Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells
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.
Tài liệu tham khảo
Meier P.J., Stieger B. (2002) Bile salt transporters. Annu. Rev. Physiol. 64:635–661
Yabuuchi H., Tamai I., Morita K., Kouda T., Miyamoto K., Takeda E., Tsuji A. (1998) Hepatic sinusoidal membrane transport of anionic drugs mediated by anion transporter Npt1. J. Pharmacol. Exp. Ther. 286:1391–1396
Kullak-Ublick G.A., Hagenbuch B., Stieger B., Schteingart C.D., Hofmann A.F., Wolkoff A.W., Meier P.J. (1995) Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology 109:1274–1282
Suzuki H., Sugiyama Y. (2000) Transport of drugs across the hepatic sinusoidal membrane: sinusoidal drug influx and efflux in the liver. Semin. Liver. Dis. 20:251–263
Abe T., Kakyo M., Tokui T., Nakagomi R., Nishio T., Nakai D., Nomura H., Unno M., Suzuki M., Naitoh T., Matsuno S., Yawo H. (1999) Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J. Biol. Chem. 274:17159–17163
Abe T., Kakyo M., Sakagami H., Tokui T., Nishio T., Tanemoto M., Nomura H., Hebert S.C., Matsuno S., Kondo H., Yawo H. (1998) Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with OATP-C. J. Biol. Chem. 273:22395–22401
Bossuyt X., Muller M., Meier P.J. (1996) Multispecific amphipathic substrate transport by an organic anion transporter of human liver. J. Hepatol. 25:733–738
Tamai I., Nezu J., Uchino H., Sai Y., Oku A., Shimane M., Tsuji A. (2000) Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem. Biophys. Res. Commun. 273:251–260
Tamai I., Nozawa T., Koshida M., Nezu J., Sai Y., Tsuji A. (2001) Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm. Res. 18:1262–1269
Tirona R.G., Leake B.F., Wolkoff A.W., Kim R.B. (2003) Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J. Pharmacol. Exp. Ther. 304:223–228
Cui Y., Konig J., Leier I., Buchholz U., Keppler D. (2001) Hepatic uptake of bilirubin and its conjugated by the human organic anion transporter SLC21A6. J. Biol. Chem. 276:9626-9630
Nordstrom D.K. (2002) Worldwide occurrences of arsenic in ground water. Science 296:2143–2145
Smith A.H., Lopipero P.A., Bates M.N., Steinmaus C.M. (2002) Arsenic epidemiology and drinking water standards. Science 296:2145–2146
Chen C.J., Chuang Y.C., Lin T.M., Wu H.Y. (1985) Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: high-arsenic artesian well water and cancers. Cancer Res. 45:5895–5899
Leonard A., Lauwerys R.R. (1980) Carcinogenicity, teratogenicity and mutagenicity of arsenic. Mutat. Res. 75:49–62
Pinto S.S., Nelson K.W. (1976) Arsenic toxicology and industrial exposure. Annu. Rev. Pharmacol. Toxicol. 16:95–100
Niu C., Yan H., Yu T., Sun H.P., Liu J.X., Li X.S., Wu W., Zhang F.Q., Chen Y., Zhou L., Li J.M., Zeng X.Y., Ou Yang R.R., Yuan M.M., Ren M.Y., Gu F.Y., Cao Q., Gu B.W., Su X.Y., Chen G.Q., Xiong S.M., Zhang T.D., Waxman S., Wang Z.Y., Chen Z., Hu J., Shen Z.X., Chen S.J. (1999) Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 94:3315–3324
Soignet S., Maslak P., Wang Z.G., Jhanwar S., Calleja E., Dardashti L.J., Corso D., DeBlasio A., Gabrilove J., Scheinberg D.A., Pandolfi P.P., Warrell Jr R.P. (1998) Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. New Engl. J. Med. 339:1341–1348
Fischer A.B., Buchet J.P., Lauwerys R.R. (1985) Arsenic uptake, cytotoxicity and detoxification studied in mammalian cells in culture. Arch. Toxicol. 57:168–172
Moore M.M., Harring-Brock K., Doerr C.L. (1997) Relative genotoxic potency of arsenic and its methylated metabolites. Mutat. Res. 386:279–290
Sakurai T., Kaisc T., Matsubara C. (1998) Inorganic and methylated arsenic compounds induce cell death in murine macrophages via different mechanisms. Chem. Res. Toxicol. 11:273–283
Buchet J.P., Lauwerys R., Roels H. (1981) Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinite in man. Int. Arch. Occup. Environ. Health. 48:71–79
Carlin A., Shi W., Dey S., Rosen B.P. (1995) The ars operon of Escherichia coli confers arsenical and antimonial resistance. J. Bacteriol. 177:981–986
Ji G., Silver S. (1992) Reduction of arsenate to arsenite by the ArsC protein of the arsenic resistance operon of Staphylococcus aureus plasmid pI258. Proc. Natl. Acad. Sci. USA 89:9474–9478
Zaman G.J., Lankelma J., van Tellingen O., Beijnen J., Dekker H., Paulusma C., Oude Elferink R.P., Baas F., Borst P. (1995) Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. Proc. Natl. Acad. Sci. U. S. A. 92:7690–7694
Leslie E.M., Haimeur A., Waalkes M.P. (2004) Arsenic transport by human multidrug resistance protein 1 (MRP1/ABCC1). J. Biol. Chem. 279:32700–32708
Kala S.V., Neely M.W., Kala G., Prater C.I., Atwood D.W. (2000) Rice J.S., Lieberman M.W., The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. J. Biol. Chem. 275:33404–33408
Liu Z., Shen J., Carbrey J.M., Mukhopadhyay R., Agre P., Rosen B.P. (2002) Arsenite transport by mammalian aquagoyceroporins AQP7 and AQP9. Proc. Natl. Acad. Sci. U. S. A. 99:6053–6058
Liu Z., Carbrey J.M., Agre P., Rosen B.P. (2004) Arsenic trioxide uptake by human and rat aquaglyceroporins. Biochem. Biophys. Res. Commun. 316:1178–1185
Zalups R.K., Barfuss D.W. (2002) Renal organic anion transport system: a mechanism for the basolsteral uptake of mercury–thiol conjugates along the pars recta of the proximal tubule. Toxicol. Appl. Pharmacol. 182:234–243
Li L., Lee T.K., Meier P.J., Ballatori N. (1998) Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter. J. Biol. Chem. 273:16184–16191
Li L., Lee T.K., Meier P.J., Ballatori N. (2000) Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione. Mol. Pharmacol. 58:335–340
Cui Y., Konig J., Leier I., Buchholz U., Spring H., Keppler D. (1999) Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol. Pharmacol. 55:929–937
Cui Y., Konig J., Nies A.T., Pfannschmidt M., Hergt M., Franke W., Alt W., Moll R., Keppler D. (2003) Detection of the human organic anion transporters SLC21A6 (OATP-C) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma. Lab. Invest. 83:527–538
Eguchi N., Kuroda K., Endo G. (1997) Metabolites of arsenic induced tetraploids and mitotic arrest in cultured cells. Arch. Environ. Contam. Toxicol. 32:141–145
Ochi T., Kaise T., Oya Ohta Y. (1994) Glutathione plays different roles in the induction of the cytotoxic effects of inorganic and organic arsenic compounds in cultured BALB/c 3T3 cells. Experientia 50:115–120
Styblo M., Del Razo L.M., Vega L., Germolec D.R., LeCluyse E.L., Hamilton G.A., Reed W., Wang C., Cullen W.R., Thomas D.J. (2000) Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch. Toxicol. 74:289–299
Nemeti B., Gregus Z. (2002) Reduction of arsenate to arsenite in hepatic cytosol. Toxicol. Sci. 70:4–12
Scott N., Hatlelid K.M., Mackenzie N.E., Carter D.E. (1993) Reactions of arsenic (III) and arsenic (V) species with glutathione. Chem. Res. Toxicol. 6:102–106
Delnomdedieu M., Basti M.M., Otvos J.D., Thomas D.J. (1994) Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic resonance study. Chem. Biol. Interact. 90:139–155
Hung R.N., Lee T.C. (1996) Cellular uptake of trivalent arsenite and pentavalent arsenate in KB cells cultured in phosphate-free medium. Toxicol. Appl. Pharmacol. 136:243–249