S-Nitrosoglutathione reductase in human lung cancer

Nadzeya V. Marozkina, Christina Wei, Sean Yemen, Horst Wallrabe, Alykhan S. Nagji, Lei Liu, Tatiana Morozkina, David R. Jones, Benjamin Gaston

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27 Scopus citations

Abstract

S-Nitrosoglutathione (GSNO) reductase regulates cell signaling pathways relevant to asthma and protects cells from nitrosative stress. Recent evidence suggests that this enzyme may prevent human hepatocellular carcinoma arising in the setting of chronic hepatitis. We hypothesized that GSNO reductase may also protect the lung against potentially carcinogenic reactions associated with nitrosative stress. We report that wild-type Ras is S-nitrosylated and activated by nitrosative stress and that it is denitrosylated by GSNO reductase. In human lung cancer, the activity and expression of GSNO reductase are decreased. Further, the distribution of the enzyme(including its colocalization with wild-type Ras) is abnormal. We conclude that decreased activity of GSNO reductase could leave the human lung vulnerable to the oncogenic effects of nitrosative stress, as is the case in the liver. This potential should be considered when developing therapies that inhibit pulmonary GSNO reductase to treat asthma and other conditions.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Lung cancer
  • Ras
  • S-nitrosoglutathione reductase

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    Marozkina, N. V., Wei, C., Yemen, S., Wallrabe, H., Nagji, A. S., Liu, L., Morozkina, T., Jones, D. R., & Gaston, B. (2012). S-Nitrosoglutathione reductase in human lung cancer. American Journal of Respiratory Cell and Molecular Biology, 46(1), 63-70. https://doi.org/10.1165/rcmb.2011-0147OC