Abnormalities in nitric oxide and its derivatives in lung cancer.
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.
Masri
Fares A
FA
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Comhair
Suzy A A
SA
Koeck
Thomas
T
Xu
Weiling
W
Janocha
Allison
A
Ghosh
Sudakshina
S
Dweik
Raed A
RA
Golish
Joseph
J
Kinter
Michael
M
Stuehr
Dennis J
DJ
Erzurum
Serpil C
SC
Aulak
Kulwant S
KS
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
D011506:Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine