Arsenic ranks first on the U.S. Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Priority superfund List of Hazardous Substances (www.atsdr.cdc.gov/cercla/05list.html) according to its toxicity and bioavailability. Arsenic exposure can cause many human diseases and is epidemic. In this study zebrafish will be established as a model organism to study arsenic metabolism and toxicity. In order to understand the toxicity of arsenic metalloids, it is necessary to identify how they are taken up into cells. Therefore we will initiate studies on the identification of uptake pathways for two major arsenic compounds in water, which are trivalent arsenite and pentavalent arsenate. Arsenite was previously demonstrated to be facilitated by family of aquaglyceroporins in microorganisms and mammals. Arsenate can be transported via phosphate transporters by molecular mimic of phosphate. The hypothesis is that members of zebrafish aquaglyceroporins and phosphate transporters are able to permeate trivalent arsenite and pentavalent arsenate and they are responsible for arsenic cellular accumulation in fish tissues. In this study, the functions of these transporters will be studied by heterologously expressing in oocytes from Xenopus leavis. Their expressions in different zebrafish tissues will also be determined. The identification of these pathways will explain the higher arsenic accumulation in fish species. My long-term goal is to identify the pathways that are involved in arsenic transport and cellular metabolism in zebrafish and study arsenic induced diseases in a zebrafish model.
This study will determine the routes of arsenic transport by two families of zebrafish membrane transporters, which are aquaglyceroporins and phosphate transporters. Uptake is the first step for metalloid arsenic to exert its cellular function, so identification of the uptake pathways is important for elucidating the first step in arsenic detoxification in fish and shed light on the arsenic toxicity and carcinogenesis in human.
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| Hamdi, Mohamad; Sanchez, Marco A; Beene, Lauren C et al. (2009) Arsenic transport by zebrafish aquaglyceroporins. BMC Mol Biol 10:104 |
