Exp Mol Med.  2005 Oct;37(5):482-487.

Centrosome amplification and multinuclear phenotypes are Induced by hydrogen peroxide

• Chae S
• Yun C
• Um H
• Lee JH
• Cho H

Abstract

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 (> 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.

Keyword

antioxidants; centrosome; giant cells; hydrogen peroxide; reactive oxygen species

MeSH Terms

Cell Line
Cell Nucleus/*drug effects/*metabolism
Centrosome/*drug effects/*metabolism
Gene Amplification
Humans
Hydrogen Peroxide/*pharmacology
MAP Kinase Signaling System
Mitotic Spindle Apparatus/drug effects
Phenotype
Reactive Oxygen Species/metabolism
Research Support, Non-U.S. Gov't