{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:25:44Z","timestamp":1791077144389,"version":"4.1.0"},"reference-count":30,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:p> Natural differences in expression and retroviral transduction techniques were used to test the hypothesis that MDR1 P-glycoprotein (P-gp) and MRP1 (multidrug resistance-related protein) contribute to xenobiotic handling by placental trophoblast. RT-PCR and Western blotting in placenta, primary cytotrophoblast cell cultures, and BeWo, JAr, and JEG choriocarcinoma cell lines showed that MRP1 was ubiquitously expressed, whereas MDR1 was absent or minimally expressed in BeWo and JEG cell lines. In syncytiotrophoblast, P-gp was localized predominantly to the microvillous, maternal facing plasma membrane, and MRP1 to the basal, fetal facing plasma membrane. Functional studies showed that cyclosporin A-sensitive accumulation of [<jats:sup>3<\/jats:sup>H]vinblastine by cells containing both transport proteins was significantly different from those expressing predominantly MRP1. Retroviral gene transfer of MDR1 to BeWo cells confirmed that this difference was due to the relative expression of MDR1. Therefore, both P-gp and MRP1 contribute to xenobiotic handling by the trophoblast. Localization of P-gp to the microvillous membrane suggests an essential role in preventing xenobiotic accumulation by the syncytiotrophoblast and, therefore, in protecting the fetus. <\/jats:p>","DOI":"10.1152\/ajpcell.00418.2002","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:16:02Z","timestamp":1368490562000},"page":"C584-C591","source":"Crossref","is-referenced-by-count":101,"title":["Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral  gene transfer"],"prefix":"10.1152","volume":"285","author":[{"given":"Diane E.","family":"Atkinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Greenwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin P.","family":"Sibley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn D.","family":"Glazier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J.","family":"Fairbairn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"REF1","unstructured":"Atkinson DE,  Sibley CP, and Greenwood SL. Comparison of multi-drug resistance activity  in two choriocarcinoma derived cell lines. J Physiol 535: 38P,  2001."},{"key":"REF2","doi-asserted-by":"crossref","unstructured":"Chen CJ, Clark  D, Ueda K, Pastan I, Gottesman MM, and Roninson IB. Genomic organization  of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins.  J Biol Chem 265:  506\u2013514, 1990.","DOI":"10.1016\/S0021-9258(19)40260-3"},{"key":"REF3","doi-asserted-by":"crossref","unstructured":"Chomzynski P and Sacchi N. Single-step method of RNA-isolation by acid guanidinium  thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156\u2013159,  1987.","DOI":"10.1006\/abio.1987.9999"},{"key":"REF4","doi-asserted-by":"crossref","unstructured":"Cole SP,  Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU,  Duncan AM, and Deeley RG. Overexpression of a transporter gene in a  multidrug-resistant human lung cancer cell line.  Science 258:  1650\u20131654, 1992.","DOI":"10.1126\/science.1360704"},{"key":"REF5","unstructured":"Cole SP, Sparks  KE, Fraser K, Loe DW, Grant CE, Wilson GM, and Deeley RG. Pharmacological  characterization of multidrug resistant MRP-transfected human tumor cells.  Cancer Res 54:  5902\u20135910, 1994."},{"key":"REF6","doi-asserted-by":"crossref","unstructured":"Deeley RG and  Cole SP. Function, evolution and structure of multidrug resistance protein  (MRP). Semin Cancer Biol 8:  193\u2013204, 1997.","DOI":"10.1006\/scbi.1997.0070"},{"key":"REF7","doi-asserted-by":"crossref","unstructured":"Eckert HG,  Stockschlader M, Just U, Hegewisch-Becker S, Grez M, Uhde A, Zander A,  Ostertag W, and Baum C. High-dose multidrug resistance in primary human  hematopoietic progenitor cells transduced with optimized retroviral vectors.  Blood 88:  3407\u20133415, 1996.","DOI":"10.1182\/blood.V88.9.3407.bloodjournal8893407"},{"key":"REF8","unstructured":"Flens MJ, Zaman  GJ, van der Valk P, Izquierdo MA, Schroeijers AB, Scheffer GL, van der Groep  P, de Haas M, Meijer CJ, and Scheper RJ. Tissue distribution of the  multidrug resistance protein. Am J Pathol 148: 1237\u20131247,  1996."},{"key":"REF9","doi-asserted-by":"crossref","unstructured":"Glazier J, Ayuk  P, Grey AM, and Sides K. Syncytiotrophoblast basal plasma membrane  isolation. Placenta 19:  443\u2013444, 1998.","DOI":"10.1016\/S0143-4004(98)90087-X"},{"key":"REF10","doi-asserted-by":"crossref","unstructured":"Glazier JD,  Jones CJ, and Sibley CP. Purification and Na+ uptake by human  placental microvillus membrane vesicles prepared by three different methods.  Biochim Biophys Acta 945:  127\u2013134, 1988.","DOI":"10.1016\/0005-2736(88)90475-0"},{"key":"REF11","doi-asserted-by":"crossref","unstructured":"Greenwood SL,  Boyd RD, and Sibley CP. Transtrophoblast and microvillus membrane  potential difference in mature intermediate human placental villi.  Am J Physiol Cell Physiol 265:  C460\u2013C466, 1993.","DOI":"10.1152\/ajpcell.1993.265.2.C460"},{"key":"REF12","doi-asserted-by":"crossref","unstructured":"Greenwood SL,  Clarson LH, Sides MK, and Sibley CP. Membrane potential difference and  intracellular cation concentrations in human placental trophoblast cells in  culture. J Physiol 492:  629\u2013640, 1996.","DOI":"10.1113\/jphysiol.1996.sp021333"},{"key":"REF13","doi-asserted-by":"crossref","unstructured":"Kliman HJ,  Nestler JE, Sermasi E, Sanger JM, and Strauss JF III. Purification,  characterization, and in vitro differentiation of cytotrophoblasts from human  term placentae. Endocrinology 118: 1567\u20131582,  1986.","DOI":"10.1210\/endo-118-4-1567"},{"key":"REF14","doi-asserted-by":"crossref","unstructured":"Lankas GR, Wise  LD, Cartwright ME, Pippert T, and Umbenhauer DR. Placental P-glycoprotein  deficiency enhances susceptibility to chemically induced birth defects in  mice. Reprod Toxicol 12:  457\u2013463, 1998.","DOI":"10.1016\/S0890-6238(98)00027-6"},{"key":"REF15","doi-asserted-by":"crossref","unstructured":"MacFarland A,  Abramovich DR, Ewen SW, and Pearson CK. Stage-specific distribution of  P-glycoprotein in first-trimester and full-term human placenta.  Histochem J 26:  417\u2013423, 1994.","DOI":"10.1007\/BF00160054"},{"key":"REF16","doi-asserted-by":"crossref","unstructured":"Mylona P,  Glazier JD, Greenwood SL, Sides MK, and Sibley CP. Expression of the  cystic fibrosis (CF) and multidrug resistance (MDR1) genes during development  and differentiation in the human placenta. Mol Hum  Reprod 2:  693\u2013698, 1996.","DOI":"10.1093\/molehr\/2.9.693"},{"key":"REF17","doi-asserted-by":"crossref","unstructured":"Nakamura Y,  Ikeda S, Furukawa T, Sumizawa T, Tani A, Akiyama S, and Nagata Y. Function  of P-glycoprotein expressed in placenta and mole. Biochem Biophys  Res Commun 235:  849\u2013853, 1997.","DOI":"10.1006\/bbrc.1997.6855"},{"key":"REF18","doi-asserted-by":"crossref","unstructured":"Nooter K and  Stoter G. Molecular mechanisms of multidrug resistance in cancer  chemotherapy. Pathol Res Pract 192: 768\u2013780,  1996.","DOI":"10.1016\/S0344-0338(96)80099-9"},{"key":"REF19","doi-asserted-by":"crossref","unstructured":"Pasanen M.  The expression and regulation of drug metabolism in human placenta.  Adv Drug Delivery Res 38:  81\u201397, 1999.","DOI":"10.1016\/S0169-409X(99)00008-3"},{"key":"REF20","doi-asserted-by":"crossref","unstructured":"Peng KC,  Cluzeaud F, Bens M, Van Huyen JP, Wioland MA, Lacave R, and Vandewalle A.  Tissue and cell distribution of the multidrug resistance-associated protein  (MRP) in mouse intestine and kidney. J Histochem  Cytochem 47:  757\u2013768, 1999.","DOI":"10.1177\/002215549904700605"},{"key":"REF21","doi-asserted-by":"crossref","unstructured":"Peters PW,  Garbis-Berkvens HM, and Bannigan JG. Drugs of choice in pregnancy: primary  prevention of birth defects. Reprod Toxicol 7: 399\u2013404,  1993.","DOI":"10.1016\/0890-6238(93)90084-K"},{"key":"REF22","doi-asserted-by":"crossref","unstructured":"Radomsky CL and  Levine N. Thalidomide. Dermatol Clin 19: 87\u2013103,  2001.","DOI":"10.1016\/S0733-8635(05)70232-1"},{"key":"REF23","doi-asserted-by":"crossref","unstructured":"Ramamoorthy S,  Leibach FH, Mahesh VB, and Ganapathy V. Selective impairment of taurine  transport by cyclosporin A in a human placental cell line. Pediatr  Res 32:  125\u2013127, 1992.","DOI":"10.1203\/00006450-199207000-00024"},{"key":"REF24","doi-asserted-by":"crossref","unstructured":"Schinkel AH. The physiological function of  drug-transporting p-glycoproteins. Semin Cancer Biol 8: 161\u2013170,  1997.","DOI":"10.1006\/scbi.1997.0068"},{"key":"REF25","doi-asserted-by":"crossref","unstructured":"Smit JW,  Huisman MT, van Tellingen O, Wiltshire HR, and Schinkel AH. Absence or  pharmacological blocking of placental P-glycoprotein profoundly increases  fetal drug exposure. J Clin Invest 104: 1441\u20131447,  1999.","DOI":"10.1172\/JCI7963"},{"key":"REF26","doi-asserted-by":"crossref","unstructured":"St-Pierre MV,  Serrano MA, Macias RI, Dubs U, Hoechli M, Lauper U, Meier PJ, and Marin  JJ. Expression of members of the multidrug resistance protein family in  human term placenta. Am J Physiol Regul Integr Comp  Physiol 279:  R1495\u2013R1503, 2000.","DOI":"10.1152\/ajpregu.2000.279.4.R1495"},{"key":"REF27","unstructured":"Swann AC.  Major system toxicities and side effects of anticonvulsants. J Clin  Psychiatry 62:  16\u201321, 2001."},{"key":"REF28","doi-asserted-by":"crossref","unstructured":"Twentyman PR and Versantvoort CH. Experimental modulation of MRP (multidrug  resistance-associated protein)-mediated resistance. Eur J  Cancer 32:  1002\u20131009, 1996.","DOI":"10.1016\/0959-8049(96)00067-6"},{"key":"REF29","doi-asserted-by":"crossref","unstructured":"Ushigome F,  Takanaga H, Matsuo H, Yanai S, Tsukimori K, Nakano H, Uchiumi T, Nakamura T,  Kuwano M, Ohtani H, and Sawada Y. Human placental transport of  vinblastine, vincristine, digoxin and progesterone: contribution of  P-glycoprotein. Eur J Pharmacol 408: 1\u201310,  2000.","DOI":"10.1016\/S0014-2999(00)00743-3"},{"key":"REF30","doi-asserted-by":"crossref","unstructured":"Utoguchi N,  Chandorkar GA, Avery M, and Audus KL. Functional expression of  p-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells.  Reprod Toxicol 14:  217\u2013224, 2000.","DOI":"10.1016\/S0890-6238(00)00071-X"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00418.2002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:04:49Z","timestamp":1718651089000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00418.2002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1152\/ajpcell.00418.2002"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00418.2002","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9]]}}}