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Abnormalities in nitric oxide and its derivatives in lung cancer.


ABSTRACT:

Rationale

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.

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

This study provides evidence in favor of a role for reactive nitrogen and oxygen species in lung cancer.

SUBMITTER: Masri FA 

PROVIDER: S-EPMC2718532 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

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Publications

Abnormalities in nitric oxide and its derivatives in lung cancer.

Masri Fares A FA   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  

American journal of respiratory and critical care medicine 20050609 5


<h4>Rationale</h4>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.<h4>Objective</h4>To determine the alteration in these NO derivatives and the role they may play in contributing to lung carcinogenesis.<h4>Methods</h4>We analyzed levels of NO, nitrite (NO2-), nitrate (  ...[more]

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