title: The nitration of platelet cytosolic proteins during agonist-induced activation of platelets.
abstract: The nitration of protein tyrosine residues by peroxynitrous acid has been associated with pathological conditions. Here it is shown, using a sensitive competitive enzyme-linked immunosorbent assay and immunoblotting for nitrotyrosine, that spontaneous nitration of specific proteins occurs during a physiological process, the activation of platelets by collagen. One of the main proteins nitrated is vasodilator-stimulated phosphoprotein. Endogenous synthesis of nitric oxide and activity of cyclo-oxygenase were required for the nitration of tyrosine. The nitration was mimicked by addition of peroxynitrite to unstimulated platelets, although the level of nitrotyrosine formation was greater and its distribution among the proteins was less specific.
authors.affiliation: Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK. k.m.naseem@bradford.ac.uk
authors.forename: K M
authors.initials: KM
authors.lastname: Naseem
authors.forename: S Y
authors.initials: SY
authors.lastname: Low
authors.forename: M
authors.initials: M
authors.lastname: Sabetkar
authors.forename: N J
authors.initials: NJ
authors.lastname: Bradley
authors.forename: J
authors.initials: J
authors.lastname: Khan
authors.forename: M
authors.initials: M
authors.lastname: Jacobs
authors.forename: K R
authors.initials: KR
authors.lastname: Bruckdorfer
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008840:Microfilament Proteins; D008970:Molecular Weight; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009608:Nitrous Acid / Q000378:metabolism / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D030421:Peroxynitrous Acid; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009566:Nitrates; D016877:Oxidants; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D030421:Peroxynitrous Acid; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; D019001:Nitric Oxide Synthase; D013917:Thrombin; D001241:Aspirin; D009608:Nitrous Acid; D019331:NG-Nitroarginine Methyl Ester