Mercury-induced toxicity: Mechanisms, molecular pathways, and gene regulation

Mercury is a well-known neurotoxicant for humans and wildlife. The epidemic of mercury poisoning in Japan has clearly demonstrated that chronic exposure to methylmercury (MeHg) results in serious neurological damage to the cerebral and cerebellar cortex, leading to the dysfunction of the central nervous system (CNS), especially in infants exposed to MeHg in utero. The occurrences of poisoning have caused a wide public concern regarding the health risk emanating from MeHg exposure; particularly those eating large amounts of fish may experience the low-level and long-term exposure. There is growing evidence that MeHg at environmentally relevant concentrations can affect the health of biota in the ecosystem. Although extensive in vivo and in vitro studies have demonstrated that the disruption of redox homeostasis and microtube assembly is mainly responsible for mercurial toxicity leading to adverse health outcomes, it is still unclear whether we could quantitively determine the occurrence of interaction between mercurial and thiols and/or selenols groups of proteins linked directly to outcomes, especially at very low levels of exposure. Furthermore, intracellular calcium homeostasis, cytoskeleton, mitochondrial function, oxidative stress, neurotransmitter release, and DNA methylation may be the targets of mercury compounds; however, the primary targets associated with the adverse outcomes remain to be elucidated. Considering these knowledge gaps, in this article, we conducted a comprehensive review of mercurial toxicity, focusing mainly on the mechanism, and genes/proteins expression. We speculated that comprehensive analyses of transcriptomics, proteomics, and metabolomics could enhance interpretation of "omics" profiles, which may reveal specific biomarkers obviously correlated with specific pathways that mediate selective neurotoxicity.