Peroxiredoxin I participates in the protection of reactive oxygen species-mediated cellular senescence

Abstract

Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16(INK4a) expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I(-/-)MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I(-/-)mice showed an increased number of cells with senescence associated-beta-galactosidase (SA-beta-gal) activity in a variety of tissues. Increased ROS levels and SA-beta-gal activity, and reduction of chemical antioxidant in Prx I-/-MEF further supported an essential role of Prx I peroxidase activity in cellular senescence that is mediated by oxidative stress. The up-regulation of p16(INK4a) expression in Prx I-/- and suppression by overexpression of Prx I indicate that Prx I possibly modulate cellular senescence through ROS/p16(INK4a) pathway.