The effect of oxysterols on the interaction of Alzheimer's amyloid beta with model membranes
The effect of oxysterols on the interaction of Alzheimer's amyloid beta with model membranes
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DOI：
10.1016/j.bbamem.2013.06.021
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发表时间：
2013-11-01
影响因子：
3.4
通讯作者：
Takagi, Masahiro
中科院分区：
文献类型：
--
作者：
Phan, Huong T. T.;Hata, Takahiro;Takagi, Masahiro
淀粉样β蛋白(Aβ)与细胞膜的相互作用受Aβ构象、细胞膜物理化学性质和脂质组成的影响。然而，胆固醇及其氧化衍生物对Aβ诱导的膜神经毒性的影响尚不完全清楚。我们使用模型膜来研究Aβ在膜中的定位，以及在胆固醇和7-酮胆固醇(7keto)或25-羟基胆固醇(25OH)存在下多肽诱导的膜动力学。我们的结果表明，与胆固醇在抑制Aβ/膜相互作用中的作用相反，氧固醇使膜对Aβ更敏感。我们已经证明，由于额外的氧基团在其结构中的不同位置，两个氧甾醇具有不同的影响。7keto细胞大小的脂质体显示出与Aβ结合的高倾向，而25OH系统更有能力对多肽产生形态变化。此外，我们还发现，42-氨基酸Aβ(Aβ-42)前原纤维物种与膜的结合程度更高，导致膜波动的速度快于40个残基的异构体(Aβ-40)。这些结果表明，氧化甾醇增强了Aβ与膜的相互作用，有助于阐明胆固醇通过其氧化作用对Aβ诱导的神经毒性的有害影响。(C)2013爱思唯尔B.V.保留所有权利。
The interaction of amyloid beta (A beta) peptide with cell membranes has been shown to be influenced by A beta conformation, membrane physicochemical properties and lipid composition. However, the effect of cholesterol and its oxidized derivatives, oxysterols, on A beta-induced neurotoxicity to membranes is not fully understood. We employed here model membranes to investigate the localization of A beta in membranes and the peptide-induced membrane dynamics in the presence of cholesterol and 7-ketocholesterol (7keto) or 25-hydroxycholesterol (25OH). Our results have indicated that oxysterols rendered membranes more sensitive to A beta, in contrast to role of cholesterol in inhibiting A beta/membrane interaction. We have demonstrated that two oxysterols had different impacts owing to distinct positions of the additional oxygen group in their structures. 7keto-containing cell-sized liposomes exhibited a high propensity toward association with A beta, while 25OH systems were more capable of morphological changes in response to the peptide. Furthermore, we have shown that 42-amino acid A beta (A beta-42) pre-fibril species had higher association with membranes, and caused membrane fluctuation faster than 40-residue isoform (A beta-40). These findings suggest the enhancing effect of oxysterols on interaction of A beta with membranes and contribute to clarify the harmful impact of cholesterol on A beta-induced neurotoxicity by means of its oxidation. (C) 2013 Elsevier B.V. All rights reserved.