S-Nitrosoglutathione reductase in human lung cancer.
Am J Respir Cell Mol Biol. 2011 Aug 4;
Authors: Marozkina NV, Yemen S, Wei C, Wallrabe H, Nagji AS, Liu L, Morozkina T, Jones DR, Gaston B
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 could also protect the lung against potentially carcinogenic reactions of 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, GSNO reductase activity and expression are decreased. Further, distribution of the enzyme – including its colocalization with wild-type Ras – is abnormal. We conclude that decreased GSNO reductase activity 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.
PMID: 21816964 [PubMed – as supplied by publisher]
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