title: Protein nitration in rat lungs during hyperoxia exposure: a possible role of myeloperoxidase.
abstract: Several studies have suggested that exposure to hyperoxia causes lung injury through increased generation of reactive oxygen and nitrogen species. The present study was aimed to investigate the effects of hyperoxia exposure on protein nitration in lungs. Rats were exposed to hyperoxia (>95%) for 48, 60, and 72 h. Histopathological analysis showed a dramatic change in the severity of lung injury in terms of edema and hemorrhage between 48- and 60-h exposure times. Western blot for nitrotyrosine showed that several proteins with molecular masses of 29-66 kDa were nitrated in hyperoxic lung tissues. Immunohistochemical analyses indicate nitrotyrosine staining of alveolar epithelial and interstitial regions. Furthermore, immunoprecipitation followed by Western blot revealed the nitration of surfactant protein A and t1alpha, proteins specific for alveolar epithelial type II and type I cells, respectively. The increased myeloperoxidase (MPO) activity and total nitrite levels in bronchoalveolar lavage and lung tissue homogenates were observed in hyperoxic lungs. Neutrophils and macrophages isolated from the hyperoxia-exposed rats, when cocultured with a rat lung epithelial L2 cell line, caused a significant protein nitration in L2 cells. Inclusion of nitrite further increased the protein nitration. These studies suggest that protein nitration during hyperoxia may be mediated in part by MPO generated from activated phagocytic cells, and such protein modifications may contribute to hyperoxia-mediated lung injury.
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
authors.forename: Telugu A
authors.initials: TA
authors.lastname: Narasaraju
authors.forename: Nili
authors.initials: N
authors.lastname: Jin
authors.forename: Chintagari R
authors.initials: CR
authors.lastname: Narendranath
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Chen
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D004487:Edema / Q000473:pathology; D006470:Hemorrhage / Q000473:pathology; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000473:pathology* / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D009566:Nitrates / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D051381:Rats; D020545:Respiratory Mucosa / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D010446:Peptide Fragments; D011506:Proteins; D037662:Pulmonary Surfactant-Associated Protein A; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase