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J Proteome Res. 2008 Nov;7(11):4955-61. doi: 10.1021/pr800295j. Epub 2008 Sep 26.

Proteomic analysis of oxidative stress-responsive proteins in human pneumocytes: insight into the regulation of DJ-1 expression.

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1
Department of Biochemistry and Department of Medicine, Division of Pulmonary Critical Care and Pulmonary Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

Abstract

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.

PMID:
18817430
DOI:
10.1021/pr800295j
[Indexed for MEDLINE]

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