Muñoz C Martínez, van Meeteren L A, Post J A, Verkleij A J, Verrips C T, Boonstra J
Institute of Biomembranes, Department of Molecular Cell Biology, Utrecht University, Utrecht, Netherlands.
Free Radic Biol Med. 2002 Oct 15;33(8):1061-72. doi: 10.1016/s0891-5849(02)00988-7.
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.
过氧化氢（H₂O₂）可引发一系列事件，这些事件也可由有丝分裂原诱导产生。由于细胞周期G1期的进程依赖于有丝分裂原刺激，我们有兴趣研究H₂O₂对细胞周期进程的影响。本研究表明，当在有丝分裂期或G1期的不同时间点给予细胞时，H₂O₂以剂量依赖的方式抑制DNA合成。有趣的是，同步化后立即处理的有丝分裂细胞对H₂O₂的敏感性明显高于G1期处理的细胞，这是由于H₂O₂抑制了有丝分裂后细胞的铺展。H₂O₂可逆地抑制有丝分裂细胞的粘着斑激活和应力纤维形成，但不影响G1期细胞。有丝分裂期和G1期细胞中MAPK的磷酸化也受到可逆抑制。综上所述，H₂O₂可能是导致两个阶段细胞中观察到的细胞周期蛋白D1和细胞周期蛋白A表达受到抑制的原因。总之，H₂O₂通过抑制有丝分裂的CHO细胞铺展来抑制细胞周期进程。这可能在H₂O₂产生的病理过程中发挥作用。
