Extracellular glutathione peroxidase in human lung epithelial lining fluid and in lung cells

Avissar, Nelly E.; Finkelstein, J. N.; Horowitz, Stuart; Willey, James C.; Coy, Erin L.; Frampton, Mark W.; Watkins, Richard H.; Khullar, P.; Xu, Y. L.; Cohen, Harvey J.

doi:10.1152/ajplung.1996.270.2.l173

Cited by 75 publications

(80 citation statements)

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“…It has been reported that incubation with extracellular GSH and increasing intracellular GSH levels protect against oxidant stress in alveolar type II cells [7,195]. In addition, extracellular GPx, which has been described recently [196], is secreted into ELF by alveolar epithelial cells and macrophages and may provide further defence against oxidants [196]. Following acute inflammation and oxidative stress, the ELF may become depleted of antioxidants such as GSH, increasing the potential for damage to the underlying epithelial cells.…”

Section: Antioxidant Protective Genesmentioning

confidence: 99%

Oxidative stress and regulation of glutathione in lung inflammation

Rahman¹,

MacNee²

2000

Eur Respir J

812

555

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Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox‐sensitive transcription factors such as nuclear factor‐κB, and activator protein‐1 (AP‐1), which regulate the genes for pro‐inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra‐ and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro‐inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate‐limiting enzyme in GSH synthesis is γ‐glutamylcysteine synthetase (γ‐GCS). The human γ‐GCS heavy and light subunits are regulated by AP‐1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti‐inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant γ‐GCS and pro‐inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro‐ and anti‐inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor‐κB and activator protein‐1 in the regulation of cellular glutathione and γ‐glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant‐mediated susceptibility/tolerance, γ‐glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

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Section: Antioxidant Protective Genesmentioning

confidence: 99%

Oxidative stress and regulation of glutathione in lung inflammation

Rahman¹,

MacNee²

2000

Eur Respir J

812

555

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“…eGPX is one of at least four genetically distinct forms of the antioxidant GPx enzyme family and is found in plasma and respiratory tract lining fluid (12,13). Under oxidative stress conditions, such as during smoking, the eGPX concentrations in the lung increase, in what is believed to be a protective response (14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

Lack of Association Between Physical Activity in Smokers and Plasma Glutathione Peroxidase Levels

Rundle¹,

Richards²,

Tang

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…42 Primary bronchial epithelial cells, alveolar macrophages and other lung cell lines can synthesize classical Gpx and extracellular Gpx and also secrete the extracellular enzyme. 56 Classical Gpx is induced by hyperoxia 57 and by the combination of hyperoxia and TNF. 58 The levels of both classical Gpx and extracellular Gpx are decreased after exposure to ozone.…”

Section: Gpxs In Normal Physiology and Lung Diseasesmentioning

confidence: 99%

Glutathione peroxidase-1 as a novel therapeutic target for COPD

Vlahos

Bozinovski

2013

Redox Report

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Oxidative stress plays a role in a variety of diseases but it is even more pertinent in chronic obstructive pulmonary disease (COPD) given the increased oxidant burden in smokers. The increased oxidant burden results from the fact that cigarette smoke contains over 4700 different chemical compounds and more than 10 15 oxidants/free radicals per puff. Other factors, such as air pollutants, infections, and occupational dusts that may exacerbate COPD, also have the potential to produce oxidative stress. These oxidants give rise to Reactive Oxygen Species (ROS) that are generated enzymatically by inflammatory and epithelial cells within the lung as part of an inflammatory immune response towards a pathogen or irritant. Thus, while ROS are necessary for host defence against invading pathogens, increased levels of ROS have been implicated in initiating inflammatory responses in the lungs through the activation of transcriptional factors, signal transduction pathways, chromatin remodelling and gene expression of proinflammatory mediators. However, the normal lung has developed defences to ROS-mediated damage, which include antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In this review we consider the therapeutic potential of the antioxidant enzyme glutathione peroxidase-1 for the treatment of cigarette smoke-induced lung inflammation and damage.

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Extracellular glutathione peroxidase in human lung epithelial lining fluid and in lung cells

Cited by 75 publications

References 0 publications

Oxidative stress and regulation of glutathione in lung inflammation

Oxidative stress and regulation of glutathione in lung inflammation

Lack of Association Between Physical Activity in Smokers and Plasma Glutathione Peroxidase Levels

Glutathione peroxidase-1 as a novel therapeutic target for COPD

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