Peroxiredoxin I is an indicator of microglia activation and protects against hydrogen peroxide-mediated microglial death.
Imbalance between oxidative stress and antioxidative defence system is generally known as one of mechanisms causing an oxidative stress-medieated neuropathogenesis. Peroxiredoxins (Prxs), a family of antioxidative enzymes neutralizing cellular hydroperoxides, was characterized recently, but their distributions and roles have not been resolved clearly or controversial in the central nervous system, Therefore, the present study was carried out to determine the specific cell types that express Prx I in the mouse brain and primary neural cells, and to examine its antioxidative role in the preferential cell types. Immunohistochemical reactivity for Prx I was detected dominantly in oligodendrocytes and rarely in microglia, whereas strong and specific immunoreactivity for Prx I was observed exclusively in microglia of primary neural cell culture. Further evidences for Prx I specificity were its relatively high expression in BV-2 microglial cells and its upregulated expression in microglia after lipopolysaccharide (LPS) stimulation. These results imply that Prx I can be used as an indicator of microglial activation. Inhibition of p38 MAPK ablated LPS-mediated Prx I upregulation and sensitized the microglia to H(2)O(2)-mediated cell death. These findings indicate that Prx I function as a scavenger for H(2)O(2) generated during microglial activation. The results of this study will help in unraveling the neuropathologic roles of the six Prx isoforms in neural function.
Kim
Sun-Uk
SU
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Hwang
Chang Nam
CN
Sun
Hu-Nan
HN
Jin
Mei-Hua
MH
Han
Ying-Hao
YH
Lee
Hwang
H
Kim
Jin-Man
JM
Kim
Sang-Keun
SK
Yu
Dae-Yeul
DY
Lee
Dong-Seok
DS
Lee
Sang Ho
SH
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000502:physiology*; D054464:Peroxiredoxins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D008070:Lipopolysaccharides; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins