Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid.
Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid.
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DOI：
10.1016/j.bbamem.2010.09.007
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Narayanaswami V
中科院分区：
文献类型：
--
作者：
Khumsupan P;Ramirez R;Khumsupan D;Narayanaswami V
姜黄素是一种抗氧化剂和抗炎生物活性物质，最近也被确定为抗淀粉样蛋白剂。为了使其更有效的形式作为一个潜在的淀粉样蛋白解聚剂，我们采用高密度脂蛋白（HDL），这是脂蛋白复合物，运输血浆胆固醇，运输姜黄素。本研究的目的是利用含有人apoE 3 N-末端（NT）结构域的重组HDL作为转运姜黄素的载体。NT结构域作为配体，通过位于细胞表面的低密度脂蛋白受体（LDLr）蛋白家族介导脂蛋白复合物的结合和摄取。在姜黄素存在或不存在的情况下，用磷脂和重组apoE 3-NT结构域制备重构HDL。非变性聚丙烯酰胺凝胶电泳表明，载姜黄素高密度脂蛋白的分子量和Stokes'直径分别为约670 kDa和约17 nm，而电子显微镜显示存在盘状颗粒。携带（固有荧光）姜黄素的HDL的荧光发射光谱表明，姜黄素的最大荧光发射波长（λmax）为λ 495 nm，这与姜黄素在不同极性的溶剂（λmax范围为515- 575 nm）或水性缓冲液中的λmax相比是高度蓝移的。此外，与姜黄素在水性缓冲液中相比，在含有姜黄素的HDL中注意到荧光发射强度的巨大增强。姜黄素荧光发射被基于脂质的猝灭剂猝灭到显著程度，但不被水性猝灭剂猝灭。这些观察结果表明，姜黄素已有效地分配到HDL的磷脂双层的疏水环境中。功能分析表明，含姜黄素的HDL与apoE 3-NT的LDLR结合能力与不含姜黄素的HDL相似。两者合计，我们报告说，载脂蛋白E含有高密度脂蛋白具有巨大的潜力，作为一个“纳米车辆”与归巢装置运输姜黄素的目标网站。
Curcumin is an antioxidant and anti-inflammatory bioflavonoid that has been recently identified as an anti-amyloid agent as well. To make it more available in its potent form as a potential amyloid disaggregation agent, we employed high-density lipoproteins (HDL), which are lipidprotein complexes that transport plasma cholesterol, to transport curcumin. The objective of this study was to employ reconstituted HDL containing human apoE3 N-terminal (NT) domain, as a vehicle to transport curcumin. The NT domain serves as a ligand to mediate binding and uptake of lipoprotein complexes via the low-density lipoprotein receptor (LDLr) family of proteins located at the cell surface. Reconstituted HDL was prepared with phospholipids and recombinant apoE3-NT domain in the absence or presence of curcumin. Non-denaturing polyacrylamide gel electrophoresis indicated that the molecular mass and Stokes' diameter of HDL bearing curcumin were ∼670 kDa and ∼17 nm, respectively, while electron microscopy revealed the presence of discoidal particles. Fluorescence emission spectra of HDL bearing (the intrinsically fluorescent) curcumin indicated that the wavelength of maximal fluorescence emission (λmax) of curcumin was ∼495 nm, which is highly blue-shifted compared to λmax of curcumin in solvents of varying polarity (λmax ranging from 515- 575 nm) or in aqueous buffers. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin-containing HDL compared to curcumin in aqueous buffers. Curcumin fluorescence emission was quenched to a significant extent by lipid-based quenchers but not by aqueous quenchers. These observations indicate that curcumin has partitioned efficiently into the hydrophobic milieu of the phospholipid bilayer of HDL. Functional assays indicated that the LDLr-binding ability of curcumin-containing HDL with apoE3-NT is similar to that of HDL without curcumin. Taken together, we report that apoE-containing HDL has tremendous potential as a ‘nanovehicle’ with a homing device to transport curcumin to target sites.
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