Interaction of 7-Ketocholesterol with Two Major Components of the Inner Leaflet of the Plasma Membrane: Phosphatidylethanolamine and Phosphatidylserine
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7-Ketocholesterol is one of the major forms of oxidized cholesterol found in vivo. Several toxic effects of this sterol have been documented, and it is suggested to have a role in atherosclerosis. We have studied how this oxysterol modifies the physical properties of bilayers composed of the major lipid components of the cytoplasmic leaflet of the plasma membrane. 7-Ketocholesterol is much less effective in promoting the formation of the Hii phase in phosphatidylethanolamines than cholesterol. This is likely due to the fact that 7-ketocholesterol is more polar than cholesterol and hence would be located closer to the membrane interface. However, in ternary mixtures of dipalmitoleoylphosphatidylethanolamine with low concentrations of both sterols, the effect of 7-ketocholesterol on lowering TH is enhanced. Both cholesterol and 7-ketocholesterol are very soluble in bilayers of phosphatidylethanolamine, particularly with 1-palmitoyl-2-oleoylphosphatidylethanolamine. There is, however, a much greater solubility of 7-ketocholesterol in bilayers of 1-stearoyl-2-oleoylphosphatidylserine than is the case for cholesterol. In ternary mixtures of 1-stearoyl-2-oleoylphosphatidylserine with both sterols, it appears that the solubility of cholesterol is enhanced by the presence of 7-ketocholesterol. It is thus to be expected that several of the biophysical properties of a membrane would change as a result of the oxidation of cholesterol to 7-ketocholesterol.

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