The Role of Hydrogen Peroxide and Peroxiredoxins throughout the Cell Cycle

Hydrogen peroxide (H(2)O(2)) is an oxidizing agent that induces cellular damage at inappropriate concentrations and gives rise to an arrest during cell cycle progression, causing cell death. Recent evidence indicates that H(2)O(2) also acts as a promoter for cell cycle progression by oxidizing specific thiol proteins. The intracellular concentration of H(2)O(2) is regulated tightly, enabling its use as a cellular signaling molecule while minimizing its potential to cause cellular damage. Peroxiredoxins (Prxs) have peroxidase activity toward H(2)O(2), organic hydroperoxides, and peroxynitrite for protecting cells from oxidative stress. They are suggested to work as signaling mediators, allowing the local accumulation of H(2)O(2) by inactivating their peroxidase activity uniquely compared with other antioxidant proteins such as catalase and glutathione peroxidase. Given that Prxs are highly sensitive to oxidation by H(2)O(2), they act as sensors and transducers of H(2)O(2) signaling via transferring their oxidation state to effector proteins. The concentrations of intracellular H(2)O(2) increase as the cell cycle progresses from G(1) to mitosis. Here, we summarize the roles of Prxs with regard to the regulation of cell cycle-dependent kinase activity and anaphase-promoting complex/cyclosome in terms of changes in H(2)O(2) levels. Protection of the cell from unwanted progression of the cell cycle is suggested to be a role of Prx. We discuss the possible roles of Prxs to control H(2)O(2) levels.