Rao Radhakrishna
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Front Biosci. 2008 May 1;13:7210-26. doi: 10.2741/3223.
Mounting body of evidence indicates that the disruption of epithelial tight junctions and resulting loss of barrier function play a crucial role in the pathogenesis of a variety of gastrointestinal, hepatic, pulmonary, kidney and ocular diseases. Increased production of inflammatory mediators such as cytokines and reactive oxygen species disrupt the epithelial and endothelial barrier function by destabilizing tight junctions. Oxidative stress induced by various reactive oxygen species such as hydrogen peroxide, nitric oxide, peroxynitrite and hypochlorous acid disrupt the epithelial and endothelial tight junctions in various tissues. The mechanism involved in oxidative stress-induced disruption of tight junction includes protein modification such as thiol oxidation, phosphorylation, nitration and carbonylation. The role of signaling molecules such as protein kinases and protein phosphatases in regulation of tight junctions is discussed in this article. Understanding such mechanisms in oxidative stress-induced disruption of epithelial and endothelial barrier functions is likely to provide insight into the pathogenesis of various inflammatory diseases, and may form a basis for the design of treatment strategies for different diseases.
越来越多的证据表明，上皮紧密连接的破坏以及由此导致的屏障功能丧失在多种胃肠道、肝脏、肺部、肾脏和眼部疾病的发病机制中起着关键作用。细胞因子和活性氧等炎症介质的产生增加，通过破坏紧密连接来破坏上皮和内皮屏障功能。过氧化氢、一氧化氮、过氧亚硝酸盐和次氯酸等各种活性氧诱导的氧化应激会破坏各种组织中的上皮和内皮紧密连接。氧化应激诱导紧密连接破坏所涉及的机制包括蛋白质修饰，如硫醇氧化、磷酸化、硝化和羰基化。本文讨论了蛋白激酶和蛋白磷酸酶等信号分子在紧密连接调节中的作用。了解氧化应激诱导上皮和内皮屏障功能破坏的此类机制，可能有助于深入了解各种炎症性疾病的发病机制，并可能为不同疾病的治疗策略设计奠定基础。
