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Journal of Lipid Research, Vol 28, 1088-1097, Copyright © 1987 by Lipid Research, Inc.
BF Smith
The binding of phosphatidylcholine and cholesterol in model bile to human
gallbladder mucin was studied by means of a rapid filtration binding assay
and sucrose density gradient ultracentrifugation. Numerous low affinity
binding sites for phosphatidylcholine and cholesterol were present on
gallbladder mucin. Binding of phosphatidylcholine and cholesterol to mucin
increased as a function of cholesterol saturation index. Proteolytic
digestion of mucin disaggregated the native mucin polymer and removed
hydrophobic domains on the mucin peptide core that bind
l-anilino-8-naphthalenesulfonic acid. Proteolytic digestion also resulted
in a 91% and 78% decrease, respectively, in the binding of
phosphatidylcholine and cholesterol to mucin. The ability of
trypsin-treated and native mucin to promote the nucleation of cholesterol
monohydrate crystals was compared in a model bile. The incidence of
cholesterol monohydrate crystal nucleation with native mucin was
significantly greater at 3 days than with trypsin- treated mucin or
controls (P less than 0.001). After 3, 6, and 9 days of incubation, samples
containing native mucin contained significantly more crystals than controls
or trypsin-digested mucin samples (P less than 0.0001 for each). These data
indicate that highly purified human gallbladder mucin binds
phosphatidylcholine and cholesterol in model bile. Furthermore, this study
demonstrates that structural integrity of the native mucin polymer and
hydrophobic domains on the peptide core are essential for the nucleation of
cholesterol monohydrate crystals by mucin in model bile.
ARTICLES
Human gallbladder mucin binds biliary lipids and promotes cholesterol crystal nucleation in model bile
Section of Gastroenterology, University Hospital, Boston, MA.
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