Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

Abstract

Using synchrotron x-ray fluorescence mapping, we have examined the uptake and localization of organic mercury in zebrafish larvae. Strikingly, the greatest accumulation of methyl and ethyl mercury compounds was highly localized in the rapidly dividing lens epithelium, with lower levels going to brain, optic nerve, and various other organs. The data suggest that the reported impairment of visual processes by mercury may arise not only from previously reported neurological effects, but also from direct effects on the ocular tissue. This novel approach is a powerful tool for directly investigating the molecular toxicology of heavy metals, and should be equally applicable to the study of a wide range of elements in developing embryos.methylmercury ͉ thimerosal ͉ x-ray fluorescence mapping ͉ eye lens T oxic organic mercury compounds worry many communities worldwide, yet the detailed mechanisms underlying their transport and toxicity remain uncertain (1). These neurotoxic compounds are particularly insidious due to the latency in onset of toxic symptoms and have caused several devastating masspoisonings of humans. Adults are affected, but exposure in utero has resulted in severe consequences such as microcephaly, cerebropalsy, seizures, and mental retardation. Methylmercury (MeHg) compounds are actively transported across cell membranes (2) although not, as originally thought, by molecular mimicry of methionine (3). Beyond this, however, our knowledge of the mechanisms underlying organic mercury (Hg) toxicity is fragmentary. MeHg-induced changes in cellular Ca 2ϩ have been shown to be important (4-7), as has oxidative stress (4), and glutamate metabolism (8). In both yeast and human cells, overexpression of the ubiquitin-targeting enzyme Cdc34 confers protection against the cytotoxic effects of MeHg, which leads to the suggestion that an unknown protein containing a signal for ubiquitination by Cdc34 is involved in the development of the cytotoxic effects of MeHg (9-11).Zebrafish (Danio rerio) are common model organisms for the study of embryonic development, and have found increasing use in vertebrate toxicology (12). While embryonic and larval zebrafish previously have been used to study the toxic effects of MeHg exposure at the whole body (13,14) and at the molecular level (15), there are no available data on MeHg uptake and accumulation with respect to different tissues and organs. Such information is critical to properly integrate information on tissue and cell specific impacts of Hg with uptake and accumulation of the metal at the whole animal level. We present herein a novel approach to the investigation of heavy-metal toxicity using synchrotron x-ray fluorescence imaging (16) to directly image metal localization within zebrafish larvae and to observe remarkable differential accumulation of organic Hg using this technique. Strikingly, we find that both methyl and ethyl Hg derivatives are concentrated to the greatest degree in lens epithelium with lower levels present in the brain, optic nerve, and other organs....

Phenylthiourea alters toxicity of mercury compounds in zebrafish larvae

“…In these previous studies, the highest mercury concentrations in zebrafish exposed to mercuric chloride were found in the olfactory epithelial cells [7]. In contrast, methylmercury chloride preferentially targeted the developing lens [5][6][7][8]. While zebrafish exposed to mercuric chloride accumulated mercury in the ventricular region of the brain, zebrafish exposed to methylmercury chloride accumulated mercury in the muscle tissue [7].…”

“…Key characteristics that make the zebrafish an excellent model vertebrate system include nearly transparent embryos, rapid development outside the mother, large egg clutch, and a fully sequenced genome [2]. As a model vertebrate system for studying the development of the embryo, researchers have used zebrafish to explore metal toxicity [2][3][4][5][6][7][8] as well as various human diseases [1,9].…”

The Chemical Nature of Mercury in Human Brain Following Poisoning or Environmental Exposure

“…For case 2, samples of sufficiently large dimension were available to measure X-ray fluorescence imaging (19). The results of such measurements are shown in Figure 5 with the Hg localization shown in red, Se in blue, and Zn in green.…”

Simple and signal-off electrochemical biosensor for mercury(II) based on thymine-mercury-thymine hybridization directly on graphene

“…As a kind of widely used heavy metal ion, the water-soluble mercuric (II) ion (Hg 2+ ) is a highly toxic environmental pollutant [1][2][3]. It is mainly methylated to organic mercury and generates enrichment effect through the food chain, resulting in the accumulation in the body [4,5], which is serious harm to the human immune system and the nervous system, and it also has been implicated in a number of fatal diseases such as minamata disease, pulmonary edema, cyanosis and nephrotic syndrome [5][6][7][8][9]. The mercury ion has been listed as the primary monitoring pollutants in the Global Environmental Monitoring System (GEMS).…”