Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome

• Published in: American journal of physiology. Lung cellular and molecular physiology 2000-05, Vol.278 (5), p.961-L967
• Main Authors: Gole, Madhura D, Souza, Jose M, Choi, Irene, Hertkorn, Caryn, Malcolm, Stuart, Foust, Raymond F., III, Finkel, Barbara, Lanken, Paul N, Ischiropoulos, Harry
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; alpha 1-Antichymotrypsin - metabolism; Blood Proteins - analysis; Blood Proteins - metabolism; Blotting, Western; Carbon Dioxide - pharmacology; Ceruloplasmin - metabolism; Enzyme Activation - physiology; Fibrinogen - metabolism; Humans; In Vitro Techniques; Nitrates - isolation & purification; Nitrates - metabolism; Nitrates - pharmacology; Nitric Oxide - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Precipitin Tests; Respiratory Distress Syndrome, Adult - metabolism; Superoxides - pharmacology; Tyrosine - analogs & derivatives; Tyrosine - analysis; Tyrosine - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2000.278.5.L961

1  Stokes Research Institute and Neonatology Division, Department of Pediatrics, Children's Hospital of Philadelphia, and 3  Department of Biochemistry and Biophysics and 2  Pulmonary and Critical Care Division, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 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, 1 -protease inhibitor, 1 -antichymotrypsin, and -chain fibrinogen. Exposure to nitrating agents did not deter the chymotrypsin-inhibiting activity of 1 -antichymotrypsin. However, the ferroxidase activity of ceruloplasmin and the elastase-inhibiting activity of 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 1 -protease inhibitor in the ARDS patients were significantly reduced (by 81 and 44%, respectively), whereas 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. nitric oxide; superoxide; ceruloplasmin; 1 -protease inhibitor; fibrinogen; oxidative stress