Role of oxysterol structure on the microdomain-induced microsolubilization of phospholipid membranes by apolipoprotein A-I.
Oxygenated derivatives of cholesterol, oxysterols, have different physicochemical properties and three-dimensional shapes. The kinetics of microsolubilization of dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles by apolipoprotein A-I (apoA-I) to form discoidal high-density lipoproteins (rHDL) was dramatically affected by oxysterol chemical structure. Under the experimental conditions of varying oxysterol chemical structure, sterol concentration, and the lipid phase state of DMPC, the kinetics varied over 3 orders of magnitude. Some oxysterols behaved similarly to cholesterol and increased the rate of microsolubilization; however, they were not as effective as cholesterol. Other oxysterols greatly inhibited this process. In general, there was no correlation of the rates with membrane fluidity as measured by fluorescence polarization. The rate of DMPC microsolubilization by apoA-I is highly dependent upon the presence of lattice defects in the membrane surface that occur due to imperfect packing of coexisting lipid phases. The differential ability of various oxysterols to induce the formation of an ordered lipid phase is the probable basis for their effects on the rates of DMPC microsolubilization. There was no effect of oxysterol chemical structure on the structure of the equilibrium rHDL products; however, there was a dramatic effect of sterol concentration on rHDL particle size. Different oxysterols regulate the kinetics of apoA-I membrane association by altering structural microheterogeneity at the membrane surface. However, once the kinetic barrier is overcome, the particle sizes of rHDL products formed are determined solely by the amount of sterol presence.
Massey
John B
JB
Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. jbm@bcm.tmc.edu
Pownall
Henry J
HJ
D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004852:Epoxy Compounds / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008832:Microchemistry; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013696:Temperature
D016632:Apolipoprotein A-I; D004852:Epoxy Compounds; D008075:Lipoproteins, HDL; D010743:Phospholipids; D002784:Cholesterol