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

Xia Chen, In Young Choi, Tong Shin Chang, You Hyun Noh, Chan Young Shin, Chun Fu Wu, Kwang Ho Ko, Won Ki Kim

Research output: Contribution to journalArticle

15 Citations (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.

Original languageEnglish
Pages (from-to)1204-1210
Number of pages7
JournalFree Radical Biology and Medicine
Volume46
Issue number8
DOIs
Publication statusPublished - 2009 Apr 15

Keywords

  • Free radicals
  • Hydrogen peroxide
  • Interferon-γ
  • Microglia
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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