Aβ peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: A NMR study
Aβ peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: A NMR study
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DOI：
10.1016/j.bbamem.2008.07.002
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Pettegrew, Jay W.
中科院分区：
文献类型：
--
作者：
Mandal, Pravat K.;Pettegrew, Jay W.
β-肽是AD(阿尔茨海默病)脑内积聚的老年斑(SP)的主要成分。来自不同实验室的报道表明，麻醉药与Aβ肽相互作用，诱导Aβ寡聚。Aβ肽与这些麻醉药相互作用的分子机制尚未确定。我们利用2D核磁共振实验报道了均匀标记的(15)N标记的Aβ40与不同麻醉剂相互作用的分子细节。在高浓度时，异氟醚和异丙酚都干扰位于铰链区的关键氨基酸残基(G29、A30和131)，导致Aβ寡聚。相反，这三个特定残基不与硫喷妥钠相互作用，因此没有观察到Aβ齐聚反应。然而，使用复合麻醉剂(硫喷妥钠和氟烷)的研究表明，这些残基(G29、A30和131)发生了扰动，随后发现了Aβ齐聚。不同麻醉剂对这些特异的Aβ残基(G29、A30和131)的干扰可能在诱导Aβ寡聚中起重要作用。(C)2008爱思唯尔B.V.保留所有权利。
A beta peptide is the major component of senile plaques (SP) which accumulates in AD (Alzheimer's disease) brain. Reports from different laboratories indicate that anesthetics interact with A beta peptide and induce A beta oligomerization. The molecular mechanism of A beta peptide interactions with these anesthetics was not determined. We report molecular details for the interactions of uniformly (15)N labeled A beta 40 with different anesthetics using 2D nuclear magnetic resonance (NMR) experiments. At high concentrations both isoflurane and propofol perturb critical amino acid residues (G29, A30 and 131) of A beta peptide located in the hinge region leading to A beta oligomerization. In contrast, these three specific residues do not interact with thiopental and subsequently no A beta oligomerization was observed. However, studies with combined anesthetics (thiopental and halothane), showed perturbation of these residues (G29, A30 and 131) and subsequently A beta oligomerization was found. Perturbation of these specific A beta residues (G29, A30 and 131) by different anesthetics could play an important role to induce A beta oligomerization. (C) 2008 Elsevier B.V. All rights reserved.