Effects of probucol on phase transition and fluidity of phosphatidylcholine membranes: a spin label study.
Spin labeling methods were applied to study the structure and dynamics of phosphatidylcholine membranes as a function of temperature and the mole fraction of probucol. Multilamellar liposomes made of dimyristoylphosphatidyclcholine, dipalmitoylphosphatidylcholine both saturated, and egg yolk phosphatidylcholine, an unsaturated membrane, were used. In fluid phase membranes probucol was found to increase the order and decrease the motional freedom of alkyl chains of lipids as shown with stearic acid spin labels. The effect of probucol on order and motional freedom is more pronounced in the membrane center (16-doxylstearic acid spin label position) than in the near polar headgroup region (5-doxylstearic acid spin label position). The presence of unsaturation in alkyl chains significantly decreased the ordering effect of probucol. The main phase transition temperature of saturated bilayers was lowered by 2 degrees C in the presence of 3 mol% of probucol and significantly broadened at higher concentrations as measured with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) partitioning. Also, pretransition was no longer observed in the presence of probucol. In gel phase membranes, the effect of probucol was complex. Close to the main phase transition the motion of alkyl chains was increased, showing a regulatory effect of probucol on membrane fluidity. It is proposed that probucol is located in the membrane center as opposed to vitamin E, which locates its phenolic -OH group at the membrane surface; therefore, it inhibits lipid peroxidation in this region which is less accessible to vitamin E.
Subczynski
W K
WK
Department of Biophysics, Jagiellonian University, Krakow, Poland.
Wojas
J
J
Pezeshk
V
V
Pezeshk
A
A
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D003497:Cyclic N-Oxides; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology*; D013113:Spin Labels; D013696:Temperature; D013816:Thermodynamics
D003497:Cyclic N-Oxides; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D013113:Spin Labels; D015060:1,2-Dipalmitoylphosphatidylcholine; D011341:Probucol; D004134:Dimyristoylphosphatidylcholine; C003959:TEMPO