Analysis of the molecular mechanism of disease based on the functional aberration of aPKC-PAR complex

自由基和氧化应激的过度产生与癌症、肝硬化和炎症性肠病的发病机制有关。然而，氧化应激对细胞极性或组织形态的影响仍然是未知的。在这里，我们证明了四氯化碳（CCl 4）诱导的氧化应激导致大鼠肝脏细胞极性的丧失。此外，极性调节蛋白复合物，aPKC-PAR复合物（Par-3-aPKC-Par-6三元复合物）的形成被CCl 4处理的aPKC的异常激活所抑制。我们的研究结果将有助于理解氧化应激诱导疾病的分子基础和诊断技术的创新。

Excessive productions of free radicals and oxidative stress are implicated in the pathogenesis of cancer, cirrhosis and inflammatory bowel diseases. However, the effect of oxidative stress on cell polarity or tissue morphology is still unknown.Here we demonstrated that carbon tetrachloride (CCl4)-induced oxidative stress resulted in the loss of cell polarity in rat liver. Furthermore, the polarity regulating protein complex, aPKC-PAR complex (Par-3-aPKC-Par-6 ternary complex) formation was inhibited by aberrant activation of aPKC through CCl4 treatment. Our findings would contribute to understanding of molecular basis of oxidative stress-induced disease and to the innovation of diagnostic techniques.