Increased Activity in the Biliary Con A-Binding Fraction Accounts for the Difference in Crystallization Behavior in Bile From Chilean Gallstone Patients Compared With Dutch Gallstone Patients

Miquel, Juan Francisco; Putten, Joris van der; Pimentel, Fernando; Mok, King-Tong; Groen, Albert K.

doi:10.1053/jhep.2001.21550

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…Gallbladder bile was obtained during laparoscopic cholecystectomy. Biliary glycoproteins were extracted with Concanavalin–A (Con‐A) sepharose beads using a method previously described 31…”

Section: Methodsmentioning

confidence: 99%

NPC2 is expressed in human and murine liver and secreted into bile

et al. 2006

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The liver plays a critical role in the metabolism of lipoprotein cholesterol and in controlling its elimination through the bile. Niemann-Pick type C 2 (NPC2), a cholesterol-binding protein, is key for normal intracellular trafficking of lipoprotein cholesterol, allowing its exit from the endolysosomal pathway into the metabolically active pool of the cell. In addition, NPC2 is a secretory protein from astrocytes and epididymal cells. Although NPC2 mRNA is detected in the liver, plasma and biliary NPC2 protein levels and function have not been reported. This study demonstrates that NPC2 is present in murine and human plasma and bile. In addition, hepatic NPC2 protein expression was dramatically increased in NPC1-deficient mice but not regulated by cholesterol feeding or pharmacological modulation of various nuclear receptors involved in cholesterol and bile acid metabolism. Interestingly, biliary NPC2 levels were 3-fold increased in gallstone-susceptible C57BL6/J versus gallstone-resistant BALB/c mice. Furthermore, NPC2 was exclusively found in the cholesterol pro-nucleating ConA-binding fraction of human bile. In conclusion, NPC2 is secreted from the liver into bile and plasma, where it may have a functional role in cholesterol transport in normal and disease conditions. (HEPATOLOGY 2006;43:126-133.)

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Section: Methodsmentioning

confidence: 99%

NPC2 is expressed in human and murine liver and secreted into bile

et al. 2006

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“…Interestingly, a cross-ethnic study comparing the lithogenic properties of bile from cholesterol GSD patients from Chile (Latinos) and The Netherlands (Dutch) clearly showed significant differences between bile samples from these two countries. Bile from Chileans showed significantly faster cholesterol nucleation time and higher protein content (mainly IgA and probably also mucin), in spite of lower cholesterol saturation index [71]. Even though histological analysis was not performed, this study suggests that the lithogenic process and degree of gallbladder inflammatory response differs between ethnic groups with different risks of GSD GBC [71].…”

Section: Gallstone Disease Chronic Inflammation and Gallbladder Cancmentioning

confidence: 99%

“…Bile from Chileans showed significantly faster cholesterol nucleation time and higher protein content (mainly IgA and probably also mucin), in spite of lower cholesterol saturation index [71]. Even though histological analysis was not performed, this study suggests that the lithogenic process and degree of gallbladder inflammatory response differs between ethnic groups with different risks of GSD GBC [71]. Of note, Native Americans and Latinos with high Native American ancestry tend to develop GSD early in life and are more likely to develop symptoms or complications and present with multiple gallstones rather than solitary gallstones [72].…”

Section: Gallstone Disease Chronic Inflammation and Gallbladder Cancmentioning

confidence: 99%

The inflammatory inception of gallbladder cancer

Espinoza

Bizama

García

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

115

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Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia–dysplasia–carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.

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“…Some publications confirmed that most biliary proteins are currently considered to be secondary to gallstone formation or inflammation, with the possible exception of mucin [11], [12]. However, other scientists reach a consensus that the biliary proteins might play an important role [23]. In general, in vivo studies that analyzed the role of putative pro-nucleating proteins have been hampered by a number of factors.…”

Section: Discussionmentioning

confidence: 99%

Comparative Proteomic Analysis of Gallbladder Bile Proteins Related to Cholesterol Gallstones

et al. 2013

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BackgroundNucleation of cholesterol monohydrate crystals following the aggregation and fusion of cholesterol-enriched vesicles is a critical procedure in the formation of cholesterol gallstone. Biliary proteins play important roles in the process. It is inefficient to screen pro-nucleating or anti-nucleating proteins with routine physiochemical techniques, by which we discovered several pro-nucleating proteins.Methodology/Principal FindingsBased on comparative proteomic technologies, we investigated the differentially expressed proteins between the cholesterol gallstone and control groups, and between the vesicular phase and micellar phase. There are 401±75 spots detected on the cholesterol gallstone group and 389±94 spots on the control group gels, 120±24 spots detected on vesicular phase and 198±37 on micellar phase gels, and accordingly 22 and 8 differentially expressed proteins were identified successfully, respectively. Three of them, HSA, Profilin and Retinol Binding Protein, were validated by Western blot.Conclusion/SignificanceSome of the identified proteins are in good agreement with proteins reported to be involved in the gallstone formation before. The information from this study might provide some important clues to uncover the key proteins involved in the formation of cholesterol gallstone.

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Increased Activity in the Biliary Con A-Binding Fraction Accounts for the Difference in Crystallization Behavior in Bile From Chilean Gallstone Patients Compared With Dutch Gallstone Patients

Cited by 10 publications

References 20 publications

NPC2 is expressed in human and murine liver and secreted into bile

NPC2 is expressed in human and murine liver and secreted into bile

The inflammatory inception of gallbladder cancer

Comparative Proteomic Analysis of Gallbladder Bile Proteins Related to Cholesterol Gallstones

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