title: Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: antioxidative systems, peroxide elimination, radical generation, lipid peroxidation.
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.
authors.affiliation: Institute of Toxicology and Pharmacology for Natural Scientists, Christian-Albrechts-University, Brunswiker Str. 10, 24105 Kiel, Germany. claudia.roehl@gmx.net
authors.forename: Claudia
authors.initials: C
authors.lastname: Röhl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Armbrust
authors.forename: Eva
authors.initials: E
authors.lastname: Herbst
authors.forename: Anne
authors.initials: A
authors.lastname: Jess
authors.forename: Michael
authors.initials: M
authors.lastname: Gülden
authors.forename: Edmund
authors.initials: E
authors.lastname: Maser
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: Christine
authors.initials: C
authors.lastname: Bösch-Saadatmandi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000502:physiology*; D001921:Brain / Q000166:cytology; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010545:Peroxides / Q000378:metabolism* / Q000494:pharmacology; D011280:Pregnanolone / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: C445420:16,17-cyclohexane-5H-pregnan-3,20-dione; D039481:CD11b Antigen; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D010545:Peroxides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D011280:Pregnanolone; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione