Does the Oxidative Stress in Chronic Obstructive Pulmonary Disease Cause Thioredoxin/Peroxiredoxin Oxidation?
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.
- SourceAvailable from: Brian J. Akerley
[Show abstract] [Hide abstract]
- "Also implicated in bacterial survival in the lung was the pgdX gene encoding a hybrid peroxiredoxin/thioredoxin glutathione-dependent peroxidase (Pauwels et al., 2003). Peroxiredoxin and thioredoxin are ubiquitous anti-oxidant enzymes present in all known organisms and have been implicated in defense against reactive oxygen species in bacteria (Zeller and Klug, 2006) and in mammalian airways (Rahman et al., 2006; Lehtonen et al., 2008). "
ABSTRACT: Haemophilus influenzae is a Gram-negative bacterium that has no identified natural niche outside of the human host. It primarily colonizes the nasopharyngeal mucosa in an asymptomatic mode, but has the ability to disseminate to other anatomical sites to cause otitis media, upper, and lower respiratory tract infections, septicemia, and meningitis. To persist in diverse environments the bacterium must exploit and utilize the nutrients and other resources available in these sites for optimal growth/survival. Recent evidence suggests that regulatory factors that direct such adaptations also control virulence determinants required to resist and evade immune clearance mechanisms. In this review, we describe the recent application of whole-genome approaches that together provide insight into distinct survival mechanisms of H. influenzae in the context of different sites of pathogenesis.Frontiers in Cellular and Infection Microbiology 03/2012; 2:23. DOI:10.3389/fcimb.2012.00023 · 3.72 Impact Factor
- [Show abstract] [Hide abstract]
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.
- [Show abstract] [Hide abstract]
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 · 7.41 Impact Factor