| Autor: |
Benjamin W. Frush, James Y. Lindsey, John W. Hollingsworth, Erin N. Potts-Kant, Robert M. Tighe, W. Michael Foster, Zhuowei Li |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Free radical biologymedicine. 113 |
| ISSN: |
1873-4596 |
| Popis: |
Emphysema is currently a leading cause of mortality with no known effective therapy to attenuate progressive loss of lung function. Previous work support that activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is protective to the lung through induction of hundreds of antioxidant genes. In models of lung injury, the expression of NAD(P)H:quinine oxidoreductase 1 (NQO1) is upregulated in a manner dependent on Nrf2 and human emphysema is associated with reduced levels of NQO1. However, the functional role of NQO1 in emphysema remains unknown. In this study, we demonstrate the protective role of NQO1 in the development of emphysema using mouse models. NQO1 deficient animals demonstrate premature age-related emphysema and were more susceptible to both elastase and inhaled lipopolysaccharide (LPS) models of emphysema. The absence of NQO1 was associated with enhanced markers of oxidant stress. Treatment of NQO1 deficient animals with the antioxidant N-acetyl cysteine reversed the NQO1-dependent emphysematous changes. In vitro studies utilizing either inhibition or induction of NQO1 demonstrate a potent antioxidant role of NQO1 in macrophages, suggesting a role of macrophage-derived oxidants in the pathogenesis of emphysema. These novel findings support a functional role of NQO1 in protecting the lung from development of emphysema. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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