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Mechanisms Involved in the Modulation of Astroglial Resistance to Oxidative Stress Induced by Activated Microglia: Antioxidative Systems, Peroxide Elimination, Radical Generation, Lipid Peroxidation

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Abstract

Microglia and astrocytes are the cellular key players in many neurological disorders associated with oxidative stress and neuroinflammation. Previously, we have shown that microglia activated by lipopolysaccharides (LPS) induce the expression of antioxidative enzymes in astrocytes and render them more resistant to hydrogen peroxide (H2O2). In this study, we examined the mechanisms involved with respect to the cellular action of different peroxides, the ability to detoxify peroxides, and the status of further antioxidative systems. Astrocytes were treated for 3 days with medium conditioned by purified quiescent (microglia-conditioned medium, MCM[−]) or LPS-activated (MCM[+]) microglia. MCM[+] reduced the cytotoxicity of the organic cumene hydroperoxide in addition to that of H2O2. Increased peroxide resistance was not accompanied by an improved ability of astrocytes to remove H2O2 or an increased expression/activity of peroxide eliminating antioxidative enzymes. Neither peroxide-induced radical generation nor lipid peroxidation were selectively affected in MCM[+] treated astrocytes. The glutathione content of peroxide resistant astrocytes, however, was increased and superoxide dismutase and heme oxygenase were found to be upregulated. These changes are likely to contribute to the higher peroxide resistance of MCM[+] treated astrocytes by improving their ability to detoxify reactive oxygen radicals and oxidation products. For C6 astroglioma cells a protective effect of microglia-derived factors could not be observed, underlining the difference of primary cells and cell lines concerning their mechanisms of oxidative stress resistance. Our results indicate the importance of microglial–astroglial cell interactions during neuroinflammatory processes.

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Acknowledgements

The authors thank Monika Grell and Rosemarie Sprang for their excellent technical assistance during these studies, and Jobst Sievers and Ralph Lucius for providing laboratory facilities.

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  1. Institute of Toxicology and Pharmacology for Natural Scientists, Christian-Albrechts-University, Brunswiker Str. 10, 24105, Kiel, Germany

    Claudia Röhl, Elisabeth Armbrust, Anne Jess, Michael Gülden & Edmund Maser

  2. Department of Anatomy, Christian-Albrechts-University, Olshausenstr. 40, 24098, Kiel, Germany

    Claudia Röhl, Elisabeth Armbrust & Eva Herbst

  3. Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Hermann-Rodewald Str. 6, 24098, Kiel, Germany

    Gerald Rimbach & Christine Bösch-Saadatmandi

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  1. Claudia Röhl
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Correspondence to Claudia Röhl.

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Röhl, C., Armbrust, E., Herbst, E. et al. Mechanisms Involved in the Modulation of Astroglial Resistance to Oxidative Stress Induced by Activated Microglia: Antioxidative Systems, Peroxide Elimination, Radical Generation, Lipid Peroxidation. Neurotox Res 17, 317–331 (2010). https://doi.org/10.1007/s12640-009-9108-z

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