title: Endogenously produced peroxynitrite induces the oxidation of mitochondrial and nuclear proteins in immunostimulated macrophages.
abstract: 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.
authors.affiliation: Children's Hospital Medical Center, Division of Critical Care, Cincinnati, OH 45229, USA.
authors.forename: C
authors.initials: C
authors.lastname: Szabó
authors.forename: M
authors.initials: M
authors.lastname: O'Connor
authors.forename: A L
authors.initials: AL
authors.lastname: Salzman
mesh_terms: 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
chemical_list: 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