Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation

Sun Uk Kim, Young Ho Park, Ju Sik Min, Hu Nan Sun, Ying Hao Han, Jin Mei Hua, Tae Hoon Lee, Sang Rae Lee, Kyu Tae Chang, Sang Won Kang, Jin Man Kim, Dae Yeul Yu, Sang Ho Lee, Dong Seok Lee

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) function as modulators of pro-inflammatory processes in microglia-associated neurodegenerative diseases.However, little is known about the involvement of specific antioxidants in regulating the microglial redox status. Here, we demonstrated that peroxiredoxin (Prx) I activity was induced by lipopolysaccharide (LPS), but not paraquat and hydrogen peroxide, through activation of the ROS/p38 MAPK signal pathway, and participated in alleviating the microglial activation and generation of nitric oxide (NO). Interestingly, a null mutation of Prx I accelerated NF-κB-mediated iNOS induction and subsequent NO secretion in LPS-stimulated microglia. Furthermore, F4/80 expression as microglial activation marker was notably up-regulated in primary cultures of microglia, hippocampal sections, and cerebral cortex of 15-month-old Prx I-/- mouse.Taken together, the results of our study indicated that Prx I is an antioxidant that is up-regulated in a ROS/p38 MAPK-dependent manner and governs the progression of neuroinflammation by suppressing microglial activation. In addition, Prx I deficiency increased the nuclear translocation of NF-κB mediated-iNOS induction as pro-inflammatory mediators.The findings of our work suggest possible strategies for developing novel therapies to treat inflammation-associated degenerative neurological diseases by targeting the induction of Prx I in microglial cells.

Original languageEnglish
Pages (from-to)26-36
Number of pages11
JournalJournal of Neuroimmunology
Volume259
Issue number1-2
DOIs
Publication statusPublished - 2013 Jun 15

Fingerprint

Peroxiredoxins
p38 Mitogen-Activated Protein Kinases
Reactive Oxygen Species
Antioxidants
Microglia
Lipopolysaccharides
Nitric Oxide
Paraquat
Neurodegenerative Diseases
Cerebral Cortex
Hydrogen Peroxide
Oxidation-Reduction
Signal Transduction
Inflammation
Mutation

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation. / Kim, Sun Uk; Park, Young Ho; Min, Ju Sik; Sun, Hu Nan; Han, Ying Hao; Hua, Jin Mei; Lee, Tae Hoon; Lee, Sang Rae; Chang, Kyu Tae; Kang, Sang Won; Kim, Jin Man; Yu, Dae Yeul; Lee, Sang Ho; Lee, Dong Seok.

In: Journal of Neuroimmunology, Vol. 259, No. 1-2, 15.06.2013, p. 26-36.

Research output: Contribution to journalArticle

Kim, SU, Park, YH, Min, JS, Sun, HN, Han, YH, Hua, JM, Lee, TH, Lee, SR, Chang, KT, Kang, SW, Kim, JM, Yu, DY, Lee, SH & Lee, DS 2013, 'Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation', Journal of Neuroimmunology, vol. 259, no. 1-2, pp. 26-36. https://doi.org/10.1016/j.jneuroim.2013.03.006
Kim, Sun Uk ; Park, Young Ho ; Min, Ju Sik ; Sun, Hu Nan ; Han, Ying Hao ; Hua, Jin Mei ; Lee, Tae Hoon ; Lee, Sang Rae ; Chang, Kyu Tae ; Kang, Sang Won ; Kim, Jin Man ; Yu, Dae Yeul ; Lee, Sang Ho ; Lee, Dong Seok. / Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation. In: Journal of Neuroimmunology. 2013 ; Vol. 259, No. 1-2. pp. 26-36.
@article{de982a190027407c9eeb4968ef47bfbc,
title = "Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation",
abstract = "Reactive oxygen species (ROS) function as modulators of pro-inflammatory processes in microglia-associated neurodegenerative diseases.However, little is known about the involvement of specific antioxidants in regulating the microglial redox status. Here, we demonstrated that peroxiredoxin (Prx) I activity was induced by lipopolysaccharide (LPS), but not paraquat and hydrogen peroxide, through activation of the ROS/p38 MAPK signal pathway, and participated in alleviating the microglial activation and generation of nitric oxide (NO). Interestingly, a null mutation of Prx I accelerated NF-κB-mediated iNOS induction and subsequent NO secretion in LPS-stimulated microglia. Furthermore, F4/80 expression as microglial activation marker was notably up-regulated in primary cultures of microglia, hippocampal sections, and cerebral cortex of 15-month-old Prx I-/- mouse.Taken together, the results of our study indicated that Prx I is an antioxidant that is up-regulated in a ROS/p38 MAPK-dependent manner and governs the progression of neuroinflammation by suppressing microglial activation. In addition, Prx I deficiency increased the nuclear translocation of NF-κB mediated-iNOS induction as pro-inflammatory mediators.The findings of our work suggest possible strategies for developing novel therapies to treat inflammation-associated degenerative neurological diseases by targeting the induction of Prx I in microglial cells.",
keywords = "Antioxidants, Inflammation, Lipopolysaccharides, Microglia activation, Peroxiredoxin, Reactive oxygen species",
author = "Kim, {Sun Uk} and Park, {Young Ho} and Min, {Ju Sik} and Sun, {Hu Nan} and Han, {Ying Hao} and Hua, {Jin Mei} and Lee, {Tae Hoon} and Lee, {Sang Rae} and Chang, {Kyu Tae} and Kang, {Sang Won} and Kim, {Jin Man} and Yu, {Dae Yeul} and Lee, {Sang Ho} and Lee, {Dong Seok}",
year = "2013",
month = "6",
day = "15",
doi = "10.1016/j.jneuroim.2013.03.006",
language = "English",
volume = "259",
pages = "26--36",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation

AU - Kim, Sun Uk

AU - Park, Young Ho

AU - Min, Ju Sik

AU - Sun, Hu Nan

AU - Han, Ying Hao

AU - Hua, Jin Mei

AU - Lee, Tae Hoon

AU - Lee, Sang Rae

AU - Chang, Kyu Tae

AU - Kang, Sang Won

AU - Kim, Jin Man

AU - Yu, Dae Yeul

AU - Lee, Sang Ho

AU - Lee, Dong Seok

PY - 2013/6/15

Y1 - 2013/6/15

N2 - Reactive oxygen species (ROS) function as modulators of pro-inflammatory processes in microglia-associated neurodegenerative diseases.However, little is known about the involvement of specific antioxidants in regulating the microglial redox status. Here, we demonstrated that peroxiredoxin (Prx) I activity was induced by lipopolysaccharide (LPS), but not paraquat and hydrogen peroxide, through activation of the ROS/p38 MAPK signal pathway, and participated in alleviating the microglial activation and generation of nitric oxide (NO). Interestingly, a null mutation of Prx I accelerated NF-κB-mediated iNOS induction and subsequent NO secretion in LPS-stimulated microglia. Furthermore, F4/80 expression as microglial activation marker was notably up-regulated in primary cultures of microglia, hippocampal sections, and cerebral cortex of 15-month-old Prx I-/- mouse.Taken together, the results of our study indicated that Prx I is an antioxidant that is up-regulated in a ROS/p38 MAPK-dependent manner and governs the progression of neuroinflammation by suppressing microglial activation. In addition, Prx I deficiency increased the nuclear translocation of NF-κB mediated-iNOS induction as pro-inflammatory mediators.The findings of our work suggest possible strategies for developing novel therapies to treat inflammation-associated degenerative neurological diseases by targeting the induction of Prx I in microglial cells.

AB - Reactive oxygen species (ROS) function as modulators of pro-inflammatory processes in microglia-associated neurodegenerative diseases.However, little is known about the involvement of specific antioxidants in regulating the microglial redox status. Here, we demonstrated that peroxiredoxin (Prx) I activity was induced by lipopolysaccharide (LPS), but not paraquat and hydrogen peroxide, through activation of the ROS/p38 MAPK signal pathway, and participated in alleviating the microglial activation and generation of nitric oxide (NO). Interestingly, a null mutation of Prx I accelerated NF-κB-mediated iNOS induction and subsequent NO secretion in LPS-stimulated microglia. Furthermore, F4/80 expression as microglial activation marker was notably up-regulated in primary cultures of microglia, hippocampal sections, and cerebral cortex of 15-month-old Prx I-/- mouse.Taken together, the results of our study indicated that Prx I is an antioxidant that is up-regulated in a ROS/p38 MAPK-dependent manner and governs the progression of neuroinflammation by suppressing microglial activation. In addition, Prx I deficiency increased the nuclear translocation of NF-κB mediated-iNOS induction as pro-inflammatory mediators.The findings of our work suggest possible strategies for developing novel therapies to treat inflammation-associated degenerative neurological diseases by targeting the induction of Prx I in microglial cells.

KW - Antioxidants

KW - Inflammation

KW - Lipopolysaccharides

KW - Microglia activation

KW - Peroxiredoxin

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=84877596486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877596486&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2013.03.006

DO - 10.1016/j.jneuroim.2013.03.006

M3 - Article

VL - 259

SP - 26

EP - 36

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 1-2

ER -