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

• Published in: FEBS letters 2005-08, Vol.579 (21), p.4897-4902
• Main Authors: Han, Ying-Hao, Kim, Hyun-Sun, Kim, Jin-Man, Kim, Sang-Keun, Yu, Dae-Yeul, Moon, Eun-Yi
• Format: Article
• Language: English
• Subjects: Acetylcysteine - metabolism; Aging; Aging - physiology; Animals; c-Jun N-terminal kinase; Cell Cycle - physiology; Cells, Cultured; Cellular Senescence; ERK; extracellular signal-regulated kinase; Fibroblasts - cytology; Fibroblasts - metabolism; Hydrogen Peroxide - metabolism; JNK; MEF; Mice; Mice, Knockout; mouse embryonic fibroblast; N-acetyl-l-cysteine; NAC; Oxidants - metabolism; Peroxidases - genetics; Peroxidases - metabolism; Peroxiredoxin II; Peroxiredoxins; Prx II; Reactive oxygen species; Reactive Oxygen Species - metabolism; ROS; SA-β-Gal; senescence-associated-β-glactosidase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.07.049

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)-β-galactosidase (Gal)-positive cell formation was about 30% higher in Prx II −/− MEF. N-Acetyl- l-cysteine (NAC) treatment attenuated SA-β-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.