title: NO2-induced acute and chronic lung injury cause imbalance of glutathione metabolism in type II pneumocytes.
abstract: BACKGROUND
  During inspiration the lung is exposed to numerous oxidants and therefore has developed a system of antioxidant defense. This organ, besides the liver, is the major source of glutathione (GSH) metabolism, from which type II pneumocytes are metabolically the most active cells.
  
  
  METHODS
  To analyze oxidative stress, rats were exposed to air (control) or to 10 ppm nitrogen dioxide (NO2) for 3 and 20 days to induce acute and chronic lung injury. As measure of oxidative stress, GSH/GSSG ratios in blood, bronchoalveolar lavage (BAL) and type II pneumocytes were determined. Lipid peroxidation (LPO) was also measured in type II cells. To investigate the basis of these observations, GSH metabolism in type II pneumocytes was studied, analyzing mRNA expression of gamma-glutamyl-cysteine synthetase (gamma-GCS), glutathione synthetase (GS), gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidases (GPXs) and glutathione reductase (GR). Furthermore, enzyme activities of GPX and GR were determined.
  
  
  RESULTS
  In acute and chronic lung injury the GSH/GSSG ratio was reduced in blood and BAL, but there was no change in type II pneumocytes. LPO in type II cells was only reduced in acute lung injury. In both kinds of lung injury mRNA expression of gamma-GCS, GS and GPX3 decreased, while expression of gamma-GT and GR increased. GPX4 mRNA expression decreased in acute lung injury and increased in the chronic state. Enzyme activity of GPX and GR was generally increased in lung injury.
  
  
  CONCLUSIONS
  In NO2 induced acute and chronic lung injury, GSH metabolism is imbalanced.
authors.affiliation: Division of Pneumology, Department of Internal Medicine, Philipps University of Marburg, Marburg, Germany. hochsche@staff.uni-marburg.de
authors.forename: Renate
authors.initials: R
authors.lastname: Hochscheid
authors.forename: Ute
authors.initials: U
authors.lastname: Schuchmann
authors.forename: Elke
authors.initials: E
authors.lastname: Kotte
authors.forename: Stephan
authors.initials: S
authors.lastname: Kranz
authors.forename: Sven
authors.initials: S
authors.lastname: Heinrichs
authors.forename: Bernd
authors.initials: B
authors.lastname: Müller
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004798:Enzymes / Q000235:genetics; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D055370:Lung Injury; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D004798:Enzymes; D012333:RNA, Messenger; D005979:Glutathione Peroxidase; D005978:Glutathione; D009585:Nitrogen Dioxide