Comparative effects of dietary methylmercury on gene expression in liver, skeletal muscle, and brain of the zebrafish (Danio rerio).
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.
Laboratoire d'Ecophysiologie et Ecotoxicologie des Systèmes Aquatiques, Université Bordeaux 1/UMR CNRS 5805, Place du Dr Peyneau, 33120 Arcachon, France.
P
P
Gonzalez
Y
Y
Dominique
J C
JC
Massabuau
A
A
Boudou
J P
JP
Bourdineaud
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009930:Organic Chemicals / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015027:Zebrafish
D000975:Antioxidants; D002614:Chelating Agents; D008767:Methylmercury Compounds; D009930:Organic Chemicals; D017382:Reactive Oxygen Species; D008668:Metallothionein