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Oxidative stress in pathogenesis of chronic obstructive pulmonary disease

Cellular and molecular mechanisms

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Abstract

Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by airflow limitation, which is largely irreversible. Oxidative stress and inflammation are the major hallmarks of COPD. Reactive oxygen species, either directly or via the formation of lipid peroxidation products, such as 4-hydroxy-2-nonenal and F2-isoprostanes, may play a role in enhancing the inflammation through the activation and phosphorylation of mitogen-activated protein kinases (MAPKs) and redox-sensitive transcription factors such as nuclear factor-ϰB and activator protein-1 in COPD. In addition, activation of the MAPK family leads to the transactivation of transcription factors and coactivators (chromatin remodeling). This eventually results in expression of genes regulating a battery of distinct proinflammatory, antioxidant, and stress response genes. The presence of an oxidative stress has important consequences on several events of lung physiology and for the pathogenesis of COPD. These include increased sequestration of neutrophils in the pulmonary microvasculature, oxidative inactivation of antiproteases and surfactants, hypersecretion of mucus, membrane lipid peroxidation, mitochondrial respiration, alveolar epithelial injury/permeability, breakdown/remodeling of extracellular matrix, and apoptosis. Oxidative stress may have a role in the poor efficacy of corticosteroids in COPD. This review discusses cellular and molecular changes that occur in response to smoking and oxidative stress in the pathogenesis of COPD.

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  1. Department of Environmental Medicine Division of Lung Biology and Disease, University of Rochester Medical Center, MRBX 3.11106, 601 Elmwood Avenue, Box 850, 14642, Rochester, NY

    Irfan Rahman

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Rahman, I. Oxidative stress in pathogenesis of chronic obstructive pulmonary disease. Cell Biochem Biophys 43, 167–188 (2005). https://doi.org/10.1385/CBB:43:1:167

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