title: Postanoxic damage of microglial cells is mediated by xanthine oxidase and cyclooxygenase.
abstract: Brain ischemia and the following reperfusion are important causes for brain damage and leading causes of brain morbidity and human mortality. Numerous observations exist describing the neuronal damage during ischemia/reperfusion, but the outcome of such conditions towards glial cells still remains to be elucidated. Microglia are resident macrophages in the brain. In this study, we investigated the anoxia/reoxygenation caused damage to a microglial cell line via determination of energy metabolism, free radical production by dichlorofluorescein fluorescence and nitric oxide production by Griess reagent. Consequences of oxidant production were determined by measurements of protein oxidation and lipid peroxidation, as well. By using site-specific antioxidants and inhibitors of various oxidant-producing pathways, we identified major sources of free radical production in the postanoxic microglial cells. The protective influences of these compounds were tested by measurements of cell viability and apoptosis. Although, numerous free radical generating systems may contribute to the postanoxic microglial cell damage, the xanthine oxidase- and the cyclooxygenase-mediated oxidant production seems to be of major importance.
authors: Research Institute of Environmental Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors: Rebecca
authors: R
authors: Widmer
authors: Martina
authors: M
authors: Engels
authors: Peter
authors: P
authors: Voss
authors: Tilman
authors: T
authors: Grune
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line / Q000187:drug effects / Q000201:enzymology; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005029:Ethylenediamines / Q000633:toxicity; D005452:Fluoresceins / Q000378:metabolism; D005609:Free Radicals; D007213:Indomethacin / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000494:pharmacology; D010117:Oxypurinol / Q000494:pharmacology; D050050:Protein Carbonylation / Q000187:drug effects; D015424:Reperfusion; D013424:Sulfanilamides / Q000633:toxicity; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005029:Ethylenediamines; D005452:Fluoresceins; D005609:Free Radicals; C095000:Griess reagent; D008565:Membrane Proteins; D016877:Oxidants; D013424:Sulfanilamides; C029569:diacetyldichlorofluorescein; C037631:2',7'-dichlorofluorescein; D000255:Adenosine Triphosphate; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D014969:Xanthine Oxidase; D010117:Oxypurinol; D010100:Oxygen; D007213:Indomethacin