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 7.3% [corrected] 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.
Han
Ying-Hao
YH
Laboratory of Human Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oun-Dong, Yusong, Taejeon 305-806, Korea.
Kim
Hyun-Sun
HS
Kim
Jin-Man
JM
Kim
Sang-Keun
SK
Yu
Dae-Yeul
DY
Moon
Eun-Yi
EY
D000111:Acetylcysteine / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016877:Oxidants / Q000378:metabolism; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D017382:Reactive Oxygen Species / Q000378:metabolism
D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D000111:Acetylcysteine