title: Membrane properties of oxysterols. Interfacial orientation, influence on membrane permeability and redistribution between membranes.
abstract: The membrane properties of cholesterol auto-oxidation products, 7-ketocholesterol, 7 beta-hydroxycholesterol, 7 alpha-hydroxycholesterol and 25-hydroxycholesterol were examined. Monolayer studies show that these oxysterols are perpendicularly orientated at the interphase. Only 7 beta-hydroxycholesterol and 7 alpha-hydroxycholesterol are tilted at low surface pressures. In mixed monolayers with dioleoylphosphatidylcholine, 7-ketocholesterol, 7 beta-hydroxycholesterol and 7 alpha-hydroxycholesterol show a condensing effect in this order, although to a lesser extent that that observed for cholesterol. In liposomes these oxysterols also reduce glucose permeability and in the same order as their condensing effect. On the other hand 25-hydroxycholesterol shows no condensing effect in monomolecular layers whereas glucose permeability in liposomes is enormously increased. The permeability increase is already maximal at 2.5 mol% 25-hydroxycholesterol. Differential scanning calorimetry experiments reveal that all four oxysterols tested reduce the heat content of the gel----liquid-crystalline phase transition. It is concluded that 7-ketocholesterol, 7 beta-hydroxycholesterol and 7 alpha-hydroxycholesterol have a cholesterol like effect, although less efficient than cholesterol, whereas 25-hydroxycholesterol showing no condensing effect acts as a spacer molecule. Packing defects in the hydrophobic core of the bilayer due to the presence of the C-25 hydroxyl group are believed to cause the permeability increase. The transfer of radiolabelled (oxy)sterols from the monolayer to lipoproteins or vesicles in the subphase was studied. The transfer rate increases in the following order 7-ketocholesterol, 7 beta-hydroxycholesterol, 7 alpha-hydroxycholesterol, 25-hydroxycholesterol. The difference in rate between 7-ketocholesterol and 25-hydroxycholesterol is 20-fold. A higher rate of transfer is observed in the presence of high density lipoproteins and small unilamellar vesicles. A transfer rate for cholesterol is hardly measurable under these conditions. The transfer measured is consistent with the involvement of a water-soluble intermediate.
mesh_terms: D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000502:physiology; D006888:Hydroxycholesterols / Q000502:physiology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D066298:In Vitro Techniques; D007653:Ketocholesterols / Q000502:physiology*; D008074:Lipoproteins / Q000378:metabolism; D008081:Liposomes; D008563:Membrane Lipids / Q000502:physiology*; D010743:Phospholipids; D013329:Structure-Activity Relationship
chemical_list: D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008074:Lipoproteins; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases