title: Abnormalities in nitric oxide and its derivatives in lung cancer.
abstract: BACKGROUND
  A cellular prooxidant state promotes cells to neoplastic growth, in part because of modification of proteins and their functions. Reactive nitrogen species formed from nitric oxide (NO) or its metabolites, can lead to protein tyrosine nitration, which is elevated in lung cancer.
  
  
  OBJECTIVE
  To determine the alteration in these NO derivatives and the role they may play in contributing to lung carcinogenesis.
  
  
  METHODS
  We analyzed levels of NO, nitrite (NO2-), nitrate (NO3-), and the location of the protein nitration and identified the proteins that are modified.
  
  
  RESULTS
  Although exhaled NO and NO2- were increased, endothelial NO synthase or inducible NO synthase expression was similar in the tumor and tumor-free regions. However, immunohistochemistry showed that nitrotyrosine was increased in the tumor relative to non-tumor-bearing sections. We used proteomics to identify the modified proteins (two-dimensional polyacrylamide gel electrophoresis; mass spectrometry). Both the degree of nitration and the protein nitration profile were altered. We identified more than 25 nitrated proteins, including metabolic enzymes, structural proteins, and proteins involved in prevention of oxidative damage. Alterations of the biology of NO metabolites and nitration of proteins may contribute to the mutagenic processes and promote carcinogenesis.
  
  
  CONCLUSIONS
  This study provides evidence in favor of a role for reactive nitrogen and oxygen species in lung cancer.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Fares A
authors.initials: FA
authors.lastname: Masri
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.forename: Weiling
authors.initials: W
authors.lastname: Xu
authors.forename: Allison
authors.initials: A
authors.lastname: Janocha
authors.forename: Sudakshina
authors.initials: S
authors.lastname: Ghosh
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
authors.forename: Joseph
authors.initials: J
authors.lastname: Golish
authors.forename: Michael
authors.initials: M
authors.lastname: Kinter
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Stuehr
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: Kulwant S
authors.initials: KS
authors.lastname: Aulak
mesh_terms: D000368:Aged; D001944:Breath Tests; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins; D040901:Proteomics; D026361:Reactive Nitrogen Species / Q000032:analysis; D017382:Reactive Oxygen Species / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D011506:Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine