Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1861, Issue 4, Pages 861-870Publisher
ELSEVIER
DOI: 10.1016/j.bbamem.2019.01.020
Keywords
Langmuir monolayers; Model membrane; Lipid rafts; Neurodegeneration; Oxysterols
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Under pathological conditions, cholesterol oxidation products (oxysterols) appear in enhanced concentration in blood and cerebrospinal fluid, which leads to cytotoxic effect, especially in central nervous system. However, the mode of action of oxysterols on the membrane level has not been fully resolved. In this paper we have investigated the interaction between 7 alpha- hydroxycholesterol, 7 alpha-OH (one of the most abundant oxysterol in human body) and two major membrane lipids: sphingomyelin, SM (basic component of lipid rafts and nerve membrane) and 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine, POPC (main phospholipid of mammalian cell membranes). 7 alpha-OH/SM mixtures may mimic pathologically changed lipid raft (ordered phase, L-O) while the SM/POPC system can model its surrounding (liquid-disordered phase, L-alpha). For our study, the Langmuir mono-layer technique (based on registration of the surface pressure/area, pi/A isotherms), complemented with surface visualization technique (Brewster angle microscopy, BAM) and theoretical calculations, have been employed. The observed affinity of 7 alpha-OH to SM, which appears to be stronger than in cholesterol/SM system, indicates that cholesterol might be partially replaced in lipid rafts by its oxidized derivative. Its incorporation significantly increases rigidity of the system in relation to normal (cholesterol-containing) raft, which can disturb its proper functioning. On the other hand, the poor effect of this oxysterol on the raft's environment was observed.
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