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

Cited 71 time in scopus
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Title
Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation
Author(s)
Sun-Uk KimYoung-Ho Park; J S Min; H N Sun; Y H Han; J M Hua; T H Lee; Sang Rae Lee; Kyu Tae Chang; S W Kang; J M Kim; Dae Yeul Yu; S H Lee; D S Lee
Bibliographic Citation
Journal of Neuroimmunology, vol. 259, no. 1, pp. 26-36
Publication Year
2013
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.
Keyword
AntioxidantsInflammationLipopolysaccharidesPeroxiredoxinReactive oxygen speciesMicroglia activation
ISSN
0165-5728
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.jneuroim.2013.03.006
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > National Primate Research Center > 1. Journal Articles
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