MECHANISMS FOR RENAL UPTAKE OF MERCURY

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DESCRIPTION (provided by applicant): Mercury is a significant environmental and occupational health hazard in many countries, including the United States. The primary site of mercury toxicity is the kidney, specifically the pars recta of the proximal tubule. Based on current data, we have formulated the following hypothesis: Inorganic mercury is taken up at the luminal and basolateral plasma membranes of the proximal tubular epithelium as a conjugate of thiol-containing biomolecules and this uptake occurs via known transporters, such as amino acid- and organic anion- transporters, through a mechanism involving molecular mimicry. The luminal uptake of mercuric ions is thought to involve amino acid transporters such as systems b0,+ , B0,+, or system ASC, while the basolateral uptake of mercury is thought to involve the organic anion transporters 1 and 3. To study the role of various transporters in the uptake of mercury, isolated perfused tubules will be used. In order to study the role of individual transporters, Xenopus oocytes will be injected with individual transporter RNA and Madin-Darby Canine Kidney and NRK- 52E cells will be stably transfected with individual amino acid- and organic anion- transport proteins. The role of each carrier in the transport of mercuric ions will be tested using functional biochemical assays. These experiments will also determine the specific species of mercury that is taken up at the plasma membrane. These studies are important in that they will determine the exact mechanisms that participate in the transport of mercury across the plasma membranes of the proximal tubular cells.