Responses in the brain proteome of Atlantic cod (Gadus morhua) exposed to methylmercury.
The molecular mechanisms underlying the neurotoxicity of methylmercury (MeHg), a ubiquitous environmental contaminant, are not yet fully understood. Furthermore, there is a lack of biomarkers of MeHg neurotoxicity for use in environmental monitoring. We have undertaken a proteomic analysis of brains from Atlantic cod (Gadus morhua) exposed to 0, 0.5 and 2 mg/kg MeHg administered by intraperitoneal injection. The doses were given in two injections, half of the dose on the first day and the second half after 1 week, and the total exposure period lasted 2 weeks. Using 2-DE coupled with MALDI-TOF MS and MS/MS, we observed the level of 71 protein spots to be 20% or more significantly altered following MeHg exposure, and successfully identified 40 of these protein spots. Many of these proteins are associated with main known molecular targets and mechanisms of MeHg-induced neurotoxicity in mammals, such as mitochondrial dysfunction, oxidative stress, altered calcium homeostasis and tubulin/disruption of microtubules. More interestingly, several of the affected proteins, with well-established or recently demonstrated critical functions in nervous system-specific processes, have not previously been associated with MeHg exposure in any species. These proteins include the strongest up-regulated protein, pyridoxal kinase (essential for synthesis of several neurotransmitters), G protein (coupled to neurotransmitter receptors), nicotinamide phosphoribosyl-transferase (protection against axonal degeneration), dihydropyrimidinase-like 5 (or collapsin response mediator protein 5, CRMP-5) (axon guidance and regeneration), septin (dendrite development), phosphatidylethanolamine binding protein (precursor for hippocampal cholinergic neurostimulating peptide) and protein phosphatase 1 (control of brain recovery by synaptic plasticity). The results of the present study aid our understanding of molecular mechanisms underlying MeHg neurotoxicity and defense responses, and provide a large panel of protein biomarker candidates for aquatic environmental monitoring.
Berg
Karin
K
Department of Molecular Biology, University of Bergen, PB 7803, N-5020 Bergen, Norway.
Puntervoll
Pål
P
Valdersnes
Stig
S
Goksøyr
Anders
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D029941:Fish Proteins / Q000378:metabolism*; D048389:Gadus morhua / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D009132:Muscles / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
D029941:Fish Proteins; D008767:Methylmercury Compounds; D020543:Proteome; D014874:Water Pollutants, Chemical