P-glycoprotein and 'lipid rafts': Some ambiguous mutual relationships (floating on them, building them or meeting them by chance?)

Cellular and Molecular Life Sciences

Volumn 63, Issue 9, 2006, Pages 1038-1059

  Orlowski, S ^a   Martin, S ^a   Escargueil, A ^a,b  

^a CEA SACLAY   (France)

^b INSERM   (France)

Author keywords

Cholesterol; Drug transport; Lipid rafts; Lipid traffic; Lipid translocase; Multidrug resistance; P glycoprotein; Sphingolipids

Indexed keywords

AMPHOPHILE; CARRIER PROTEIN; CHOLESTEROL; GLYCOPROTEIN P; MEMBRANE PROTEIN;

CELL MEMBRANE TRANSPORT; CYTOSOL; DETOXIFICATION; HUMAN; LIPID RAFT; LIPID TRANSPORT; MULTIDRUG RESISTANCE; NONHUMAN; PROTEIN PROTEIN INTERACTION; REVIEW; TECHNIQUE; TUMOR CELL;

ADENOSINE TRIPHOSPHATASES; ANIMALS; BIOLOGICAL TRANSPORT; CAVEOLIN 1; CELL MEMBRANE STRUCTURES; CHOLESTEROL; ENDOCYTOSIS; GLYCOSPHINGOLIPIDS; HUMANS; LIPIDS; MEMBRANE MICRODOMAINS; MICE; MODELS, BIOLOGICAL; P-GLYCOPROTEIN; PROTEIN STRUCTURE, SECONDARY; SIGNAL TRANSDUCTION; VIRUS DISEASES;

EID: 33744483102     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-005-5554-9     Document Type: Review

References (207)

1. Gerlach J. H., Kartner N., Bell D. R. and Ling V. (1986) Multidrug resistance. Cancer Surv. 5: 25-46
2. Nooter K. and Herweijer H. (1991) Multidrug resistance (mdr) genes in human cancer. Br. J. Cancer 63: 663-669
3. Nielsen D. and Skovsgaard T. (1992) P-glycoprotein as multidrug transporter: a critical review of current multidrug resistant cell lines. Biochim. Biophys. Acta 1139: 169-183
4. Gottesman M. M. and Pastan I. (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62: 385-427
5. Sauna Z. E., Smith M. M., Muller M., Kerr K. M. and Ambudkar S. V. (2001) The mechanism of action of multidrug-resistance-linked P-glycoprotein. J. Bioenerg. Biomembr. 33: 481-491
6. Rosenberg M. F., Velarde G., Ford R. C., Martin C., Berridge G., Kerr I. D. et al. (2001) Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. EMBO J. 20: 5615-5625
7. Ambudkar S. V., Dey S., Hrycyna C. A., Ramachandra M., Pastan I. and Gottesman M. M. (1999) Biochemical, cellular and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39: 361-398
8. Bosch I. and Croop J. (1996) P-glycoprotein multidrug resistance and cancer. Biochim. Biophys. Acta 1288: F37-F54
9. Schinkel A. H. (1997) The physiological function of drug-transporting P-glycoproteins. Semin. Cancer Biol. 8: 161-170
10. Sarkadi B., Muller M., Homolya L., Hollo Z., Seprodi J., Germann U. A. et al. (1994) Interaction of bioactive hydrophobic peptides with the human multidrug transporter. FASEB J. 8: 766-770
11. Drach J., Gsur A., Hamilton G., Zhao S., Angerler J., Fiegl M. et al. (1996) Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4 and interferon-gamma in normal human T lymphocytes. Blood 88: 1747-1754
12. Barnes K. M., Dickstein B., Cutler G. B. Jr, Fojo T. and Bates S. E. (1996) Steroid treatment, accumulation and antagonism of P-glycoprotein in multidrug-resistant cells. Biochemistry 35: 4820-4827
13. van Helvoort A., Smith A. J., Sprong H., Fritzsche I., Schinkel A. H., Borst P. et al. (1996) MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87: 507-517
14. Bosch I., Dunussi-Joannopoulos K., Wu R. L., Furlong S. T. and Croop J. (1997) Phosphatidylcholine and phosphatidyl-ethanolamine behave as substrates of the human MDR1 P-glycoprotein. Biochemistry 36: 5685-5694
15. Higgins C. F. and Gottesman M. M. (1992) Is the multidrug transporter a flippase? Trends Biochem. Sci. 17: 18-21
16. Sharom F. J. (1997) The P-glycoprotein efflux pump: how does it transport drugs? J. Membr. Biol. 160: 161-175
17. Ferte J. (2000) Analysis of the tangled relationships between P-glycoprotein-mediated multidrug resistance and the lipid phase of the cell membrane. Eur. J. Biochem. 267: 277-294
18. Simons K. and Ikonen E. (1997) Functional rafts in cell membranes. Nature 387: 569-572
19. Brown R. E. (1998) Sphingolipid organization in biomembranes: what physical studies of model membranes reveal. J. Cell Sci. 111: 1-9
20. van Meer G. and Sprong H. (2004) Membrane lipids and vesicular traffic. Curr. Opin. Cell Biol. 16: 373-378
21. Brown D. A. and London E. (2000) Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J. Biol. Chem. 275: 17221-17224
22. Galbiati F., Razani B. and Lisanti M. P. (2001) Emerging themes in lipid rafts and caveolae. Cell 106: 403-411
23. Anderson R. G. (1998) The caveolae membrane system. Annu. Rev. Biochem. 67: 199-225
24. Maxfield F. R. (2002) Plasma membrane microdomains. Curr. Opin. Cell Biol. 14: 483-487
25. Gaus K., Gratton E., Kable E. P., Jones A. S., Gelissen I., Kritharides L. et al. (2003) Visualizing lipid structure and raft domains in living cells with two-photon microscopy. Proc. Natl. Acad. Sci. USA 100: 15554-15559
26. Munro S. (2003) Lipid rafts: elusive or illusive? Cell 115: 377-388
27. Hao M., Mukherjee S. and Maxfield F. R. (2001) Cholesterol depletion induces large scale domain segregation in living cell membranes. Proc. Natl. Acad. Sci. USA 98: 13072-13077
28. Devaux P. F. and Morris R. (2004) Transmembrane asymmetry and lateral domains in biological membranes. Traffic 5: 241-246
29. Schuck S., Honsho M., Ekroos K., Shevchenko A. and Simons K. (2003) Resistance of cell membranes to different detergents. Proc. Natl. Acad. Sci. USA 100: 5795-5800
30. Chamberlain L. H. (2004) Detergents as tools for the purification and classification of lipid rafts. FEBS Lett. 559: 1-5
31. Pike L. J. (2004) Lipid rafts: heterogeneity on the high seas. Biochem. J. 378: 281-292
32. Ilangumaran S. and Hoessli D. C. (1998) Effects of cholesterol depletion by cyclodextrin on the sphingolipid microdomains of the plasma membrane. Biochem. J. 335: 433-440
33. Simons K. and Toomre D. (2000) Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1: 31-39
34. Anderson R. G. and Jacobson K. (2002) A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296: 1821-1825
35. Lavie Y., Fiucci G. and Liscovitch M. (1998) Upregulation of caveolae and caveolar constituents in multidrug-resistant cancer cells. J. Biol. Chem. 273: 32380-32383
36. Barakat S., Gayet L., Dayan G., Labialle S., Lazar A., Oleinikov V. et al. (2005) Multidrug-resistant cancer cells contain two populations of P-glycoprotein with differently stimulated P-gp ATPase activities: evidence from atomic force microscopy and biochemical analysis. Biochem. J. 388: 563-571
37. Ghetie M. A., Marches R., Kufert S. and Vitetta E. S. (2004) An anti-CD 19 antibody inhibits the interaction between P-glycoprotein (P-gp) and CD19. causes P-gp to translocate out of lipid rafts, and chemosensitizes a multidrug-resistant (MDR) lymphoma cell line. Blood 104: 178-183
38. Troost J., Lindenmaier H., Haefeli W. E. and Weiss J. (2004) Modulation of cellular cholesterol alters P-glycoprotein activity in multidrug-resistant cells. Mol. Pharmacol. 66: 1332-1339
39. Kamau S. W., Kramer S. D., Gunthert M. and Wunderli-Allenspach H. (2005) Effect of the modulation of the membrane lipid composition on the localization and function of P-glycoprotein in Mdr1-Mdck cells. In Vitro Cell Dev. Biol. Anim. 41: 207-216
40. Yunomae K., Arima H., Hirayama F. and Uekama K. (2003) Involvement of cholesterol in the inhibitory effect of dimethyl-beta-cyclodextrin on P-glycoprotein and MRP2 function in Caco-2 cells. FEBS Lett. 536: 225-231
41. Luker G. D., Pica C. M., Kumar A. S., Covey D. F. and Piwnica-Worms D. (2000) Effects of cholesterol and enantiomeric cholesterol on P-glycoprotein localization and function in low-density membrane domains. Biochemistry 39: 7051-7661
42. Garrigos M., Belehradek J. Jr, Mir L. M. and Orlowski S. (1993) Absence of cooperativity for MgATP and verapamil effects on the ATPase activity of P-glycoprotein containing membrane vesicles. Biochem. Biophys. Res. Commun. 196: 1034-1041
43. Reungpatthanaphong P., Marbeuf-Gueye C., Le Moyec L., Salerno M. and Garnier-Suillerot A. (2004) Decrease of P-glycoprotein activity in K562/ADR cells by MbetaCD and filipin and lack of effect induced by cholesterol oxidase indicate that this transporter is not located in rafts. J. Bioenerg. Biomembr. 36: 533-543
44. Demeule M., Jodoin J., Gingras D. and Beliveau R. (2000) P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries. FEBS Lett. 466: 219-224
45. Jodoin J., Demeule M., Fenart L., Cecchelli R., Farmer S., Linton K. J. et al. (2003) P-glycoprotein in blood-brain barrier endothelial cells: interaction and oligomerization with caveolins. J. Neurochem. 87: 1010-1023
46. Ronaldson P. T., Bendayan M., Gingras D., Piquette-Miller M. and Bendayan R. (2004) Cellular localization and functional expression of P-glycoprotein in rat astrocyte cultures. J. Neurochem. 89: 788-800
47. Bacso Z., Nagy H., Goda K., Bene L., Fenyvesi F., Matko J. et al. (2004) Raft and cytoskeleton associations of an ABC transporter: P-glycoprotein. Cytometry A 61: 105-116
48. Luciani F., Molinari A., Lozupone F., Calcabrini A., Lugini L., Stringaro A. et al. (2002) P-glycoprotein-actin association through ERM family proteins: a role in P-glycoprotein function in human cells of lymphoid origin. Blood 99: 641-648
49. Slimane T. A., Trugnan G., Van I. S. C. and Hoekstra D. (2003) Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells: role of distinct lipid microdomains. Mol. Biol. Cell 14: 611-624
50. Hinrichs J. W., Klappe K., Hummel I. and Kok J. W. (2004) ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells. J. Biol. Chem. 279: 5734-5738
51. Radeva G., Perabo J. and Sharom F. J. (2005) P-Glycoprotein is localized in intermediate-density membrane microdomains distinct from classical lipid rafts and caveolar domains. FEBS J. 272: 4924-4937
52. Belanger M. M., Gaudreau M., Roussel E. and Couet J. (2004) Role of caveolin-1 in etoposide resistance development in A549 lung cancer cells. Cancer Biol. Ther. 3: 954-959
53. Willingham M. C., Richert N. D., Cornwell M. M., Tsuruo T., Hamada H., Gottesman M. M. et al. (1987) Immunocytochemical localization of P170 at the plasma membrane of multidrug-resistant human cells. J. Histochem. Cytochem. 35: 1451-1456
54. Molinari A., Cianfriglia M., Meschini S., Calcabrini A. and Arancia G. (1994) P-glycoprotein expression in the Golgi apparatus of multidrug-resistant cells. Int. J. Cancer 59: 789-795
55. Lee G., Schlichter L., Bendayan M. and Bendayan R. (2001) Functional expression of P-glycoprotein in rat brain microglia. J. Pharmacol. Exp. Ther. 299: 204-212
56. Rajagopal A. and Simon S. M. (2003) Subcellular localization and activity of multidrug resistance proteins. Mol. Biol. Cell 14: 3389-3399
57. Shapiro A. B., Fox K., Lee P., Yang Y. D. and Ling V. (1998) Functional intracellular P-glycoprotein. Int. J. Cancer 76: 857-864
58. Keizer H. G., Schuurhuis G. J., Broxterman H. J., Lankelma J., Schoonen W. G., van Rijn J. et al. (1989) Correlation of multidrug resistance with decreased drug accumulation, altered subcellular drug distribution and increased P-glycoprotein expression in cultured SW-1573 human lung tumor cells. Cancer Res. 49: 2988-2993
59. Sognier M. A., Zhang Y., Eberle R. L. and Belli J. A. (1992) Characterization of adriamycin-resistant and radiation-sensitive Chinese hamster cell lines. Biochem. Pharmacol. 44: 1859-1868
60. Labroille G., Belloc F., Bilhou-Nabera C., Bonnefille S., Bascans E., Boisseau M. R. et al. (1998) Cytometric study of intracellular P-gp expression and reversal of drug resistance. Cytometry 32: 86-94
61. Sai Y., Nies A. T. and Arias I. M. (1999) Bile acid secretion and direct targeting of mdr1-green fluorescent protein from Golgi to the canalicular membrane in polarized WIF-B cells. J. Cell Sci. 112: 4535-4545
62. Kim H., Barroso M., Samanta R., Greenberger L. and Sztul E. (1997) Experimentally induced changes in the endocytic traffic of P-glycoprotein alter drug resistance of cancer cells. Am. J. Physiol. 273: C687-C702
63. De Rosa M. F., Sillence D., Ackerley C. and Lingwood C. (2004) Role of multiple drug resistance protein 1 in neutral but not acidic glycosphingolipid biosynthesis. J. Biol. Chem. 279: 7867-7876
64. Orlowski S., Selosse M. A., Boudon C., Micoud C., Mir L. M., Belehradek J. Jr et al. (1998) Effects of detergents on P-glycoprotein atpase activity: differences in perturbations of basal and verapamil-dependent activities. Cancer Biochem. Biophys. 16: 85-110
65. Callaghan R., Stafford A. and Epand R. M. (1993) Increased accumulation of drugs in a multidrug resistant cell line by alteration of membrane biophysical properties. Biochim. Biophys. Acta 1175: 277-282
66. Sinicrope F. A., Dudeja P. K., Bissonnette B. M., Safa A. R. and Brasitus T. A. (1992) Modulation of P-glycoprotein-mediated drug transport by alterations in lipid fluidity of rat liver canalicular membrane vesicles. J. Biol. Chem. 267: 24995-25002
67. Dudeja P. K., Anderson K. M., Harris J. S., Buckingham L. and Coon J. S. (1995) Reversal of multidrug resistance phenotype by surfactants: relationship to membrane lipid fluidity. Arch. Biochem. Biophys. 319: 309-315
68. Regev R., Assaraf Y. G. and Eytan G. D. (1999) Membrane fluidization by ether, other anesthetics and certain agents abolishes P-glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells. Eur. J. Biochem. 259: 18-24
69. Urbatsch I. L. and Senior A. E. (1995) Effects of lipids on AT-Pase activity of purified Chinese hamster P-glycoprotein. Arch. Biochem. Biophys. 316: 135-140
70. Romsicki Y. and Sharom F. J. (1998) The ATPase and ATP-binding functions of P-glycoprotein - modulation by interaction with defined phospholipids. Eur. J. Biochem. 256: 170-178
71. Romsicki Y. and Sharom F. J. (1999) The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter. Biochemistry 38: 6887-6896
72. Lu P., Liu R. and Sharom F. J. (2001) Drug transport by reconstituted P-glycoprotein in proteoliposomes. Effect of substrates and modulators, and dependence on bilayer phase state. Eur. J. Biochem. 268: 1687-1697
73. Saeki T., Shimabuku A. M., Ueda K. and Komano T. (1992) Specific drug binding by purified lipid-reconstituted P-glycoprotein: dependence on the lipid composition. Biochim. Biophys. Acta 1107: 105-110
74. Modok S., Heyward C. and Callaghan R. (2004) P-glycoprotein retains function when reconstituted into a sphingolipid-and cholesterol-rich environment. J. Lipid Res. 45: 1910-1918
75. Asawakarn T., Cladera J. and O'Shea P. (2001) Effects of the membrane dipole potential on the interaction of saquinavir with phospholipid membranes and plasma membrane receptors of Caco-2 cells. J. Biol. Chem. 276: 38457-38463
76. Rothnie A., Theron D., Soceneantu L., Martin C., Traikia M., Berridge G. et al. (2001) The importance of cholesterol in maintenance of P-glycoprotein activity and its membrane perturbing influence. Eur. Biophys. J. 30: 430-442
77. Wang E., Casciano C. N., Clement R. P. and Johnson W. W. (2000) Cholesterol interaction with the daunorubicin binding site of P-glycoprotein. Biochem. Biophys. Res. Commun. 276: 909-916
78. Gayet L., Dayan G., Barakat S., Labialle S., Michaud M., Cogne S. et al. (2005) Control of P-glycoprotein activity by membrane cholesterol amounts and their relation to multidrug resistance in human CEM leukemia cells. Biochemistry 44: 4499-4509
79. Garrigues A., Escargueil A. E. and Orlowski S. (2002) The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane. Proc. Natl. Acad. Sci. USA 99: 10347-10352
80. Mazzoni A. and Trave F. (1993) Cytoplasmic membrane cholesterol and doxorubicin cytotoxicity in drug-sensitive and multidrug-resistant human ovarian cancer cells. Oncol. Res. 5: 75-82
81. Pallares-Trujillo J., Domenech C., Grau-Oliete M. R. and Rivera-Fillat M. P. (1993) Role of cell cholesterol in modulating vincristine uptake and resistance. Int. J. Cancer 55: 667-671
82. Troost J., Albermann N., Emil Haefeli W. and Weiss J. (2004) Cholesterol modulates P-glycoprotein activity in human peripheral blood mononuclear cells. Biochem. Biophys. Res. Commun. 316: 705-711
83. Warren L., Jardillier J. C., Malarska A. and Akeli M. G. (1992) Increased accumulation of drugs in multidrug-resistant cells induced by liposomes. Cancer Res. 52: 3241-3245
84. Grosse P. Y. Bressolle F. and Pinguet F. (1997) Methyl-beta-cyclodextrin in HL-60 parental and multidrug-resistant cancer cell lines: effect on the cytotoxic activity and intracellular accumulation of doxorubicin. Cancer Chemother. Pharmacol. 40: 489-494
85. Veldman R. J., Sietsma H., Klappe K., Hoekstra D. and Kok J. W. (1999) Inhibition of P-glycoprotein activity and chemosensitization of multidrug-resistant ovarian carcinoma 2780AD cells by hexanoylglucosylceramide. Biochem. Biophys. Res. Commun. 266: 492-496
86. di Bartolomeo S. and Spinedi A. (2001) Differential chemosensitizing effect of two glucosylceramide synthase inhibitors in hepatoma cells. Biochem. Biophys. Res. Commun. 288: 269-274
87. Liu Y. Y., Han T. Y., Giuliano A. E. and Cabot M. C. (1999) Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells. J. Biol. Chem. 274: 1140-1146
88. Liu Y. Y., Han T. Y., Giuliano A. E. and Cabot M. C. (2001) Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J. 15: 719-730
89. Liu Y. Y., Han T. Y., Giuliano A. E., Hansen N. and Cabot M. C. (2000) Uncoupling ceramide glycosylation by transfection of glucosylceramide synthase antisense reverses adriamycin resistance. J. Biol. Chem. 275: 7138-7143
90. Liu Y. Y., Han T. Y., Yu J. Y., Bitterman A., Le A., Giuliano A. E. et al. (2004) Oligonucleotides blocking glucosylceramide synthase expression selectively reverse drug resistance in cancer cells. J. Lipid Res. 45: 933-940
91. Plo I., Lehne G., Beckstrom K. J., Maestre N., Bettaieb A., Laurent G. et al. (2002) Influence of ceramide metabolism on P-glycoprotein function in immature acute myeloid leukemia KG1a cells. Mol. Pharmacol. 62: 304-312
92. Bucher K., Besse C. A., Kamau S. W., Wunderli-Allenspach H. and Kramer S. D. (2005) Isolated rafts from adriamycin-resistant P388 cells contain functional ATPases and provide an easy test system for P-glycoprotein-related activities. Pharm. Res. 22: 449-457
93. Banerjee P., Buse J. T. and Dawson G. (1990) Asymmetric extraction of membrane lipids by CHAPS. Biochim. Biophys. Acta 1044: 305-314
94. Xiao Z. and Devreotes RN. (1997) Identification of detergent-resistant plasma membrane microdomains in dictyostelium: enrichment of signal transduction proteins. Mol. Biol. Cell 8: 855-869
95. Doige C. A., Yu X. and Sharom F. J. (1992) ATPase activity of partially purified P-glycoprotein from multidrug-resistant Chinese hamster ovary cells. Biochim. Biophys. Acta 1109: 149-160
96. Cai C., Zhu H. and Chen J. (2004) Overexpression of caveolin-1 increases plasma membrane fluidity and reduces P-glycoprotein function in Hs578T/Dox. Biochem. Biophys. Res. Commun. 320: 868-874
97. Klucken J., Buchler C., Orso E., Kaminski W. E., Porsch-Ozcurumez M., Liebisch G. et al. (2000) ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc. Natl. Acad. Sci. USA 97: 817-822
98. Batetta B., Dessi S., Putzolu M., Sanna F., Spano O., Mulas M. F. et al. (1999) MDR1 gene expression in normal and atherosclerotic human arteries(1). J. Vasc. Res. 36: 261-271
99. Batetta B., Mulas M. F., Petruzzo P., Putzolu M., Bonatesta R. R., Sanna F. et al. (2001) Opposite pattern of MDR1 and caveolin-1 gene expression in human atherosclerotic lesions and proliferating human smooth muscle cells. Cell Mol. Life Sci. 58: 1113-1120
100. Zhu H., Cai C. and Chen J. (2004) Suppression of P-glycoprotein gene expression in Hs578T/Dox by the overexpression of caveolin-1. FEBS Lett. 576: 369-374
101. Cai C. and Chen J. (2004) Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T breast adenocarcinoma cells. Int. J. Cancer 111: 522-529
102. Yang C. P., Galbiati F., Volonte D., Horwitz S. B. and Lisanti M. P. (1998) Upregulation of caveolin-1 and caveolae organelles in Taxol-resistant A549 cells. FEBS Lett. 439: 368-372
103. Pang A., Au W. Y. and Kwong Y. L. (2004) Caveolin-1 gene is coordinately regulated with the multidrug resistance 1 gene in normal and leukemic bone marrow. Leuk. Res. 28: 973-977
104. Gargalovic P. and Dory L. (2003) Caveolins and macrophage lipid metabolism. J. Lipid Res. 44: 11-21
105. Liscovitch M. and Lavie Y. (2000) Multidrug resistance: a role for cholesterol efflux pathways? Trends Biochem. Sci. 25: 530-534
106. Abulrob A. G. and Gumbleton M. (1999) Transport of phosphatidylcholine in MDR3-negative epithelial cell lines via drug-induced MDR1 P-glycoprotein. Biochem. Biophys. Res. Commun. 262: 121-126
107. Pohl A., Lage H., Muller P., Pomorski T. and Herrmann A. (2002) Transport of phosphatidylserine via MDR1 (multidrug resistance 1) P-glycoprotein in a human gastric carcinoma cell line. Biochem. J. 365: 259-268
108. Sugawara S., Hosono M., Ogawa Y., Takayanagi M. and Nitta K. (2005) Catfish egg lectin causes rapid activation of multidrug resistance 1 P-glycoprotein as a lipid translocase. Biol. Pharm. Bull. 28: 434-441
109. van Helvoort A., Giudici M. L., Thielemans M. and van Meer G. (1997) Transport of sphingomyelin to the cell surface is inhibited by brefeldin A and in mitosis, where C6-NBD-sphingomyelin is translocated across the plasma membrane by a multidrug transporter activity. J. Cell Sci. 110: 75-83
110. Romsicki Y. and Sharom F. J. (2001) Phospholipid flippase activity of the reconstituted P-glycoprotein multidrug transporter. Biochemistry 40: 6937-6947
111. Eckford P. D. and Sharom F. J. (2005) The reconstituted P-glycoprotein multidrug transporter is a flippase for glucosylceramide and other simple glycosphingolipids. Biochem. J. 389: 517-526
112. Ruetz S. and Gros P. (1994) Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell 77: 1071-1081
113. Borst P., Zelcer N. and van Helvoort A. (2000) ABC transporters in lipid transport. Biochim. Biophys. Acta 1486: 128-144
114. Aoki S., Chen Z. S., Higasiyama K., Setiawan A., Akiyama S. and Kobayashi M. (2001) Reversing effect of agosterol A, a spongean sterol acetate, on multidrug resistance in human carcinoma cells. Jpn. J. Cancer Res. 92: 886-895
115. Mitsuo M., Noguchi T., Nakajima Y., Aoki S., Ren X. Q., Sumizawa T. et al. (2003) Binding site(s) on P-glycoprotein for a newly synthesized photoaffinity analog of agosterol A. Oncol. Res. 14: 39-48
116. Wright L. C., Dyne M., Holmes K. T. and Mountford C. E. (1985) Phospholipid and ether linked phospholipid content alter with cellular resistance to vinblastine. Biochem. Biophys. Res. Commun. 133: 539-545
117. Holleran W. M., DeGregorio M. W., Ganapathi R., Wilbur J. R. and Macher B. A. (1986) Characterization of cellular lipids in doxorubicin-sensitive and -resistant P388 mouse leukemia cells. Cancer Chemother. Pharmacol. 17: 11-15
118. Montaudon D., Vrignaud P., Londos-Gagliardi D. and Robert J. (1986) Fluorescence anisotropy of cell membranes of doxorubicin-sensitive and -resistant rodent tumoral cells. Cancer Res. 46: 5602-5605
119. Vrignaud P., Montaudon D., Londos-Gagliardi D. and Robert J. (1986) Fatty acid composition transport and metabolism in doxorubicin-sensitive and-resistant rat glioblastoma cells. Cancer Res. 46: 3258-3261
120. Santini M. T., Romano R., Rainaldi G., Filippini P., Bravo E., Porcu L. et al. (2001) The relationship between 1H-NMR mobile lipid intensity and cholesterol in two human tumor multidrug resistant cell lines (MCF-7 and LoVo). Biochim. Biophys. Acta 1531: 111-131
121. Santini M. T., Napolitano M., Ferrante A., Rainaldi G., Arancia G. and Bravo E. (2003) Differential control of cholesterol and fatty acid biosynthesis in sensitive and multidrug-resistant LoVo tumor cells. Anticancer Res. 23: 4737-4746
122. Le Moyec L., Tatoud R., Degeorges A., Calabresse C., Bauza G., Eugene M. et al. (1996) Proton nuclear magnetic resonance spectroscopy reveals cellular lipids involved in resistance to adriamycin and taxol by the K562 leukemia cell line. Cancer Res. 56: 3461-3467
123. Ramu A., Ramu N. and Rosario L. M. (1991) Circumvention of multidrug-resistance in P388 cells is associated with a rise in the cellular content of phosphatidylcholine. Biochem. Pharmacol. 41: 1455-1461
124. Le Goff W., Settle M., Greene D. J., Morton R. E. and Smith J. D. (2006) Reevaluation of the role of the multidrug resistant P-glycoprotein in cellular cholesterol homeostasis. J. Lipid Res. 47: 51-58
125. Le Moyec L., Legrand O., Larue V., Kawakami M., Marie J. P., Calvo F. et al. (2000) Magnetic resonance spectroscopy of cellular lipid extracts from sensitive, resistant and reverting K562 cells and flow cytometry for investigating the P-glycoprotein function in resistance reversion. NMR Biomed. 13: 92-101
126. Sehested M., Skovsgaard T., van Deurs B. and Winther-Niel-sen H. (1987) Increase in nonspecific adsorptive endocytosis in anthracycline- and vinca alkaloid-resistant Ehrlich ascites tumor cell lines. J. Natl. Cancer Inst. 78: 171-179
127. Sehested M., Skovsgaard T., van Deurs B. and Winther-Nielsen H. (1987) Increased plasma membrane traffic in daunorubicin resistant P388 leukaemic cells. Effect of daunorubicin and verapamil. Br. J. Cancer 56: 747-751
128. Warren L., Jardillier J. C. and Ordentlich P. (1991) Secretion of lysosomal enzymes by drug-sensitive and multiple drug-resistant cells. Cancer Res. 51: 1996-2001
129. Tatidis L., Masquelier M. and Vitols S. (2002) Elevated uptake of low density lipoprotein by drug resistant human leukemic cell lines. Biochem. Pharmacol. 63: 2169-2180
130. Ambudkar S. V., Sauna Z. E., Gottesman M. M. and Szakacs G. (2005) A novel way to spread drug resistance in tumor cells: functional intercellular transfer of P-glycoprotein (ABCB1). Trends Pharmacol. Sci. 26: 385-387
131. Tessner T. G. and Stenson W. F. (2000) Overexpression of MDR1 in an intestinal cell line results in increased cholesterol uptake from micelles. Biochem. Biophys. Res. Commun. 267: 565-571
132. Liscum L. and Munn N. J. (1999) Intracellular cholesterol transport. Biochim. Biophys. Acta 1438: 19-37
133. Fielding C. J. and Fielding P. E. (2000) Cholesterol and caveolae: structural and functional relationships. Biochim. Biophys. Acta 1529: 210-222
134. Simons K. and Ikonen E. (2000) How cells handle cholesterol. Science 290: 1721-1726
135. Metherall J. E., Li H. and Waugh K. (1996) Role of multidrug resistance P-glycoproteins in cholesterol biosynthesis. J. Biol. Chem. 271: 2634-2640
136. Debry P., Nash E. A., Neklason D. W. and Metherall J. E. (1997) Role of multidrug resistance P-glycoproteins in cholesterol esterification. J. Biol. Chem. 272: 1026-1031
137. Field F. J., Born E., Chen H., Murthy S. and Mathur S. N. (1995) Esterification of plasma membrane cholesterol and triacylglycerol-rich lipoprotein secretion in CaCo-2 cells: possible role of p-glycoprotein. J. Lipid Res. 36: 1533-1543
138. Field F. J., Born E., Murthy S. and Mathur S. N. (1998) Transport of cholesterol from the endoplasmic reticulum to the plasma membrane is constitutive in CaCo-2 cells and differs from the transport of plasma membrane cholesterol to the endoplasmic reticulum. J. Lipid Res. 39: 333-343
139. Luker G. D., Nilsson K. R., Covey D. F. and Piwnica-Worms D. (1999) Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma membrane cholesterol. J. Biol. Chem. 274: 6979-6991
140. Pani A., Batetta B., Putzolu M., Sanna F., Spano O., Piras S. et al. (2000) MDR1, cholesterol certification and cell growth: a comparative study in normal and multidrug-resistant KB cell lines. Cell Mol. Life Sci. 57: 1094-1102
141. Issandou M. and Grand-Perret T. (2000) Multidrug resistance P-glycoprotein is not involved in cholesterol esterification. Biochem. Biophys. Res. Commun. 279: 369-377
142. Luker G. D., Dahlheimer J. L., Ostlund R. E. Jr and Piwnica-Worms D. (2001) Decreased hepatic accumulation and enhanced esterification of cholesterol in mice deficient in mdrla and mdr1b P-glycoproteins. J. Lipid Res. 42: 1389-1394
143. Dimitroulakos J. and Yeger H. (1996) HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets P-glycoprotein-expressing cells. Nat. Med. 2: 326-333
144. Maksumova L., Ohnishi K., Muratkhodjaev F., Zhang W., Pan L., Takeshita A. et al. (2000) Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to lovastatin. Leukemia 14: 1444-1450
145. Lavie Y., Cao H., Bursten S. L., Giuliano A. E. and Cabot M. C. (1996) Accumulation of glucosylceramides in multidrug-resistant cancer cells. J. Biol. Chem. 271: 19530-19536
146. Lavie Y., Cao H., Volner A., Lucci A., Han T. Y., Geffen V. et al. (1997) Agents that reverse multidrug resistance, tamoxifen, verapamil and cyclosporin A, block glycosphingolipid metabolism by inhibiting ceramide glycosylation in human cancer cells. J. Biol. Chem. 272: 1682-1687
147. Morjani H., Aouali N., Belhoussine R., Veldman R. J., Levade T. and Manfait M. (2001) Elevation of glucosylceramide in multidrug-resistant cancer cells and accumulation in cytoplasmic droplets. Int. J. Cancer 94: 157-165
148. Gouaze V., Yu J. Y., Bleicher R. J., Han T. Y., Liu Y. Y., Wang H. et al. (2004) Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol. Cancer Ther. 3: 633-639
149. Veldman R. J., Klappe K., Hinrichs J., Hummel I., van der Schaaf G., Sietsma H. et al. (2002) Altered sphingolipid metabolism in multidrug-resistant ovarian cancer cells is due to uncoupling of glycolipid biosynthesis in the Golgi apparatus. FASEB J. 16: 1111-1113
150. Hummel I., Klappe K. and Kok J. W. (2005) Upregulation of lactosylceramide synthase in MDR1 overexpressing human liver tumour cells. FEBS Lett. 579: 3381-3384
151. Lala P., Ito S. and Lingwood C. A. (2000) Retroviral transfection of Madin-Darby canine kidney cells with human MDR1 results in a major increase in globotriaosylceramide and 10(5)-to 10(6)-fold increased cell sensitivity to verocytotoxin. Role of p-glycoprotein in glycolipid synthesis. J. Biol. Chem. 275: 6246-6251
152. Shabbits J. A. and Mayer L. D. (2002) P-glycoprotein modulates ceramide-mediated sensitivity of human breast cancer cells to tubulin-binding anticancer drugs. Mol. Cancer Ther. 1: 205-213
153. Veldman R. J., Mita A., Cuvillier O., Garcia V., Klappe K., Medin J. A. et al. (2003) The absence of functional glucosylceramide synthase does not sensitize melanoma cells for anticancer drugs. FASEB J. 17: 1144-1146
154. Grazide S., Terrisse A. D., Lerouge S., Laurent G. and Jaffrezou J. P. (2004) Cytoprotective effect of glucosylceramide synthase inhibition against daunorubicin-induced apoptosis in human leukemic cell lines. J. Biol. Chem. 279: 18256-18261
155. Johnstone R. W., Ruefli A. A. and Smyth M. J. (2000) Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem. Sci. 25: 1-6
156. Pettus B. J., Chalfant C. E. and Hannun Y. A. (2002) Ceramide in apoptosis: an overview and current perspectives. Biochim. Biophys. Acta 1585: 114-125
157. Bezombes C., Maestre N., Laurent G., Levade T., Bettaieb A. and Jaffrezou J. P. (1998) Restoration of TNF-alpha-induced ceramide generation and apoptosis in resistant human leukemia KG1a cells by the P-glycoprotein blocker PSC833. FASEB J. 12: 101-109
158. Pallis M. and Russell N. (2000) P-glycoprotein plays a drug-efflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway. Blood 95: 2897-2904
159. Turzanski J., Grundy M., Shang S., Russell N. and Pallis M. (2005) P-glycoprotein is implicated in the inhibition of ceramide-induced apoptosis in TF-1 acute myeloid leukemia cells by modulation of the glucosylceramide synthase pathway. Exp. Hematol. 33: 62-72
160. Ruefli A. A., Tainton K. M., Darcy P. K., Smyth M. J. and Johnstone R. W. (2002) P-glycoprotein inhibits caspase-8 activation but not formation of the death inducing signal complex (disc) following Fas ligation. Cell Death Differ. 9: 1266-1272
161. Matarrese P., Testa U., Cauda R., Vella S., Gambardella L. and Malorni W. (2001) Expression of P-170 glycoprotein sensitizes lymphoblastoid CEM cells to mitochondria-mediated apoptosis. Biochem. J. 355: 587-595
162. Lecureur V., Thottassery J. V., Sun D., Schuetz E. G., Lahti J., Zambetti G. P. et al. (2001) Mdrlb facilitates p53-mediated cell death and p53 is required for Mdr1b upregulation in vivo. Oncogene 20: 303-313
163. Gulbins E. and Grassme H. (2002) Ceramide and cell death receptor clustering. Biochim. Biophys. Acta 1585: 139-145
164. Bezombes C., Laurent G. and Jaffrezou J. P. (2003) Implication of raft microdomains in drug induced apoptosis. Curr. Med. Chem. Anti-Canc. Agents 3: 263-270
165. Dimanche-Boitrel M. T., Meurette O., Rebillard A. and Lacour S. (2005) Role of early plasma membrane events in chemotherapy-induced cell death. Drug Resist. Updat. 8: 5-14
166. Randolph G. J., Beaulieu S., Pope M., Sugawara I., Hoffman L., Steimnan R. M. et al. (1998) A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels. Proc. Natl. Acad. Sci. USA 95: 6924-6929
167. Pawlik A., Baskiewicz-Masiuk M., Machalinski B., Safranow K. and Gawronska-Szklarz B. (2005) Involvement of P-glycoprotein in the release of cytokines from peripheral blood mononuclear cells treated with methotrexate and dexamethasone. J. Pharm. Pharmacol. 57: 1421-1426
168. Theron D., Barraud de Lagerie S., Tardivel S., Pelerin H., Demeuse P., Mercier C. et al. (2003) Influence of tumor necrosis factor-alpha on the expression and function of P-glycoprotein in an immortalised rat brain capillary endothelial cell line, GPNT. Biochem. Pharmacol. 66: 579-587
169. Rao R., Logan B., Forrest K., Roszman T. L. and Goebel J. (2004) Lipid rafts in cytokine signaling. Cytokine Growth Factor Rev. 15: 103-110
170. Ikonen E. (2001) Roles of lipid rafts in membrane transport. Curr. Opin. Cell Biol. 13: 470-477
171. Lam F. C., Liu R., Lu P., Shapiro A. B., Renoir J. M., Sharom F. J. et al. (2001) beta-Amyloid efflux mediated by p-glycoprotein. J. Neurochem. 76: 1121-1128
172. Cirrito J. R., Deane R., Fagan A. M., Spinner M. L., Parsadanian M., Finn M. B. et al. (2005) P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J. Clin. Invest. 115: 3285-3290
173. Ehehalt R., Keller P., Haass C., Thiele C. and Simons K. (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J. Cell Biol. 160: 113-123
174. Kaneko K., Vey M., Scott M., Pilkuhn S., Cohen F. E. and Prusiner S. B. (1997) COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform. Proc. Natl. Acad. Sci. USA 94: 2333-2338
175. Hooper N. M. (2005) Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. Biochem. Soc. Trans. 33: 335-338
176. Raviv Y., Puri A. and Blumenthal R. (2000) P-glycoprotein-overexpressing multidrug-resistant cells are resistant to infection by enveloped viruses that enter via the plasma membrane. FASEB J. 14: 511-515
177. Lee C. G., Ramachandra M., Jeang K. T., Martin M. A., Pastan I. and Gottesman M. M. (2000) Effect of ABC transporters on HIV-1 infection: inhibition of virus production by the MDR1 transporter. FASEB J. 14: 516-522
178. Wang J. K., Kiyokawa E., Verdin E. and Trono D. (2000) The Nef protein of HIV-1 associates with rafts and primes T cells for activation. Proc. Natl. Acad. Sci. USA 97: 394-399
179. Scheiffele P., Rietveld A., Wilk T. and Simons K. (1999) Influenza viruses select ordered lipid domains during budding from the plasma membrane. J. Biol. Chem. 274: 2038-2044
180. Chazal N. and Gerlier D. (2003) Virus entry, assembly, budding and membrane rafts. Microbiol. Mol. Biol. Rev. 67: 226-237
181. Hinrichs J. W., Klappe K. and Kok J. W. (2005) Rafts as missing link between multidrug resistance and sphingolipid metabolism. J. Membr. Biol. 203: 57-64
182. Germann U. A. (1996) P-glycoprotein - a mediator of multidrug resistance in tumour cells. Eur. J. Cancer 32A: 927-944
183. Holthuis J. C. and Levine T. P. (2005) Lipid traffic: floppy drives and a superhighway. Nat. Rev. Mol. Cell Biol. 6: 209-220
184. Seigneuret M. and Garnier-Suillerot A. (2003) A structural model for the open conformation of the mdr1 P-glycoprotein based on the MsbA crystal structure. J. Biol. Chem. 278: 30115-30124
185. Chang G. and Roth C. B. (2001) Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293: 1793-1800
186. Chang G. (2003) Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation. J. Mol. Biol. 330: 419-430
187. Megha and London E. (2004) Ceramide selectively displaces cholesterol from ordered lipid domains (rafts): implications for lipid raft structure and function. J. Biol. Chem. 279: 9997-10004
188. Slotte J. P. and Bierman E. L. (1988) Depletion of plasma-membrane sphingomyelin rapidly alters the distribution of cholesterol between plasma membranes and intracellular cholesterol pools in cultured fibroblasts. Biochem. J. 250: 653-658
189. Ridgway N. D. (2000) Interactions between metabolism and intracellular distribution of cholesterol and sphingomyelin. Biochim. Biophys. Acta 1484: 129-141
190. Incardona J. P. and Eaton S. (2000) Cholesterol in signal transduction. Curr. Opin. Cell Biol. 12: 193-203
191. Parton R. G. and Richards A. A. (2003) Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic 4: 724-738
192. Rajendran L. and Simons K. (2005) Lipid rafts and membrane dynamics. J. Cell Sci. 118: 1099-1102
193. Kamp D. and Haest C. W. (1998) Evidence for a role of the multidrug resistance protein (MRP) in the outward translocation of NBD-phospholipids in the erythrocyte membrane. Biochim. Biophys. Acta 1372: 91-101
194. Dekkers D. W., Comfurius P., Schroit A. J., Bevers E. M. and Zwaal R. F. (1998) Transbilayer movement of NBD-labeled phospholipids in red blood cell membranes: outward-directed transport by the multidrug resistance protein 1 (MRP1). Biochemistry 37: 14833-14837
195. Raggers R. J., van Helvoort A., Evers R. and van Meer G. (1999) The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. J. Cell Sci. 112: 415-422
196. Klappe K., Hinrichs J. W., Kroesen B. J., Sietsma H. and Kok J. W. (2004) MRP1 and glucosylceramide are coordinately over expressed and enriched in rafts during multidrug resistance acquisition in colon cancer cells. Int. J. Cancer 110: 511-522
197. Janvilisri T., Venter H., Shahi S., Reuter G., Balakrishnan L. and van Veen H. W. (2003) Stero1 transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J. Biol. Chem. 278: 20645-20651
198. Smit J. J., Schinkel A. H., Oude Elferink R. P., Groen A. K., Wagenaar E., van Deemter L. et al. (1993) Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75: 451-462
199. Shinnoh N., Yamada T., Yoshimura T., Furuya H., Yoshida Y., Suzuki Y. et al. (1995) Adrenoleukodystrophy: the restoration of peroxisomal beta-oxidation by transfection of normal cDNA. Biochem. Biophys. Res. Commun. 210: 830-836
200. Boujaoude L. C., Bradshaw-Wilder C., Mao C., Cohn J., Ogretmen B., Hannun Y. A. et al. (2001) Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate. J. Biol. Chem. 276: 35258-35264
201. Hamon Y., Broccardo C., Chambenoit O., Luciani M. F., Toti F., Chaslin S. et al. (2000) ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat. Cell Biol. 2: 399-406
202. Fielding P. E., Nagao K., Hakamata H., Chimini G. and Fielding C. J. (2000) A two-step mechanism for free cholesterol and pliospholipid efflux from human vascular cells to apolipoprotein A-1. Biochemistry 39: 14113-14120
203. Venkateswaran A., Repa J. J., Lobaccaro J. M., Bronson A., Mangelsdorf D. J. and Edwards P. A. (2000) Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J. Biol. Chem. 275: 14700-14707
204. Berge K. E., Tian H., Graf G. A., Yu L., Grishin N. V., Schultz J. et al. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290: 1771-1775
205. Wu J. E., Basso F., Shamburek R. D., Amar M. J., Vaisman B., Szakacs G. et al. (2004) Hepatic ABCG5 and ABCG8 overexpression increases hepatobiliary sterol transport but does not alter aortic atherosclerosis in transgenic mice. J. Biol. Chem. 279: 22913-22925
206. Raggers R. J., Pomorski T., Holthuis J. C., Kalin N. and van Meer G. (2000) Lipid traffic: the ABC of transbilayer movement. Traffic 1: 226-234
207. Pohl A., Devaux P. F. and Herrmann A. (2005) Function of prokaryotic and eukaryotic ABC proteins in lipid transport. Biochim. Biophys. Acta 1733: 29-52