Centrosome amplification and multinuclear phenotypes are Induced by hydrogen peroxide.
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.
Chae
Sunyoung
S
Department of Biochemistry and Molecular Biology, Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 442-749, Korea.
Yun
Chawon
C
Um
Haeryun
H
Lee
Jae Ho
JH
Cho
Hyeseong
H
D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D018385:Centrosome / Q000187:drug effects* / Q000378:metabolism*; D005784:Gene Amplification; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide