Does the oxidative stress in chronic obstructive pulmonary disease cause thioredoxin/peroxiredoxin oxidation?

Department of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
Antioxidants and Redox Signaling (Impact Factor: 7.67). 05/2008; 10(4):813-9. DOI: 10.1089/ars.2007.1952
Source: PubMed

ABSTRACT The thioredoxin/peroxiredoxin system comprises a redox-regulated antioxidant family in human lung; its significance, regulation, or oxidation has not been evaluated in smoking-related lung diseases. Here, we present the expression of the thioredoxin/peroxiredoxin system in lung biopsies from normal lung (n = 14), smokers (n = 21), and patients with chronic obstructive pulmonary disease (COPD, n = 38), and assess the possible inactivation/oxidation of this system by nonreducing Western blotting, two-dimensional gel electrophoresis, and mass spectrometry. Our study shows that the thiol status of the Trx/Prx-system can be modulated in vitro, but it appears to have high resistance against the oxidative stress in COPD.

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    ABSTRACT: Background: Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are disorders of the lung parenchyma. They share the common denominators of a progressive nature and poor prognosis. The goal was to use non-biased proteomics to discover new markers for these diseases. Methods: Proteomics of fibrotic vs. control lung tissue suggested decreased levels of several spots in the lung specimens of IPF patients, which were identified as Hemoglobin (Hb) alpha and beta monomers and Hb alpha complexes. The Hb alpha and beta monomers and complexes were investigated in more detail in normal lung and lung specimens of patients with IPF and COPD by immunohistochemistry, morphometry and mass spectrometry (MS). Results: Both Hb monomers, in normal lung, were expressed especially in the alveolar epithelium. Levels of Hb alpha and beta monomers and complexes were reduced/lost in IPF but not in the COPD lungs when compared to control lung. MS-analyses revealed Hb alpha modification at cysteine105 (Cys alpha 105), preventing formation of the Hb alpha complexes in the IPF lungs. Hb alpha and Hb beta were expressed as complexes and monomers in the lung tissues, but were secreted into the bronchoalveolar lavage fluid and/or induced sputum supernatants as complexes corresponding to the molecular weight of the Hb tetramer. Conclusions: The abundant expression of the oxygen carrier molecule Hb in the normal lung epithelium and its decline in IPF lung are new findings. The loss of Hb complex formation in IPF warrants further studies and may be considered as a disease-specific modification.
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    ABSTRACT: Because oxidative stress is such a common factor of lung diseases, we cannot help asking why so many diseases are caused by the same oxidative stress. It is likely to be a consequence of diversity in sources and location of oxidative stress, and concomitant factors. The aim of this forum is to characterize the disease-specific involvement of oxidative stress and to make use of it for therapeutics. It is also of note that oxidative-stress biomarkers are useful tools for disease management. Exhaled nitric oxide has been established as a marker of bronchial asthma in clinical practice. By using recent noninvasive techniques, such as exhaled breath condensate, other markers of lipid peroxidation or antioxidants are now under evaluation. Antioxidant therapy, as represented by N-acetylcysteine, has widely been tested as a treatment for lung disorders, but it has had limited success in clinical practice. The clinical outcome might be improved by combination therapy or better patient selection. Novel antioxidant drugs are also under investigation. Molecular targeted therapy against redox-sensitive signaling pathways could be an alternative therapeutic approach. Moreover, disease-specific pathways have been identified whose regulation could be more efficient and less toxic than regulating universal pathways.
    Antioxidants and Redox Signaling 05/2008; 10(4):701-4. DOI:10.1089/ars.2007.1961 · 7.67 Impact Factor
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    ABSTRACT: Oxidant burden has been suggested to be a contributor to the pathogenesis of idiopathic pulmonary fibrosis (IPF). The study focused on peroxiredoxin (Prx) II, an antioxidant that has been associated with platelet-derived growth factor (PDGF) signaling and consequent cell proliferation. Localization and expression of Prx II, PDGF receptors (PDGFRalpha, PDGFRbeta), Ki67, and nitrotyrosine were assessed in control (n=10) and IPF/usual interstitial pneumonia (UIP) (n=10) lung biopsies by immunohistochemistry and morphometry. Prx II oxidation was determined by standard and non-reducing Western blots, two-dimensional gel electrophoresis, and mass spectrometry. Prx II localized in the IPF/UIP epithelium and alveolar macrophages. Prx II-positive area in the fibroblastic foci (FF) was smaller than in other parenchymal areas (p=0.03) or in the hyperplastic epithelium (p=0.01). There was no major Prx II oxidation in IPF/UIP compared with the normal lung. The FF showed only minor immunoreactivity to the PDGFRs; Ki67, a marker of cell proliferation; and nitrotyrosine, a marker of oxidative/nitrosative stress. The results suggest that Prx II oxidation does not relate to the pathogenesis of IPF/UIP and that Prx II, PDGFRs, and proliferating cells colocalize in the IPF/UIP lung. Unexpectedly, FF represented areas of low cell proliferation.
    Journal of Histochemistry and Cytochemistry 08/2008; 56(10):951-9. DOI:10.1369/jhc.2008.951806 · 2.40 Impact Factor
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