Disease relevance of cholate

• Here we show that 5-LO-positive macrophages localize to the adventitia of diseased mouse and human arteries in areas of neoangiogenesis and that these cells constitute a main component of aortic aneurysms induced by an atherogenic diet containing cholate in mice deficient in apolipoprotein E [1].
• Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene [2].
• The marked decrease in 7 alpha-dehydroxylase activity of fecal bacteria of some patients with alcoholic cirrhosis results in impaired conversion of cholate to deoxycholate and explains the lack of biliary deoxycholate in these patients [3].
• The lamB protein, the receptor for phage lambda, was purified from the outer membrane of Escherichia coli K-12 by extraction with Triton X-100 and EDTA, chromatography on DEAE-Sephacel in Triton X-100, exchange of Triton for cholate by gel filtration, and chromatography on Sephacryl S-200 in cholate, NaCl, and EDTA [4].
• Plasma membrane fractions isolated from mouse fibroblast BALB/c 3T3 cells transformed by simian virus 40 were partially purified by treatment with dimethylmaleic anhydride followed by extraction with 2% cholate [5].

High impact information on cholate

• This altered pattern of adenylate cyclase regulation was reproduced when a cholate extract of the tumour membranes (which contains G proteins) was reconstituted with Gs-free, cyc- S49 cell membranes [6].
• The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor [7].
• Human LDL and HDL3 reconstituted with radiolabeled lipids were incubated with purified porcine CEL without or with cholate (10 or 100 microM, concentrations achievable in systemic or portal plasma, respectively) [8].
• Pancreatic carboxyl ester lipase (CEL) hydrolyzes cholesteryl esters (CE), triglycerides (TG), and lysophospholipids, with CE and TG hydrolysis stimulated by cholate [8].
• METHODS: Mice (+/+) wild type or (-/-) knockout for the mdr2 gene were fed with either purified control diet or this diet supplemented with cholate (0.1%) or ursodeoxycholate (0.5%) for 3, 6, or 22 weeks after weaning [2].

Chemical compound and disease context of cholate

• Plasma membranes, isolated from Ehrlich ascites tumor cells, were dissolved in 2% cholate, 4 M urea and then reformed into liposomes upon dialysis at 4 degrees with exogenous phospholipids [9].
• Two proteins serving as substrates for ADP-ribosylation catalyzed by islet-activating protein (IAP), pertussis toxin, and binding guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) with high affinities were purified from the cholate extract of rat brain membranes [10].
• C6 rat glioma cells were investigated for a shared unidirectional efflux system for cAMP and cholate [11].
• The membrane carrier for L-proline (product of the putP gene) of Escherichia coli K12 was solubilized and functionally reconstituted with E. coli phospholipid by the cholate dilution method [12].
• The role of the stimulatory guanine nucleotide regulatory protein (Gs) in this dysautonomia was studied by cholate extraction of Gs from erythrocytes from 11 normal subjects and 14 symptomatic dysautonomic patients and reconstitution into cyc-S49 lymphoma membranes, which have normal receptor and adenylyl cyclase but lack Gs [13].

Biological context of cholate

• HDL3-TG hydrolysis was also observed, but was only approximately 5-10% of that for HDL3-CE at either 10 or 100 microM cholate [8].
• When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene [14].
• Cholate feeding to rats with intact enterohepatic circulation increased mdr2 transcriptional activity by 4-fold and protein mass by 1.9-fold [15].
• AOM, in unsupplemented or cholate-supplemented groups, caused significant down-regulation of PKC-alpha, -delta and -zeta and up-regulation of PKC-beta II, while increasing particulate PKC-alpha, -beta II, and -zeta in carcinogen-induced tumors compared to normal colonocytes [16].
• The results with free cholate indicate the presence of an activator binding domain on the enzyme with minimal overlap on the substrate binding sites [17].

Anatomical context of cholate

• This indicates the intestinal contents as the source of the plasma cholate and shows an equilibrium between intestinal and plasma bile acid even without bile flow [18].
• In contrast, cholate, taurocholate, tauroursodeoxycholate, glycoursodeoxycholate, and taurochenodeoxycholate inhibited pancreatic secretion and increase in the plasma cholecystokinin concentration produced by exclusion of bile and pancreatic juice [19].
• Sedimentable complexes without ribosomes containing both ribophorins could also be obtained by dissolving RM previously stripped of ribosomes by puromycin-KCl using cholate, a milder detergent than DOC [20].
• The integral membrane protein Band 3 of the human erythrocyte, either purified or in a crude Triton X-100 extract of ghosts, was combined with egg lecithin in a cholate solution [21].
• Acetylcholine receptor, solubilized and purified from Torpedo californica electric organ under conditions that preserve the activity of its ion channel, was reconstituted into vesicles of soybean lipid by the cholate-dialysis technique [22].

Associations of cholate with other chemical compounds

• Peripheral tissues contained virtually only cleared taurocholate, but the intestinal contents were mainly free cholate [18].
• Serosal exposure to deoxycholate (0.2-2 mM), cholate (2-8 mM), or taurocholate (4-80 mM), at pH 7.4, decreased acid secretion depending on the concentration and time of exposure [23].
• (i) Purified beta-receptor polypeptides were coupled in phospholipid (asolectin) vesicles with GS from a crude cholate or lauroyl sucrose extract of turkey erythrocyte membranes [24].
• D2 dopamine receptors have been extracted from bovine brain using the detergent cholate and purified approximately 20,000-fold by affinity chromatography on haloperidol-sepharose and wheat germ agglutinin-agarose columns [25].
• IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls [14].

Gene context of cholate

• In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size [14].
• PyrR100 cells showed a 4-fold decrease in cholate (an MRP substrate) efflux with a 6-fold increase in cellular cholate accumulation compared with wild-type cells [26].
• We report here that beta-dystroglycan is actually present at normal levels in mdx mouse muscle plasma membrane: treatment with cholate detergent is able to reveal its presence by SDS-PAGE and immunoblotting [27].
• METHODS: Apolipoprotein E-/- mice were fed a low-fat or high saturated fat, cholate-containing diet with or without ethanol for 3 to 10 weeks, and LDLR-/- mice were fed a low-fat, high saturated fat, or high saturated fat diet with cholate with or without ethanol for 7 weeks [28].
• On a high cholesterol/cholate diet, transgenic mice overexpressing ABCA1 have increased HDL, reduced LDL, increased HDL-mediated cholesterol flux to the liver, and reduced atherosclerosis [29].

Analytical, diagnostic and therapeutic context of cholate

• The amino-terminus of M13 coat protein is also found exclusively on the outside of dilauroyl or dimyristoyl lecithin vesicles, formed with coat protein by the cholate dilution technique [Racker, E., et al. (1975) FEBS Lett. 57, 14-18] near the lipid phase transition temperature [30].
• During dialysis to remove cholate, lipid bilayer vesicles formed in which Band 3 existed as a dimer and in which intramembrane particles indistinguishable from those in the native membrane were exposed by freeze-fracturing [21].
• To define further the ontogeny of bile acid metabolism in mammals, we examined maturational changes in the serum concentration of total cholate conjugates by radioimmunoassay in fetal, neonatal, suckling, and mature Sprague-Dawley rats [31].
• De novo and preformed cholesterol directly secreted into bile or used for cholate and chenodeoxycholate synthesis were quantitated by high-pressure liquid chromatography (HPLC)-liquid scintillation [32].
• After 40% partial hepatectomy (PH), CA- and DCA-treated groups underwent a deterioration of cholestatic hepatitis [33].

References