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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32ES012556-02
Application #
6789311
Study Section
Special Emphasis Panel (ZRG1-F10 (21))
Program Officer
Shreffler, Carol K
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$48,928
Indirect Cost
Name
Mercer University Macon
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
065365041
City
Macon
State
GA
Country
United States
Zip Code
31207
Bridges, Christy C; Battle, Jamie R; Zalups, Rudolfs K (2007) Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells. Toxicol Appl Pharmacol 221:251-60
Bridges, Christy C; Zalups, Rudolfs K (2006) System b0,+ and the transport of thiol-s-conjugates of methylmercury. J Pharmacol Exp Ther 319:948-56
Bridges, Christy C; Zalups, Rudolfs K (2005) Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol 204:274-308
Bridges, Christy C; Zalups, Rudolfs K (2005) Cystine and glutamate transport in renal epithelial cells transfected with human system x(-) (c). Kidney Int 68:653-64
Bridges, Christy C; Zalups, Rudolfs K (2004) Homocysteine, system b0,+ and the renal epithelial transport and toxicity of inorganic mercury. Am J Pathol 165:1385-94
Bridges, Christy C; Bauch, Christian; Verrey, Francois et al. (2004) Mercuric conjugates of cysteine are transported by the amino acid transporter system b(0,+): implications of molecular mimicry. J Am Soc Nephrol 15:663-73