Abstract
Compared to cholesterol, hydroxycholesterols contain an additional hydroxy group in the alkyl chain and are able to efficiently cross the brain–blood barrier. Therefore, they are responsible for the sterol transfer between brain and circulation. The current study compares the membrane properties of several hydroxycholesterols with those of cholesterol using 2H NMR spectroscopy, a membrane permeability assay, and fluorescence microscopy experiments. It is shown that hydroxycholesterols do not exert the unique impact on membrane properties characteristic for cholesterol with regard to the influence on lipid chain order, membrane permeability and formation of lateral domains.
Highlights
Cholesterol is a major component of mammalian cell membranes with various biological functions
The influence of the hydroxycholesterols on the lipid chain order and the degree of lipid condensation was investigated by 2H NMR measurements on lipid membranes of chain deuterated 1-palmitoyl-d31-2-oleoyl-sn-glycero-3-phosphocholine (POPC-d31) in the presence of 20 mol % of the respective hydroxysterols or cholesterol
All three hydroxycholesterols did not induce such a cholesterol-like increase in POPC lipid chain order; in contrast, they caused a small decrease in lipid chain order compared with pure POPC membranes
Summary
Cholesterol is a major component of mammalian cell membranes with various biological functions. It plays a key role in maintaining the membrane’s barrier function by increasing the bilayer packing density through condensing the phospholipids. A large amount of cholesterol in the human body is located in the brain, where it constitutes an integral part of myelin membranes acting as electrical insulators [4]. Cholesterol is a major component of the plasma membranes of astrocytes and neurons [5]. The tight control of the cholesterol concentration and homeostasis is of paramount importance for the functions of all cells of the body but for the brain. More so as the rate of cholesterol accumulation and synthesis is subject to subtle alterations over the lifetime of a human being [4,6]
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