Chae Sunyoung, Yun Chawon, Um Haeryun, Lee Jae Ho, Cho Hyeseong
Department of Biochemistry and Molecular Biology, Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 442-749, Korea.
Exp Mol Med. 2005 Oct 31;37(5):482-7. doi: 10.1038/emm.2005.59.
Multinucleated cells resulted from mitosis defect have been noted in pathophysiological states of the cells such as inflammation, senescence and cancer. Since oxidative stress has been known to correlate with these pathophysiological conditions, we tested the effect of H2O2 on the cell cycle progression and formation of multinucleated cells. H2O2 induced a significant delay in cell cycle progression in Chang liver cells. Interestingly, H2O2 actively induced hyperamplification of centrosomes (n>or=3) and multipolar spindle formation during mitosis and subsequently increased the generation of multinucleated cells. A significant increase of the phospho-ERK level was observed upon H2O2 treatment but PD98059, an MEK1/2 inhibitor, didn't reduce the frequency of cells with hyperamplified centrosomes. On the other hand, treatment of either H2O2 or adriamycin increased intracellular ROS levels and multinucleated cells, which were significantly suppressed by antioxidants, N-acetylcysteine and PDTC. Thus, our results suggest that oxidative stress can trigger centrosome hyperamplification and multinucleated cell formation, which may promote pathophysiological progression.
在细胞的病理生理状态如炎症、衰老和癌症中，已发现有丝分裂缺陷导致的多核细胞。由于已知氧化应激与这些病理生理状况相关，我们测试了过氧化氢（H2O2）对细胞周期进程和多核细胞形成的影响。H2O2导致Chang肝细胞的细胞周期进程显著延迟。有趣的是，H2O2在有丝分裂期间积极诱导中心体超扩增（n≥3）和多极纺锤体形成，随后增加了多核细胞的产生。H2O2处理后观察到磷酸化ERK水平显著升高，但MEK1/2抑制剂PD98059并未降低中心体超扩增细胞的频率。另一方面，H2O2或阿霉素处理均增加了细胞内活性氧水平和多核细胞，而抗氧化剂N-乙酰半胱氨酸和PDTC可显著抑制这些现象。因此，我们的结果表明氧化应激可引发中心体超扩增和多核细胞形成，这可能促进病理生理进程。
