Proteomic analysis of oxidative stress-responsive proteins in human pneumocytes: insight into the regulation of DJ-1 expression.
J Proteome Res
; 7(11): 4955-61, 2008 Nov.
Article
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| MEDLINE
| ID: mdl-18817430
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Alveolos Pulmonares
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Regulación de la Expresión Génica
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Proteínas Oncogénicas
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Estrés Oxidativo
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Proteoma
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Péptidos y Proteínas de Señalización Intracelular
Límite:
Humans
Idioma:
En
Revista:
J Proteome Res
Asunto de la revista:
BIOQUIMICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos