Comparative toxicogenomic responses of mercuric and methyl-mercury

Abstract

BackgroundMercury is a ubiquitous environmental toxicant that exists in multiple chemical forms. A paucity of information exists regarding the differences or similarities by which different mercurials act at the molecular level.ResultsTranscriptomes of mixed-stage C. elegans following equitoxic sub-, low- and high-toxicity exposures to inorganic mercuric chloride (HgCl2) and organic methylmercury chloride (MeHgCl) were analyzed. In C. elegans, the mercurials had highly different effects on transcription, with MeHgCl affecting the expression of significantly more genes than HgCl2. Bioinformatics analysis indicated that inorganic and organic mercurials affected different biological processes. RNAi identified 18 genes that were important in C. elegans response to mercurial exposure, although only two of these genes responded to both mercurials. To determine if the responses observed in C. elegans were evolutionarily conserved, the two mercurials were investigated in human neuroblastoma (SK-N-SH), hepatocellular carcinoma (HepG2) and embryonic kidney (HEK293) cells. The human homologs of the affected C. elegans genes were then used to test the effects on gene expression and cell viability after using siRNA during HgCl2 and MeHgCl exposure. As was observed with C. elegans, exposure to the HgCl2 and MeHgCl had different effects on gene expression, and different genes were important in the cellular response to the two mercurials.ConclusionsThese results suggest that, contrary to previous reports, inorganic and organic mercurials have different mechanisms of toxicity. The two mercurials induced disparate effects on gene expression, and different genes were important in protecting the organism from mercurial toxicity.

Interrogating conserved elements of diseases using Boolean combinations of orthologous phenotypes

“…The mechanisms for mercury toxicity are incompletely understood, but it seems clear that even if the two mechanisms are the same or similar (as argued by Clarkson et al [18]), the organismal and cellular responses differ. Thus, we believe this phenolog to be consistent with the findings of McElwee et al [17].…”

“…However, the response to methylmercury GO annotation is a child node of response to organic substance in the directed acyclic graph, not response to metal ion. A recent article by McElwee et al examines the effects of organic (MeHgCl) and inorganic mercury (HgCl 2 ) on C. elegans, finding eighteen genes which were important to mercurial exposure response -and only two which responded to both types of mercury [17]. The mechanisms for mercury toxicity are incompletely understood, but it seems clear that even if the two mechanisms are the same or similar (as argued by Clarkson et al [18]), the organismal and cellular responses differ.…”

Bioactivity of nanosilver in Caenorhabditis elegans : Effects of size, coat, and shape

“…Comparing our results to published gene expression data sets, we found many alternately regulated genes in common with C. elegans response to infection, including Microbacterium nematophilum [51] , Pseudomonas aeruginosa [52] , [53] , Drechmeria coniospora [43] , Leucobacter chromiireducens [54] , Candida albicans [55] , Vibrio cholerae [56] , and other pathogens [57] . Genes that were included in the 20nmAgCit general metal response category included those that were differentially regulated in the same direction as by mercury [58] , cadmium [59] , [60] , and/or arsenic [61] , [62] . Gene regulation in the same direction as in response to oxidative stress [63] , [64] , heat shock [65] , ethanol [66] , organophosphates [62] , [67] , [68] , [69] and other xenobiotics including glucose [70] , [71] , [72] , was combined together into a single category, Xen/Str.…”

Adverse effects of coal combustion related fine particulate matter (PM 2.5 ) on nematode Caenorhabditis elegans

“…A series of sublethal endpoints such as lifespan, reproduction, locomotion behavior, intestinal development, and oxidative stress have been employed to evaluate the adverse effects of different environmental toxicants on nematodes (Donkin and Dusenbery, 1993;Wang et al, 2010;Liu et al, 2012;Li et al, 2013;Tseng et al, 2013;Zhang et al, 2013;McElwee et al, 2013;Rui et al, 2013;Leelaja and Rajini, 2013).…”