Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Journal of Biomedical Science - Tập 13 - Trang 525-533 - 2006
Wen-Jen Lu1,2, Ikumi Tamai3, Jun-ichi Nezu4, Ming-Liang Lai5, Jin-ding Huang1,2,6
1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
4Chugai Pharmaceutical Co. Ltd., Ibaraki, Japan
5Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
6Department of Pharmacology, Medical College, National Cheng Kung University, Tainan, Taiwan

Tóm tắt

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-17β-D-glucuronide, by 10-fold. In addition, we measured uptake and cytotoxicity of arsenate, arsenite, monomethylarsonate(MMAV), and dimethylarsinate (DMAV). Transfection of OATP-C increased uptake and cytotoxicity of arsenate and arsenite, but not of MMAV or DMAV. 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-17β-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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