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Chen X, Choi IY, Chang TS, Noh YH, Shin CY, Wu CF, Ko KH, Kim WK: Pretreatment with interferon-gamma protects microglia from oxidative stress via up-regulation of Mn-SOD. Free Radic Biol Med. 2009 Apr 15;46(8):1204-10. Epub 2009 Feb 9.
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-gamma (IFN-gamma) and found that pretreatment with IFN-gamma for 20 h protected microglial cells from the toxicity of various reactive species such as hydrogen peroxide (H (2) O (2)), superoxide anion, 4-hydroxy-2 (E)-nonenal, and peroxynitrite. The cytoprotective effect of IFN-gamma pretreatment was abolished by the protein synthesis inhibitor cycloheximide. In addition, treatment of microglial cells with both IFN-gamma and H (2) O (2) together did not protect them from the H (2) O (2)-evoked toxicity. These results imply that protein synthesis is required for the protection by IFN-gamma. 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-gamma-pretreated microglial cells. Transfection with siRNA of Mn-SOD abolished both up-regulation of Mn-SOD expression and protection from H (2) O (2) toxicity by IFN-gamma pretreatment. Furthermore, whereas the activities of Mn-SOD and catalase were up-regulated by IFN-gamma pretreatment, those of Cu/Zn-SOD and GPx were not. These results indicate that IFN-gamma pretreatment protects microglial cells from oxidative stress via selective up-regulation of the level of Mn-SOD and activity of Mn-SOD and catalase. |
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