Cell membrane mediated (-)-epicatechin effects on upstream endothelial cell signaling: Evidence for a surface receptor
Cell membrane mediated (-)-epicatechin effects on upstream endothelial cell signaling: Evidence for a surface receptor
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DOI：
10.1016/j.bmcl.2014.04.038
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发表时间：
2014-06-15
影响因子：
2.7
通讯作者：
Ramirez-Sanchez, Israel
中科院分区：
文献类型：
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作者：
Moreno-Ulloa, Aldo;Romero-Perez, Diego;Ramirez-Sanchez, Israel
众所周知，食用可可衍生产品，特别是黑巧克力的形式，对正常人和血管功能障碍者(降低一氧化氮[NO]的生物利用度和/或合成)具有有益的心血管效应。黄酮类化合物发挥这些作用的上游机制尚不清楚，可能涉及细胞膜受体的参与。我们先前已经证明，黄烷醇(-)-表儿茶素(EPI)通过非钙依赖的eNOS激活/磷酸化来刺激NO的产生。我们希望利用一种新型的细胞膜不透性EPI-葡聚糖偶联物(EPI-Dx)来研究细胞表面受体的可能参与。在无钙条件下，用等摩尔浓度(100 NM)的EPI或EPI-Dx处理人冠状动脉内皮细胞(HCAEC)10min。结果表明，EPI和EPI-Dx均可诱导PI3K、PDK-1、AKT和eNOS的磷酸化/活化。有趣的是，EPI-Dx效应的幅度明显高于EPI单独作用。EPI-Dx刺激细胞反应的能力支持EPI细胞膜受体介导eNOS激活的存在。(C)2014爱思唯尔有限公司。保留所有权利。
The consumption of cacao-derived products, particularly in the form of dark chocolate is known to provide beneficial cardiovascular effects in normal individuals and in those with vascular dysfunction (reduced nitric oxide [NO] bioavailability and/or synthesis). Upstream mechanisms by which flavonoids exert these effects are poorly understood and may involve the participation of cell membrane receptors. We previously demonstrated that the flavanol (-)-epicatechin (EPI) stimulates NO production via Ca+2-independent eNOS activation/phosphorylation. We wished to investigate the plausible participation of a cell surface receptor using a novel cell-membrane impermeable EPI-Dextran conjugate (EPI-Dx). Under Ca2+-free conditions, human coronary artery endothelial cells (HCAEC) were treated for 10 min with EPI or EPI-Dx at equimolar concentrations (100 nM). Results demonstrate that both EPI and EPI-Dx induced the phosphorylation/activation of PI3K, PDK-1, AKT and eNOS. Interestingly, EPI-Dx effects were significantly higher in magnitude than those of EPI alone. The capacity of EPI-Dx to stimulate cell responses supports the existence of an EPI cell membrane receptor mediating eNOS activation. (C) 2014 Elsevier Ltd. All rights reserved.