Inhibitory effect of peroxiredoxin II (Prx II) on Ras-ERK-NFkappaB pathway in mouse embryonic fibroblast (MEF) senescence.
Intracellular reactive oxygen species (ROS) were attenuated by the expression of peroxiredoxin II (Prx II). Cellular senescence as judged by senescence-associated (SA)-beta-galactosidase (Gal) positive cell formation was increased in Prx II-deficient mouse embryonic fibroblast (MEF). Ras expression was increased following passages. The level of Ras expression was higher in Prx II-/- MEF than wild type MEF. ERK activity was also augmented by the deletion of Prx II. SA-beta-Gal-positive cell formation was reduced by PD98059, ERK inhibitor. Activated nuclear transcription factor, nuclear factor-kappaB (NFkappaB) by the deletion of Prx II was inhibited by the treatment with PD98059. In contrast, no changes in SA-beta-Gal-positive cell formation were detected by NFkappaB inhibitor, N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK). Collectively, results suggest that Prx II deletion activate Ras-ERK-NFkappaB pathways and cellular senescence in Prx II-/- MEF cells was mediated by ERK activation but not by NFkappaB activation.
Han
Ying-Hao
YH
Department of Human Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Taejeon, 305-806, South Korea.
Kwon
Jeong-Hoon
JH
Yu
Dae-Yeul
DY
Moon
Eun-Yi
EY
D000818:Animals; D016922:Cellular Senescence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D017353:Gene Deletion; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D010544:Peroxidases / Q000235:genetics* / Q000502:physiology*; D054464:Peroxiredoxins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D016328:NF-kappa B; D010544:Peroxidases; D054464:Peroxiredoxins; D048049:Extracellular Signal-Regulated MAP Kinases; D001616:beta-Galactosidase; D018631:ras Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one