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Pretreatment with interferon-γ protects microglia from oxidative stress via up-regulation of Mn-SOD

Title
Pretreatment with interferon-γ protects microglia from oxidative stress via up-regulation of Mn-SOD
Authors
Chen X.Choi I.Y.Chang T.-S.Noh Y.H.Shin C.Y.Wu C.-F.Ko K.H.Kim W.-K.
Ewha Authors
창동신
SCOPUS Author ID
창동신scopus
Issue Date
2009
Journal Title
Free Radical Biology and Medicine
ISSN
0891-5849JCR Link
Citation
vol. 46, no. 8, pp. 1204 - 1210
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Microglial cells, resident macrophage-like immune cells in the brain, are exposed to intense oxidative stress under various pathophysiological conditions. For self-defense against oxidative injuries, microglial cells must be equipped with antioxidative mechanisms. In this study, we investigated the regulation of antioxidant enzyme systems in microglial cells by interferon-γ (IFN-γ) and found that pretreatment with IFN-γ for 20 h protected microglial cells from the toxicity of various reactive species such as hydrogen peroxide (H2O2), superoxide anion, 4-hydroxy-2(E)-nonenal, and peroxynitrite. The cytoprotective effect of IFN-γ pretreatment was abolished by the protein synthesis inhibitor cycloheximide. In addition, treatment of microglial cells with both IFN-γ and H2O2 together did not protect them from the H2O2-evoked toxicity. These results imply that protein synthesis is required for the protection by IFN-γ. Among various antioxidant enzymes such as manganese or copper/zinc superoxide dismutase (Mn-SOD or Cu/Zn-SOD), catalase, and glutathione peroxidase (GPx), only Mn-SOD was up-regulated in IFN-γ-pretreated microglial cells. Transfection with siRNA of Mn-SOD abolished both up-regulation of Mn-SOD expression and protection from H2O2 toxicity by IFN-γ pretreatment. Furthermore, whereas the activities of Mn-SOD and catalase were up-regulated by IFN-γ pretreatment, those of Cu/Zn-SOD and GPx were not. These results indicate that IFN-γ pretreatment protects microglial cells from oxidative stress via selective up-regulation of the level of Mn-SOD and activity of Mn-SOD and catalase. © 2009 Elsevier Inc. All rights reserved.
DOI
10.1016/j.freeradbiomed.2009.01.027
Appears in Collections:
약학대학 > 약학과 > Journal papers
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