Effects of cyclodextrins on the structure of LDL and its susceptibility to copper-induced oxidation
Effects of cyclodextrins on the structure of LDL and its susceptibility to copper-induced oxidation
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环糊精对 LDL 结构及其对铜诱导氧化的敏感性的影响
DOI：
10.1016/j.ejps.2016.04.037
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发表时间：
2016-08-25
影响因子：
4.6
通讯作者：
Chen, Yong
中科院分区：
文献类型：
--
作者：
Ao, Meiying;Gan, Chaoye;Chen, Yong
环糊精（CD）长期以来一直被广泛用作药物/食品载体，最近被开发为治疗疾病（例如尼曼-匹克C1和癌症）的药物。目前还不清楚环糊精是否会影响低密度脂蛋白（LDL）的结构、氧化敏感性和动脉粥样硬化形成。在这项研究中，招募了四种广泛使用的环糊精，包括α-CD，β-CD和β-CD的两种衍生物（HP β CD和M β CD）。有趣的是，琼脂糖凝胶电泳（分别但同时用苏丹黑B和考马斯亮蓝染色LDL的脂质和蛋白质组分）显示，相对高浓度的环糊精引起LDL条带的消失和/或额外的无蛋白质脂质条带的出现，这意味着相对高浓度的环糊精可以诱导显著的LDL的脂质耗竭。原子力显微镜（AFM）检测到M β CD（作为环糊精的代表）以剂量依赖性方式诱导LDL颗粒尺寸减小，进一步证实了环糊精的脂质消耗作用。此外，从琼脂糖凝胶电泳，共轭二烯的形成，MDA的生产，和铜氧化的LDL的氨基封闭的数据表明，环糊精可以削弱LDL对氧化的敏感性。这意味着环糊精可能通过降低LDL氧化来帮助抑制动脉粥样硬化形成。(C)© 2016 Elsevier B. V.版权所有。
Cyclodextrins (CDs) have long been widely used as drug/food carriers and were recently developed as drugs for the treatment of diseases (e.g. Niemann-Pick C1 and cancers). It is unknown whether cyclodextrins may influence the structure of low-density lipoprotein (LDL), its susceptibility to oxidation, and atherogenesis. In this study, four widely used cyclodextrins including alpha-CD,beta-CD, and two derivatives of beta-CD (HP beta CD and M beta CD) were recruited. Interestingly, agarose gel electrophoresis (staining lipid and protein components of LDL with Sudan Black B and Coomassie brilliant blue, respectively but simultaneously) shows that cyclodextrins at relatively high concentrations caused disappearance of the LDL band and/or appearance of an additional protein-free lipid band, implying that cyclodextrins at relatively high concentrations can induce significant electrophoresis-detectable lipid depletion of LDL. Atomic force microscopy (AFM) detected that M beta CD (as a representative of cyclodextrins) induced size decrease of LDL particles in a dose-dependent manner, further confirming the lipid depletion effects of cyclodextrins. Moreover, the data from agarose gel electrophoresis, conjugated diene formation, MDA production, and amino group blockage of copper-oxidized LDL show that cyclodextrins can impair LDL susceptibility to oxidation. It implies that cyclodextrins probably help to inhibit atherogenesis by lowering LDL oxidation. (C) 2016 Elsevier B.V. All rights reserved.