The Role of Hydrogen Peroxide and Peroxiredoxins throughout the Cell Cycle

Abstract

Hydrogen peroxide (H2O2) 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 H2O2 also acts as a promoter for cell cycle progression by oxidizing specific thiol proteins. The intracellular concentration of H2O2 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 H2O2, organic hydroperoxides, and peroxynitrite for protecting cells from oxidative stress. They are suggested to work as signaling mediators, allowing the local accumulation of H2O2 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 H2O2, they act as sensors and transducers of H2O2 signaling via transferring their oxidation state to effector proteins. The concentrations of intracellular H2O2 increase as the cell cycle progresses from G1 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 H2O2 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 H2O2 levels.

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

“…Such oxidation can result in structural modification leading to the selective regulation of protein functions (as in phosphatase, kinases, etc.) and can thus have an important impact on regulating signaling pathways in a large range of physiological contexts [277][278][279][280].…”

Knockout of PRDX6 induces mitochondrial dysfunction and cell cycle arrest at G2/M in HepG2 hepatocarcinoma cells

“…NADPH oxidases (NOX), particularly NOX1 and NOX4 may be the source of H 2 O 2 [ 26 ] and H 2 O 2 generated by NOX in response to growth factors are required to activate the extracellular signal-regulated kinase (ERK) and p38 which increase the expression of cyclin D to promote the transition from G0 to G1 phase. Several key proteins involved in different phases of the cell cycle with redox sensitive residues at their active sites, like Cdc14B, PP1, PP2, Cdc25C, could be the targets [ 27 , 28 ] and it has been proposed that Prdx1, Prdx2 and Prdx3 play important roles to maintain the redox state of those target proteins thus protecting the cell against an undesired progression through the cell cycle [ 29 , 30 ]. More specifically and pertinent to the study reported herein, PRDX6 has been described to activate NOX1 oxidase activity through physical interaction with NOX1 components and through its PLA2 activity [ 31 ] as occurred also with NOX2 [ 20 ].…”

Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis

“…Therefore, we focused on Prdx3 as a critical player involved in senescence, especially in a MondoA-regulated pathway. Prdx1-6, enzymatic antioxidants with redox signaling, are involved in the proper cell-cycle progression (Heo et al, 2020;Rhee and Kil, 2017). Consistent with this role, there is a report that Prdx3 levels are reduced in intrahepatic cholestasis pregnancy placenta with mitochondrial dysfunction and senescence (Wu et al, 2016).…”