Methylmercury has been well-known as a neurotoxicant since the fateful disasters in Japan in 1956 and 1965. However, we now have some more “recent insights into this old topic,” as Dr. Nicholas Ralston introduced in Monday’s symposium session Methylmercury’s Modes of Action: New Approaches to Understanding an Old Problem. The symposium approached the issue of methylmercury toxicity from a number of angles: from C. elegans to risk assessment of gene-environment interactions.
Dr. Michael Aschner presented how C. elegans has proven an effective tool to understand how methylmercury is able to get into the brain to cause cellular damage via amino acid transporters. This takes place through what he called “molecular mimicry,” as the structure of a methylmercury-cysteine conjugate is structurally similar to that of the amino acid methionine, and amino acid transporters are unable to discriminate between them.
Dr. Cristina Carvalho gave us something to think about related to the benefits of selenium and its role in the prevention of methylmercury toxicity due to the importance of enzymes containing selenocysteine, such as thioredoxin reductase. Thioredoxin reductase is necessary for a number of key physiological processes and signaling pathways and is inhibited by methylmercury and other mercury compounds.
Dr. Ralston followed up on this topic with a number of cleverly titled “SOS” mechanisms for methylmercury toxicity via selenocysteine (the last S in SOS was always selenium-related!). The “suicide substrate” free thiols of glutathione and thioredoxin will bind to methylmercury and then deliver the methylmercury to the much more reactive selenocysteines present in key selenoproteins like thioredoxin and glutathione peroxidase. High levels of selenium allow a much more rapid clearance of methylmercury. He encouraged us to eat more ocean fish that are high in selenium content to counteract the small amount of methylmercury that may also be present.
Prenatal exposure to methylmercury is known to cause long-term problems for development. Dr. Sandra Ceccatelli illustrated just how readily the consequences of exposure can be passed along through embryonic neural stem cells. Exposure of the parent neural stem cells to methylmercury led to a number of changes in the parent and methylmercury-naïve daughter cells, even beyond the second generation, including decreased proliferation, decreased methylation of DNA, and changes in the expression of genes associated with mitochondrial function.
Dr. Niladri Basu reminded us of the fact that genetic polymorphisms and epigenetics are important to consider when it comes to methylmercury toxicity and may even be critical in improving our ability to associate exposure with detectable levels of mercury. He illustrated that many of the pathways and enzymes we had previously heard about have polymorphisms that could explain differences in population-related responses to exposure. He also briefly mentioned his studies of mercury levels in the brains of polar bears and other animals and a similar decrease in global DNA methylation as Dr. Ceccatelli had discussed.
The speakers left us all with much to think about and a new, deeper understanding of the toxicity of the “old” toxicant methylmercury.