Jiang W G, Bryce R P, Horrobin D F, Mansel R E
Department of Surgery, University of Wales College of Medicine, Cardiff, United Kingdom.
Biochem Biophys Res Commun. 1998 Mar 17;244(2):414-20. doi: 10.1006/bbrc.1998.8288.
Tight junctions (TJ) are the topical most structure in epithelial and endothelial cells and play a key role in the control of permeability and prevention of tumour cell invasion of endothelium. In this study we examined the effects of a range of polyunsaturated fatty acids on the function of TJs and the expression of occludin, a key molecule in the TJs of the human vascular endothelial cell line, ECV304. Treatment of the endothelial cells with gamma linolenic acid, an anti-cancer PUFA, increased the transendothelial cell resistance (TER) and reduced the paracellular permeability to large molecules. The effects were seen without any changes in the viability of the endothelial cells. Occludin, a recently identified molecule, which plays a major role in tight junctions was up-regulated by this fatty acid as revealed by both Western blotting and immunofluorescence. Other fatty acids were also tested. Eicosapentaenoic acid (EPA) also exerted an up-regulatory effect, but LA and AA down-regulated the expression. We conclude that GLA and EPA which also have other anti-cancer effects, regulate the expression of occludin in endothelial cells and thus contribute to the modification of the TER of these cells.
紧密连接（TJ）是上皮细胞和内皮细胞中最外层的结构，在控制通透性以及防止肿瘤细胞侵袭内皮方面发挥关键作用。在本研究中，我们检测了一系列多不饱和脂肪酸对紧密连接功能以及闭合蛋白（人血管内皮细胞系ECV304紧密连接中的关键分子）表达的影响。用γ-亚麻酸（一种具有抗癌作用的多不饱和脂肪酸）处理内皮细胞，可增加跨内皮细胞电阻（TER），并降低大分子的细胞旁通透性。在内皮细胞活力未发生任何变化的情况下观察到了这些效应。如蛋白质免疫印迹法和免疫荧光所示，这种脂肪酸可上调闭合蛋白（一种最近鉴定出的在紧密连接中起主要作用的分子）的表达。我们还检测了其他脂肪酸。二十碳五烯酸（EPA）也发挥上调作用，但亚油酸（LA）和花生四烯酸（AA）下调了其表达。我们得出结论，同样具有其他抗癌作用的γ-亚麻酸和二十碳五烯酸可调节内皮细胞中闭合蛋白的表达，从而有助于改变这些细胞的跨内皮细胞电阻。
