| 16479312 |
Lu WJ, Tamai I, Nezu J, Lai ML, Huang JD: Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells. J Biomed Sci. 2006 Jul;13(4):525-33. Epub 2006 Feb 15.
Arsenic is an established human carcinogen. The role of aquaglyroporins (AQPs) in arsenic disposition was recently identified. In order to examine whether organic anion transporting polypeptide-C (OATP-C) also plays a role in arsenic transport, OATP-C cDNA was transfected into cells of a human embryonic kidney cell line (HEK-293). Transfection increased uptake of the model OATP-C substrate, estradiol-17beta-D-glucuronide, by 10-fold. In addition, we measured uptake and cytotoxicity of arsenate, arsenite, monomethylarsonate (MMA (V)), and dimethylarsinate (DMA (V)). Transfection of OATP-C increased uptake and cytotoxicity of arsenate and arsenite, but not of MMA (V) or DMA (V). Rifampin and taurocholic acid (a substrate of OATP-C) reversed the increased toxicity of arsenate and arsenite seen in OATP-C-transfected cells. The increase in uptake of inorganic arsenic was not as great as that of estradiol-17beta-D-glucuronide. Our results suggest that OATP-C can transport inorganic arsenic in a (GSH)-dependent manner. However, this may not be the major pathway for arsenic transport. |
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