Expression of xenobiotic transporters in the human renal proximal tubule cell line RPTEC/TERT1

Toxicology in Vitro

Volumn 30, Issue 1, 2015, Pages 95-105

  Aschauer, Lydia ^a   Carta, Giada ^a   Vogelsang, Nadine ^b   Schlatter, Eberhard ^b   Jennings, Paul ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b UNIVERSITY HOSPITAL MÜNSTER   (Germany)

Author keywords

ABC; Epithelia; OAT; OCT; RPTEC TERT1; Transport

Indexed keywords

ABC TRANSPORTER; ANION; AQUAPORIN 1; CARNITINE TRANSPORTER 2; CATION; CYCLOSPORIN A; FLUORESCENT DYE; GLYCOPROTEIN P INHIBITOR; MEMBRANE PROTEIN; MESSENGER RNA; MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1; MULTIDRUG AND TOXIN EXTRUSION PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN; ORGANIC ANION TRANSPORTER 1; ORGANIC ANION TRANSPORTER 3; ORGANIC ANION TRANSPORTER 4; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3; CARRIER PROTEIN;

AQP1 GENE; ARTICLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CONTROLLED STUDY; GENE EXPRESSION REGULATION; GLYCOSYLATION; HUMAN; HUMAN CELL; KIDNEY PROXIMAL TUBULE; KIDNEY TUBULE CELL; MATE1 GENE; MATE2 GENE; MOLECULAR WEIGHT; OAT1 GENE; OAT3 GENE; OAT4 GENE; OCT2 GENE; OCT3 GENE; OCTN2 GENE; PROTEIN EXPRESSION; PROTEIN PROCESSING; RPTEC CELL LINE; SENSITIVITY ANALYSIS; TERT1 CELL LINE; CELL LINE; CYTOLOGY; GENETICS; METABOLISM; PHYSIOLOGY;

CARRIER PROTEINS; CELL LINE; GENE EXPRESSION REGULATION; HUMANS; KIDNEY TUBULES, PROXIMAL; RNA, MESSENGER;

EID: 84921368101     PISSN: 08872333     EISSN: 18793177     Source Type: Journal    
DOI: 10.1016/j.tiv.2014.12.003     Document Type: Article

References (70)

1. Aschauer L., Gruber L.N., Pfaller W., Limonciel A., Athersuch T.J., Cavill R., Khan A., Gstraunthaler G., Grillari J., Grillari R., Hewitt P., Leonard M.O., Wilmes A., Jennings P. Delineation of the key aspects in the regulation of epithelial monolayer formation. Mol. Cell. Biol. 2013, 33:2535-2550.
2. Aschauer L., Limonciel A., Wilmes A., Stanzel S., Kopp-Schneider A., Hewitt P., Lukas A., Leonard M.O., Pfaller W., Jennings P. Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: a transcriptomic study. Toxicol. In Vitro 2015, 30:106-116.
3. Babu E., Takeda M., Narikawa S., Kobayashi Y., Enomoto A., Tojo A., Cha S.H., Sekine T., Sakthisekaran D., Endou H. Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim. Biophys. Acta 2002, 1590:64-75.
4. Biermann J., Lang D., Gorboulev V., Koepsell H., Sindic A., Schroter R., Zvirbliene A., Pavenstadt H., Schlatter E., Ciarimboli G. Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am. J. Physiol. Cell Physiol. 2006, 290:C1521-1531.
5. Cetinkaya I., Ciarimboli G., Yalcinkaya G., Mehrens T., Velic A., Hirsch J.R., Gorboulev V., Koepsell H., Schlatter E. Regulation of human organic cation transporter hOCT2 by PKA, PI3K, and calmodulin-dependent kinases. Am. J. Physiol. Renal. Physiol. 2003, 284:F293-302.
6. Ciarimboli G., Holle S.K., Vollenbrocker B., Hagos Y., Reuter S., Burckhardt G., Bierer S., Herrmann E., Pavenstadt H., Rossi R., Kleta R., Schlatter E. New clues for nephrotoxicity induced by ifosfamide: preferential renal uptake via the human organic cation transporter 2. Mol. Pharm. 2011, 8:270-279.
7. Ciarimboli G., Ludwig T., Lang D., Pavenstadt H., Koepsell H., Piechota H.J., Haier J., Jaehde U., Zisowsky J., Schlatter E. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am. J. Pathol. 2005, 167:1477-1484.
8. Ciarimboli G., Struwe K., Arndt P., Gorboulev V., Koepsell H., Schlatter E., Hirsch J.R. Regulation of the human organic cation transporter hOCT1. J. Cell. Physiol. 2004, 201:420-428.
9. Cihlar T., Lin D.C., Pritchard J.B., Fuller M.D., Mendel D.B., Sweet D.H. The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Mol. Pharmacol. 1999, 56:570-580.
10. Crean D., Bellwon P., Aschauer L., Limonciel A., Moenks K., Hewitt P., Schmidt T., Herrgen K., Dekant W., Lukas A., Bois F., Wilmes A., Jennings P., Leonard M.O. Development of an in vitro renal epithelial disease state model for xenobiotic toxicity testing. Toxicol. In Vitro 2015, 30:128-137.
11. Daniel H., Kottra G. The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch. 2004, 447:610-618.
12. De Broe M., Roch-Ramel F. Renal handling of drugs and xenobiotics. Clinical Nephrotoxins 2008, 43-71. Springer, US. M. De Broe, G. Porter, W. Bennett, G. Deray (Eds.).
13. El-Sheikh A.A., Masereeuw R., Russel F.G. Mechanisms of renal anionic drug transport. Eur. J. Pharmacol. 2008, 585:245-255.
14. Filippo C.A., Ardon O., Longo N. Glycosylation of the OCTN2 carnitine transporter: study of natural mutations identified in patients with primary carnitine deficiency. Biochim. Biophys. Acta 2011, 1812:312-320.
15. Foxwell B.M., Mackie A., Ling V., Ryffel B. Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein. Mol. Pharmacol. 1989, 36:543-546.
16. Heise M., Lautem A., Knapstein J., Schattenberg J.M., Hoppe-Lotichius M., Foltys D., Weiler N., Zimmermann A., Schad A., Grundemann D., Otto G., Galle P.R., Schuchmann M., Zimmermann T. Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance. BMC Cancer 2012, 12:109.
17. Ho E.S., Lin D.C., Mendel D.B., Cihlar T. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J. Am. Soc. Nephrol. 2000, 11:383-393.
18. Huls M., Brown C.D., Windass A.S., Sayer R., van den Heuvel J.J., Heemskerk S., Russel F.G., Masereeuw R. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int. 2008, 73:220-225.
19. Imaoka T., Kusuhara H., Adachi M., Schuetz J.D., Takeuchi K., Sugiyama Y. Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol. Pharmacol. 2007, 71:619-627.
20. Jennings P., Koppelstaetter C., Aydin S., Abberger T., Wolf A.M., Mayer G., Pfaller W. Cyclosporine A induces senescence in renal tubular epithelial cells. Am. J. Physiol. Renal. Physiol. 2007, 293:F831-838.
21. Jennings P., Weiland C., Limonciel A., Bloch K.M., Radford R., Aschauer L., McMorrow T., Wilmes A., Pfaller W., Ahr H.J., Slattery C., Lock E.A., Ryan M.P., Ellinger-Ziegelbauer H. Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch. Toxicol. 2012, 86:571-589.
22. Keppler D., Kamisako T., Leier I., Cui Y., Nies A.T., Tsujii H., Konig J. Localization, substrate specificity, and drug resistance conferred by conjugate export pumps of the MRP family. Adv. Enzyme Regul. 2000, 40:339-349.
23. Koepsell H., Lips K., Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm. Res. 2007, 24:1227-1251.
24. Komatsu T., Hiasa M., Miyaji T., Kanamoto T., Matsumoto T., Otsuka M., Moriyama Y., Omote H. Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter. Int. J. Biochem. Cell Biol. 2011, 43:913-918.
25. Kuo K.L., Zhu H., McNamara P.J., Leggas M. Localization and functional characterization of the rat Oatp4c1 transporter in an in vitro cell system and rat tissues. PLoS ONE 2012, 7:e39641.
26. Lee W., Kim R.B. Transporters and renal drug elimination. Annu. Rev. Pharmacol. Toxicol. 2004, 44:137-166.
27. Limonciel A., Aschauer L., Wilmes A., Prajczer S., Leonard M.O., Pfaller W., Jennings P. Lactate is an ideal non-invasive marker for evaluating temporal alterations in cell stress and toxicity in repeat dose testing regimes. Toxicol. In Vitro 2011, 25:1855-1862.
28. Limonciel A., Jennings P. A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity. Toxins (Basel) 2014, 6:371-379.
29. Limonciel A., Wilmes A., Aschauer L., Radford R., Bloch K.M., McMorrow T., Pfaller W., van Delft J.H., Slattery C., Ryan M.P., Lock E.A., Jennings P. Oxidative stress induced by potassium bromate exposure results in altered tight junction protein expression in renal proximal tubule cells. Arch. Toxicol. 2012, 86:1741-1751.
30. Liu W., Liang R., Ramamoorthy S., Fei Y.J., Ganapathy M.E., Hediger M.A., Ganapathy V., Leibach F.H. Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney. Biochim. Biophys. Acta 1995, 1235:461-466.
31. Ludwig T., Riethmuller C., Gekle M., Schwerdt G., Oberleithner H. Nephrotoxicity of platinum complexes is related to basolateral organic cation transport. Kidney Int. 2004, 66:196-202.
32. Maekawa S., Mori D., Nishiya T., Takikawa O., Horinouchi T., Nishimoto A., Kajita E., Miwa S. OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2. Biochim. Biophys. Acta 2007, 1773:1000-1006.
33. Mandikova J., Volkova M., Pavek P., Cesnek M., Janeba Z., Kubicek V., Trejtnar F. Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates. Toxicol. 2013, 311:135-146.
34. Massmann V., Edemir B., Schlatter E., Al-Monajjed R., Harrach S., Klassen P., Holle S.K., Sindic A., Dobrivojevic M., Pavenstadt H., Ciarimboli G. The organic cation transporter 3 (OCT3) as molecular target of psychotropic drugs: transport characteristics and acute regulation of cloned murine OCT3. Pflugers Arch. 2014, 466:517-527.
35. Masuda S., Terada T., Yonezawa A., Tanihara Y., Kishimoto K., Katsura T., Ogawa O., Inui K. Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J. Am. Soc. Nephrol. 2006, 17:2127-2135.
36. Miller M.D., Margot N.A., Lamy P.D., Fuller M.D., Anton K.E., Mulato A.S., Cherrington J.M. Adefovir and tenofovir susceptibilities of HIV-1 after 24-48 weeks of adefovir dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408. J. Acquir. Immune Defic. Syndr. 2001, 27:450-458.
37. Moestrup S.K., Cui S., Vorum H., Bregengard C., Bjorn S.E., Norris K., Gliemann J., Christensen E.I. Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. J. Clin. Invest. 1995, 96:1404-1413.
38. Motohashi H., Sakurai Y., Saito H., Masuda S., Urakami Y., Goto M., Fukatsu A., Ogawa O., Inui K. Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J. Am. Soc. Nephrol. 2002, 13:866-874.
39. Mulato A.S., Ho E.S., Cihlar T. Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J. Pharmacol. Exp. Ther. 2000, 295:10-15.
40. Nakamura T., Yonezawa A., Hashimoto S., Katsura T., Inui K. Disruption of multidrug and toxin extrusion MATE1 potentiates cisplatin-induced nephrotoxicity. Biochem. Pharmacol. 2010, 80:1762-1767.
41. Nies A.T., Koepsell H., Winter S., Burk O., Klein K., Kerb R., Zanger U.M., Keppler D., Schwab M., Schaeffeler E. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 2009, 50:1227-1240.
42. Otsuka M., Matsumoto T., Morimoto R., Arioka S., Omote H., Moriyama Y. A human transporter protein that mediates the final excretion step for toxic organic cations. Proc. Natl. Acad. Sci. USA 2005, 102:17923-17928.
43. Pelis R.M., Suhre W.M., Wright S.H. Functional influence of N-glycosylation in OCT2-mediated tetraethylammonium transport. Am. J. Physiol. Renal. Physiol. 2006, 290:F1118-1126.
44. Perri D., Ito S., Rowsell V., Shear N.H. The kidney-the body's playground for drugs: an overview of renal drug handling with selected clinical correlates. Can. J. Clin. Pharmacol. 2003, 10:17-23.
45. Qiu R., Kalhorn T.F., Slattery J.T. ABCC2-mediated biliary transport of 4-glutathionylcyclophosphamide and its contribution to elimination of 4-hydroxycyclophosphamide in rat. J. Pharmacol. Exp. Ther. 2004, 308:1204-1212.
46. Reid G., Wielinga P., Zelcer N., De Haas M., Van Deemter L., Wijnholds J., Balzarini J., Borst P. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol. Pharmacol. 2003, 63:1094-1103.
47. Schmidt-Lauber C., Harrach S., Pap T., Fischer M., Victor M., Heitzmann M., Hansen U., Fobker M., Brand S.M., Sindic A., Pavenstadt H., Edemir B., Schlatter E., Bertrand J., Ciarimboli G. Transport mechanisms and their pathology-induced regulation govern tyrosine kinase inhibitor delivery in rheumatoid arthritis. PLoS ONE 2012, 7:e52247.
48. Schmitz C., Hilpert J., Jacobsen C., Boensch C., Christensen E.I., Luft F.C., Willnow T.E. Megalin deficiency offers protection from renal aminoglycoside accumulation. J. Biol. Chem. 2002, 277:618-622.
49. Schramm U., Fricker G., Wenger R., Miller D.S. P-glycoprotein-mediated secretion of a fluorescent cyclosporin analogue by teleost renal proximal tubules. Am. J. Physiol. 1995, 268:F46-52.
50. Schuetz J.D., Connelly M.C., Sun D., Paibir S.G., Flynn P.M., Srinivas R.V., Kumar A., Fridland A. MRP4: a previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat. Med. 1999, 5:1048-1051.
51. Scudamore K.A., Banks J.N., Rizvi R., Jennings P. Formation of ochratoxin A and aflatoxins following the use of propionic acid as a grain preservative for storing damp barley. Mycotoxin Res. 2004, 20:68-79.
52. Takenaka K., Morgan J.A., Scheffer G.L., Adachi M., Stewart C.F., Sun D., Leggas M., Ejendal K.F., Hrycyna C.A., Schuetz J.D. Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution. Cancer Res. 2007, 67:6965-6972.
53. Tamai I., Safa A.R. Competitive interaction of cyclosporins with the Vinca alkaloid-binding site of P-glycoprotein in multidrug-resistant cells. J. Biol. Chem. 1990, 265:16509-16513.
54. Tanaka K., Xu W., Zhou F., You G. Role of glycosylation in the organic anion transporter OAT1. J. Biol. Chem. 2004, 279:14961-14966.
55. Tanihara Y., Masuda S., Katsura T., Inui K. Protective effect of concomitant administration of imatinib on cisplatin-induced nephrotoxicity focusing on renal organic cation transporter OCT2. Biochem. Pharmacol. 2009, 78:1263-1271.
56. Thiebaut F., Tsuruo T., Hamada H., Gottesman M.M., Pastan I., Willingham M.C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA 1987, 84:7735-7738.
57. Tian Q., Zhang J., Tan T.M., Chan E., Duan W., Chan S.Y., Boelsterli U.A., Ho P.C., Yang H., Bian J.S., Huang M., Zhu Y.Z., Xiong W., Li X., Zhou S. Human multidrug resistance associated protein 4 confers resistance to camptothecins. Pharm. Res. 2005, 22:1837-1853.
58. Uwai Y., Motohashi H., Tsuji Y., Ueo H., Katsura T., Inui K. Interaction and transport characteristics of mycophenolic acid and its glucuronide via human organic anion transporters hOAT1 and hOAT3. Biochem. Pharmacol. 2007, 74:161-168.
59. van Aubel R.A., Smeets P.H., Peters J.G., Bindels R.J., Russel F.G. The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J. Am. Soc. Nephrol. 2002, 13:595-603.
60. Wieser M., Stadler G., Jennings P., Streubel B., Pfaller W., Ambros P., Riedl C., Katinger H., Grillari J., Grillari-Voglauer R. HTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics. Am. J. Physiol. Renal. Physiol. 2008, 295:F1365-1375.
61. Wijnholds J., Mol C.A., van Deemter L., de Haas M., Scheffer G.L., Baas F., Beijnen J.H., Scheper R.J., Hatse S., De Clercq E., Balzarini J., Borst P. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc. Natl. Acad. Sci. USA 2000, 97:7476-7481.
62. Wilmes, A., Bielow, C., Ranninger, C., Bellwon, P., Aschauer, L., Limonciel, A., Chassaigne, H., Kristl, T., Aiche, S., Huber, C.G., Guillou, C., Hewitt, P., Leonard, M.O., Dekant, W., Bois, F., Jennings, P., 2015. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol. In Vitro 30, 117-127.
63. Wilmes, A., Aschauer, L., Limonciel, A., Pfaller, W., Jennings, P., 2014. Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol.
64. Wilmes A., Limonciel A., Aschauer L., Moenks K., Bielow C., Leonard M.O., Hamon J., Carpi D., Ruzek S., Handler A., Schmal O., Herrgen K., Bellwon P., Burek C., Truisi G.L., Hewitt P., Di Consiglio E., Testai E., Blaauboer B.J., Guillou C., Huber C.G., Lukas A., Pfaller W., Mueller S.O., Bois F.Y., Dekant W., Jennings P. Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress. J. Proteomics 2013, 79:180-194.
65. Wright S.H., Dantzler W.H. Molecular and cellular physiology of renal organic cation and anion transport. Physiol. Rev. 2004, 84:987-1049.
66. Wu X., Huang W., Ganapathy M.E., Wang H., Kekuda R., Conway S.J., Leibach F.H., Ganapathy V. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am. J. Physiol. Renal. Physiol. 2000, 279:F449-458.
67. Yonezawa A., Inui K. Organic cation transporter OCT/SLC22A and H(+)/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents. Biochem. Pharmacol. 2011, 81:563-568.
68. Zhang Q., Wu J., Pan Z., You G. The role of dileucine in the expression and function of human organic anion transporter 1 (hOAT1). Int. J. Biochem. Mol. Biol. 2011, 2:31-38.
69. Zhang R., Yang X., Li J., Wu J., Peng W.X., Dong X.Q., Zhou S.F., Yu X.Q. Upregulation of rat renal cortical organic anion transporter (OAT1 and OAT3) expression in response to ischemia/reperfusion injury. Am. J. Nephrol. 2008, 28:772-783.
70. Zhou F., Xu W., Hong M., Pan Z., Sinko P.J., Ma J., You G. The role of N-linked glycosylation in protein folding, membrane targeting, and substrate binding of human organic anion transporter hOAT4. Mol. Pharmacol. 2005, 67:868-876.