Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.
Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.
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DOI：
10.1155/2016/7124251
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发表时间：
2016
影响因子：
--
通讯作者：
Samson AO
中科院分区：
文献类型：
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作者：
Atrahimovich D;Khatib S;Sela S;Vaya J;Samson AO
高水平的循环低密度脂蛋白（LDL）是动脉粥样硬化发展的主要起始事件。最近，多酚的抗动脉粥样硬化作用已被证明通过与其抗氧化能力无关的机制发挥作用，而源于它们与特定的细胞内或血浆蛋白的相互作用。在这项研究中，我们研究了石榴中主要的多酚，punicalagin，与LDL周围载脂蛋白B-100 （ApoB100）的相互作用。Punicalagin在低浓度（0.25-4 μM）下与ApoB100结合。结合后，它以浓度依赖的方式诱导LDL流入巨噬细胞，高达2.5倍。相比之下，另一种与ApoB100结合的多酚光甘草定对LDL内流没有影响。我们进一步表明LDL内流是通过LDL受体特异性发生的，然后LDL在细胞质中积累。结合Aviram等人2000年的发现，石榴汁和槟榔苷诱导血浆LDL去除并抑制巨噬细胞胆固醇合成和积累，我们的研究结果表明，在结合后，槟榔苷刺激LDL流入巨噬细胞，从而降低循环胆固醇水平。
High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.