Molecular basis of mercury interference in the body
Mercury, Mercury binding protein, Metabolic pathways altered by mercury, Systems Biology, Systems toxicology.
Mercury (Hg) is a heavy metal naturally present in the environment, but anthropogenic actions over the last five centuries are responsible for increasing the availability of mercury in the environment by 450%. Its economic importance is related to its ability to form amalgams with other metals, being used for the mining of silver and gold. Mercury exposure includes: occupational exposure, such as from people working in silver, gold and coal mines; use of dental amalgams; volcanic activity; and the consumption of food contaminated by methylmercury (MeHg), that is bioaccumulative and the main form of contamination of humans and other animals. Symptoms resulting from exposure include: nausea, vomiting, tremor, difficulty breathing, sensory disturbances, ataxia, dysarthria, visual field constriction, hearing disorders. The symptoms are a consequence of the accumulation of mercury in the body, but the acting mechanism of the Hg in the body, generating these symptoms is no fully elucidated yet. In purpose to understand the mechanism by which mercury causes intoxication and to identify the metabolic pathways which are being altered, the information present in the literature regarding the proteins to which mercury binds was curated. From the search for transcriptional data present in public repositories, we identified and analyzed a dataset of cell culture (hESCs) exposed to mercury compounds (MeHG, HgCl2 and HgBr2) to validate information from the literature. Through a search in the literature we found 21 proteins linked to mercury, which the most likely binding site are the thiol residues. In the differential expression assay, we identified 53 genes up-regulated and enriched for 139 biological processes, as for the down- regulated genes, 4 genes and 43 enriched biological processes were detected, however the PTPRZ1 gene is involved in 34 of them. Through this analysis, it is possible to conclude that mercury is capable of altering biological pathways related to cell death, as the cellular senescence pathway described in the literature, that precedes the process of cell death, and the pathways related to cell migration.