title: Effects of peroxynitrite-induced protein modifications on tyrosine phosphorylation and degradation.
abstract: The ability of protein tyrosine kinases to phosphorylate a synthetic peptide was inhibited 51% by peroxynitrite-mediated nitration of tyrosine. Exposure of endothelial cells to peroxynitrite decreased the intensity of tyrosine phosphorylated proteins and increased the intensity of nitrotyrosine-containing proteins. Peroxynitrite-modified BSA was degraded by human red blood cell lysates. However, human plasma in a concentration-, time-, and temperature-dependent manner, removed the protein nitrotyrosine epitope. These results suggest that tyrosine nitration interferes with phosphorylation and targets proteins for degradation. Specific enzymatic process(es) for removing nitrotyrosine may be present in vivo.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania, School of Medicine, Philadelphia, 19104-6068, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Gow
authors.forename: D
authors.initials: D
authors.lastname: Duran
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: H
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000818:Animals; D002417:Cattle; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D006801:Humans; D009566:Nitrates / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010949:Plasma; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D005755:Gastrins; D009566:Nitrates; D010455:Peptides; D011506:Proteins; C039642:peroxynitric acid; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases