Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells.
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.
Lu
Wen-Jen
WJ
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Tamai
Ikumi
I
Nezu
Jun-ichi
J
Lai
Ming-Liang
ML
Huang
Jin-Ding
JD
D001149:Arsenates / Q000378:metabolism; D001151:Arsenic / Q000378:metabolism*; D018053:Arsenites / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D002101:Cacodylic Acid / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007928:Lethal Dose 50; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012293:Rifampin; D013656:Taurocholic Acid; D013778:Tetrazolium Salts; D013844:Thiazoles; D018675:Toxicity Tests; D014162:Transfection
D001149:Arsenates; D018053:Arsenites; D017931:DNA Primers; D018076:DNA, Complementary; D027381:Liver-Specific Organic Anion Transporter 1; D013778:Tetrazolium Salts; D013844:Thiazoles; C025483:estradiol-17 beta-glucuronide; D004958:Estradiol; D013656:Taurocholic Acid; D002101:Cacodylic Acid; C022616:thiazolyl blue; C015001:arsenite; D001151:Arsenic; C025657:arsenic acid; D012293:Rifampin