Peroxiredoxin I is an indicator of microglia activation and protects against hydrogen peroxide-mediated microglial death

Abstract

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 H2O2-mediated cell death. These findings indicate that Prx I function as a scavenger for H2O2 generated during microglial activation. The results of this study will help in unraveling the neuropathologic roles of the six Prx isoforms in neural function. © 2008 Pharmaceutical Society of Japan.