Alteration of Sulfation of Glycoconjugates, but Not Sulfate Transport and Intracellular Inorganic Sulfate Content in Cystic Fibrosis Airway Epithelial Cells

Mohapatra, Nirupama; Cheng, Pi-Wan; Parker, John C.; Paradiso, Anthony M.; Yankaskas, James R.; Boucher, Richard C.; Boat, Thomas F.

doi:10.1203/00006450-199507000-00008

Cited by 31 publications

(13 citation statements)

References 26 publications

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“…Particular changes in GAG chains and sulphation patterns may allow increased interactions, normally of ionic nature, with various proteins including antimicrobial peptides [21] and proinflammatory stimuli [36, 38–40]. Data supporting this phenomenon have demonstrated synthesises of oversulphated glycoconjugates by CF tissue in organ culture [41] and airway epithelial cells [42, 43]. Fundamentally, regardless of the exact or combined cause of increased viscosity, the thickened mucus within the CF airways becomes detached from the cilia and mucociliary transport is impaired, the major cause of lung morbidity and mortality in CF.…”

Section: Physical Properties Of Airway Mucus In Cystic Fibrosismentioning

confidence: 99%

Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

Reeves

Molloy

Pohl

et al. 2012

The Scientific World Journal

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The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

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Section: Physical Properties Of Airway Mucus In Cystic Fibrosismentioning

confidence: 99%

Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

Reeves

Molloy

Pohl

et al. 2012

The Scientific World Journal

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“…It was proposed that CFTR may normally provide a Cl in CF airway epithelial cells be accounted for by changes in plasma membrane sulfate transport or cell content of inorganic sulfate (31,49). Intracellular sulfation reactions utilize sulfate that has been "activated" by its incorporation into PAPS (50).…”

Section: Fig 4 Cftr CLmentioning

confidence: 99%

Cystic Fibrosis Transmembrane Conductance Regulator-associated ATP and Adenosine 3′-Phosphate 5′-Phosphosulfate Channels in Endoplasmic Reticulum and Plasma Membranes

Pasyk

Foskett

1997

Journal of Biological Chemistry

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Cystic fibrosis (CF) is characterized by abnormal regulation of epithelial ion and fluid transport due to mutations in the CF transmembrane conductance regulator (CFTR), an apical membrane-localized Cl ؊ channel, that usually prevent it from exiting the endoplasmic reticulum. Defective or absent CFTR in the epithelium is believed to disrupt fluid balance in human airways and thereby contribute to chronic respiratory inflammation. Patch-clamp of the plasma membrane and outer membrane of the nuclear envelope of nuclei isolated from CFTR-expressing Chinese hamster ovary cells revealed that CFTR is associated with a regulated ATP channel in both membrane compartments. CFTR expression was also shown to be associated with permeability to another adenine nucleotide, adenosine 3-phosphate 5-phosphosulfate, the universal sulfate donor in cells. These results may provide a link between the ion channel function of CFTR and abnormal glycoprotein processing observed in CF.

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“…Part of the increased acidity is caused by mucin oversulphation [7,81, possibly due to perturbations in intracellular sulphate activation or the transfer of activated sulphate to the mucin molecule [9], and part is the result of degradation of neutral mucin oligosaccharides by I? aeruginosa [ lo].…”

Section: Introductionmentioning

confidence: 99%

A novel mucin-sulphatase activity found in Burkholderia cepacia and Pseudomonas aeruginosa

Jansen

Hart

Rhodes

et al. 1999

Journal of Medical Microbiology

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Lung infections due to Burkholderia cepacia and Pseudomonas aeruginosa in patients with cystic fibrosis (CF) are common, are associated with respiratory morbidity and are a cause of mortality. Respiratory mucin in CF patients is highly sulphated, which increases its resistance to bacterial degradation. Desulphation increases the susceptibility of mucin to degradation by bacterial glycosidases and proteinases, and subsequent deglycosylation may facilitate bacterial colonisation by increasing available substrates and binding sites. This study determined whether clinical and environmental strains of B. cepacia and I! aeruginosa had the ability to desulphate mucin. Mucin-sulphatase activity was tested by incubating bacterial cell suspensions with 35S-sulphated mucins purified from LSl74T and HT29-MTX human colon carcinoma cell lines. These mucins were also used to test for differences in substrate specificities. Mucin-sulphatase activity was detected in all nine B. cepacia strains and in four of six I! aeruginosa strains. There was strain variability in the level of mucin-sulphatase activity. Aryl-sulphatase activities of Pseudomonas isolates (determined with methylumbelliferyl sulphate) were c. 20-fold higher than those of B. cepacia strains, and were independent of mucin-sulphatase activity. This is the first report to demonstrate desulphation of mucin by B. cepacia and I! aeruginosa. It is concluded that B. cepacia and I! aeruginosa produce one or more cell-bound glycosulphatase(s), in addition to aryl-sulphatase activity. Mucin-sulphatase activity of B. cepacia and I! aeruginosa may contribute to their association with airway infections in patients with cystic fibrosis.

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Alteration of Sulfation of Glycoconjugates, but Not Sulfate Transport and Intracellular Inorganic Sulfate Content in Cystic Fibrosis Airway Epithelial Cells

Cited by 31 publications

References 26 publications

Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

Cystic Fibrosis Transmembrane Conductance Regulator-associated ATP and Adenosine 3′-Phosphate 5′-Phosphosulfate Channels in Endoplasmic Reticulum and Plasma Membranes

A novel mucin-sulphatase activity found in Burkholderia cepacia and Pseudomonas aeruginosa

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