Document Detail


Oxidation of extracellular cysteine/cystine redox state in bleomycin-induced lung fibrosis.
MedLine Citation:
PMID:  18931052     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-17
Journal Detail:
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:
Created Date:  2008-12-30     Completed Date:  2009-02-23     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L37-45     Citation Subset:  IM    
Affiliation:
Nutrition and Health Sciences Program, Emory University, Atlanta, GA 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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

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