NO2-induced acute and chronic lung injury cause imbalance of glutathione metabolism in type II pneumocytes.

Authors: Hochscheid, R  Schuchmann, U  Kotte, E  Kranz, S  Heinrichs, S  Muller, B 
Citation: Hochscheid R, etal., Med Sci Monit. 2005 Aug;11(8):BR273-9. Epub 2005 Jul 25.
Pubmed: (View Article at PubMed) PMID:16049373

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. MATERIAL/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.


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CRRD ID: 2312626
Created: 2009-08-26
Species: All species
Last Modified: 2009-08-26
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.