Abstract

Membrane lipids, due to diverse molecular structures, electric charge and different functional characteristic, have a profound role in multiple cytophysiological processes. A better understanding of the membrane structure and changes of its function in a wide range of diseases gave rise to a new approach termed membrane lipid therapy and directed to modifying the membranes. The strategies directed to membrane involve a direct regulation of membrane lipid composition that causes a change of the transmembrane protein function and modifies the organization of membrane microdomains, or regulation of enzyme activity and gene expression to alter membrane lipid composition. Membrane therapy assumes the use of new molecules specifically designed to modify lipid composition and function of abnormal signaling proteins. Therefore, modifications of the lipid composition and organization of membrane microdomains become pharmacological targets to reverse pathological changes in the profile of enzymatically and non-enzymatically generated lipid derivatives or to modify signaling pathways in the cell. The present monography is an update of the canonical membrane model by Singer-Nicolson and describes the therapeutic targets related to the regulation of the composition and organization of the lipids in the plasma membrane.

References

• 1. Alder-Baerens N., Müller P., Pohl A., Korte T., Hamon Y., Chimini G., Pomorski T., Herrmann A.: Headgroup-specific exposure of phospholipids in ABCA1-expressing cells. J. Biol. Chem., 2005; 280: 26321-26329
  Google Scholar
• 2. Asea A., Kraeft S.K., Kurt-Jones E.A., Stevenson M.A., Chen L.B., Finberg R.W., Koo G.C., Calderwood S.K.: HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med., 2000; 6: 435-442
  Google Scholar
• 3. Balla T.: Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol. Rev., 2013; 93: 1019-1137
  Google Scholar
• 4. Balla T.: Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions. J. Cell Sci., 2005; 118: 2093-2104
  Google Scholar
• 5. Baradaran R., Berrisford J.M., Minhas G.S., Sazanov L.A.: Crystal structure of the entire respiratory complex I. Nature, 2013; 494: 443-448
  Google Scholar
• 6. Barceló-Coblijn G., Martin M.L., de Almeida R.F. Noguera-Salvà M.A., Marcilla-Etxenike A., Guardiola-Serrano F., Lüth A., Kleuser B., Halver J.E., Escribá P.V.: Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy. Proc. Natl. Acad. Sci. USA, 2011; 108: 19569-19574
  Google Scholar
• 7. Bevers E.M., Williamson P.L.: Phospholipid scramblase: an update. FEBS Lett., 2010; 584: 2724-2730
  Google Scholar
• 8. Bickel P.E.: Lipid rafts and insulin signaling. Am. J. Physiol. Endocrinol. Metab., 2002; 282: E1-E10
  Google Scholar
• 9. Bigay J., Antonny B.: Curvature, lipid packing, and electrostatics of membrane organelles: defining cellular territories in determining specificity. Dev. Cell, 2012; 23: 886-895
  Google Scholar
• 10. Broquet A.H., Thomas G., Masliah J., Trugnan G., Bachelet M.: Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J. Biol. Chem., 2003; 278: 21601-21606
  Google Scholar
• 11. Burd C.G., Emr S.D.: Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. Mol. Cell, 1998; 2: 157-162
  Google Scholar
• 12. Calderwood S.K., Mambula S.S., Gray P.J.Jr., Theriault J.R.: Extracellular heat shock proteins in cell signaling. FEBS Lett., 2007; 581: 3689-36894
  Google Scholar
• 13. Chatterjee S., Mayor S.: The GPI-anchor and protein sorting. Cell. Mol. Life Sci., 2001; 58: 1969-1987
  Google Scholar
• 14. Cheng X., Li L., Uttamchandani M., Yao S.Q.: In situ proteome profiling of C75, a covalent bioactive compound with potential anticancer activities. Org. Lett., 2014; 16: 1414-1417
  Google Scholar
• 15. Cheong N., Zhang H., Madesh M., Zhao M., Yu K., Dodia C., Fisher A.B., Savani R., Shuman H.: ABCA3 is critical for lamellar body biogenesis in vivo. J. Biol. Chem., 2007; 282: 23811-23817
  Google Scholar
• 16. Chung J., Nguyen A.K., Henstridge D.C., Holmes A.G., Chan M.H., Mesa J.L., Lancaster G.I., Southgate R.J., Bruce C.R., Duffy S.J., Horvath I., Mestril R., Watt M.J., Hooper P.L., Kingwell B.A. i wsp.: HSP72 protects against obesity-induced insulin resistance. Proc. Natl. Acad. Sci. USA, 2008; 105: 1739-1744
  Google Scholar
• 17. Cisowski J., O’Callaghan K., Kuliopulos A., Yang J., Nguyen N., Deng Q., Yang E., Fogel M., Tressel S., Foley C., Agarwal A., Hunt S.W. 3rd., McMurry T., Brinckerhoff L., Covic L.: Targeting protease-activated receptor-1 with cell-penetrating pepducins in lung cancer. Am. J. Pathol., 2011; 179: 513-523
  Google Scholar
• 18. Cohen A.W., Combs T.P., Scherer P.E., Lisanti M.P.: Role of caveolin and caveolae in insulin signaling and diabetes. Am. J. Physiol. Endocrinol. Metab., 2003; 285: E1151-E1160
  Google Scholar
• 19. Coleman J.A., Quazi F., Molday R.S.: Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport. Biochim. Biophys. Acta, 2013; 1831: 555-574
  Google Scholar
• 20. Corbalán-García S., Gómez-Fernández J.C.: Protein kinase C regulatory domains: the art of decoding many different signals in membranes. Biochim. Biophys. Acta, 2006; 1761: 633-654
  Google Scholar
• 21. Covic L., Gresser A.L., Talavera J., Swift S., Kuliopulos A.: Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides. Proc. Natl. Acad. Sci. USA, 2002; 99: 643-648
  Google Scholar
• 22. Crul M., Rosing H., de Klerk G.J., Dubbelman R., Traiser M., Reichert S., Knebel N.G., Schellens J.H., Beijnen J.H., ten Bokkel Huinink W.W.: Phase I and pharmacological study of daily oral administration of perifosine (D-21266) in patients with advanced solid tumours. Eur. J. Cancer, 2002; 38: 1615-1621
  Google Scholar
• 23. De Tullio L., Fanani M.L., Maggio B.: Surface mixing of products and substrate of PLA2 in enzyme-free mixed monolayers reproduces enzyme-driven structural topography. Bioch. Bioph. Acta, 2013; 1828: 2056-2063
  Google Scholar
• 24. de Vree J.M., Jacquemin E., Sturm E., Cresteil D., Bosma P.J., Aten J., Deleuze J.F., Desrochers M., Burdelski M., Bernard O., Oude Elferink R.P., Hadchouel M.: Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc. Natl. Acad. Sci. USA, 1998; 95: 282-287
  Google Scholar
• 25. de Vries L., Zheng B., Fischer T., Elenko E., Farquhar M.G.: The regulator of G protein signaling family. Annu. Rev. Pharmacol. Toxicol., 2000; 40: 235-271
  Google Scholar
• 26. Donejko M., Niczyporuk M., Galicka E., Przylipiak A.: Anti-cancer properties epigallocatechin-gallate contained in green tea. Postępy Hig. Med. Dośw., 2013; 67: 26-34
  Google Scholar
• 27. Eibl H., Hilgard P., Unger C. (red.): Alkylphosphocholines: New Drugs in Cancer Therapy. Progress in experimental tumor research. Karger, Basel 1992
  Google Scholar
• 28. Engelman D.M.: Membranes are more mosaic than fluid. Nature, 2005; 438: 578-580
  Google Scholar
• 29. Escribá P.V., Ozaita A., Ribas C., Miralles A., Fodor E., Farkas T., García-Sevilla J.A.: Role of lipid polymorphism in G protein-membrane interactions: Nonlamellar-prone phospholipids and peripheral protein binding to membranes. Proc. Natl. Acad. Sci. USA, 1997; 94: 11375-11380
  Google Scholar
• 30. Escribá P.V., Sastre M., García-Sevilla J.A.: Disruption of cellular signaling pathways by daunomycin through destabilization of nonlamellar membrane structures. Proc. Natl. Acad. Sci. USA, 1995; 92: 7595-7599
  Google Scholar
• 31. Escribá P.V., Wedegaertner P.B., Goñi F.M., Vögler O.: Lipid-protein interactions in GPCR-associated signaling. Biochim. Biophys. Acta, 2007; 1768: 836-852
  Google Scholar
• 32. Faini M., Beck R., Wieland F.T., Briggs J.A.: Vesicle coats: structure, function, and general principles of assembly. Trends Cell Biol., 2013; 23: 279-288
  Google Scholar
• 33. Freeman M.R., Solomon K.R.: Cholesterol and prostate cancer. J. Cell. Biochem., 2004; 91: 54-69
  Google Scholar
• 34. Gajate C., Mollinedo F.: Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Blood, 2007; 109: 711-719
  Google Scholar
• 35. Golebiewska U., Scarlata S.: The effect of membrane domains on the G protein-phospholipase Cβ signaling pathway. Crit. Rev. Biochem. Mol. Biol., 2010; 45: 97-105
  Google Scholar
• 36. Gombos I., Crul T., Piotto S., Güngör B., Török Z., Balogh G., Péter M., Slotte J.P., Campana F., Pilbat A.M., Hunya A., Tóth N., Literati-Nagy Z., Vígh L. Jr., Glatz A. i wsp.: Membrane-lipid therapy in operation: the HSP co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts. PLoS One, 2011; 6: e28818
  Google Scholar
• 37. Goñi F.M.: The basic structure and dynamics of cell membranes: an update of the Singer-Nicolson model. Biochim. Biophys. Acta, 2014; 1838: 1467-1476
  Google Scholar
• 38. Goñi F.M., Alonso A.: Structure and functional properties of diacylglycerols in membranes. Prog. Lipid Res., 1999; 38: 1-48
  Google Scholar
• 39. Han X., Holtzman D.M., McKeel D.W.Jr.: Plasmalogen deficiency in early Alzheimer’s disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J. Neurochem., 2001; 77: 1168-1180
  Google Scholar
• 40. Hartl F.U.: Molecular chaperones in cellular protein folding. Nature, 1996; 381: 571-579
  Google Scholar
• 41. Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R., McMahon H.T.: FCHo proteins are nucleators of clathrin-mediated endocytosis. Science, 2010; 328: 1281-1284
  Google Scholar
• 42. Herrmann D.B., Pahlke W., Opitz H.G., Bicker U.: In vivo antitumor activity of ilmofosine. Cancer Treat. Rev., 1990; 17: 247-252
  Google Scholar
• 43. Hightower L.E.: Heat shock, stress proteins, chaperones, and proteotoxicity. Cell, 1991; 66: 191-197
  Google Scholar
• 44. Hjort Ipsen J., Karlström G., Mourtisen O.G., Wennerström H., Zuckermann M.J.: Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim. Biophys. Acta, 1987; 905: 162-172
  Google Scholar
• 45. Ibarguren M., López D.J., Encinar J.A., González-Ros J.M., Busquets X., Escribá P.V.: Partitioning of liquid-ordered/liquid-disordered membrane microdomains induced by the fluidifying effect of 2-hydroxylated fatty acid derivatives. Biochim. Biophys. Acta, 2013; 1828: 2553-2563
  Google Scholar
• 46. Jendrossek V., Erdlenbruch B., Hunold A., Kugler W., Eibl H., Lakomek M.: Erucylphosphocholine, a novel antineoplastic ether lipid, blocks growth and induces apoptosis in brain tumor cell lines in vitro. Int. J. Oncol., 1999; 14: 15-22
  Google Scholar
• 47. Jones J.W., Lue L., Saiani A., Tiddy G.J.: Density, DSC, X-ray and NMR measurements through the gel and lamellar phase transitions of 1-myristoyl-2-stearoyl-sn-glycero-3-phosphatidylcholine (MSPC) and 1-stearoyl-2-myristoyl-sn-glycero-3-phosphatidylcholine (SMPC): observation of slow relaxation processes and mechanisms of phase transitions. Phys. Chem. Chem. Phys., 2012; 14: 5452-5469
  Google Scholar
• 48. Kamioka Y., Fukuhara S., Sawa H., Nagashima K., Masuda M., Matsuda M., Mochizuki N.: A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis. J. Biol. Chem., 2004; 279: 40091-40099
  Google Scholar
• 49. Kawashima N., Yoon S.J., Itoh K., Nakayama K.: Tyrosine kinase activity of epidermal growth factor receptor is regulated by GM3 binding through carbohydrate to carbohydrate interactions. J. Biol. Chem., 2009; 284: 6147-6155
  Google Scholar
• 50. Khan M.A., Wood P.L., Goodenowe D., Mankidy R., Ahiahonu P.: Plasmalogen compounds, pharmaceutical compositions containing the same and methods for treating diseases of the aging. Zgłoszenie patentowe PCT/CA2009/001853, 2009
  Google Scholar
• 51. Krause M.R., Regen S.L.: The structural role of cholesterol in cell membranes: from condensed bilayers to lipid rafts. Acc. Chem. Res., 2014; 47: 3512-3521
  Google Scholar
• 52. Kuhajda F.P., Jenner K., Wood F.D., Hennigar R.A., Jacobs L.B., Dick J.D., Pasternack G.R.: Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc. Natl. Acad. Sci. USA, 1994; 91: 6379-6383
  Google Scholar
• 53. Kuhajda F.P., Pizer E.S., Li J.N., Mani N.S., Frehywot G.L., Townsend C.A.: Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc. Natl. Acad. Sci. USA, 2000; 97: 3450-3454
  Google Scholar
• 54. Lin L., Kim S.C., Wang Y., Gupta S., Davis B., Simon S.I., Torre-Amione G., Knowlton A.A.: HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis. Am. J. Physiol. Heart Circ. Physiol., 2007; 293: 2238-2247
  Google Scholar
• 55. Lingwood D., Simons K.: Lipid rafts as a membrane-organizing principle. Science, 2010; 327: 46-50
  Google Scholar
• 56. Llado V., Gutierrez A., Martínez J., Casas J., Terés S., Higuera M., Galmés A., Saus C., Besalduch J., Busquets X., Escribá P.V.: Minerval induces apoptosis in Jurkat and other cancer cells. J. Cell Mol. Med., 2010; 14: 659-670
  Google Scholar
• 57. Lladó V., López D.J., Ibarguren M., Alonso M., Soriano J.B., Escribá P.V., Busquets X.: Regulation of the cancer cell membrane lipid composition by NaCHOleate: effects on cell signaling and therapeutical relevance in glioma. Biochim. Biophys. Acta, 2014; 1838: 1619-1627
  Google Scholar
• 58. Mammoto T., Mukai M., Mammoto A., Yamanaka Y., Hayashi Y., Mashimo T., Kishi Y., Nakamura H.: Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett., 2002; 184: 165-170
  Google Scholar
• 59. Marsh D.: Intrinsic curvature in normal and inverted lipid structures and in membranes. Bioph. J., 1996; 70: 2248-2255
  Google Scholar
• 60. Martínez J., Vögler O., Casas J., Barceló F., Alemany R., Prades J., Nagy T., Baamonde C., Kasprzyk P.G., Terés S., Saus C., Escribá P.V.: Membrane structure modulation, protein kinase Cα activation, and anticancer activity of minerval. Mol. Pharmacol., 2005; 67: 531-540
  Google Scholar
• 61. Menendez J.A., Ropero S., Mehmi I., Atlas E., Colomer R., Lupu R.: Overexpression and hyperactivity of breast cancer-associated fatty acid synthase (oncogenic antigen-519) is insensitive to normal arachidonic fatty acid-induced suppression in lipogenic tissues but it is selectively inhibited by tumoricidal α-linolenic and γ-linolenic fatty acids: a novel mechanism by which dietary fat can alter mammary tumorigenesis. Int. J. Oncol., 2004; 24: 1369-1383
  Google Scholar
• 62. Menendez J.A., Vellon L., Lupu R.: Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann. Oncol., 2005; 16: 1253-1267
  Google Scholar
• 63. Moffett S., Brown D.A., Linder M.E.: Lipid-dependent targeting of G proteins into rafts. J. Biol. Chem., 2000; 275: 2191-2198
  Google Scholar
• 64. Mrówczyńska L., Mrówczyński W.: Physiological and pathological roles of gangliosides. Postępy Hig. Med. Dośw., 2013; 67: 938-949
  Google Scholar
• 65. Oberle C., Massing U., Krug H.F.: On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells. Biol. Chem., 2005; 386: 237-245
  Google Scholar
• 66. O’Flaherty J.T., Chadwell B.A., Kearns M.W., Sergeant S., Daniel L.W.: Protein kinases C translocation responses to low concentrations of arachidonic acid. J. Biol. Chem., 2001; 276: 24743-24750
  Google Scholar
• 67. Pfister G., Stroh C.M., Perschinka H., Kind M., Knoflach M., Hinterdorfer P., Wick G.: Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy. J. Cell. Sci., 2005; 118: 1587-1594
  Google Scholar
• 68. Poccia D., Larijani B.: Phosphatidylinositol metabolism and membrane fusion. Biochem. J., 2009; 418: 233-246
  Google Scholar
• 69. Quazi F., Lenevich S., Molday R.S.: ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nat. Commun., 2012; 3: 925
  Google Scholar
• 70. Rao Y., Haucke V.: Membrane shaping by the Bin/amphiphysin/ Rvs (BAR) domain protein superfamily. Cell. Mol. Life Sci., 2011; 68: 3983-3993
  Google Scholar
• 71. Riedl S., Zweytick D., Lohner K.: Membrane-active host defense peptides – challenges and perspectives for the development of novel anticancer drugs. Chem. Phys. Lipids, 2011; 164: 766-781
  Google Scholar
• 72. Sakai H., Tanaka Y., Tanaka M., Ban N., Yamada K., Matsumura Y., Watanabe D., Sasaki M., Kita T., Inagaki N.: ABCA2 deficiency results in abnormal sphingolipid metabolism in mouse brain. J. Biol. Chem., 2007; 282: 19692-19699
  Google Scholar
• 73. Sánchez-Magraner L., Cortajarena A.L., Goñi F.M., Ostolaza H.: Insertion of Escherichia coli α-hemolysin is independent from membrane lysis. J. Biol. Chem., 2006; 281: 5461-5467
  Google Scholar
• 74. Shin B.K., Wang H., Yim A.M., Le Naour F., Brichory F., Jang J.H., Zhao R., Puravs E., Tra J., Michael C.W., Misek D.E., Hanash S.M.: Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J. Biol. Chem., 2003; 278: 7607-7616
  Google Scholar
• 75. Shulenin S., Nogee L.M., Annilo T., Wert S.E., Whitsett J.A., Dean M.: ABCA3 gene mutations in newborns with fatal surfactant deficiency. N. Engl. J. Med., 2004; 350: 1296-1303
  Google Scholar
• 76. Siddiqui R.A., Zerouga M., Wu M., Castillo A., Harvey K., Zaloga G.P., Stillwell W.: Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells. Breast Cancer Res., 2005; 7: 645-654
  Google Scholar
• 77. Simons K., Ehehalt R.: Cholesterol, lipid rafts, and disease. J. Clin. Invest., 2002; 110: 597-603
  Google Scholar
• 78. Simons K., Sampaio J.L.: Membrane organization and lipid rafts. Cold Spring Harb. Perspect. Biol., 2011; 3: a004697
  Google Scholar
• 79. Singer S.J., Nicolson G.L.: The fluid mosaic model of the structure of cell membranes. Science, 1972; 175: 720-731
  Google Scholar
• 80. Slagel D.E., Dittmer J.C., Wilson C.B.: Lipid composition of human glial tumour and adjacent brain. J. Neurochem., 1967; 14: 789-798
  Google Scholar
• 81. Sottocornola E., Misasi R., Mattei V., Ciarlo L., Gradini R., Garofalo T., Berra B., Colombo I., Sorice M.: Role of gangliosides in the association of ErbB2 with lipid rafts in mammary epithelial HC11 cells. FEBS J., 2006; 273: 1821-1830
  Google Scholar
• 82. Sparagna G.C., Lesnefsky E.J.: Cardiolipin remodeling in the heart. J. Cardiovasc. Pharmacol., 2009; 53: 290-301
  Google Scholar
• 83. Stoorvogel W., Kleijmeer M.J., Geuze H.J., Raposo G.: The biogenesis and functions of exosomes. Traffic, 2002; 3: 321-330
  Google Scholar
• 84. Suetsugu S., Kurisu S., Takenawa T.: Dynamic shaping of cellular membranes by phospholipids and membrane-deforming proteins. Physiol. Rev., 2014; 94: 1219-1248
  Google Scholar
• 85. Suzuki J., Denning D.P., Imanishi E., Horvitz H.R., Nagata S.: Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science, 2013; 341: 403-406
  Google Scholar
• 86. Tchernychev B., Ren Y., Sachdev P., Janz J.M., Haggis L., O’Shea A., McBride E., Looby R., Deng Q., McMurry T., Kazmi M.A., Sakmar T.P., Hunt S. 3rd, Carlson K.E.: Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cells. Proc. Natl. Acad. Sci. USA, 2010; 107: 22255-22259
  Google Scholar
• 87. Terés S., Lladó V., Higuera M., Barceló-Coblijn G., Martin M.L., Noguera-Salvà M.A., Marcilla-Etxenike A., García-Verdugo J.M., Soriano-Navarro M., Saus C., Gómez-Pinedo U., Busquets X., Escribá P.V.: 2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy. Proc. Natl. Acad. Sci. USA, 2012; 109: 8489-8494
  Google Scholar
• 88. Triton T.R., Yee G.: The anticancer agent adriamycin can be actively cytotoxic without entering cells. Science, 1982; 217: 248-250
  Google Scholar
• 89. Tsuchiya H., Nagayama M., Tanaka T., Furusawa M., Kashimata M., Takeuchi H.: Membrane-rigidifying effects of anti-cancer dietary factors. Biofactors, 2002; 16: 45-56
  Google Scholar
• 90. van Blitterswijk W.J., Verheij M.: Anticancer alkylphospholipids: mechanisms of action, cellular sensitivity and resistance, and clinical prospects. Curr. Pharm. Des., 2008; 14: 2061-2074
  Google Scholar
• 91. van der Luit A.H., Vink S.R., Klarenbeek J.B., Perrissoud D., Solary E., Verheij M., van Blitterswijk W.J.: A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol. Cancer Ther., 2007; 6: 2337-2345
  Google Scholar
• 92. van Helvoort A., Smith A.J., Sprong H., Fritzsche I., Schinkel A.H., Borst P., van Meer G.: MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell, 1996; 87: 507-517
  Google Scholar
• 93. Veldman R.J., Klappe K., Hinrichs J., Hummel I., van der Schaaf G., Sietsma H., Kok J.W.: Altered sphingolipid metabolism in multidrug-resistant ovarian cancer cells is due to uncoupling of glycolipid biosynthesis in the Golgi apparatus. FASEB J., 2002; 16: 1111-1113
  Google Scholar
• 94. Verdaguer N., Corbalan-Garcia S., Ochoa W.F., Fita I., Gómez-Fernández J.C.: Ca2+ bridges the C2 membrane-binding domain of protein kinase Cα directly to phosphatidylserine. EMBO J., 1999; 18: 6329-6338
  Google Scholar
• 95. Vigh L., Escribá P.V., Sonnleitner A., Sonnleitner M., Piotto S., Maresca B., Horváth I., Harwood J.L.: The significance of lipid composition for membrane activity: new concepts and ways of assessing function. Prog. Lipid Res., 2005; 44: 303-344
  Google Scholar
• 96. Vígh L., Literáti P.N., Horváth I., Török Z., Balogh G., Glatz A., Kovács E., Boros I., Ferdinándy P., Farkas B., Jaszlits L., Jednákovits A., Korányi L., Maresca B.: Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat. Med., 1997; 3: 1150-1154
  Google Scholar
• 97. Vigh L., Maresca B., Harwood J.L.: Does the membrane’s physical state control the expression of heat shock and other genes? Trends Biochem. Sci., 1998; 23: 369-374
  Google Scholar
• 98. Vink S.R., Schellens J.H., van Blitterswijk W.J., Verheij M.: Tumor and normal tissue pharmacokinetics of perifosine, an oral anti-cancer alkylphospholipid. Invest. New Drugs, 2005; 23: 279-286
  Google Scholar
• 99. Vögler O., Casas J., Capó D., Nagy T., Borchert G., Martorell G., Escribá P.V.: The Gβγ dimer drives the interaction of heterotrimeric Gi proteins with nonlamellar membrane structures. J. Biol. Chem., 2004; 279: 36540-36545
  Google Scholar
• 100. Wang R., Kovalchin J.T., Muhlenkamp P., Chandawarkar R.Y.: Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens. Blood, 2006; 107: 1636-1642
  Google Scholar
• 101. Wedegaertner P.B., Wilson P.T., Bourne H.R.: Lipid modifications of trimeric G proteins. J. Biol. Chem., 1995; 270: 503-506
  Google Scholar
• 102. Wettschureck N., Offermanns S.: Mammalian G proteins and their cell type specific functions. Physiol. Rev., 2005; 85: 1159-1204
  Google Scholar
• 103. Williamson P., Bevers E.M., Smeets E.F., Comfurius P., Schlegel R.A., Zwaal R.F.: Continuous analysis of the mechanism of activated transbilayer lipid movement in platelets. Biochemistry, 1995; 34: 10448-10455
  Google Scholar
• 104. Wood P.L., Smith T., Lane N., Khan M.A., Ehrmantraut G., Goodenowe D.B.: Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the rabbit: a new therapeutic strategy for Alzheimer’s disease. Lipids Health Dis., 2011; 10: 227
  Google Scholar
• 105. Xie X.S., Tsai S.J., Stone D.K.: Lipid requirements for reconstitution of the proton-translocating complex of clathrin-coated vesicles. Proc. Natl. Acad. Sci. USA, 1986; 83: 8913-8917
  Google Scholar
• 106. Yamashita T, Hashiramoto A, Haluzik M, Mizukami H, Beck S, Norton A, Kono M, Tsuji S, Daniotti J.L., Werth N., Sandhoff R., Sandhoff K., Proia R.L.: Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc. Natl. Acad. Sci. USA, 2000; 100: 3445-3449
  Google Scholar
• 107. Yang Q., Alemany R., Casas J., Kitajka K., Lanier S.M., Escribá P.V.: Influence of the membrane lipid structure on signal processing via G protein-coupled receptors. Mol. Pharmacol., 2005; 68: 210-217
  Google Scholar
• 108. Yetukuri L., Ekroos K., Vidal-Puig A., Oresic M.: Informatics and computational strategies for the study of lipids. Mol. Biosyst., 2008; 4: 121-127
  Google Scholar
• 109. Zhu Z., Tan Z., Li Y., Luo H., Hu X., Tang M., Hescheler J., Mu Y., Zhang L.: Docosahexaenoic acid alters Gsα localization in lipid raft and potentiates adenylate cyclase. Nutrition, 2015; 31: 1025-1030
  Google Scholar

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