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

doi:10.1016/j.jneuroim.2013.03.006

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

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 language	English
Pages (from-to)	26-36
Number of pages	11
Journal	Journal of Neuroimmunology
Volume	259
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2013.03.006
State	Published - 15 Jun 2013

Bibliographical note

Funding Information:
This research was supported by Kyungpook National University Research Fund, 2012, by the SRC program (Center for Food & Nutritional Genomics: grant number 2012-0000639 ) of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology , by a grant (no. 2012-008880 ) from the Korean Ministry of Education, Science and Technology , by a grant (nos. 110056-03-3-HD110 and 112020-03-1-CG000 ) from the ARPC program of the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries , and by a grant from the National Research Foundation of Korea funded by the Korean Government (no. 2012M3A9B6055362 ).

Keywords

Antioxidants
Inflammation
Lipopolysaccharides
Microglia activation
Peroxiredoxin
Reactive oxygen species

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10.1016/j.jneuroim.2013.03.006

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Kim, S. U., Park, Y. H., Min, J. S., Sun, H. N., Han, Y. H., Hua, J. M., Lee, T. H., Lee, S. R., Chang, K. T., Kang, S. W., Kim, J. M., Yu, D. Y., Lee, S. H., & Lee, D. S. (2013). Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation. Journal of Neuroimmunology, 259(1-2), 26-36. https://doi.org/10.1016/j.jneuroim.2013.03.006

@article{db246f47e9bf43c79113c0864cbf5095,

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}",

note = "Funding Information: This research was supported by Kyungpook National University Research Fund, 2012, by the SRC program (Center for Food & Nutritional Genomics: grant number 2012-0000639 ) of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology , by a grant (no. 2012-008880 ) from the Korean Ministry of Education, Science and Technology , by a grant (nos. 110056-03-3-HD110 and 112020-03-1-CG000 ) from the ARPC program of the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries , and by a grant from the National Research Foundation of Korea funded by the Korean Government (no. 2012M3A9B6055362 ).",

year = "2013",

month = jun,

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 B.V.",

number = "1-2",

}

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

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

N1 - Funding Information: This research was supported by Kyungpook National University Research Fund, 2012, by the SRC program (Center for Food & Nutritional Genomics: grant number 2012-0000639 ) of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology , by a grant (no. 2012-008880 ) from the Korean Ministry of Education, Science and Technology , by a grant (nos. 110056-03-3-HD110 and 112020-03-1-CG000 ) from the ARPC program of the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries , and by a grant from the National Research Foundation of Korea funded by the Korean Government (no. 2012M3A9B6055362 ).

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

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U2 - 10.1016/j.jneuroim.2013.03.006

DO - 10.1016/j.jneuroim.2013.03.006

M3 - Article

C2 - 23602274

AN - SCOPUS:84877596486

SN - 0165-5728

VL - 259

SP - 26

EP - 36

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

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

Abstract

Bibliographical note

Keywords

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