Inhibitory role of peroxiredoxin II (Prx II) on cellular senescence

Reactive oxygen species (ROS) were generated in all oxygen-utilizing organisms. Peroxiredoxin II (Prx II) as one of antioxidant enzymes may play a protective role against the oxidative damage caused by ROS. In order to define the role of Prx II in organismal aging, we evaluated cellular senescence in Prx II-/- mouse embryonic fibroblast (MEF). As compared to wild type MEF, cellular senescence was accelerated in Prx II-/- MEF. Senescence-associated (SA)-beta-galactosidase (Gal)-positive cell formation was about 30% higher in Prx II-/- MEF. N-Acetyl-L-cysteine (NAC) treatment attenuated SA-beta-Gal-positive cell formation. Prx II-/- MEF exhibited the higher G2/M (41%) and lower S (1.6%) phase cells as compared to 24% and 7.4% in wild type MEF, respectively. A high increase in the p16 and a slight increase in the p21 and p53 levels were detected in PrxII(-/-) MEF cells. The cellular senescence of Prx II-/- MEF was correlated with the organismal aging of Prx II-/- mouse skin. While extracellular signal-regulated kinase (ERK) and p38 activation was detected in Prx II-/- MEF, ERK and c-Jun N-terminal kinase (JNK) activation was detected in Prx II-/- skin. These results suggest that Prx II may function as an enzymatic antioxidant to prevent cellular senescence and skin aging. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.