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生物相容的辅酶 Q 富集脂质纳米粒子的组装与表征。

Assembly and Characterization of Biocompatible Coenzyme Q -Enriched Lipid Nanoparticles.

机构信息

Department of Biochemistry and Molecular Biology, University of Nevada, Reno, Reno, NV, 89557, USA.

Department of Pharmacology, Reno School of Medicine, University of Nevada, Reno, NV, 89557, USA.

出版信息

Lipids. 2020 Mar;55(2):141-149. doi: 10.1002/lipd.12218. Epub 2020 Feb 19.

Abstract

Coenzyme Q (CoQ ) is a strongly hydrophobic lipid that functions in the electron transport chain and as an antioxidant. CoQ was conferred with aqueous solubility by incorporation into nanoparticles containing phosphatidylcholine (PtdCho) and apolipoprotein (apo) A-I. These particles, termed CoQ nanodisks (ND), contain 1.0 mg CoQ /5 mg PtdCho/2 mg apoA-I (97% CoQ solubilization efficiency). UV/Vis absorbance spectroscopy of CoQ ND revealed a characteristic absorbance peak centered at 275 nm. Incorporation of CoQ into ND resulted in quenching of apoA-I tryptophan fluorescence emission. Gel filtration chromatography of CoQ ND gave rise to a single major absorbance peak and HPLC of material extracted from this peak confirmed the presence of CoQ . Incubation of cultured cells with CoQ ND, but not empty ND, resulted in a significant increase in the CoQ content of mitochondria as well as enhanced oxidative phosphorylation, as observed by a ~24% increase in maximal oxygen consumption rate. Collectively, a facile method to solubilize significant quantities of CoQ in lipid nanoparticles has been developed. The availability of CoQ ND provides a novel means to investigate biochemical aspects of CoQ uptake by cells and/or administer it to subjects deficient in this key lipid as a result of inborn errors of metabolism, statin therapy, or otherwise.

摘要

辅酶 Q(CoQ)是一种强疏水性脂质,在电子传递链中发挥作用,并具有抗氧化作用。通过将其纳入含有磷脂酰胆碱(PtdCho)和载脂蛋白(apo)A-I 的纳米颗粒中,CoQ 被赋予了水溶性。这些颗粒被称为 CoQ 纳米盘(ND),含有 1.0mg CoQ/5mg PtdCho/2mg apoA-I(97% CoQ 溶解效率)。CoQ ND 的紫外/可见吸收光谱显示出特征吸收峰,中心位于 275nm。CoQ 纳入 ND 导致 apoA-I 色氨酸荧光发射猝灭。CoQ ND 的凝胶过滤色谱产生一个单一的主要吸收峰,从该峰提取的材料的 HPLC 证实了 CoQ 的存在。与空 ND 相比,培养细胞与 CoQ ND 孵育导致线粒体中 CoQ 含量显著增加,氧化磷酸化增强,最大耗氧量增加约 24%。总之,已经开发出一种将大量 CoQ 溶解在脂质纳米颗粒中的简便方法。CoQ ND 的可用性为研究细胞摄取 CoQ 的生化方面提供了一种新方法,或者为由于代谢缺陷、他汀类药物治疗或其他原因导致这种关键脂质缺乏的受试者提供了给药途径。

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