Hydrogen peroxide inhibits cell cycle progression by inhibition of the spreading of mitotic CHO cells.
Hydrogen peroxide (H(2)O(2)) induces a number of events, which are also induced by mitogens. Since the progression through the G1 phase of the cell cycle is dependent on mitogen stimulation, we were interested to study the effect of H(2)O(2) on the cell cycle progression. This study demonstrates that H(2)O(2) inhibits DNA synthesis in a dose-dependent manner when given to cells in mitosis or at different points in the G1 phase. Interestingly, mitotic cells treated immediately after synchronization are significantly more sensitive to H(2)O(2) than cells treated in the G1, and this is due to the inhibition of the cell spreading after mitosis by H(2)O(2). H(2)O(2) reversibly inhibits focal adhesion activation and stress fiber formation of mitotic cells, but not those of G1 cells. The phosphorylation of MAPK is also reversibly inhibited in both mitotic and G1 cells. Taken together, H(2)O(2) is probably responsible for the inhibition of the expression of cyclin D1 and cyclin A observed in cells in both phases. In conclusion, H(2)O(2) inhibits cell cycle progression by inhibition of the spreading of mitotic CHO cells. This may play a role in pathological processes in which H(2)O(2) is generated.
Muñoz
C Martínez
CM
Institute of Biomembranes, Department of Molecular Cell Biology, Utrecht University, Utrecht, Netherlands.
van Meeteren
L A
LA
Post
J A
JA
Verkleij
A J
AJ
Verrips
C T
CT
Boonstra
J
J
D000818:Animals; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008938:Mitosis; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D022502:Stress Fibers / Q000648:ultrastructure
D019925:Cyclin A; D017382:Reactive Oxygen Species; D019938:Cyclin D1; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases