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

51 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

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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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