PHYSICAL EFFECTS OF BIOLOGICALLY FORMED CHOLESTEROL OXIDATION-PRODUCTS ON LIPID-MEMBRANES INVESTIGATED WITH FLUORESCENCE DEPOLARIZATION SPECTROSCOPY AND ELECTRON-SPIN-RESONANCE
Jcd. Verhagen et al., PHYSICAL EFFECTS OF BIOLOGICALLY FORMED CHOLESTEROL OXIDATION-PRODUCTS ON LIPID-MEMBRANES INVESTIGATED WITH FLUORESCENCE DEPOLARIZATION SPECTROSCOPY AND ELECTRON-SPIN-RESONANCE, Journal of lipid research, 37(7), 1996, pp. 1488-1502
Planar oriented membranes of 1-palmitoyl, 2-oleoyl-phosphatidylcholine
(POPC) containing cholesterol, 19-hydroxycholesterol, 22S-hydroxychol
esterol, or 25-hydroxycholesterol in concentrations up to 5 mol % were
investigated with angle-resolved fluorescence depolarization and elec
tron spin resonance measurements. Analyses of the data with the Browni
an diffusion model show that the oxysterols have structural effects si
milar to those of cholesterol: an increase in molecular order and no c
hange in the rotational diffusion coefficients of the probe molecules.
Time-resolved fluorescence anisotropy measurements on diphenylhexatri
ene (DPH) in small unilamellar vesicles of POPC and DOPC were performe
d using oxysterols commonly found in oxidized low density lipoproteins
(LDL) in comparison to membranes containing lipoproteins (LDL) in com
parison to membranes containing cholesterol or no sterols. Analyses us
ing the Brownian rotational diffusion model show that most LDL-oxyster
ols affect the vesicle physical structure in a manner similar to chole
sterol, viz. an increase in molecular order and a decrease in the dyna
mics. Cholesterol-alpha-epoxode has a much smaller ordering effect tha
n cholesterol in POPC-vesicles. A similar effect was found for 7 beta-
hydroxycholesterol in DOPC-vesicles. The tendency of the oxysterols to
influence the molecular order as compared to pure cholesterol may con
tribute to cell membrane permeability changes affecting crucial cell f
unctions and events leading to vascular cell injury. Increased LDL oxy
sterol levels may account for some of the structural changes noted for
oxidatively modified LDL as well as its toxicity to vascular cells.