The mechanism of epithelial apical membrane domain development and diseases.

自由基和氧化应激的过度产生与癌症和炎症性肠病的发病机制有关。这些疾病扰乱了根尖膜域和组织结构。然而，氧化应激诱导细胞损伤的分子机制以及细胞极性的影响仍有待阐明。四氯化碳(CCl4)强烈促进大鼠肝脏氧化应激，导致细胞-细胞连接解体，并使Par3和aPKC的定位从胞浆改变到胞浆。重要的是，氧化应激抑制了Par3-aPKC的相互作用。此外，aPKC Thr410/403的磷酸化水平增加，并激活了其调节激酶、PI3-激酶的信号通路。这些结果表明，氧化应激抑制了Par3和aPKC之间的相互作用，从而破坏了肝细胞的极性。

Excessive productions of free radicals and oxidative stress are implicated in the pathogenesis of cancer and inflammatory bowel diseases. These diseases disturb the apical membrane domains and tissue architectures. However, the molecular mechanisms of oxidative stress-induced cell injuries and the effect of cell polarity remain to be clarified. The treatment of carbon tetrachloride (CCl4), which strongly promotes oxidative stress in rat liver, resulted in the disassembly of cell-cell junctions and also changes the localization of Par3 and aPKC from it to cytosol. Importantly, the Par3-aPKC interaction was inhibited by oxidative stress. Furthermore, phosphorylation level of aPKC Thr410/403 increased and it's regulating kinase, PI3-kinase signaling is activated. These results suggested that oxidative stress inhibit the interaction between Par3 and aPKC and consequently the hepatocyte polarity is disrupted.