新型生物活性脂质通过 ABCA1 受体途径增强了高密度脂蛋白介导的巨噬细胞胆固醇外流。

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ali Khattib , Manar Shmet , Rasha Ashkar , Tony Hayek , Soliman Khatib
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引用次数: 0

摘要

高密度脂蛋白(HDL)历来被认为是 "好胆固醇",因为它与降低动脉粥样硬化的风险有着重要的联系。这种关联主要归因于高密度脂蛋白直接参与胆固醇外流的能力,它在胆固醇逆向运输中发挥着关键作用。以前曾从 Nannochloropsis 微藻中分离出一种新的活性化合物,称为溶解-DGTS(一种含有 EPA 脂肪酸的脂质),发现它能提高副氧合酶 1 的活性,增强 HDL 介导的胆固醇外流和 HDL 诱导的内皮一氧化氮释放。本文研究了不同的溶血-DGTS 衍生物和类似物对高密度脂蛋白介导的巨噬细胞胆固醇外流的影响,并探讨了其机制。通过建立结构-活性关系,确定了 HDL 介导巨噬细胞胆固醇外流的重要脂质分子的特征。溶菌酶-DGTS、1-羧基-N-N-三甲基-3-油酰胺丙-1-铵和溶菌酶-血小板活化因子主要通过 ABCA1 介导的胆固醇外流途径,剂量依赖性地增加了 HDL 介导的巨噬细胞胆固醇外流。使用劳尔丹广义极化(GP)试验检测了溶菌-DGTS 衍生物和类似物对 HDL 表面极性的影响。劳尔丹 GP 值与 HDL 介导的胆固醇外流之间存在反向皮尔逊线性回归。由于生物活性脂质加入高密度脂蛋白表面磷脂层会导致劳尔丹 GP 值下降,因此这些生物活性脂质可能会降低磷脂的有序性,扩大高密度脂蛋白颗粒表面的自由空间,从而增强脂蛋白 A1 与 ABCA1 受体的结合,改善 ABCA1 介导的胆固醇外流。我们的研究结果表明,溶菌酶-DGTS 及其生物活性脂质衍生物对提高高密度脂蛋白介导的巨噬细胞胆固醇外流活性有益,这可能会影响动脉粥样硬化的缓解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel bioactive lipids enhanced HDL-mediated cholesterol efflux from macrophages through the ABCA1 receptor pathway

High-density lipoprotein (HDL) has traditionally been acknowledged as "good cholesterol" owing to its significant association with a decreased risk of atherosclerosis. This association is primarily attributed to HDL's direct involvement in cholesterol efflux capacity, which plays a pivotal role in reverse cholesterol transport. A novel active compound from Nannochloropsis microalgae termed lyso-DGTS, a lipid that contains EPA fatty acids, was previously isolated and found to increase paraoxonase 1 activity and enhance HDL-mediated cholesterol efflux and HDL-induced endothelial nitric oxide release. Here, the effect of different lyso-DGTS derivatives and analogs on HDL-mediated cholesterol efflux from macrophages was examined, and the mechanism was explored. Structure–activity relationships were established to characterize the essential lipid moieties responsible for HDL-mediated cholesterol efflux from macrophages. Lyso-DGTS, 1-carboxy-N-N-N-trimethyl-3-oleamidopropan-1-aminium, and lyso-platelet-activating factor increased HDL-mediated cholesterol efflux from macrophages dose-dependently, mainly via the ABCA1-mediated cholesterol efflux pathway. The effect of lyso-DGTS derivatives and analogs on the surface polarity of HDL was examined using the Laurdan generalized polarization (GP) assay. A reverse Pearson linear regression was obtained between Laurdan GP values and HDL-mediated cholesterol efflux. Because the incorporation of bioactive lipids into the surface phospholipid layer of HDL leads to a decrease in Laurdan GP, these bioactive lipids may induce lower phospholipid ordering and greater free space on the HDL particle surface, thereby enhancing apolipoprotein A1 binding to the ABCA1 receptor and improving ABCA1 cholesterol-mediated efflux. Our findings suggest a beneficial effect of lyso-DGTS and its bioactive lipid derivatives on increasing HDL-mediated cholesterol efflux activity from macrophages, which may impact atherosclerosis attenuation.

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来源期刊
Chemistry and Physics of Lipids
Chemistry and Physics of Lipids 生物-生化与分子生物学
CiteScore
7.60
自引率
2.90%
发文量
50
审稿时长
40 days
期刊介绍: Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.
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