Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells

Rahman, Irfan; Bel, Agnes; Mulier, Brigitte; Donaldson, Kenneth; MacNee, William

doi:10.1152/ajplung.1998.275.1.l80

Cited by 43 publications

(32 citation statements)

References 28 publications

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“…In this study, changes in glutamylcysteine ligase mRNA were not found, but the airways were sampled after 12 h of hyperoxia, and earlier time of induction would not have been detected. However, other interacting components of the glutathione-antioxidant system, including ␥-glutamyltransferase, glutathione peroxidases, and glutathione reductase, were not induced in this study, or in previous in vitro studies of primary human bronchial epithelial cells and bronchial epithelial cell lines exposed to hyperoxia (15,24,(49)(50)(51). Other data support that upregulation of glutathione antioxidant systems are not requisite for defense against hyperoxia (25,38,52,53).…”

Section: Discussionsupporting

confidence: 63%

Gene Expression Profile of Human Airway Epithelium Induced by Hyperoxia In Vivo

Chambellan

Cruickshank²,

McKenzie³

et al. 2006

Am J Respir Cell Mol Biol

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Hyperoxia leads to oxidative modification and damage of macromolecules in the respiratory tract with loss of biological functions. Given the lack of antioxidant gene induction with acute exposure to 100% oxygen, we hypothesized that clearance pathways for oxidatively modified proteins may be induced and serve in the immediate cellular response to preserve the epithelial layer. To test this, airway epithelial cells were obtained from individuals under ambient oxygen conditions and after breathing 100% oxygen for 12 h. Gene expression profiling identified induction of genes in the chaperone and proteasome-ubiquitin-conjugation pathways that together comprise an integrated cellular response to manage and degrade damaged proteins. Analyses also revealed gene expression changes associated with oxidoreductase function, cell cycle regulation, and ATP synthesis. Increased HSP70, protein ubiquitination, and intracellular ATP were validated in cells exposed to hyperoxia in vitro. Inhibition of proteasomal degradation revealed the importance of accelerated protein catabolism for energy production of cells exposed to hyperoxia. Thus, the human airway early response to hyperoxia relies predominantly upon induction of cytoprotective chaperones and the ubiquitin-proteasome-dependent protein degradation system to maintain airway homeostatic integrity.Keywords: airways; gene expression; hyperoxia; proteasome; ubiquitin Oxygen, one of the most abundant elements in our world, is essential for the oxidation of organic compounds to generate the energy needed to sustain life. Under ambient conditions, reactive oxygen species (ROS) are generated at a low level in lung cells during aerobic metabolism. To minimize the oxidant injury that is a consequence of aerobic life, the human lung is endowed with an integrated antioxidant system, which detoxifies reactive products (1-4). However, excessive ROS may overwhelm the antioxidant system and result in damage to major cellular components, including membrane lipids, proteins, carbohydrates, and DNA (1,(5)(6)(7)(8). The pathophysiologic consequences of this injury may include cell death, and tissue inflammation and damage. This is particularly evident during conditions of increased oxygen exposure for medical therapy (4, 9, 10). The bronchial epithelium is particularly vulnerable to the effects of airborne oxidative stress as the moist mucosal surface of the airway is in direct contact with the environment (11). Hyperoxia leads to oxidant injury in the respiratory tract, which is manifest as acute tracheobronchitis with edema and decrease in mucocili-(Received in original form July 8, 2005 and in final form May 4, 2006 ) This study was supported by AI70649, HL60917, and M01 RR018390 from the National Center for Research Resources. A.C. was supported by grants from the Collège des Professeurs de Pneumologie.Correspondence and requests for reprints should be addressed to Serpil C. (12,13). Oxidative damage of proteins and loss of biological function is one defined end-point of hyperoxic inj...

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Section: Discussionsupporting

confidence: 63%

Gene Expression Profile of Human Airway Epithelium Induced by Hyperoxia In Vivo

Chambellan

Cruickshank²,

McKenzie³

et al. 2006

Am J Respir Cell Mol Biol

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“…The most prominent finding of the current study, the increase in antioxidants in the alveolar compartment, may provoke the speculation that antioxidant metabolism in [31] found that both glutathione and c-glutamylcysteine synthetase levels increase in alveolar type II cells after oxidant treatment. This may be induced by activation of redox-sensitive transcription factors, such as nuclear factor-kB and activator protein-1, which are involved in regulation of antioxidant genes.…”

Section: Discussionmentioning

confidence: 65%

Alveolar antioxidant status in patients with acute respiratory distress syndrome

Schmidt

Luboeinski²,

Markart³

et al. 2004

European Respiratory Journal

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In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20).Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), a-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas-liquid chromatography), and F 2 -isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF.GSSG (ARDS: 0.13¡0.02 mM; control: 0.03¡0.01 mM; mean¡SEM) and F 2 -isoprostanes (ARDS: 78¡10 pM; control: 26¡5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77¡15 nM; control: 26¡3 nM) and uric acid (ARDS: 11.8¡2.2 mM; control: 0.7¡0.0 mM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of y3 in patients, but plasmalogens showed a significant decrease.In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding. Eur Respir J 2004; 24: 994-999.

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“…As described previously (Rahman et al, 1998), smoke extract "strength" was evaluated by measuring nitrite using the Griess reaction (Bishop-Bailey et al, 1997) to ensure continuity between batches. In all experiments, nitrite levels in 100% cigarette smoke extract was between 12 and 16 M.…”

Section: Methodsmentioning

confidence: 99%

Cigarette Smoke Activates Human Monocytes by an Oxidant-AP-1 Signaling Pathway: Implications for Steroid Resistance

Walters

Paul-Clark

McMaster³

et al. 2005

Mol Pharmacol

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Smoking cigarettes is a major risk factor for the development of cardiovascular and respiratory disease. Moreover, smokinginduced pathophysiology is often resistant to the anti-inflammatory effects of glucocorticoids. The nature of cigarette smoke-induced inflammation is still not defined, although neutrophil recruitment and activation seem to be consistent features. In the current study, we have used a range of approaches to demonstrate that cigarette smoke activates human monocytes and macrophages to release the CXC chemokine CXCL8 ]. Furthermore, we show for the first time that cigarette smoke synergizes with proinflammatory cytokines IL-1␤ and tumor necrosis factor-␣, and it is this interaction that confers steroid resistance to smoke-induced CXCL8 release. We go on to show that smoke-induced activation of human cells is an oxidant-mediated phenomenon acting through activator protein-1, but not nuclear factor B, pathway. These observations add significantly to our understanding of smoke as an inflammatory stimulus that has implications for potential the development of treatments of smoking or related disease.

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Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells

Cited by 43 publications

References 28 publications

Gene Expression Profile of Human Airway Epithelium Induced by Hyperoxia In Vivo

Gene Expression Profile of Human Airway Epithelium Induced by Hyperoxia In Vivo

Alveolar antioxidant status in patients with acute respiratory distress syndrome

Cigarette Smoke Activates Human Monocytes by an Oxidant-AP-1 Signaling Pathway: Implications for Steroid Resistance

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