TY - JOUR
T1 - S-Nitrosoglutathione reductase in human lung cancer
AU - Marozkina, Nadzeya V.
AU - Wei, Christina
AU - Yemen, Sean
AU - Wallrabe, Horst
AU - Nagji, Alykhan S.
AU - Liu, Lei
AU - Morozkina, Tatiana
AU - Jones, David R.
AU - Gaston, Benjamin
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - Lung cancer
KW - Ras
KW - S-nitrosoglutathione reductase
UR - http://www.scopus.com/inward/record.url?scp=84855400707&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2011-0147OC
DO - 10.1165/rcmb.2011-0147OC
M3 - Article
C2 - 21816964
AN - SCOPUS:84855400707
SN - 1044-1549
VL - 46
SP - 63
EP - 70
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 1
ER -