Deficiency of Alveolar Fluid Glutathione in Patients with Sepsis and the Adult Respiratory Distress Syndrome

Pacht, Eric R.; Timerman, Anthony P.; Lykens, Michael; Merola, Assunta

doi:10.1378/chest.100.5.1397

Cited by 239 publications

(142 citation statements)

References 32 publications

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“…138 Patients with ARDS who abuse alcohol also have decreased levels of glutathione in bronchoalveolar lavage fluid compared with normal controls. 139,140 In addition to alterations in glutathione homeostasis, chronic alcohol abuse may alter surfactant synthesis and secretion, 136 alveolar epithelial cell apoptosis, 141,142 alveolar capillary barrier permeability, 143,144 alveolar epithelial fluid transport function, 143 and alveolar macrophage function. [145][146][147] Transfusion-Related Acute Lung Injury Transfusion-related ALI (TRALI) is defined as the development of noncardiogenic pulmonary edema that is temporally related to the transfusion of blood products.…”

Section: Alcohol Abusementioning

confidence: 99%

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Ware¹

2006

Semin Respir Crit Care Med

424

324

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Since the adult respiratory distress syndrome was first described substantial progress has been made in understanding the pathogenesis of this complex syndrome. This review summarizes our current understanding of the pathophysiology of what is now termed the acute respiratory distress syndrome (ARDS) and its less severe form acute lung injury (ALI), with an emphasis on cellular and molecular mechanisms of injury that may represent potential therapeutic targets. Although it is difficult to synthesize all of these abnormalities into a single, unified, pathogenetic pathway, a theme that emerges repeatedly is that of imbalance, be it between pro-and anti-inflammatory cytokines, oxidants and antioxidants, procoagulants and anticoagulants, neutrophil recruitment and activation and mechanisms of neutrophil clearance, or proteases and protease inhibitors. Future therapies aimed at restoring the overall balance of cytokines, oxidants, coagulants, and proteases may ultimately be successful where therapies that target individual cytokines or other mediators have not.

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Section: Alcohol Abusementioning

confidence: 99%

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Ware¹

2006

Semin Respir Crit Care Med

424

324

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“…It maintains the thiol redox potential in cells keeping sulfhydryl groups of intracellular proteins in the reduced form 5 . Decreased GSH levels have been reported in several diseases, such as acquired immune deficiency syndrome (AIDS 6 ), adult respiratory distress syndrome, 7 Parkinson's disease 8 , and diabetes 9 . In addition, recent results suggest that GSH is essential for cell proliferation, 10 and it plays a role in the regulation of apoptosis 11 .…”

Section: Introductionmentioning

confidence: 99%

Assesment of metal inhibition of antioxidant enzyme glutathione reductase from rainbow trout liver

Ekinci

Şentürk

2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…mented (3)(4)(5)(6)(7)(8). For the purpose of detoxification and to respond to extracellular oxidative stress, cells express membrane proteins capable of transporting GSH, glutathione disulfide (GSSG), and GSH conjugates (GS-X).…”

mentioning

confidence: 99%

Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2

Brechbuhl

Gould

Kachadourian

et al. 2010

Journal of Biological Chemistry

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Glutathione (GSH) transport is vital for maintenance of intracellular and extracellular redox balance. Only a few human proteins have been identified as transporters of GSH, glutathione disulfide (GSSG) and/or GSH conjugates (GS-X). Human epithelial MDA1586, A549, H1975, H460, HN4, and H157 cell lines were exposed to 2,5-dihydroxychalcone, which induces a GSH efflux response. A real-time gene superarray for 84 proteins found in families that have a known role in GSH, GSSG, and/or GS-X transport was employed to help identify potential GSH transporters. ABCG2 was identified as the only gene in the array that closely corresponded with the magnitude of 2,5-dihydroxychalcone (2,5-DHC)-induced GSH efflux. The role of human ABCG2 as a novel GSH transporter was verified in a Saccharomyces cerevisiae galactose-inducible gene expression system. Yeast expressing human ABCG2 had 2.5-fold more extracellular GSH compared with those not expressing ABCG2. GSH efflux in ABCG2-expressing yeast was abolished by the ABCG2 substrate methotrexate (10 M), indicating competitive inhibition. In contrast, 2,5-DHC treatment of ABCG2-expressing yeast increased extracellular GSH levels in a dose-dependent manner with a maximum 3.5-fold increase in GSH after 24 h. In addition, suppression of ABCG2 with short hairpin RNA or ABCG2 overexpression in human epithelial cells decreased or increased extracellular GSH levels, respectively. Our data indicate that ABCG2 is a novel GSH transporter.Glutathione (GSH) is a tripeptide (␥-glutamyl-cysteinyl-glycine) that is maintained at millimolar concentrations within the cell. It is important in many signaling processes, including cell proliferation, post-translational modification of proteins, immune responses, and apoptosis (1, 2). The importance of GSH in normal cell function as well as its role in disease states such as cancer, cystic fibrosis, Parkinson disease, AIDS, liver dysfunction, and a host of other maladies has been well documented (3-8). For the purpose of detoxification and to respond to extracellular oxidative stress, cells express membrane proteins capable of transporting GSH, glutathione disulfide (GSSG), and GSH conjugates (GS-X).2 Currently, there are only a handful of proteins identified as capable of transporting GSH across membranes.The first human protein identified as a GS-X and/or GSSG transporter was the ATP-binding cassette (ABC) protein ABCC1, first called the GSH S-conjugate pump and later identified as the multidrug resistance protein MRP1 (9 -11). Since the discovery of ABCC1 as a GSH transporter, five other ABC family members have been shown to transport GSH and/or GS-X, including ABCC2, ABCC3, ABCC4, ABCC5, and ABCC7 (12-17). GSH transport has also been linked to the organic anion transporting polypeptide protein family, a subfamily of the solute carrying (SLC) protein superfamily. The SLC superfamily also contains mitochondria-specific membrane proteins (SLC25) capable of transporting GSH (18).Numerous compounds stimulate GSH, GSSG, and GS-X efflux through the ABC protei...

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Deficiency of Alveolar Fluid Glutathione in Patients with Sepsis and the Adult Respiratory Distress Syndrome

Cited by 239 publications

References 32 publications

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Assesment of metal inhibition of antioxidant enzyme glutathione reductase from rainbow trout liver

Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2

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