scholarly journals Deoxycholic Acid Could Induce Apoptosis and Trigger Gastric Carcinogenesis on Gastric Epithelial Cells by Quantitative Proteomic Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Yanyan Shi ◽  
Ying Wei ◽  
Ting Zhang ◽  
Jing Zhang ◽  
Ye Wang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gastric Mucosa ◽  
Bile Acids ◽  
Molecular Mechanisms ◽  
Deoxycholic Acid ◽  
Bile Reflux ◽  
Epithelial Cell Line ◽  
Gastric Mucosal Lesions ◽  
Tandem Mass Spectrometric ◽  
String Programs

Background.Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. Bile reflux has been generally considered to be associated with intestinal metaplasia and gastric cancer. However, the pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown.Methods.To explore the mechanisms by which bile acids induce gastric mucosal lesions, we examined cell apoptosis in the gastric epithelial cell line GES-1 and investigated the changes in protein profiles of GES-1 cells in response to a bile acid deoxycholic acid using a proteomics approach. Changes in the profiles of the differently expressed proteins were analyzed using the DAVID and STRING programs.Results.We found apoptosis was significantly induced in GES-1 cells by deoxycholic acid. Using liquid chromatographic/tandem mass spectrometric (LC-MS/MS) methods, 134 upregulated proteins and 214 downregulated proteins were identified in the bile acid treated GES-1 cells. Bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins.Conclusion.These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa.

scholarly journals Human and livestock faecal biomarkers at the prehistorical encampment site of Ullafelsen in the Fotsch Valley, Stubai Alps, Austria – potential and limitations

2021 ◽  
Author(s):  
Marcel Lerch ◽  
Tobias Bromm ◽  
Clemens Geitner ◽  
Jean Nicolas Haas ◽  
Dieter Schäfer ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Deoxycholic Acid ◽  
Soil Samples ◽  
Hunter Gatherers ◽  
Amazonian Dark Earths ◽  
Biomarker Pattern ◽  
Mesolithic Period ◽  
Exact Timing ◽  
Cattle And Sheep

Abstract. The Ullafelsen at 1869 m a.s.l. in the Tyrolean Stubai Alps next to Innsbruck is an important (geo-)archaeological reference site for the Mesolithic period. Buried fireplaces on the Ullafelsen plateau were dated at 10.9–9.5 cal. kyrs BP and demonstrate together with thousands of flint stone artifacts the presence of hunter-gatherers during the Early Holocene. Most recently, we demonstrated the great potential of n-alkane and black carbon biomarkers for contributing to a better understanding of pedogenesis and landscape evolution. In order to study the importance of human and/or animals for occupation of this relevant geoarchaeological site, we carried out steroid and bile acid analyses on two modern faeces samples from cattle and sheep and on 37 soil samples from seven soil profiles at the Ullafelsen. The modern animal faeces show a dominance of 5β-stigmastanol and deoxycholic acid for ruminants (cattle and sheep), which is in agreement with literature data. The OAh horizons, which have accumulated and developed since the Mesolithic, revealed high contents of steroids and bile acids; the E (LL) horizon coinciding with the Mesolithic living floor is characterized by medium contents of steroids and bile acids. By contrast, the subsoil horizons Bh, Bs and BvCv contain low contents of faecal biomarkers indicating that leaching of steroids and bile acids into the podsolic subsoils is not an important factor. Deoxycholic acid is the most abundant bile acid in all soil samples and gives evidence for strong faeces input of ruminants. The steroid and bile acid patterns and ratios indicate a negligible input of human faeces on the Ullafelsen. β-Sitosterol as plant-derived steroid has also a strong influence on the faecal biomarker pattern in our soils. Root input into the subsoils is likely reflected by β-sitosterol contents. In conclusion, our results reflect a strong faecal input by livestock, rather than by humans as found for other Anthrosols such as Amazonian Dark Earths. Further studies need to focus on the question of the exact timing of faeces deposition.

Radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid from human serum, with use of 125I-labeled ligands.

1979 ◽  
Vol 25 (2) ◽  
pp. 264-268 ◽  
Author(s):  
O Mäentausta ◽  
O Jänne
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Chenodeoxycholic Acid ◽  
Deoxycholic Acid ◽  
Serum Samples ◽  
Analytical Recovery ◽  
Hepatobiliary Diseases ◽  
Polyethylene Glycol Precipitation ◽  
Free Serum

Abstract We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). Before radioimmunoassay, 0.1-mL serum samples were precipitated with nine volumes of ethanol, and portions from the supernate were used in the assays. The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates. 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 3.2 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +/- SD) of the bile acid conjugates in serum from apparently healthy women and men (in mumol/L) were: cholic acid conjugates, 0.43 +/- 0.17 (n = 126); chenodeoxycholic acid conjugates, 0.47 +/- 0.23 (n = 111); and deoxycholic acid conjugates, 0.33 +/- 0.11 (n = 96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases.

III. Bile acids and nuclear receptors

2003 ◽  
Vol 284 (3) ◽  
pp. G349-G356 ◽  
Author(s):  
John Y. L. Chiang
Keyword(s):  
Bile Acid ◽  
Cardiovascular Diseases ◽  
Bile Acids ◽  
Nuclear Receptors ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Regulatory Genes ◽  
Cholesterol Homeostasis ◽  
Physiological Pathways ◽  
Bile Acid Receptor

Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Recent studies reveal that bile acids also are signaling molecules that activate several nuclear receptors and regulate many physiological pathways and processes to maintain bile acid and cholesterol homeostasis. Mutations of the principal regulatory genes in bile acid biosynthetic pathways have recently been identified in human patients with hepatobiliary and cardiovascular diseases. Genetic manipulation of key regulatory genes and bile acid receptor genes in mice have been obtained. These advances have greatly improved our understanding of the molecular mechanisms underlying complex liver physiology but also raise many questions and controversies to be resolved. These developments will lead to early diagnosis and discovery of drugs for treatment of liver and cardiovascular diseases.

scholarly journals Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria

2018 ◽  
Vol 84 (10) ◽  
Author(s):  
Heidi Doden ◽  
Lina A. Sallam ◽  
Saravanan Devendran ◽  
Lindsey Ly ◽  
Greta Doden ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Deoxycholic Acid ◽  
Gut Bacteria ◽  
Dietary Lipids ◽  
Human Gut ◽  
Content Type ◽  
Low Activity

ABSTRACTBile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacteriumClostridium leptum; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such asClostridium scindens,Clostridium hylemonae, andClostridium hiranonis. Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread amongFirmicutes,Actinobacteriain theCoriobacteriaceaefamily, and human gutArchaea.IMPORTANCE12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteriaC. scindens,C. hiranonis, andC. hylemonae. Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract.

scholarly journals Bile salts of the green turtle Chelonia mydas (L.)

1978 ◽  
Vol 171 (2) ◽  
pp. 409-412 ◽  
Author(s):  
G A D Haslewood ◽  
S Ikawa ◽  
L Tökés ◽  
D Wong
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Green Turtle ◽  
Bile Salts ◽  
Deoxycholic Acid ◽  
Enterohepatic Circulation ◽  
Chelonia Mydas ◽  
Independent Evolution ◽  
Alpha 7

1. Bile salts of the green turtle Chelonia mydas (L.) were analysed as completely as possible. 2. They consist of taurine conjugates of 3 alpha, 7 alpha, 12 alpha, 22 xi-tetrahydroxy-5 beta-cholestan-26-oic acid (tetrahydroxysterocholanic acid) and 3 alpha 12 alpha, 22 xi-trihydroxy-5 beta-cholestan-26-oic acid, with minor amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5beta-cholan-24-oic acid (cholic acid), 3alpha, 12 alpha-dihydroxy-5beta-cholan-24-oic acid (deoxycholic acid) and possibly other bile acids. 3. Cholic acid and deoxycholic acid represent the first known examples of bile acids common to chelonians and other animal forms: they may indicate independent evolution in chelonians to C24 bile acids. 4. The discovery of a 7-deoxy C27 bile acid is the first evidence that C27 bile acids or their conjugates have an enterohepatic circulation.

scholarly journals 1039. Rapid Restoration of Bile Acid Compositions After Treatment with RBX2660 for Recurrent Clostridioides difficile Infection—Results from the PUNCH CD3 Phase 3 Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S610-S610
Author(s):  
Romeo Papazyan ◽  
Bryan Fuchs ◽  
Ken Blount ◽  
Carlos Gonzalez ◽  
Bill Shannon
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Deoxycholic Acid ◽  
Lithocholic Acid ◽  
Point Group ◽  
Bile Acid Metabolism ◽  
Phase 3 ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Time Point

Abstract Background Microbiota-based treatments are increasingly evaluated as a strategy to reduce recurrence of Clostridioides difficile infection (rCDI), and their proposed mechanisms include restoration of the microbiota and microbiota-mediated functions, including bile acid metabolism. RBX2660—a broad-consortium investigational live biotherapeutic—has been evaluated in >600 participants in 6 clinical trials, with consistent reduction of rCDI recurrence. Here we report that fecal bile acid compositions were significantly restored in treatment-responsive participants in PUNCH CD3—a Phase 3 randomized, double-blinded, placebo-controlled trial of RBX2660. Methods PUNCH CD3 participants received a single dose of RBX2660 or placebo between 24 to 72 hours after completing rCDI antibiotic treatment. Clinical response was the absence of CDI recurrence at eight weeks after treatment. Participants voluntarily submitted stool samples prior to blinded study treatment (baseline), 1, 4 and 8 weeks, 3 and 6 months after receiving study treatment. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 33 bile acids from all participant fecal samples received up to the 8-week time point. Mean bile acid compositions were fit to a Dirichlet multinomial distribution and compared across time points and between RBX2660- and placebo-treated participants. Results Clinically, RBX2660 demonstrated superior efficacy versus placebo (70.4% versus 58.1%). RBX2660-treated clinical responders’ bile acid compositions shifted significantly from before to after treatment. Specifically, primary bile acids predominated before treatment, whereas secondary bile acids predominated after treatment (Figure 1A). These changes trended higher among RBX2660 responders compared to placebo responders. Importantly, median levels of lithocholic acid (LCA) and deoxycholic acid (DCA) showed large, significant increases after treatment (Figure 1B). A. Bile acid compositions before (BL) and up to 8 weeks after RBX2660 treatment among treatment responders. Compositions are shown as the fraction of total bile acids classified as primary or secondary conjugated or deconjugated bile acids. B. Concentrations of lithocholic acid (LCA) and deoxycholic acid (DCA) among RBX2660 treatment responders, shown with individual samples and time point group median with interquartile ranges. Conclusion Among PUNCH CD3 clinical responders, RBX2660 significantly restored bile acids from less to more healthy compositions. These clinically correlated bile acid shifts are highly consistent with results from a prior trial of RBX2660. Disclosures Romeo Papazyan, PhD, Ferring Research Institute (Employee) Bryan Fuchs, PhD, Ferring Pharmaceuticals (Employee) Ken Blount, PhD, Rebiotix Inc., a Ferring Company (Employee)

Differential effects of calcium ions and calcium phosphate on cytotoxicity of bile acids

1991 ◽  
Vol 260 (1) ◽  
pp. G142-G147 ◽  
Author(s):  
R. Van der Meer ◽  
D. S. Termont ◽  
H. T. De Vries
Keyword(s):  
Bile Acid ◽  
Calcium Phosphate ◽  
Bile Acids ◽  
Colonic Mucosa ◽  
Molecular Mechanisms ◽  
Epithelial Proliferation ◽  
Cytotoxic Potential ◽  
Glycine Conjugate ◽  
Taurine Conjugate ◽  
Secondary Bile Acids

Unconjugated secondary bile acids can promote colon cancer by damaging colonic mucosa and consequently increasing epithelial proliferation. It has been proposed that dietary calcium inactivates intestinal bile acids either by a Ca2(+)-dependent precipitation or by binding to insoluble calcium phosphate (CaPi). We studied the molecular mechanisms of these opposing hypotheses by using hemolysis of erythrocytes as a model parameter for cytotoxicity. Washed human erythrocytes were incubated for 15 min with buffered media (pH 7.4) containing increasing amounts of different bile acids. Deconjugation and 7 alpha-dehydroxylation of mixtures of glycine- or taurine-conjugated cholate and chenodeoxycholate drastically increased their cytotoxicity. Parallel measurements, using a fluorescent micellar probe, indicated that micellar aggregation is a prerequisite for this bile acid-induced lysis. Ca2+ concentrations up to 15 mM did not precipitate bile acids but stimulated cytotoxicity of both deoxycholate (DC) and its glycine conjugate (GDC). Cytotoxicity of the taurine conjugate (TDC) was stimulated to a much lesser extent. Increasing amounts of CaPi precipitated micellar DC and GDC, but not TDC, and consequently inhibited only cytotoxicity of the former two. These findings indicate that 1) hydrophobicity and micellar aggregation are important determinants of bile acid-induced cytotoxicity that explain the high cytotoxic potential of secondary bile acids in colon, and 2) cytotoxicity of bile acids is stimulated by free Ca2+ and inhibited by CaPi. This inhibition is due to binding of carboxylic (including secondary) bile acids to CaPi.

Mechanisms of Tauroursodeoxycholate-Mediated Hepatoprotection

2017 ◽  
Vol 35 (3) ◽  
pp. 224-231 ◽  
Author(s):  
Dieter Häussinger ◽  
Claus Kordes
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Molecular Mechanisms ◽  
Clinical Medicine ◽  
Basolateral Membrane ◽  
Sodium Taurocholate ◽  
Growth Factor Receptor ◽  
Adenosine Monophosphate ◽  
Farnesoid X Receptor ◽  
Integrin Subunit

Ursodeoxycholate and its taurine conjugate tauroursodeoxycholate (TUDC) promote choleresis by triggering the insertion of transport proteins for bile acids into the canalicular and basolateral membranes of hepatocytes. In addition, TUDC exerts hepatoprotective and anti-apoptotic effects, can counteract the action of toxic bile acids and reduce endoplasmic reticulum stress. TUDC can also initiate the differentiation of multipotent mesenchymal stem cells (MSC) including hepatic stellate cells and promote their development into hepatocyte-like cells. Although the hepatoprotective and choleretic action of TUDC is empirically used in clinical medicine since decades, the underlying molecular mechanisms remained largely unclear. Since TUDC has little or no potency to activate known bile acid receptors, such as farnesoid X receptor and transmembrane G protein-coupled bile acid receptor, other receptors must be involved in TUDC-mediated signaling. Recent research demonstrates that integrins serve as sensors for TUDC. After binding of TUDC to α5β1-integrin, the β1-integrin subunit becomes activated through a conformational change, thereby triggering integrin signaling with the downstream activation of focal adhesion kinase, c-Src, the epidermal growth factor receptor and activation of the mitogen-activated protein kinases, Erks and p38. These events trigger choleresis through a coordinated insertion of the sodium-taurocholate cotransporting polypeptide into the basolateral membrane and of the bile salt export pump into the canalicular membrane. In addition to its choleretic action, TUDC-induced integrin activation triggers a cyclic adenosine monophosphate-dependent protein kinase A activation in hepatocytes, which provides the basis for the anti-apoptotic effect of TUDC. On the other hand, the TUDC-induced stimulation of MSC differentiation appears not to be mediated by integrins. This article gives a brief overview about our work on the signaling network-mediating hepatoprotection by TUDC.

scholarly journals Preparation of the 3-monosulphates of cholic acid, chenodeoxycholic acid and deoxycholic acid

1976 ◽  
Vol 155 (2) ◽  
pp. 401-404 ◽  
Author(s):  
E S. Haslewood ◽  
G A. D. Haslewood
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Chenodeoxycholic Acid ◽  
Deoxycholic Acid ◽  
Single Step ◽  
Acid Sulphate

1. The 3-sulphates of cholic, chenodeoxycholic and deoxycholic acids were prepared as crystalline disodium salts. 2. The method described shows that it is possible to prepare specific sulphate esters of polyhydroxy bile acids and to remove protecting acyl groups without removing the sulphate. 3. A study of bile acid sulphate solvolysis showed that none of the usual methods give the original bile acid in major yield in a single step. 4. An understanding of the preparation, properties and methods of solvolysis of bile acid sulphates is basic for investigations of cholestasis and liver disease.

Influence of Deoxycholic Acid Feeding on the Elimination of Cholesterol in Normolipaemic Subjects

1974 ◽  
Vol 47 (5) ◽  
pp. 425-433
Author(s):  
K. Einarsson ◽  
K. Hellström ◽  
M. Kallner
Keyword(s):  
Bile Acid ◽  
Total Synthesis ◽  
Bile Acids ◽  
Cholic Acid ◽  
Chenodeoxycholic Acid ◽  
Deoxycholic Acid ◽  
Cholesterol Metabolism ◽  
Pool Size ◽  
Faecal Excretion ◽  
The Mean

1. The turnover of [24−14C]cholic acid and [3H]chenodeoxycholic acid and the faecal excretion of neutral steroids were studied in six normolipaemic subjects before and during the ingestion of 1.3–2.6 mmol (0.5–1.0 g) of deoxycholic acid/day. Before the second study the subjects had been fed deoxycholic acid for 2 weeks. 2. The administration of deoxycholic acid did not appear to influence cholesterol metabolism as judged by the absence of change in the serum concentrations and the overall transformation into primary bile acids and neutral faecal steroids. 3. During the deoxycholic acid feeding period the mean total synthesis of bile acids was reduced by about 30%, corresponding to approximately 0.25 mmol (100 mg)/day. In one subject the pool size and in another the synthesis of cholic acid remained unchanged; otherwise the cholic acid pool size and its rate of formation decreased in all subjects. No consistent effects were observed with regard to the turnover of chenodeoxycholic acid. 4. Assuming that the bile acid turnover is equivalent to bile acid excretion then the total amount of cholesterol eliminated as bile acids and neutral faecal steroids averaged between 1.6 and 1.8 mmol/day before and during the administration of deoxycholic acid.

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