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Mechanisms of Arsenic Transport
in Kidney  |
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3-D-QSAR of substrates. |
Background
A fundamental element in the development, calibration, and validation of a physiological kinetic model of the behavior of heavy metals (including arsenic) in the body is knowledge of the pathways and rates of their flux across target tissue cell membranes.
Goal
To determine how the major forms of arsenic enter and leave cells of the kidney.
Objectives
1. Define the mechanisms of cellular transport of heavy metals and metal-containing conjugates (e.g., As(III), As(V), methylarsonic acid and dimethylarsinic acid).
2. Determine the kinetics of interaction of As(III), As(V), methylarsonic acid and dimethylarsinic acid with transporters in test tissue.
3. Determine if the interactions of several arsenic species with intracellular glutathione will exert a profound effect on the export of arsenic from cells and, therefore, influences the nature of the arsenic species to which other target cells are exposed.Significant Findings
1. Cloning and characterization of two anion transporters in renal tissue: OAT1 and OAT3.
2. Demonstration that anionic arsenic chelators (including DMPS and DMSA) enter kidney cells via OAT1/3 and the Na-dicarboxylate transporter, NaDC-3.
3. Development of a 3D structural model of the anion transporter proteins, OAT1 and OAT3.
Contact
Stephen Wright
shwright@email.arizona.edu
520-626-4253
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Southwest Hazardous Waste Program |
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1996-2006,
The University of Arizona Last update: April 11, 2006 |
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