title: Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome.
abstract: The present study identifies proteins modified by nitration in the plasma of patients with ongoing acute respiratory distress syndrome (ARDS). The proteins modified by nitration in ARDS were revealed by microsequencing and specific antibody detection to be ceruloplasmin, transferrin, alpha(1)-protease inhibitor, alpha(1)-antichymotrypsin, and beta-chain fibrinogen. Exposure to nitrating agents did not deter the chymotrypsin-inhibiting activity of alpha(1)-antichymotrypsin. However, the ferroxidase activity of ceruloplasmin and the elastase-inhibiting activity of alpha(1)-protease inhibitor were reduced to 50.3 +/- 1.6 and 60.3 +/- 5.3% of control after exposure to the nitrating agent. In contrast, the rate of interaction of fibrinogen with thrombin was increased to 193.4 +/- 8.5% of the control value after exposure of fibrinogen to nitration. Ferroxidase activity of ceruloplasmin and elastase-inhibiting activity of the alpha(1)-protease inhibitor in the ARDS patients were significantly reduced (by 81 and 44%, respectively), whereas alpha(1)-antichymotrypsin activity was not significantly altered. Posttranslational modifications of plasma proteins mediated by nitrating agents may offer a biochemical explanation for the reported diminished ferroxidase activity, elevated levels of elastase, and fibrin deposits detected in patients with ongoing ARDS.
authors.affiliation: Stokes Research Institute and Neonatology Division, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Gole
authors.forename: J M
authors.initials: JM
authors.lastname: Souza
authors.forename: I
authors.initials: I
authors.lastname: Choi
authors.forename: C
authors.initials: C
authors.lastname: Hertkorn
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: R F
authors.initials: RF
authors.lastname: Foust
authors.forename: B
authors.initials: B
authors.lastname: Finkel
authors.forename: P N
authors.initials: PN
authors.lastname: Lanken
authors.forename: H
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000208:Acute Disease; D000328:Adult; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western; D002245:Carbon Dioxide / Q000494:pharmacology; D002570:Ceruloplasmin / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009566:Nitrates / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011233:Precipitin Tests; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D009566:Nitrates; D000514:alpha 1-Antichymotrypsin; D013481:Superoxides; D002245:Carbon Dioxide; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D005340:Fibrinogen; D002570:Ceruloplasmin