Jepson M A
Cell Imaging Facility and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Cell Mol Biol (Noisy-le-grand). 2003 Feb;49(1):101-12.
Modulation of epithelial function by oxidants such as hydrogen peroxide may contribute to a variety of disease processes. The effects of hydrogen peroxide (H2O2) on epithelial barrier function and tight junction protein distribution were compared in three distinct types of polarised epithelial cell, each of which was found to respond differently to H2O2. Of the cell-lines examined, Madin-Darby canine kidney (MDCK) stain II was the most susceptible to H2O2 and Caco-2 the least H2O2 induced a decrease in transepithelial electrical resistance in all three epithelial cell-lines which was accompanied by redistribution of the tight junction protein occludin in Caco-2 and MDCK II but not MDCK I, cell layers. The effects of H2O2 on epithelia displayed marked asymmetry, each cell-line being affected more by basal than apical application of H2O2. Genistein partially prevented the effects of H2O2 on Caco-2 cells suggesting a role for protein tyrosine phosphorylation in H2O2-induced epithelial barrier dysfunction. However, genistein was without effect on the responses of MDCK cells to H2O2. Taken together these data indicate that H2O2 has distinct effects onthe tight junctions of epithelial cells from different origins and suggest that enhanced tyrosine phosphorylation is a contributory factor inthe enhanced permeability of some, but possibly not all, epithelial cell-lines.
诸如过氧化氢等氧化剂对上皮功能的调节可能会导致多种疾病进程。研究人员比较了过氧化氢（H₂O₂）对三种不同类型的极化上皮细胞上皮屏障功能和紧密连接蛋白分布的影响，发现每种细胞对H₂O₂的反应都不同。在所检测的细胞系中，Madin-Darby犬肾（MDCK）II型细胞对H₂O₂最为敏感，而Caco-2细胞最不敏感。H₂O₂导致所有三种上皮细胞系的跨上皮电阻降低，同时Caco-2细胞层和MDCK II细胞层中的紧密连接蛋白闭合蛋白发生重新分布，但MDCK I细胞层未出现这种情况。H₂O₂对上皮细胞的影响表现出明显的不对称性，即每种细胞系受H₂O₂基底侧施加的影响比顶侧施加的影响更大。染料木黄酮部分阻止了H₂O₂对Caco-2细胞的影响，这表明蛋白酪氨酸磷酸化在H₂O₂诱导的上皮屏障功能障碍中发挥作用。然而，染料木黄酮对MDCK细胞对H₂O₂的反应没有影响。综合这些数据表明，H₂O₂对来自不同来源的上皮细胞紧密连接有不同影响，并表明酪氨酸磷酸化增强是部分（但可能不是全部）上皮细胞系通透性增强的一个促成因素。
