Endogenously produced peroxynitrite induces the oxidation of mitochondrial and nuclear proteins in immunostimulated macrophages.
Here we investigated the role of endogenous nitric oxide (NO) and peroxynitrite in the process of protein oxidation (as measured by the detection of 2,4-dinitrophenylhydrazine-reactive carbonyls) in immunostimulated macrophages. Immunostimulation of the macrophages by bacterial lipopolysaccharide and gamma-interferon (LPS/IFNgamma) resulted in a marked increase in the oxidation of a large number of mitochondrial and nuclear proteins. The inhibitor of NO synthase, N(G)-methyl-L-arginine (3 mM), and the cell-permeable superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (300 microM) both reduced the extent of protein oxidation in response to LPS/IFNgamma. These results support the view that endogenously produced peroxynitrite induces protein oxidation in the mitochondria and nucleus of immunostimulated macrophages.
Szabó
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Children's Hospital Medical Center, Division of Critical Care, Cincinnati, OH 45229, USA.
O'Connor
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Salzman
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D009566:Nitrates; D009687:Nuclear Proteins; C039642:peroxynitric acid; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester