title: Effect of cholesterol on apolipoprotein A-I binding to lipid bilayers and emulsions.
abstract: The effects of cholesterol (Chol) on the interaction of apolipoprotein A-I (apoA-I) with phospholipid bilayer vesicles and lipid emulsions were investigated. ApoA-I bound to phosphatidylcholine (PC) vesicles with higher affinity and lower capacity compared to triglyceride-PC emulsions. An increase in surface Chol in triglyceride-PC emulsions decreased the binding capacity without changing the binding affinity. In contrast, addition of Chol to PC vesicles caused a marked increase in capacity and decrease in affinity for apoA-I binding. ApoA-I caused a large release of entrapped aqueous dye, calcein, from PC vesicles, whereas this apoA-I-induced leakage was relatively small in the vesicles containing Chol. The incorporation of phosphatidylethanolamine into the vesicles also exerted effects similar to those of Chol on apoA-I binding and calcein leakage. The shifts of fluorescence emission maximum of dansyl lysine, probing the surface region of membranes, indicated that Chol as well as phosphatidylethanolamine increased the headgroup space of the vesicles. The binding maximum of apoA-I was closely correlated with the emission maximum of dansyl lysine, not with the fluorescence anisotropy of I-[4-(trimethylamino)phenyl]phenylhexatriene, suggesting that the binding capacity of apoA-I to the bilayer surface was modulated by the headgroup space rather than the acyl chain fluidity. These results show that Chol affects the bilayer surface so as to allow more apoA-I to bind to bilayers and may suggest the possibility of the interaction of apoA-I with Chol-enriched membrane domains.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Miyako
authors.forename: T
authors.initials: T
authors.lastname: Handa
authors.forename: K
authors.initials: K
authors.lastname: Miyajima
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005452:Fluoresceins / Q000378:metabolism; D005454:Fluorescence Polarization; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D013552:Swine; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D004655:Emulsions; D005452:Fluoresceins; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014280:Triglycerides; C014409:cholesteryl oleate; D002784:Cholesterol; C007740:fluorexon