Mucin-vesicle interactions in model bile: Evidence for vesicle aggregation and fusion before cholesterol crystal formation

Afdhal, Nezam H.; Niu, Niu; Nunes, David; Bansil, Rama; Cao, Xing Xiang; Gantz, Donald; Small, Donald; Offner, Gwynneth D.

doi:10.1002/hep.1840220325

Cited by 25 publications

(50 citation statements)

References 37 publications

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“…[1][2][3][4][5][23][24][25][26][27][28][36][37][38] Although evidence is mounting that dimin-mucin was a dominant force in stone formation in the cholesished gallbladder emptying, in response to a meal and/or terol / MK-329 group. MK-329 was not only effective in CCK infusion, is present in a large proportion of patients inducing stasis in control animals, but clearly aggravated with cholesterol gallstones, neither the sequential events nor gallbladder stasis in animals on the 1% high-cholesterol diet, the overall influence of gallbladder stasis on the whole pro-as evidenced by the greatest reduction in gallbladder contraccess of stone formation is fully understood.…”

Section: Aid Hepa 0040mentioning

confidence: 99%

“…1A) might indicate that mucin productial stage of cholesterol gallstone formation with an emphasis tion was already near maximal in the presence of bile satuon its local effect on the gallbladder. 1,5,19,[23][24][25][26][27][28] rated with cholesterol (Table 1). It may also suggest that The present findings showed that sustained suppression stasis in itself or altered intraluminal pressure alone is less of gallbladder emptying with MK-329 reduces the CSI in important for provoking gallbladder mucin production in bile.…”

Section: Aid Hepa 0040mentioning

confidence: 99%

“…[9][10][11][12][13][14] We have previously pro-in experimental animals. [23][24][25][26][27][28]34 The reduced evacuation of posed that the MK-329-induced fall in CSI is largely caused gallbladder contents, 1,5,36 especially in animals on the 1%-by the increased hepatic secretion of bile salts.…”

Section: Aid Hepa 0040mentioning

confidence: 99%

“…i.e., in the presence of supersaturated bile, gallbladder stasis may cause an increased production and/or accumulation of Gallbladder motility defects are present in most patients mucin within the gallbladder, thereby providing both the with cholesterol gallstones, yet the sequential events are unresidence time and the medium necessary for the nucleation clear and the question remains whether gallbladder stasis is of cholesterol crystals. [17][18][19][23][24][25][26][27][28] a causative factor of gallstone disease or merely a conseTo further explore the nature of gallbladder stasis in the whole process of cholesterol gallstone formation, we used a specific CCK-A receptor antagonist 29,30 ) to pro- HEPATOLOGY October 1997 mental animals were then divided randomly into two dietary groups and gallbladder washings was analyzed using a nitrocellulose slotblot assay stained with periodic acid-Schiff (PAS) reagent. 32 Stained and maintained for an additional 4 weeks on either a control chow diet (n Å 64) with a trace (standard) cholesterol content (0.027%) blots were scanned on a laser densitometer, and the amount of mucin present in each test sample was determined by comparing (United States Biochemical, Cleveland, OH) or a high-cholesterol diet (n Å 64) comprised of an identical chow, enriched with 1% its peak area with standard curves obtained by applying purified rat intestinal mucin (0.3-25 mg) to the nitrocellulose blot.…”

mentioning

confidence: 99%

“…[17][18][19][23][24][25][26][27][28] a causative factor of gallstone disease or merely a conseTo further explore the nature of gallbladder stasis in the whole process of cholesterol gallstone formation, we used a specific CCK-A receptor antagonist (MK-329 14,29,30 ) to proAbbreviations: CCK, cholecystokinin; CSI, cholesterol saturation index; PAS, periduce prolonged gallbladder hypomotility in ground squirrels odic acid-Schiff.…”

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Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel

Xu¹

1997

Hepatology

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Although gallbladder stasis exists in most patients with quence of it. [1][2][3][4][5] Identifying events in a chronological fashion is particularly difficult in humans before gallstone formation. 5 cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of Defective gallbladder emptying likely occurs before stone formation, followed by the appearance of cholesterol crysit. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)-A receptor antagonist (MK-tals. 1,6,7 In one report on patients with cholesterol crystals alone (without gallstones), gallbladder emptying was im-329) on gallstone formation in ground squirrels fed either a trace or a high-cholesterol diet. MK-329 markedly inhibited paired. 6 Unfortunately, all the patients in this study had chronic cholecystitis, a confounding factor, which in itself gallbladder contraction in vitro in response to CCK (at EC 100 , control: 3.6 { 0.5 vs. MK-329: 1.1 { 0.3 g; P õ .05) and could have adversely affected gallbladder motor function. 1,5,8 Ground squirrels fed a high-cholesterol diet form cholesincreased gallbladder fasting volume in vivo (control: 462 { 66 vs. MK-329: 1,004 { 121 mL; P õ .05). Whereas the terol crystals and/or gallstones within a reasonably short period. [9][10][11][12][13] Defective gallbladder contractility develops very high-cholesterol diet alone (1%-cholesterol diet / placebo) increased the cholesterol saturation index (CSI) in control early in these animals, concurrent with a rise in cholesterol saturation of bile and the appearance of cholesterol crystals, animals (trace-cholesterol diet / placebo), MK-329 significantly (P õ .05) decreased the CSI in both hepatic and gall-but before stone formation. A major limitation in this model is the inability to assess directly the primary role of gallbladbladder bile in animals on the trace-(trace-cholesterol diet / MK-329) as well as on the high-cholesterol diets (1%-choles-der hypomotility in the process of gallstone formation because of the concurrent changes in both hepatic bile formaterol diet / MK-329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than tion and gallbladder motility.13-14 Our previous study in the same animal model showed that a cholecystokinin (CCK)-A doubled (P õ .05) with the high-cholesterol diet; adding MK-329 to the latter group produced a further 82% increase (P receptor antagonist (MK-329) suppressed gallbladder emptying, but reduced the cholesterol saturation in both hepatic õ .05). The cholesterol diet / MK-329 group had the highest (100%) incidence of cholesterol crystals that were evident in and gallbladder bile.14 This apparent paradox challenges the traditional concept that gallbladder stasis is a primary fresh gallbladder bile, coincident with a shortened nucleation time (2.5 { 0.6 days; P õ .05 vs. the cholesterol diet / and/or contributing factor in cholesterol gallstone formation. [1][2][3][15][16][17][18] placebo ...

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Section: Aid Hepa 0040mentioning

confidence: 99%

Section: Aid Hepa 0040mentioning

confidence: 99%

Section: Aid Hepa 0040mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel

Xu¹

1997

Hepatology

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Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel

Chen

Mantle

et al. 1997

Hepatology

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Although gallbladder stasis exists in most patients with cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of it. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)-A receptor antagonist (MK-329) on gallstone formation in ground squirrels fed either a trace or a high-cholesterol diet. MK-329 markedly inhibited gallbladder contraction in vitro in response to CCK (at EC100, control: 3.6 +/- 0.5 vs. MK-329: 1.1 +/- 0.3 g; P < .05) and increased gallbladder fasting volume in vivo (control: 462 +/- 66 vs. MK-329: 1,004 +/- 121 microL; P < .05). Whereas the high-cholesterol diet alone (1%-cholesterol diet + placebo) increased the cholesterol saturation index (CSI) in control animals (trace-cholesterol diet + placebo), MK-329 significantly (P < .05) decreased the CSI in both hepatic and gallbladder bile in animals on the trace-(trace-cholesterol diet + MK-329) as well as on the high-cholesterol diets (1%-cholesterol diet + MK-329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than doubled (P < .05) with the high-cholesterol diet; adding MK-329 to the latter group produced a further 82% increase (P < .05). The cholesterol diet + MK-329 group had the highest (100%) incidence of cholesterol crystals that were evident in fresh gallbladder bile, coincident with a shortened nucleation time (2.5 +/- 0.6 days; P < .05 vs. the cholesterol diet + placebo group, 5.8 +/- 1.0 days or the other 2 groups, >21 days). Bile from animals on the trace-cholesterol diet, whether or not receiving MK-329, lacked crystals in bile and exhibited a normal nucleation time (>21 days). Thus, stasis per se may lower the CSI, but its detrimental effect on the gallbladder predominates locally, and so accelerates cholesterol crystal formation in this model.

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Comprehensive proteomic analysis of human bile

et al. 2011

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Bile serves diverse functions from metabolism to transport. In addition to acids and salts, bile is composed of proteins secreted or shed by the hepatobiliary system. Although there have been previous efforts to catalog biliary proteins, an in-depth analysis of the bile proteome has not yet been reported. We carried out fractionation of non-cancerous bile samples using a multipronged approach (SDS-PAGE, SCX and OFFGEL) followed by MS analysis on an LTQ-Orbitrap Velos mass spectrometer using high resolution at both MS and MS/MS levels. We identified 2552 proteins - the largest number of proteins reported in human bile till date. To our knowledge, there are no previous studies employing high-resolution MS reporting a more detailed catalog of any body fluid proteome in a single study. We propose that extensive fractionation coupled to high-resolution MS can be used as a standard methodology for in-depth characterization of any body fluid. This catalog should serve as a baseline for the future studies aimed at discovering biomarkers from bile in gallbladder, hepatic, and biliary cancers.

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Mucin-vesicle interactions in model bile: Evidence for vesicle aggregation and fusion before cholesterol crystal formation

Cited by 25 publications

References 37 publications

Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel

Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel

Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel

Comprehensive proteomic analysis of human bile

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