The mechanism of epithelial apical membrane domain development and diseases.

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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.