Effects of Calcium on Intestinal Mucin: Implications for Cystic Fibrosis

Forstner, Janet F.; Forstner, G.

doi:10.1203/00006450-197606000-00009

Cited by 45 publications

(24 citation statements)

References 12 publications

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“…The presence of salts also affects the properties of normal mucins, generally causing a decrease in both solubility and viscosity (46). In our laboratory we found that the addition of 15 mM CaCl2 to purified rat intestinal mucin in isotonic buffers at pH 7.4, caused a 30% decrease in mucin solubility.…”

Section: B Physical and Functional Propertiesmentioning

confidence: 62%

“…There is indirect evidence, for example, that the rheological properties and solubility of mucus depend strongly on interactions of mucins with other luminal constituents such as lipids (55,94), nucleic acids (55), inorganic acid and alkalis (12,47,56), salts (46,56), serum proteins (47,55,133), and enzymes (6,56,116). There is also evidence for significant interaction of mucins with orally administered drugs (78).…”

Section: B Physical and Functional Propertiesmentioning

confidence: 99%

See 1 more Smart Citation

Intestinal Mucins in Health and Disease

Jf¹

1978

Digestion

252

115

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Intestinal mucins are complex glycoproteins which are secreted from goblet cells, and form a gel-like covering over the mucosal surface. They are assumed to provide lubrication and protection of the underlying epithelium against potentially injurious chemicals, enzymes, bacteria and dietary constituents. Recent advances in our understanding of mucin structure, secretion and functional properties are reviewed in this paper. Implications for diseases such as cystic fibrosis, peptic ulcer, malignancy and inflammatory bowel disease are briefly discussed.

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Section: B Physical and Functional Propertiesmentioning

confidence: 62%

Section: B Physical and Functional Propertiesmentioning

confidence: 99%

Intestinal Mucins in Health and Disease

Jf¹

1978

Digestion

252

115

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“…The potential role of Ca2+ in the production of exocrine products of decreased solubility has been suggested and demonstrated (22). source of cytosolic Ca2+ in eukaryotic cells (23).…”

Section: Resultsmentioning

confidence: 99%

Mitrochondrial NADH dehydrogenase in cystic fibrosis.

Shapiro¹,

Feigal²,

Lam³

1979

Proc. Natl. Acad. Sci. U.S.A.

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We have shown that skin fibroblasts from patients with cystic fibrosis (CF) and from carriers for CF [heterozygotes (HZ)] consume more 02 than do their controls. When the mitochondrial electron transport inhibitor rotenone was added to the cells, the relative inhibition of 02 consumption was CF > HZ > controls (P < 0.005 in both comparisons). Because rotenone specifically inhibits NADH dehydrogenase, [NADH:(acceptor) oxidoreductase, EC 1.6.99.31, which is the enzyme of energy-conserving site 1 of the mitochondrial electron transport system, activity and kinetics of this enzyme system were studied in fibroblast homogenates. NADH dehydrogenase activity was equal in cells from the three genotypes. At pH 8.0, affinity of the enzyme for its substrate was CF < HZ = controls; at pH 8.6, affinity was CF> HZ = controls (P < 0.005 for the differences). pH optima for the genotypes were without exception 8.6 (CF), 8.3 (HZ), and 8.0 (control). HZ and control lines were distinguished unequivocally in a blind test on the basis of differences in pH optima. Purified mitochondrial preparations revealed pH optima identical to those found in whole cell homogenates. These data suggest that the mutant gene responsible for CF is expressed in the complex mitochondrial NADH dehydrogenase system.

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“…The binding had a K d of about 7 ϫ 10 Ϫ6 M, and it was specific for calcium. Previous studies have reported calcium binding on mucins and mucus (4,30,31,(33)(34)(35)(36), but the properties have generally lacked specificity and have been determined after exposure to denaturing conditions. Effects on purified mucins (3,(33)(34)(35) have shown the characteristics of electrostatic interactions involving carbohydrate structures such as sialic acids (3,33,35) and have not been specific for calcium (3,31).…”

Section: Table III Peptides Identified By Esi-ms-ms Analysismentioning

confidence: 99%

Calcium-dependent Protein Interactions in MUC5B Provide Reversible Cross-links in Salivary Mucus

Raynal

Hardingham

Sheehan³

et al. 2003

Journal of Biological Chemistry

136

114

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The macromolecular organization within saliva was investigated by tracer diffusion measurements of fluorescent polystyrene microspheres by fluorescence recovery after photobleaching using a confocal microscope (confocal-FRAP). There was a concentrationdependent reduction in microsphere diffusion; this was much greater in the presence of calcium (10 mM) and was reduced by the addition of EGTA (10 mM). These effects on tracer diffusion showed that native saliva contained a macromolecular organization that was sensitive to free calcium concentrations. This was supported by a major increase in the weight average molecular weight of the high molecular weight mucin fraction in saliva (10 -62 ؋ 10 6 ) and an increase in intrinsic viscosity of saliva (733 to 1203 ml/g) both caused by calcium. Analysis of the change in tracer diffusion in saliva showed a 20-fold increase in the apparent pore size (from 130 nm in 10 mM CaCl 2 to 2600 nm in 10 mM EGTA at physiological concentration). The effect was specific for calcium and was unaffected by up to 2 M NaCl. The calcium binding activity was contained in a high buoyant density fraction of saliva excluded from Sepharose CL-2B. Calcium binding to this fraction gave an approximate K d of 7 ؋ 10 ؊6 M, and the binding was irreversibly destroyed by treatment with 6 M guanidinium chloride and by mild reduction, suggesting it to be to a protein site. This fraction of saliva was shown to contain MUC5B as the single major protein species by positive ion electrospray ionization-tandem mass spectrometry analysis. The results suggested that oligomeric MUC5B in saliva is assembled into much larger linear or branched assemblies through calcium-mediated protein cross-links.Mucus forms a viscoelastic gel that coats the epithelial surfaces in humans and other vertebrates. The properties of the gel have been interpreted as being predominantly due to entanglement of the long, high molecular weight oligomeric mucins (1, 2). Mucus has also been described as a network weakly cross-linked by non-covalent bonds (3, 4) and suggested mechanisms of interaction have included interchain hydrophobic interactions (5) and carbohydrate-carbohydrate interactions between the mucins (6 -9). Mucus rheology is affected by many factors, including hydration (2), pH (10), and ion content (11-13). Thus the supramolecular organization of the mucus layer is complex, and the molecular basis of this organization remains poorly defined.A layer of mucus coats the surfaces of the gastrointestinal, reproductive, and respiratory tracts as well as the eyes and oral cavity (14). This layer is the bodies' first line of defense against chemical, physical, and biological insult and a change in this barrier will compromise health. For example, in the airways overproduction of mucus with aberrant rheological properties is a feature of asthma, cystic fibrosis, and chronic obstructive pulmonary disease. In these situations the change in the physical properties of the barrier leads to a breakdown in mucus clearance from the airways with...

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Effects of Calcium on Intestinal Mucin: Implications for Cystic Fibrosis

Cited by 45 publications

References 12 publications

Intestinal Mucins in Health and Disease

Intestinal Mucins in Health and Disease

Mitrochondrial NADH dehydrogenase in cystic fibrosis.

Calcium-dependent Protein Interactions in MUC5B Provide Reversible Cross-links in Salivary Mucus

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