Reactive oxygen species mediated DNA damage is essential for abnormal erythropoiesis in peroxiredoxin II−/− mice

Erythroid cells are highly prone to oxidative damage generated during erythropoiesis and thus are well equipped with antioxidant defense systems. However, their roles have been poorly characterized. Here, we investigated the role of peroxiredoxin II in mouse erythropoiesis. Loss of Prx II significantly increased apoptosis and cell cycle arrest leading to abnormal erythropoiesis at 3 weeks of age when erythropoietin levels were almost same between wild type and Prx II−/−. In Prx II−/− bone marrow cells, DNA tail length as an indicator of the oxidative damage was greatly increased and mRNAs of the molecules associated with DNA damage and repair and transcription regulators of antioxidant enzymes were also significantly increased. In addition, N-Acetyl-l-Cysteine treatment significantly decreased immature erythroblasts and apoptotic cells increased in Prx II−/− BMCs. These results strongly demonstrate that Prx II plays an essential role in maintaining normal erythropoiesis by protecting DNA damage.

► Prx II plays a role in protecting DNA damage induced by the increased ROS in BMCs.
► Prx II deletion induced p53 signal pathway activation to respond the oxidative stress induced DNA damage.
► Prx II has a function of inhibiting apoptosis and cell cycle arrest of immature erythroblasts during erythroid differentiation under oxidative stress.