| Oxidation of extracellular cysteine/cystine redox state in bleomycin-induced lung fibrosis. | |
MedLine Citation:
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PMID: 18931052 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
Authors:
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Smita S Iyer; Allan M Ramirez; Jeffrey D Ritzenthaler; Edilson Torres-Gonzalez; Susanne Roser-Page; Ana L Mora; Kenneth L Brigham; Dean P Jones; Jesse Roman; Mauricio Rojas |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-17 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 296 ISSN: 1040-0605 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-30 Completed Date: 2009-02-23 Revised Date: 2013-06-05 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L37-45 Citation Subset: IM |
Affiliation:
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Nutrition and Health Sciences Program, Emory University, Atlanta, GA 30322, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / toxicity Bleomycin / toxicity Bronchoalveolar Lavage Fluid Cysteine / metabolism* Cystine / metabolism* Disease Models, Animal Eating Extracellular Space / metabolism Female Glutathione / metabolism Glutathione Disulfide / metabolism Interleukin-6 / metabolism Lung / metabolism, pathology Mice Mice, Inbred C57BL Oxidation-Reduction Oxidative Stress / physiology* Pulmonary Fibrosis / chemically induced*, metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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5K01-HL-084683-02/HL/NHLBI NIH HHS; ES-009047/ES/NIEHS NIH HHS; ES-011195/ES/NIEHS NIH HHS; K08-HL-077533-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Interleukin-6; 11056-06-7/Bleomycin; 27025-41-8/Glutathione Disulfide; 52-90-4/Cysteine; 56-89-3/Cystine; 70-18-8/Glutathione |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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