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This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/L37    most recent 90401.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Iyer, S. S. Articles by Rojas, M. Search for Related Content PubMed PubMed Citation Articles by Iyer, S. S. Articles by Rojas, M.

Oxidation of extracellular cysteine/cystine redox state in bleomycin-induced lung fibrosis

¹Nutrition and Health Sciences Program, Emory University; and ²Division of Pulmonary, Allergy, and Critical Care Medicine, ³Center for Translational Research in the Lung, ⁴McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, ⁵Clinical Biomarkers Laboratory, and ⁶Atlanta Veterans Affairs Medical Center, Department of Medicine, Emory University, Atlanta, Georgia

Submitted 25 July 2008 ; accepted in final form 13 October 2008

Several lines of evidence indicate that depletion of glutathione (GSH), a critical thiol antioxidant, is associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, GSH synthesis depends on the amino acid cysteine (Cys), and relatively little is known about the regulation of Cys in fibrosis. Cys and its disulfide, cystine (CySS), constitute the most abundant low-molecular weight thiol/disulfide redox couple in the plasma, and the Cys/CySS redox state (E_h Cys/CySS) is oxidized in association with age and smoking, known risk factors for IPF. Furthermore, oxidized E_h Cys/CySS in the culture media of lung fibroblasts stimulates proliferation and expression of transitional matrix components. The present study was undertaken to determine whether bleomycin-induced lung fibrosis is associated with a decrease in Cys and/or an oxidation of the Cys/CySS redox state and to determine whether these changes were associated with changes in E_h GSH/glutathione disulfide (GSSG). We observed distinct effects on plasma GSH and Cys redox systems during the progression of bleomycin-induced lung injury. Plasma E_h GSH/GSSG was selectively oxidized during the proinflammatory phase, whereas oxidation of E_h Cys/CySS occurred at the fibrotic phase. In the epithelial lining fluid, oxidation of E_h Cys/CySS was due to decreased food intake. Thus the data show that decreased precursor availability and enhanced oxidation of Cys each contribute to the oxidation of extracellular Cys/CySS redox state in bleomycin-induced lung fibrosis.

idiopathic pulmonary fibrosis; oxidative stress; glutathione; diet

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