coxI and cytoplasmic and mitochondrial sod gene expressions were induced early in skeletal muscle and later in liver, indicating an impact on the mitochondrial metabolism and production of reactive oxygen species. Results demonstrated that skeletal muscle was not only an important storage reservoir but was also affected by MeHg contamination. The expression of the metallothionein mt2 and the DNA repair rad51 genes was up-regulated in liver between 21 and 63 days, whereas in skeletal muscle, mt2 remained uninduced, and gadd and rad51 were found to be repressed.

Download full-text

Full-text

Available from: Jean-Charles Massabuau, Nov 28, 2014
  • Source
    • "In Hg contaminated areas, studies with fish have demonstrated high Hg burdens in the liver (Navarro et al., 2009; Mieiro et al., 2012), 70% of which was accumulated in the inorganic form (I-Hg) (Mieiro et al., 2009). Liver has been acknowledged to be the primary target organ for Hg (Wang et al., 2013) as well as the main detoxifying organ, being able to demethylate organic mercury (O-Hg) into I-Hg forms (Gonzalez et al., 2005). Yasutake and Hirayama (2001) found that Hg demethylation occurs mainly in mitochondria, which is in agreement with findings by Wang et al. (2013) that HgCl 2 affects several proteins related with mitochondrial function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this work was to understand the extent of mercury toxic effects in liver metabolism under an episode of acute contamination. Hence, the effects of in vitro mercuric chloride in liver mitochondria were assessed in two commercial marine fish: Senegalese sole (Solea senegalensis) and gilthead seabream (Sparus aurata). Liver mitochondria were exposed to 0.2mgL(-1) of mercury, the average concentration found in fish inhabiting contaminated areas. Mercuric chloride depressed mitochondrial respiration state 3 and the maximal oxygen consumption in the presence of FCCP indicating inhibitory effects on the oxidative phosphorylation and on the electron transport chain, respectively. The inhibition of F1Fo-ATPase and succinate-dehydrogenase activities also corroborated the ability of mercury to inhibit ADP phosphorylation and the electron transport chain. This study brings new understanding on the mercury levels able to impair fish mitochondrial function, reinforcing the need for further assessing bioenergetics as a proxy for fish health status. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · May 2015 · Marine Pollution Bulletin
  • Source
    • "The cytotoxicity of MeHg has been attributed to disturbance of intracellular Ca 2+ levels, induction of oxidative stress or by disrupting function of proteins and peptides containing cysteine and methionine (Ceccatelli et al., 2010). In fish, apoptosis has been proposed to be one of the main effects of MeHg exposure (Gonzalez et al., 2005; Klaper et al., 2008). Klaper et al. (2008) also showed that MeHg exposure could affect the transcriptional levels of immune system genes in gonads and liver. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Selenium (Se) and its derivatives are known to have protective effects against mercury (Hg) toxicity in mammals. In this study we wanted to evaluate whether Se co-exposure affect the transcription of methylmercury (MeHg) toxicity-relevant genes in early life stages of fish. Juvenile Atlantic cod were exposed to regular feed (control), Se-spiked feed (3mg Sekg(-1)), MeHg-spiked feed (10mg Hgkg(-1)) or to Se- and MeHg-spiked feed (3mg Sekg(-1) and 10mg Hgkg(-1), respectively) for ten weeks. Liver tissue was harvested for transcriptional analysis when the fish were weighing 11.4±3.2g. Accumulated levels of Hg in liver of the two groups of fish exposed to MeHg were 1.5mg Hgkg(-1) wet weight, or 44-fold higher than in the control group, while the Se concentrations differed with less than 2-fold between the fish groups. Selenium co-exposure had no effect on the accumulated levels of Hg in liver tissue; however, MeHg co-exposure reduced the accumulated level of Se. Dietary exposure to MeHg had no effect on fish growth. Interaction effects between Se and MeHg exposure were observed for the transcriptional levels of CAT, GPX1, GPX3, NFE2L2, UBA52, SEPP1 and DNMT1. Significant effects of MeHg exposure were seen for DNMT1 and PPARG, while effects of Se exposure were seen for GPX4B and SEPP1A, as well as for DNA methyltransferase activity. The transcriptional results suggest, by considering up-regulation as a proxy for negative impact and at the tested concentrations, a pro-oxidative effect of Se co-exposure with MeHg, rather than an antioxidative effect.
    Full-text · Article · Jul 2014 · Chemosphere
  • Source
    • "Fish studies suggest that MeHg may disturb reproductive hormones, mediating smaller gonad development or atrophy, delays in spawning and effects on fecundity (Klaper et al., 2006, 2008), and act gender-specifically (Liu et al., 2013). Oxidative stress and apoptosis have been suggested to be two of the main effects of MeHg exposure in fish (Gonzalez et al., 2005; Klaper et al., 2008; Berg et al., 2010; Cambier et al., 2010; Richter et al., 2011). Conducting studies with Atlantic salmon (Salmo salar), it has recently been shown that oxidative stress is one of the major effects of MeHg exposure (Olsvik et al., 2011a; Nøstbakken et al., 2012a,b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent findings have shown that deep-water fish from coastal areas may contain elevated levels of mercury (Hg). Tusk (Brosme brosme) was collected from six locations in Hardangerfjord, a fjord system where the inner parts are contaminated by metals due to historic industrial activity. ICPMS was used to determine the accumulated levels of metals (Hg, MeHg, Cd, Pb, As, and Se) in the fish, whereas oxidative status of the liver was assessed by measuring TBARS, vitamin C, vitamin E and catalase activity. To find out whether accumulated Hg triggers toxicologically relevant transcriptional responses and in order to gain genomic knowledge from a non-model species, the liver transcriptome of the gadoid fish was sequenced and assembled, and RNA-seq and RT-qPCR were used to screen for effects of Hg. The results showed high levels of accumulated Hg in tusk liver, probably reflecting an adaptation to deep-water life history, and only a weak declining outward fjord gradient of Hg concentration in tusk liver. MeHg only accounted for about 17% of total Hg in liver, suggesting hepatotoxicity of both inorganic and organic Hg. Pathway analysis suggested an effect of Hg exposure on lipid metabolism and beta-oxidation in liver. Oxidative stress markers glutathione peroxidase 1 and ferritin mRNA, as well as vitamin C and vitamin E (alpha and gamma tocopherol) showed a significant correlation with accumulated levels of Hg. Many transcripts of genes encoding established markers for Hg exposure were co-regulated in the fish. In conclusion, tusk from Hardangerfjord contains high levels of Hg, with possible hepatic effects on lipid metabolism and oxidative stress.
    Full-text · Article · Oct 2013 · Aquatic toxicology (Amsterdam, Netherlands)
Show more