Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Pineal Res. 2011 Sep;51(2):220-5. doi: 10.1111/j.1600-079X.2011.00882.x. Epub 2011 May 3.
Melatonin is a key factor in the coordination of circadian rhythms and seasonal reproduction. Melatonin and its metabolites directly scavenge free radicals, increase the expression of antioxidant enzymes, and play a role in the anti-inflammatory phase of defense responses. At present, there are no direct data available as to melatonin's possible influence on endothelial cell monolayer permeability, which is a major biological process responsible for vascular diseases. The aim of this study was to investigate the effect of melatonin on IL-1β-induced human umbilical vein endothelial cells (HUVECs) monolayer permeability and then to test the involvement of small GTPase Rac in the melatonin-induced endothelial barrier-protective effects as well as cell contact reorganization. It was found that IL-1β treatment increased the permeability of HUVECs monolayer, disrupted adherens junctions, and down-regulated the expression of VE-cadherin which is the main functional protein of adherens junctions. Melatonin, however, decreased dextran permeability and increased intercellular adherens junction areas reflecting an endothelial cell barrier-protective response. Furthermore, melatonin dramatically improved IL-1β-induced Rac inactivation. Our results show that the barrier-protective effects of melatonin on endothelial cells are mediated by Rac activation and leads to enhancement of adherens junctions.
褪黑素是调节昼夜节律和季节性生殖的关键因素。褪黑素及其代谢物直接清除自由基，增加抗氧化酶的表达，并在防御反应的抗炎阶段发挥作用。目前，尚无褪黑素对内皮细胞单层通透性可能产生影响的直接数据，而内皮细胞单层通透性是导致血管疾病的主要生物学过程。本研究旨在探讨褪黑素对白细胞介素-1β（IL-1β）诱导的人脐静脉内皮细胞（HUVEC）单层通透性的影响，然后检测小 GTP 酶 Rac 在褪黑素诱导的内皮屏障保护作用以及细胞接触重排中的作用。结果发现，IL-1β处理增加了 HUVEC 单层的通透性，破坏了黏附连接，并下调了黏附连接的主要功能蛋白 VE-钙黏蛋白的表达。然而，褪黑素降低了葡聚糖的通透性，并增加了细胞间黏附连接区域，反映了内皮细胞的屏障保护反应。此外，褪黑素显著改善了 IL-1β诱导的 Rac 失活。我们的结果表明，褪黑素对内皮细胞的屏障保护作用是通过 Rac 激活介导的，并导致黏附连接增强。
