Abstract | RATIONALE: 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. MEASUREMENTS AND MAIN 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:
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Authors | Fares A Masri, Suzy A A Comhair, Thomas Koeck, Weiling Xu, Allison Janocha, Sudakshina Ghosh, Raed A Dweik, Joseph Golish, Michael Kinter, Dennis J Stuehr, Serpil C Erzurum, Kulwant S Aulak |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 172
Issue 5
Pg. 597-605
(Sep 01 2005)
ISSN: 1073-449X [Print] United States |
PMID | 15947282
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Proteins
- Reactive Nitrogen Species
- Reactive Oxygen Species
- Nitric Oxide
- 3-nitrotyrosine
- Tyrosine
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Topics |
- Aged
- Breath Tests
- Female
- Humans
- Lung Neoplasms
(metabolism, physiopathology)
- Male
- Middle Aged
- Nitric Oxide
(analysis, metabolism)
- Oxidative Stress
(physiology)
- Proteins
- Proteomics
- Reactive Nitrogen Species
(analysis)
- Reactive Oxygen Species
(analysis)
- Tyrosine
(analogs & derivatives, analysis)
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