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Original

Inhibitory effect of peroxiredoxin II (Prx II) on Ras–ERK–NFκB pathway in mouse embryonic fibroblast (MEF) senescence

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Pages 1182-1189 | Received 27 Mar 2006, Published online: 07 Jul 2009
 

Abstract

Intracellular reactive oxygen species (ROS) were attenuated by the expression of peroxiredoxin II (Prx II). Cellular senescence as judged by senescence-associated (SA)-β-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-β-Gal-positive cell formation was reduced by PD98059, ERK inhibitor. Activated nuclear transcription factor, nuclear factor-kappaB (NFκB) by the deletion of Prx II was inhibited by the treatment with PD98059. In contrast, no changes in SA-β-Gal-positive cell formation were detected by NFκB inhibitor, N-alpha-tosyl-l-phenylalanyl chloromethyl ketone (TPCK). Collectively, results suggest that Prx II deletion activate Ras–ERK–NFκB pathways and cellular senescence in Prx II− / − MEF cells was mediated by ERK activation but not by NFκB activation.

Abbreviations
ROS=

reactive oxygen species

ERK=

extracellular receptor kinase

MEF=

mouse embryonic fibroblast

Prx II=

peroxiredoxin II

SA-β-Gal=

senescence-associated-β-glactosidase

SOD=

superoxide dismutase

SEAP=

secreted alkaline phosphatase

MBP=

myelin basic protein

PMA=

phorbol 12-myristate 13-acetate

TPCK=

N-alpha-tosyl-l-phenylalanyl chloromethyl ketone

NFκB=

nuclear factor kappaB

EMSA=

electrophoretic mobility shift assay

IOM=

ionomycin

Abbreviations
ROS=

reactive oxygen species

ERK=

extracellular receptor kinase

MEF=

mouse embryonic fibroblast

Prx II=

peroxiredoxin II

SA-β-Gal=

senescence-associated-β-glactosidase

SOD=

superoxide dismutase

SEAP=

secreted alkaline phosphatase

MBP=

myelin basic protein

PMA=

phorbol 12-myristate 13-acetate

TPCK=

N-alpha-tosyl-l-phenylalanyl chloromethyl ketone

NFκB=

nuclear factor kappaB

EMSA=

electrophoretic mobility shift assay

IOM=

ionomycin

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