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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lung is a unique organ in terms of its direct exposure to high levels of oxygen and reactive compounds. Several parenchymal lung diseases (e.g. emphysema associated with smoking and a number of fibrotic lung disorders) have been proposed to be due to the exposure of the lung to exogenous irritants leading to local redox imbalance in the alveolar epithelium. The disease progression of emphysema/chronic obstructive pulmonary disease (COPD) and fibrosis share several common factors, such as the role of reactive oxygen species, disturbances of the pulmonary thiol status and activation of growth factors and tissue destructing proteases. Importantly in COPD or fibrosis, medication does not provide any significant therapeutic effect. This review concentrates on the key thiol (-SH)-regulated mechanisms leading to the development of COPD and/or pulmonary fibrosis and the major redox-regulated defense/oxidant repair mechanisms, thioredoxin/peroxiredoxin and glutaredoxin protein families in the lung. Redox-regulated proteins, both proteases and oxidant repair enzymes, undergo conformational changes during oxidative stress, a process that modulates their activation or inactivation. In addition, some of the redox-regulated proteins influence the metabolism of glutathione (GSH), a major small molecular antioxidant of human lung, and participate in the crosstalk between numbers of GSH associated enzymes functioning in the detoxification pathways of human lung. An understanding of the processes involved in oxidant-mediated lung damage may provide the key to devising interventional strategies that can actually prevent the progression of lung parenchymal disease.
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PMID:Thiol proteins, redox modulation and parenchymal lung disease. 1726 80

Oxidative injury is believed to play an important role in the pathogenesis of lung diseases such as emphysema and lung cancer. We examined the effects of a classic reactive oxygen species, H 2O 2, on the hydrogen peroxide response proteins (HPRP) in human pneumocytes using comparative two-dimensional gel electrophoresis (2DE) and peptide mass fingerprinting. Four HPRP-associated proteins (DJ-1, peroxiredoxins [Prxs] I and IV and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) were changed upon exposure to H 2O 2 (1 mM for 24 h). H 2O 2 exposure increased the acid (oxidized) form and decreased the basic (reduced) form of DJ-1 (pI 5.8 and 6.2, respectively), Prx I and IV and GAPDH. Mechanistic studies on DJ-1 indicated that the slow recovery of the reduced form was blocked by cyclohexamide, suggesting that the recovery was due to new protein synthesis. Total DJ-1 expression was decreased by increasing concentrations of H 2O 2. In contrast, a more complex mix of oxidants in the form of cigarette smoke extract (CSE) dose-dependently increased DJ-1 expression and produced a novel DJ-1 isoform (p I 5.6). Moreover, DJ-1 expression was higher in the lungs of chronic cigarette smokers compared with nonsmokers, a result which resembled the effects of CSE in cultured cells. These data indicate that in human pneumocytes, DJ-1 functions as an antioxidant but that no enzymatic system converts the oxidized to the reduced form. Up-regulation of DJ-1 by cigarette smoke may be a compensatory mechanism that protects the lung from oxidative stress-related injury.
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PMID:Proteomic analysis of oxidative stress-responsive proteins in human pneumocytes: insight into the regulation of DJ-1 expression. 1881 30