Microglial peroxiredoxin v acts as an inducible anti-inflammatory antioxidant through cooperation with redox signaling cascades

Hu Nan Sun, Sun Uk Kim, Song Mei Huang, Jin Man Kim, Young Ho Park, Seok Ho Kim, Hee Young Yang, Kyoung Jin Chung, Tae Hoon Lee, Hoon Sung Choi, Ju Sik Min, Moon Ki Park, Sang Keun Kim, Sang Rae Lee, Kyu Tae Chang, Sang Ho Lee, Dae Yeul Yu, Dong Seok Lee

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) actively participate in microglia-mediated pathogenesis as pro-inflammatory molecules. However, little is known about the involvement of specific antioxidants in maintaining the microglial oxidative balance. We demonstrate that microglial peroxiredoxin (Prx) 5 expression is up-regulated by lipopolysaccharide (LPS) through activation of the ROS-sensitive signaling pathway and is involved in attenuation of both microglial activation and nitric oxide (NO) generation. Unlike in stimulation of oxidative insults with paraquat and hydrogen peroxide, Prx V expression is highly sensitive to LPS-stimulation in microglia. Reduction of ROS level by treatment with either NADPH oxidase inhibitor or antioxidant ablates LPS-mediated Prx V up-regulation in BV-2 microglial cells and is closely associated with the activation of the c-jun N-terminal kinase (JNK) signaling pathway. This suggests the involvement of ROS/JNK signaling in LPS-mediated Prx V induction. Furthermore, NO induces Prx V up-regulation that is ablated by the addition of inducible nitric oxide synthase inhibitor or deleted mutation of inducible nitric oxide synthase in LPS-stimulated microglia. Therefore, these results suggest that Prx V is induced by cooperative action among the ROS, RNS, and JNK signaling cascades. Interestingly, knockdown of Prx V expression causes the acceleration of microglia activation, including augmented ROS generation and JNK-dependent NO production. In summary, we demonstrate that Prx V plays a key role in the microglial activation process through modulation of the balance between ROS/NO generation and the corresponding JNK cascade activation.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalJournal of Neurochemistry
Volume114
Issue number1
DOIs
Publication statusPublished - 2010 Jul 1

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Peroxiredoxins
Oxidation-Reduction
Anti-Inflammatory Agents
Antioxidants
Reactive Oxygen Species
Chemical activation
Lipopolysaccharides
Microglia
Nitric Oxide
Phosphotransferases
Nitric Oxide Synthase Type II
Up-Regulation
Paraquat
JNK Mitogen-Activated Protein Kinases
NADPH Oxidase
Hydrogen Peroxide
Modulation
Mutation
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Microglial peroxiredoxin v acts as an inducible anti-inflammatory antioxidant through cooperation with redox signaling cascades. / Sun, Hu Nan; Kim, Sun Uk; Huang, Song Mei; Kim, Jin Man; Park, Young Ho; Kim, Seok Ho; Yang, Hee Young; Chung, Kyoung Jin; Lee, Tae Hoon; Choi, Hoon Sung; Min, Ju Sik; Park, Moon Ki; Kim, Sang Keun; Lee, Sang Rae; Chang, Kyu Tae; Lee, Sang Ho; Yu, Dae Yeul; Lee, Dong Seok.

In: Journal of Neurochemistry, Vol. 114, No. 1, 01.07.2010, p. 39-50.

Research output: Contribution to journalArticle

Sun, HN, Kim, SU, Huang, SM, Kim, JM, Park, YH, Kim, SH, Yang, HY, Chung, KJ, Lee, TH, Choi, HS, Min, JS, Park, MK, Kim, SK, Lee, SR, Chang, KT, Lee, SH, Yu, DY & Lee, DS 2010, 'Microglial peroxiredoxin v acts as an inducible anti-inflammatory antioxidant through cooperation with redox signaling cascades', Journal of Neurochemistry, vol. 114, no. 1, pp. 39-50. https://doi.org/10.1111/j.1471-4159.2010.06691.x
Sun, Hu Nan ; Kim, Sun Uk ; Huang, Song Mei ; Kim, Jin Man ; Park, Young Ho ; Kim, Seok Ho ; Yang, Hee Young ; Chung, Kyoung Jin ; Lee, Tae Hoon ; Choi, Hoon Sung ; Min, Ju Sik ; Park, Moon Ki ; Kim, Sang Keun ; Lee, Sang Rae ; Chang, Kyu Tae ; Lee, Sang Ho ; Yu, Dae Yeul ; Lee, Dong Seok. / Microglial peroxiredoxin v acts as an inducible anti-inflammatory antioxidant through cooperation with redox signaling cascades. In: Journal of Neurochemistry. 2010 ; Vol. 114, No. 1. pp. 39-50.
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abstract = "Reactive oxygen species (ROS) actively participate in microglia-mediated pathogenesis as pro-inflammatory molecules. However, little is known about the involvement of specific antioxidants in maintaining the microglial oxidative balance. We demonstrate that microglial peroxiredoxin (Prx) 5 expression is up-regulated by lipopolysaccharide (LPS) through activation of the ROS-sensitive signaling pathway and is involved in attenuation of both microglial activation and nitric oxide (NO) generation. Unlike in stimulation of oxidative insults with paraquat and hydrogen peroxide, Prx V expression is highly sensitive to LPS-stimulation in microglia. Reduction of ROS level by treatment with either NADPH oxidase inhibitor or antioxidant ablates LPS-mediated Prx V up-regulation in BV-2 microglial cells and is closely associated with the activation of the c-jun N-terminal kinase (JNK) signaling pathway. This suggests the involvement of ROS/JNK signaling in LPS-mediated Prx V induction. Furthermore, NO induces Prx V up-regulation that is ablated by the addition of inducible nitric oxide synthase inhibitor or deleted mutation of inducible nitric oxide synthase in LPS-stimulated microglia. Therefore, these results suggest that Prx V is induced by cooperative action among the ROS, RNS, and JNK signaling cascades. Interestingly, knockdown of Prx V expression causes the acceleration of microglia activation, including augmented ROS generation and JNK-dependent NO production. In summary, we demonstrate that Prx V plays a key role in the microglial activation process through modulation of the balance between ROS/NO generation and the corresponding JNK cascade activation.",
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AU - Sun, Hu Nan

AU - Kim, Sun Uk

AU - Huang, Song Mei

AU - Kim, Jin Man

AU - Park, Young Ho

AU - Kim, Seok Ho

AU - Yang, Hee Young

AU - Chung, Kyoung Jin

AU - Lee, Tae Hoon

AU - Choi, Hoon Sung

AU - Min, Ju Sik

AU - Park, Moon Ki

AU - Kim, Sang Keun

AU - Lee, Sang Rae

AU - Chang, Kyu Tae

AU - Lee, Sang Ho

AU - Yu, Dae Yeul

AU - Lee, Dong Seok

PY - 2010/7/1

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N2 - Reactive oxygen species (ROS) actively participate in microglia-mediated pathogenesis as pro-inflammatory molecules. However, little is known about the involvement of specific antioxidants in maintaining the microglial oxidative balance. We demonstrate that microglial peroxiredoxin (Prx) 5 expression is up-regulated by lipopolysaccharide (LPS) through activation of the ROS-sensitive signaling pathway and is involved in attenuation of both microglial activation and nitric oxide (NO) generation. Unlike in stimulation of oxidative insults with paraquat and hydrogen peroxide, Prx V expression is highly sensitive to LPS-stimulation in microglia. Reduction of ROS level by treatment with either NADPH oxidase inhibitor or antioxidant ablates LPS-mediated Prx V up-regulation in BV-2 microglial cells and is closely associated with the activation of the c-jun N-terminal kinase (JNK) signaling pathway. This suggests the involvement of ROS/JNK signaling in LPS-mediated Prx V induction. Furthermore, NO induces Prx V up-regulation that is ablated by the addition of inducible nitric oxide synthase inhibitor or deleted mutation of inducible nitric oxide synthase in LPS-stimulated microglia. Therefore, these results suggest that Prx V is induced by cooperative action among the ROS, RNS, and JNK signaling cascades. Interestingly, knockdown of Prx V expression causes the acceleration of microglia activation, including augmented ROS generation and JNK-dependent NO production. In summary, we demonstrate that Prx V plays a key role in the microglial activation process through modulation of the balance between ROS/NO generation and the corresponding JNK cascade activation.

AB - Reactive oxygen species (ROS) actively participate in microglia-mediated pathogenesis as pro-inflammatory molecules. However, little is known about the involvement of specific antioxidants in maintaining the microglial oxidative balance. We demonstrate that microglial peroxiredoxin (Prx) 5 expression is up-regulated by lipopolysaccharide (LPS) through activation of the ROS-sensitive signaling pathway and is involved in attenuation of both microglial activation and nitric oxide (NO) generation. Unlike in stimulation of oxidative insults with paraquat and hydrogen peroxide, Prx V expression is highly sensitive to LPS-stimulation in microglia. Reduction of ROS level by treatment with either NADPH oxidase inhibitor or antioxidant ablates LPS-mediated Prx V up-regulation in BV-2 microglial cells and is closely associated with the activation of the c-jun N-terminal kinase (JNK) signaling pathway. This suggests the involvement of ROS/JNK signaling in LPS-mediated Prx V induction. Furthermore, NO induces Prx V up-regulation that is ablated by the addition of inducible nitric oxide synthase inhibitor or deleted mutation of inducible nitric oxide synthase in LPS-stimulated microglia. Therefore, these results suggest that Prx V is induced by cooperative action among the ROS, RNS, and JNK signaling cascades. Interestingly, knockdown of Prx V expression causes the acceleration of microglia activation, including augmented ROS generation and JNK-dependent NO production. In summary, we demonstrate that Prx V plays a key role in the microglial activation process through modulation of the balance between ROS/NO generation and the corresponding JNK cascade activation.

KW - C-jun N-terminal kinase

KW - Lipopolysaccharide

KW - Microglia

KW - Nitric oxide

KW - Peroxiredoxin V

KW - Reactive oxygen species

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