title: S-nitrosoglutathione reductase in human lung cancer.
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.
authors.affiliation: Department of Pediatric Respiratory Medicine, University of Virginia, Charlottesville, 22908-0386, USA.
authors.forename: Nadzeya V
authors.initials: NV
authors.lastname: Marozkina
authors.forename: Christina
authors.initials: C
authors.lastname: Wei
authors.forename: Sean
authors.initials: S
authors.lastname: Yemen
authors.forename: Horst
authors.initials: H
authors.lastname: Wallrabe
authors.forename: Alykhan S
authors.initials: AS
authors.lastname: Nagji
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Morozkina
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D015538:Nitrosation; D012307:Risk Factors; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism
chemical_list: D009566:Nitrates; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent; D018631:ras Proteins