Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway
Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway
复制标题
血管内皮细胞通过被动扩散和 SGLT1 介导的途径吸收白藜芦醇
DOI：
10.1016/j.jnutbio.2013.04.003
复制
发表时间：
2013-11-01
影响因子：
5.6
通讯作者：
Mi, Man-tian
中科院分区：
文献类型：
--
作者：
Chen, Ming-liang;Yi, Long;Mi, Man-tian
白藜芦醇是一种天然多酚，对抑制动脉粥样硬化有很强的作用。然而，它在血浆中的低浓度让人对这种作用产生了怀疑。因此，白藜芦醇的作用可能依赖于它向血管内皮细胞的转运，这是一个以前没有解决的问题，尽管它具有明显的和根本的重要性。通过高效液相色谱和液-质联用技术，我们发现白藜芦醇被人脐静脉内皮细胞以温度、浓度和时间依赖的方式吸收，表明白藜芦醇参与了被动扩散和主动转运。激光共聚焦扫描显微镜显示，白藜芦醇主要分布于细胞质中。此外，白藜芦醇的吸收受血清蛋白和钠依赖的葡萄糖转运蛋白1(SGLT1)的调节，但受葡萄糖(SGLT1底物)和根茎苷(SGLT1选择性抑制剂)以及SGLT1 siRNA的抑制。此外，给SD大鼠灌胃100 mg/kg白藜芦醇后，白藜芦醇在血管中的浓度下降到24小时比在血液中的浓度下降得更慢。我们的结果表明，血管内皮细胞摄取白藜芦醇既涉及被动扩散，也涉及SGLT1介导的过程，至少部分参与。此外，细胞内的白藜芦醇库可能比体内的血清水平更重要。这些为白藜芦醇的心血管益处提供了新的见解。(C)2013 Elsevier Inc.保留所有权利。
Resveratrol is a natural polyphenol that exerts potent effects to suppress atherosclerosis. However, its low concentration in plasma has placed this role in doubt. Thus, resveratrol effects might be dependent on its transport into vascular endothelium, a question not previously addressed in spite of its obvious and fundamental importance. Via high-performance liquid chromatography and liquid chromatography/mass spectrometry, we found that resveratrol was absorbed by human umbilical vein endothelial cells in a temperature-, concentration- and time-dependent manner, suggesting the involvement of passive diffusion and active transport. As determined by confocal laser scanning microscopy, resveratrol primarily distributed throughout the cytoplasm. Furthermore, resveratrol absorption was modulated by serum proteins and sodium-dependent glucose transporter 1 (SGLT1) yet inhibited by glucose (an SGLT1 substrate) and phlorizin (an SGLT1 selective inhibitor), as well as SGLT1 siRNA transfection. Additionally, Sprague-Dawley rats were intragastrically administrated with 100 mg/kg of resveratrol and the concentration of resveratrol in blood vessels declined more slowly up to 24 h compared to that in the blood. Our results suggested that resveratrol uptake by vascular endothelial cells involved both passive diffusion and an SGLT1-mediated process, at least partially. Moreover, the intracellular resveratrol pool may be more important than the serum level in vivo. These provide new insights into the cardiovascular benefits of resveratrol. (C) 2013 Elsevier Inc. All rights reserved.