Degradation of oxidized extracellular proteins by microglia.
In living organisms a permanent oxidation of protein oxidation occurs. The degradation of intracellular oxidized proteins is intensively studied, but knowledge about the fate of oxidatively modified extracellular proteins is still limited. We studied the fate of exogenously added oxidized proteins in microglial cells. Both primary microglial cells and RAW cells are able to remove added oxidized laminin and myelin basic protein from the extracellular environment. Moderately oxidized proteins are degraded most efficiently, whereas strongly oxidized proteins are taken up by the microglial cells without an efficient degradation. Activation of microglial cells enhances the selective recognition and degradation of moderately oxidized protein substrates by proteases. Inhibitor studies also revealed an involvement of the lysosomal and the proteasomal system in the degradation of extracellular proteins. These studies let us conclude that microglial cells are able to remove oxidized proteins from the extracellular environment in the brain.
Stolzing
Alexandra
A
Neuroscience Research Center, Medical Faculty, Charité, Humboldt University Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany.
Wengner
Antje
A
Grune
Tilman
T
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004791:Enzyme Inhibitors; D005110:Extracellular Space / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D004676:Myelin Basic Protein / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D007797:Laminin; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate