Abstract
Plant flavonoids are not only known as powerful antioxidants, but also as cell metabolism regulators. It has been postulated that they are able to control cell signal pathways by targeting receptors on the cell surface or by intercalating the lipid bilayer of membranes. Some flavonoids can increase lipid viscosity and decrease the cooperativity of hydrocarbon chain melting, while others can considerably decrease the lipid melting temperature, thus providing additional freedom for lipid diffusion. Here we discuss the ability of flavonoids to influence phase transition and lateral segregation of lipids, responsible for the formation of membrane compartments known as lipid rafts. The thermodynamic parameters of the bilayer determined by lipid packing characteristics and by lateral segregation of the bilayer are expected to depend on the location of flavonoid molecules in the bilayer. Flavonoid molecules preferably located in the hydrophobic region of the bilayer can initiate formation of raft-like domains (raft-making effect), while the molecules located in the polar interface region of the bilayer can fluidize membranes (raft-breaking effect), or initiate formation of interdigitated or micellar structures. Accordingly, we expect that in cellular membranes flavonoids can influence the appearance and development of rafts or raft-like membrane domains and thus influence the lateral diffusion of lipid molecules. Because rafts participate in cellular signal transduction, endocytosis and transmembrane translocation of different compounds, flavonoids may control cell metabolism by modulating the bilayer state.
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References
Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9:7–14
Lichtenberg D, Goni F, Heerklotz H (2005) Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem Sci 30:430–436
Shaikh SR, Edidin MA (2006) Membranes are not just rafts. Chem Phys Lipids 144:1–3
Riethmuller J, Riehle A, Grassme H et al (2006) Membrane rafts in host-pathogen interactions. Biochim Biophys Acta 1758:2139–2147
Landry A, Xavier R (2006) Isolation and analysis of lipid rafts in cell-cell interactions. Methods Mol Biol 341:251–282
Danielsen EM, Hansen GH (2006) Lipid raft organization and function in brush borders of epithelial cells. Mol Membr Biol 23:71–79
Kabouridis PS (2006) Lipid rafts in T cell receptor signalling. Mol Membr Biol 23:49–57
Zeyda M, Stulnig TM (2006) Lipid Rafts & Co.: an integrated model of membrane organization in T cell activation. Prog Lipid Res 45:187–202
Cordy JM, Hooper NM, Turner AJ (2006) The involvement of lipid rafts in Alzheimer’s disease. Mol Membr Biol 23:111–122
Murphy SC, Hiller NL, Harrison T et al (2006) Lipid rafts and malaria parasite infection of erythrocytes. Mol Membr Biol 23:81–88
Simons K, Vaz WL (2004) Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct 33:269–295
Silvius JR (2005) Partitioning of membrane molecules between raft and non-raft domains: insights from model-membrane studies. Biochim Biophys Acta 1746:193–202
Szabo G, Dolganiuc A, Dai Q et al (2007) TLR4, ethanol, and lipid rafts: a new mechanism of ethanol action with implications for other receptor-mediated effects. J Immunol 178:1243–1249
Siddiqui RA, Harvey KA, Zaloga GP et al (2007) Modulation of lipid rafts by Omega-3 fatty acids in inflammation and cancer: implications for use of lipids during nutrition support. Nutr Clin Pract 22:74–88
Saija A, Scalese M, Lanza M et al (1995) Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol Med 19:481–486
Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34
Williams RJ, Spencer JP, Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36:838–849
Kroon P, Williamson G (2005) Polyphenols: dietary components with established benefits to health? J Sci Food Agric 85:1239–1240
Dajas F, Rivera-Megret F, Blasina F et al (2003) Neuroprotection by flavonoids. Braz J Med Biol Res 36:1613–1620
Rietjens IM, Boersma MG, van der Woude H et al (2005) Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk. Mutat Res 574:124–138
Lopez-Lazaro M (2002) Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anticancer Agents 2:691–714
Jovanovic SV, Steenken S, Tosic M et al (1994) Flavonoids as antioxidants. J Am Chem Soc 116:4846–4851
Gamet-Payrastre L, Manenti S, Gratacap MP et al (1999) Flavonoids and the inhibition of PKC and PI3-kinase. Gen Pharmacol 32:279–286
Barzilai A, Rahamimoff H (1983) Inhibition of Ca2+-transport ATPase from synaptosomal vesicles by flavonoids. Biochim Biophys Acta 730:245–254
Bito T, Roy S, Sen CK et al (2002) Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. FEBS Lett 520:145–152
Fujimura Y, Yamada K, Tachibana H (2005) A lipid raft-associated 67 kDa laminin receptor mediates suppressive effect of epigallocatechin-3-O-gallate on FcepsilonRI expression. Biochem Biophys Res Commun 336:674–681
Fujimura Y, Umeda D, Kiyohara Y et al (2006) The involvement of the 67 kDa laminin receptor-mediated modulation of cytoskeleton in the degranulation inhibition induced by epigallocatechin-3-O-gallate. Biochem Biophys Res Commun 348:524–531
Tachibana H, Fujimura Y, Yamada K (2004) Tea polyphenol epigallocatechin-3-gallate associates with plasma membrane lipid rafts: lipid rafts mediate anti-allergic action of the catechin. Biofactors 21:383–385
Fujimura Y, Tachibana H, Kumai R et al (2004) A difference between epigallocatechin-3-gallate and epicatechin-3-gallate on anti-allergic effect is dependent on their distinct distribution to lipid rafts. Biofactors 21:133–135
Fujimura Y, Tachibana H, Yamada K (2004) Lipid raft-associated catechin suppresses the FcepsilonRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2. FEBS Lett 556:204–210
Hendrich AB (2006) Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Acta Pharmacol Sin 27:27–40
van Dijk C, Driessen AJ, Recourt K (2000) The uncoupling efficiency and affinity of flavonoids for vesicles. Biochem Pharmacol 60:1593–1600
Scheidt HA, Pampel A, Nissler L et al (2004) Investigation of the membrane localization and distribution of flavonoids by high-resolution magic angle spinning NMR spectroscopy. Biochim Biophys Acta 1663:97–107
Klymchenko AS, Duportail G, Demchenko AP et al (2004) Bimodal distribution and fluorescence response of environment-sensitive probes in lipid bilayers. Biophys J 86:2929–2941
Sengupta B, Chaudhuri S, Banerjee A et al (2004) Characterization of serotonin in protein and membrane mimetic environments: a spectroscopic study. Chem Biodivers 1:868–877
Chaudhuri S, Banerjee A, Basu K et al (2007) Interaction of flavonoids with red blood cell membrane lipids and proteins: antioxidant and antihemolytic effects. Int J Biol Macromol 41:42–48
Tsuchiya H, Nagayama M, Tanaka T et al (2002) Membrane-rigidifying effects of anti-cancer dietary factors. Biofactors 16:45–56
McConnell HM, Vrljic M (2003) Liquid-liquid immiscibility in membranes. Annu Rev Biophys Biomol Struct 32:469–492
McConnell HM, Radhakrishnan A (2003) Condensed complexes of cholesterol and phospholipids. Biochim Biophys Acta 1610:159–173
Lairion F, Disalvo EA (2004) Effect of phloretin on the dipole potential of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol monolayers. Langmuir 20:9151–9155
Taylor AM, Watts A (1998) Spin-label studies of lipid-protein interactions with reconstituted band 3, the human erythrocyte chloride-bicarbonate exchanger. Biochem Cell Biol 76:815–822
Sabra MC, Uitdehaag JC, Watts A (1998) General model for lipid-mediated two-dimensional array formation of membrane proteins: application to bacteriorhodopsin. Biophys J 75:1180–1188
Franklin JC, Cafiso DS (1993) Internal electrostatic potentials in bilayers: measuring and controlling dipole potentials in lipid vesicles. Biophys J 65:289–299
Gawrisch K, Ruston D, Zimmerberg J et al (1992) Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. Biophys J 61:1213–1223
Bechinger B, Seelig J (1991) Interaction of electric dipoles with phospholipid head groups. A 2H and 31P NMR study of phloretin and phloretin analogues in phosphatidylcholine membranes. Biochemistry 30:3923–3929
Dill KA, Stigter D (1988) Lateral interactions among phosphatidylcholine and phosphatidylethanolamine head groups in phospholipid monolayers and bilayers. Biochemistry 27:3446–3453
Cseh R, Benz R (1999) Interaction of phloretin with lipid monolayers: relationship between structural changes and dipole potential change. Biophys J 77:1477–1488
Cseh R, Hetzer M, Wolf K et al (2000) Interaction of phloretin with membranes: on the mode of action of phloretin at the water-lipid interface. Eur Biophys J 29:172–183
Andersen OS, Finkelstein A, Katz I et al (1976) Effect of phloretin on the permeability of thin lipid membranes. J Gen Physiol 67:749–771
Melnik E, Latorre R, Hall JE et al (1977) Phloretin-induced changes in ion transport across lipid bilayer membranes. J Gen Physiol 69:243–257
Auner BG, O’Neill MA, Valenta C et al (2005) Interaction of phloretin and 6-ketocholestanol with DPPC-liposomes as phospholipid model membranes. Int J Pharm 294:149–155
Valenta C, Steininger A, Auner BG (2004) Phloretin and 6-ketocholestanol: membrane interactions studied by a phospholipid/polydiacetylene colorimetric assay and differential scanning calorimetry. Eur J Pharm Biopharm 57:329–336
Huang C (1990) Mixed-chain phospholipids and interdigitated bilayer systems. Klin Wochenschr 68:149–165
Lu JZ, Hao YH, Chen JW (2001) Effect of cholesterol on the formation of an interdigitated gel phase in lysophosphatidylcholine and phosphatidylcholine binary mixtures. J Biochem (Tokyo) 129:891–898
Bondar OP, Pivovarenko VG, Rowe ES (1998) Flavonols—new fluorescent membrane probes for studying the interdigitation of lipid bilayers. Biochim Biophys Acta 1369:119–130
Rietveld A, Simons K (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochim Biophys Acta 1376:467–479
Zhao D, Sonawane ND, Levin MH et al (2007) Comparative transport efficiencies of urea analogues through urea transporter UT-B. Biochim Biophys Acta 1768:1815–1821
Kaur AR, Kanwar U, Nath SS (2006) Characteristics of glucose transport across the microvillous membranes of human term placenta. Nutr Hosp 21:38–46
Olson ML, Kargacin ME, Honeyman TW et al (2006) Effects of phytoestrogens on sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and Ca2+ uptake into cardiac sarcoplasmic reticulum. J Pharmacol Exp Ther 316:628–635
Peerce BE, Fleming RY, Clarke RD (2003) Inhibition of human intestinal brush border membrane vesicle Na+-dependent phosphate uptake by phosphophloretin derivatives. Biochem Biophys Res Commun 301:8–12
Jennings ML, Solomon AK (1976) Interaction between phloretin and the red blood cell membrane. J Gen Physiol 67:381–383
Pohl P, Rokitskaya TI, Pohl EE et al (1997) Permeation of phloretin across bilayer lipid membranes monitored by dipole potential and microelectrode measurements. Biochim Biophys Acta 1323:163–172
Verkman AS, Solomon AK (1982) A stepwise mechanism for the permeation of phloretin through a lipid bilayer. J Gen Physiol 80:557–581
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Tarahovsky, Y.S., Muzafarov, E.N. & Kim, Y.A. Rafts making and rafts braking: how plant flavonoids may control membrane heterogeneity. Mol Cell Biochem 314, 65–71 (2008). https://doi.org/10.1007/s11010-008-9766-9
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DOI: https://doi.org/10.1007/s11010-008-9766-9
Keywords
- Biological membranes
- Lipid polymorphism
- Lipid bilayer
- Non-lamellar lipid structures
- Membrane rafts
- Membrane structural heterogeneity
- Membrane compartmentalization
- Lipid phase transition
- Cubic phases
- Hexagonal HII phase
- Interdigitation
- Membrane permeability
- Lipid melting
- Flavonoids
- Plant polyphenols
- Tannins
- Quercetin