| First Author | Kim SU | Year | 2013 |
| Journal | J Neuroimmunol | Volume | 259 |
| Issue | 1-2 | Pages | 26-36 |
| PubMed ID | 23602274 | Mgi Jnum | J:294797 |
| Mgi Id | MGI:6458616 | Doi | 10.1016/j.jneuroim.2013.03.006 |
| Citation | Kim SU, et al. (2013) Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-kappaB-mediated iNOS induction and microglial activation. J Neuroimmunol 259(1-2):26-36 |
| abstractText | 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-kappaB-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-kappaB 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. |
