Isolation of a human biliary glycoprotein inhibitor of cholesterol crystallization

Ohya, Toshihide; Schwarzendrube, Jörg; Busch, Norbert; Gresky, Susan; Chandler, Kimberly; Takabayashi, Arimachi; Igimi, Hirotsune; Egami, Kaku; Holzbach, Rüdiger

doi:10.1016/0016-5085(93)90423-a

Cited by 62 publications

(26 citation statements)

References 40 publications

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“…They reduced the kinetics of crystallization (growth rate) and the final crystal concentration with the 28-kD protein showing the strongest inhibiting effect. Even our protein with the lowest inhibiting potency performed better than the recently reported 58/63-kD heterodimer (6). Promoter proteins, although known to be present in the lectin-bound protein fractions (5), were not found among the crystal-binding proteins.…”

Section: Discussioncontrasting

confidence: 50%

“…These include a 130-kD glycoprotein (23) which recently was shown to be aminopeptidase N (24), biliary Igs (25), a-1 acid glycoprotein (26), phospholipase C (27), and fibronectin (28). As to inhibiting activity, however, only a 120-kD heterodimer glycoprotein with subunits of 58 and 63 kD was isolated from Helix pomatia lectin-bound proteins of normal human bile (6 We report new data on inhibition of cholesterol crystallization by biliary proteins. A new subgroup of four glycoproteins was isolated from different lectin-bound protein fractions that were known to contain both promoting and inhibiting factors of cholesterol crystallization (5).…”

Section: Discussionmentioning

confidence: 96%

“…By combining lectin affinity chromatography and a newly developed crystal growth assay (4) in a systematic study, various glycoprotein mixtures were separated from normal human bile, some of which primarily promoted and others primarily inhibited crystallization (5). Inhibiting activity was most potent in the Helix pomatia lectin-bound fraction from which a 120-kD heterodimer glycoprotein was isolated with subunits of 58 and 63 kD (6). Inhibiting potency of the heterodimer, however, was lower than the effect of total Helix pomatia lectin-bound fraction indicating other inhibitors do exist.…”

Section: Introductionmentioning

confidence: 95%

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A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization.

Busch

Lammert²,

Marschall³

et al. 1995

J. Clin. Invest.

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Biliary proteins inhibiting or promoting cholesterol crystallization are assumed to play a major role in cholesterol gallstone pathogenesis. We now report a new group of biliary proteins that bind to cholesterol crystals, modify crystal morphology, and inhibit cholesterol crystallization. Various glycoprotein mixtures were extracted from abnormal human gallbladder bile using lectin affinity chromatography on concanavalin A, lentil, and Helix pomatia columns and were added to supersaturated model bile. Independent of the protein mixtures added, from the cholesterol crystals harvested, the same four GPs were isolated having molecular masses of 16, 28, 63, and 74 kD, respectively. Each protein was purified using preparative SDS-PAGE, and influence on cholesterol crystallization in model bile was tested at 10 jig/ml. Crystal growth was reduced by 76% (GP63), 65% (GP16), 55% (GP74), and 40% (GP28), respectively. Thus, these glycoproteins are the most potent biliary inhibitors of cholesterol crystallization known so far. Evidence that the inhibiting effect on cholesterol crystallization is mediated via protein-crystal interaction was further provided from scanning electron microscopy studies. Crystals grown in presence of inhibiting proteins showed significantly more ordered structures. Incidence of triclinic crystals and regular aggregates was shifted from 30 to 70% compared with controls. These observations may have important implications for understanding the role of biliary proteins in cholesterol crystallization and gallstone pathogenesis. (J. Clin. Invest. 1995. 96:3009-3015.)

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Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 95%

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A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization.

Busch

Lammert²,

Marschall³

et al. 1995

J. Clin. Invest.

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“…In future investigations we might be looking for inhibitors for the AAG Protein, like the promising cholesterol antinucleating 120kDa glycoprotein found by Ohya et al [29]; or look for strategies to turn the genes off related to the over-expression of this AAG protein in vivo to control the cholesterol crystallization.…”

Section: Resultsmentioning

confidence: 99%

Macromolecular Biosensors Based on Proteins Involved in Bile Stones Formation

Bravo-Arredondo¹,

Robles-Aguila²,

Marín-García³

et al. 2013

State of the Art in Biosensors - Environmental and Medical Applications

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“…Holzbach et al7'23 identified apolipoprotein Al and AII as antinucleating agents, and this same group recently further characterized an antinucleating glycoprotein of 120 kD with subunits of 63 and 58 kD. 24 Mucous glycoprotein has been proposed as a pronucleating agent in both model bile and in native gallbladder bile. 25 Groen et al5 further described a 130-kD biliary nonmucin glycoprotein, isolated with Con-A- Single cholesterol 8 88 63 100 38 38 75 50 50 Multiple cholesterol 8 38 88 100 63 38 50 75 63 Pigment 7 71 86 100 71 43 71 57 29 Sepharose chromatography, with pronucleating activity.…”

Section: Discussionmentioning

confidence: 99%

Human Gallstones Contain Pronucleating Nonmucin Glycoproteins That are Immunoglobulins

et al. 1994

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ObjectivePronucleating nonmucin glycoproteins in human cholesterol and black gallstones were isolated and identified. Summary Background DataGallbladder bile contains nonmucin glycoproteins that are pronucleating of cholesterol monohydrate crystals. Little is known about the presence or activity of these proteins within gallstones. MethodsNonmucin glycoproteins were isolated from single cholesterol (n = 8), multiple cholesterol (n 8). and black pigment (n = 8) gallstones by concanavalin A lectin-affinity chromatography. The proteins were separated by sodium dodecyl sulfate gradient electrophoresis. Western blot analysis was performed for Fab immunoglobulin fragments, and heavy chains from the immunoglobulin G, A, E, and M subclasses. A crystal observation time assay was performed on the combination of isolated nonmucin glycoproteiris from gallstones and isolated Fab fragments. ResultsNonmucin glycoproteins of molecular weights 10, 15, 17, 22, 28, and

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Isolation of a human biliary glycoprotein inhibitor of cholesterol crystallization

Cited by 62 publications

References 40 publications

A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization.

A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization.

Macromolecular Biosensors Based on Proteins Involved in Bile Stones Formation

Human Gallstones Contain Pronucleating Nonmucin Glycoproteins That are Immunoglobulins

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