Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cholates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed2004

Low-fat, high-carbohydrate and high-fat, low-carbohydrate diets decrease primary bile acid synthesis in humans.

BACKGROUND: Dietary fat content influences bile salt metabolism, but quantitative data from controlled studies in humans are scarce. OBJECTIVE: The objective of the study was to establish the effect of dietary fat content on the metabolism of primary bile salts. DESIGN: The effects of eucaloric extremely low-fat (0%), intermediate-fat (41%; control diet), and extremely high-fat (83%) diets on kinetic values of cholate and chenodeoxycholate metabolism were determined after 11 d by using stable isotope dilution in 6 healthy men. All diets contained identical amounts of cholesterol. RESULTS: The total primary bile salt pool size was not significantly affected by dietary fat content, although the chenodeoxycholate pool was significantly higher during the low-fat diet. Fractional turnover rates of both primary bile salts were 30-50% lower during the low- and high-fat diets than during the control diet. Total hepatic bile salt synthesis was approximately 30% lower during both the high- and low-fat diets, but synthesis rates of the 2 primary bile salts were differentially affected. The molar ratio of cholate to total bile salt synthesis increased from 0.50 +/- 0.05 ( +/- SD) to 0.59 +/- 0.05 and 0.66 +/- 0.04 with increasing fat intake, whereas the molar ratio of chenodeoxycholate to total bile salt synthesis decreased from 0.50 +/- 0.05 to 0.41 +/- 0.05 and 0.34 +/- 0.04. The relative concentration of deoxycholate in plasma increased during the low-fat period, which indicated increased absorption from the colon. CONCLUSIONS: Both low- and high-fat diets reduce the synthesis and turnover rates of primary bile salts in humans, although probably through different mechanisms, and consequently they affect the removal of cholesterol from the body.

Adult↗
PubMed1990

Comparison of the central and renal dopamine-1 receptor.

The dopamine D-1 receptor from striatal membranes was compared with the dopamine DA-1 receptor from renal proximal tubules. The dopamine-1 receptors were solubilized with 1% sodium cholate and phospholipids after pretreatment with the dopamine-1 agonist, SKF R-38393. The soluble receptors were reconstituted into phospholipid vesicles after removal of sodium cholate. The receptors were studied by radioligand binding using the dopamine-1 antagonist [125I]-SCH 23982. The reconstituted dopamine D-1 and DA-1 receptor densities were similar. However, the affinity of the solubilized D-1 receptor was 17-fold greater than the solubilized DA-1 receptor. The affinity of membrane bound D-1 receptor to the radioligand was also greater than that noted for membrane bound DA-1 receptor. The mechanism for this difference remains to be determined.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Increased c-fos mRNA and binding to the AP-1 recognition sequence accompanies the proliferative response to deoxycholate of HT29 cells.

To further understand the molecular mechanisms of bile acid-mediated colon tumor promotion, we have examined the possible role of AP-1 activity in this process. The AP-1 complex has been reported to play an important role in control of cell growth. Our studies show that lithocholate, deoxycholate and ursodeoxycholate exhibited marked proliferative effects on a human adenocarcinoma cell line (HT29), while cholate was without effect. The proliferative effects appeared to be confined to narrow concentration windows which differed for the different bile acids. We demonstrate that deoxycholate caused an increase in expression of c-fos mRNA and increased binding to the AP-1 site, effects which were maximum at the concentration at which the bile acid induced the maximum proliferative effect on the cells. Cholate was without effect on AP-1 binding activity. In addition, we show that the AP-1 complex induced by treatment of the cells with the bile acid contained the c-fos protein. This could suggest that prolonged deregulated expression of AP-1 activity in colonic cells by certain bile acids may contribute to tumor promotion in the colon.

Base Sequence↗
PubMed1998

Dietary soy protein isolate, compared with casein, reduces atherosclerotic lesion area in apolipoprotein E-deficient mice.

The objective of this study was to compare the effects of dietary soy protein isolate and casein on atherosclerotic lesion development in apolipoprotein (apo) E-deficient mice. Male C57BL/6J apoE-deficient mice (9-10 wk old) in groups of 6-9 were used in a series of feeding studies. In the first experiment, mice were fed purified diets containing cholesterol (1 g/100 g) and cholate (0.25 g/100 g) for 6 wk; soy protein isolate or casein was used as the protein source. Although serum total cholesterol concentration did not differ between groups, the lesion area of the thoracic aorta in the soy protein isolate group was lower than that of the casein group (P < 0.01). In the second and third experiments, mice were fed the same purified diet as in Experiment 1, only without supplementation of cholesterol and cholate for 24 and 9 wk, respectively. In each of these two experiments, serum total cholesterol concentrations again did not differ between soy protein isolate- and casein-fed groups. Serum homocysteine concentrations did not differ between groups in Experiment 3. Dietary soy protein isolate, compared with casein, lowered the thoracic aorta lesion area (Experiment 2; P < 0.001) and the percentage of the aortic arch inner surface covered by lesions (P < 0.05). In the final experiment, mice were fed the cholesterol-free diets containing ethanol-extracted soy protein isolate or casein plus the soy protein ethanol extracts for 9 wk. There were no differences in serum total cholesterol concentration or thoracic aorta lesion areas between the two groups. These results indicate that the antiatherogenic effect of native soy protein isolate cannot be explained by its effect on serum lipids or homocysteine and suggest that both the protein component and the ethanol extracts of the soy protein isolate may contribute to the antiatherogenic effect of the native soy protein isolate.

Animals↗
PubMed1999

An allosteric synthetic DNA.

Allosteric DNA oligonucleotides are potentially useful diagnostic reagents. Here we develop a model system for the study of allosteric interactions in DNAs. A DNA that binds either Cibacron blue or cholic acid was isolated and partially characterized. Isolation was performed using a multi-stage SELEX. First, short oligos that bind either Cibacron blue or cholic acid were enriched from random oligonucleotide pools. Then, members of the two pools were fused to form longer oligos, which were then selected for theability to bind Cibacron blue columns and elute with cholic acid. One resulting isolate (A22) was studied. Dye- and cholate-binding functions can be separated on sequences from the 5'- and 3'-regions, respectively. Ligand-column affinity assays indicate that each domain binds only its respective ligand. However, the full-length A22 will bind either dye or cholate columns and elute with the other ligand, as if binding by the ligands is mutually exclusive. Furthermore, S1 nuclease protection assays show that Cibacron blue causes a structural change in A22 and that cholic acid inhibits this change. This system will be useful for elucidating mechanisms of allosteric interactions in synthetic DNAs.

Allosteric Regulation↗
PubMed1998

Purification and characterization of a membrane-associated ganglioside sialidase from bovine brain.

A membrane-associated ganglioside-hydrolyzing sialidase was purified to apparent homogeneity from bovine brain. The enzyme was solubilized with Triton X-100 plus sodium cholate from the particulate fraction and purified over 100,000-fold by sequential chromatography on DEAE-cellulose, octyl-Sepharose, heparin-Sepharose, Sephacryl S-200, MonoQ, RCA-agarose, thiol-activated Sepharose, and ganglioside-affinity Sepharose. The final enzyme preparation exhibited a specific activity of 4,851.3 micromol/h/mg protein and an apparent molecular mass of 52 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme preferentially hydrolyzed gangliosides other than GM1 and GM2 but demonstrated hardly any activity against glycoproteins and oligosaccharides. Gangliosides GD3, GD1a, and GT1b were much better substrates than GM3 and GD1b in the presence of Triton X-100, but the latter became more sensitive to the sialidase with addition of sodium cholate. The enzyme was activated by dithiothreitol, strongly inhibited by 4-hydroxy-mercuribenzoate, and firmly adsorbed to thiol-activated Sepharose, indicating that free sulfhydryl groups are essential for its catalytic activity. Subcellular fractionation experiments revealed that the enzyme is mainly located in the synaptosomal fraction.

Animals↗
PubMed1987

Physical and functional association of cytosolic inositolphospholipid-specific phospholipase C of calf thymocytes with a GTP-binding protein.

A soluble inositolphospholipid-specific phospholipase C (PI-phospholipase C) has been purified 5,800-fold from the cytosolic fraction of calf thymocytes. The purification was achieved by sequential column chromatographies on DEAE-Sepharose CL-6B, heparin-Sepharose CL-6B, Sephacryl S-300, Mono S, and Superose 12, followed by column chromatography on Sephadex G-100 in the presence of 1% sodium cholate. The enzyme thus purified was found to be homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight of the enzyme was estimated to be 68 kDa by SDS-PAGE. The enzyme is specific for inositol phospholipids. Phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate (PIP2) were hydrolyzed, but phosphatidylcholine and phosphatidylethanolamine were not affected by the enzyme. GTP gamma S-binding activity was detected in the enzyme fractions after all the purification steps, but not in the final enzyme preparation. The PI-phospholipase C and GTP gamma S-binding activities in the partially purified enzyme preparation could be separated by the column chromatography on Sephadex G-100 only in the presence of 1% sodium cholate. Thus, the soluble PI-phospholipase C has affinity to a GTP-binding protein. SDS-PAGE of the GTP-binding fractions eluted from the Sephadex G-100 column gave three visible bands of 54, 41, and 27 kDa polypeptide was specifically ADP-ribosylated by pertussis toxin. Furthermore, it was found that GTP and GTP gamma S (10 microM and 1 mM) could enhance the PIP2 hydrolysis activity of the partially purified enzyme in the presence of 3 mM EGTA, but the purified enzyme after separation from the GTP-binding activity was not affected by GTP and GTP gamma S. The soluble PI-phospholipase C of calf thymocytes may be not only physically but also functionally associated with a GTP-binding protein.

Animals↗
PubMed1988

Constitutive testosterone 6 beta-hydroxylase in rat liver.

The cytochrome P-450 that was purified from hepatic microsomes of male rats treated with phenobarbital and designated P450 PB-1 (Funae and Imaoka (1985) Biochim. Biophys. Acta 842, 119-132) had high testosterone 6 beta-hydroxylation activity (turnover rate, 13.5 nmol of product/min/nmol of P-450) in a reconstituted system consisting of cytochrome P-450, NADPH-cytochrome P-450 reductase, cytochrome b5, and a 1:1 mixture of lecithin and phosphatidylserine in the presence of sodium cholate. In ordinary conditions in the reconstituted system with cytochrome P-450, reductase, and dilauroylphosphatidylcholine, P450 PB-1 had little 6 beta-hydroxylase activity. The catalytic activities toward testosterone of two major constitutive forms, P450 UT-2 and P450 UT-5, were not affected by cytochrome b5, phospholipid, or sodium cholate. P450 PB-1 in rat liver microsomes was assayed by immunoblotting with specific antibody to P450 PB-1. P450 PB-1 accounted for 24.4 +/- 5.6% (mean +/- SD) of the total spectrally-measured cytochrome P-450 in hepatic microsomes of untreated adult male rats, and was not found in untreated adult female rats. P450 PB-1 was induced twofold with phenobarbital in male rats. P450 PB-1 was purified from untreated male rats and identified as P450 PB-1 from phenobarbital-treated rats by its NH2-terminal sequence, peptide mapping, and immunochemistry. These results showed that P450 PB-1 is a constitutive male-specific form in rat liver. There was a good correlation (r = 0.925) between the P450 PB-1 level and testosterone 6 beta-hydroxylase activity in rat liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Purification and characterization of galactocerebrosidase from human lymphocytes.

Galactocerebrosidase was purified about 22,600-fold using several hydrophobic column and gel filtration steps with a 4.8% recovery, from human lymphocytes. Its specific activity was 1.54 x 10(5) nmol/h/mg with tritium-labeled galactocerebroside as the substrate in the taurocholate system. The optimal pH for galactocerebroside was 4.2 in the taurocholate system and 4.6 in the cholate system. The Km values for galactocerebroside were 5 microM in the taurocholate system and 25 microM in the cholate system. The molecular weight of the purified enzyme was estimated to be 90 kDa by sodium dodecylsulfate polyacrylamide gel electrophoresis and gel filtration. However, 70, 50, 40, and 30 kDa bands were also recognized on SDS-PAGE. The N-terminal amino acid sequences of the 70 kDa molecule and the three 50 kDa molecules were the same as that of the 90 kDa molecule. The N-terminal amino acid sequences of the 40 and 30 kDa molecules were unique. A monoclonal antibody raised against the purified enzyme effectively immunoprecipitated galactocerebrosidase activity, and an affinity column prepared with this monoclonal antibody bound the 90 and 50 kDa proteins. These results suggest that this enzyme is probably processed from the 90 kDa protein.

Amino Acid Sequence↗
PubMed1979

A neutral proteinase of monkey liver microsomes. Solubilization, partial purification, and properties.

Conditions for the solubilization of membrane-bound neutral proteinase associated with monkey liver microsomes were investigated. Among the reagents tested, deoxycholate, cholate, and some nonionic detergents, including Triton X-100, with hydrophilic-lipophilic balance values of around 13, were effective. The solubilization profile indicated that the enzyme is bound to the microsomal membranes by strong hydrophobic interaction. The enzyme was partially purified from monkey liver microsomal fraction, previously washed with 1 M KCl and 0.05% sodium dodecyl sulfate, by Triton X-100 extraction, followed by chromatography on columns of hydroxylapatite and Sepharose CL-6B. The apparent molecular weight of the enzyme was estimated to be about 88,000 from the elution position on Sepharose CL-6B column chromatography in the presence of 0.5% sodium cholate. It was optimally active at pH 8.0 with heat-denatured casein as a substrate. It was strongly inhibited by diisopropyl phosphorofluoridate and phenylmethanesulfonyl fluoride, indicating that the enzyme is a serine proteinase. EDTA, EGTA, and chymostatin also inhibited the enzyme strongly. Among urea-denatured protein substrates tested, calf thymus histone was hydrolyzed most rapidly, followed by casein, hemoglobin, and bovine serum albumin, whereas practically no hydrolysis occurred with denatured ovalbumin, fibrinogen, and gamma-globulin as substrates.

Aminopeptidases↗
PubMed1982

Occurrence and some properties of membrane-bound neutral proteinase in the microsomal fraction of rat skeletal muscle.

Membrane-bound neutral proteinase was found in the microsomal fraction of rat skeletal muscle as assayed with heat-denatured casein as a substrate. The enzyme was solubilized from 1 M KC1-washed microsomal fraction by 1% sodium cholate containing 0.1 M NaCl, and partially purified by chromatography on a column of Sepharose CL-6B in the presence of 0.5% sodium cholate and 0.1 M NaCl. The enzyme was eluted from the Sepharose column as a single but rather broad peak at a position corresponding to a molecular weight of about 190,000. The pH optimum for hydrolysis of heat-denatured casein was about 8.0. It was inhibited to significant extents by various reagents including diisopropyl phosphorofluoridate, phenylmethanesulfonyl fluoride, N alpha-tosyl-L-phenylalanine chloromethyl ketone, N alpha-tosyl-L-lysine chloromethyl ketone, p-chloromercuriphenyl sulfonate, chymostatin, EDTA, EGTA, and o-phenanthroline. This inhibition profile suggests that the present muscle proteinase is a mixture of proteinases, such as serine proteinase and a metallo-proteinase similar to those occurring in the microsomal membranes of liver and kidney (or small intestine), respectively. Among urea-denatured proteins tested as substrates, calf thymus histone was hydrolyzed most rapidly, followed by protamine, hemoglobin, and casein.

Animals↗
PubMed1983

Studies on the ferricytochrome a-ferrocytochrome a3-carbon monoxide complex of mammalian cytochrome oxidase. Conditions for preparation and some properties.

The conditions for the preparation of the ferricytochrome a-ferrocytochrome a3-carbon monoxide complex (a3+, a3(2)+CO) of cytochrome oxidase [EC 1.9.3.1] by the ferricyanide-reoxidation method and some properties of the prepared complex were studied. The addition of a small volume of concentrated ferricyanide solution to the dithionite-reduced and carbon monoxide-treated cytochrome oxidase preparation was required to obtain the (a3+, a3(2)+CO) spectrum showing absorption maxima at 590, 545, and 429 nm. The addition of larger volumes of ferricyanide solution, thus introducing larger amounts of oxygen into the preparation, caused decomposition of the carbon monoxide complex. A part of the added ferricyanide was immediately reduced by dithionite whereas the remainder was gradually reduced by partial oxidation product(s) of dithionite. The (a3+, a3(2)+CO) complex was stable only when excess ferricyanide remained in the reaction mixture. The formation of the (a3+, a3(2)+CO) spectrum was observed when sodium citrate, phosphate or borate buffer containing either cholate or a non-ionic detergent was employed as the solvent buffer, but not with the buffers containing sodium dodecyl sulfate (SDS) or cetyltrimethyl-ammonium bromide (CETAB). The formation was considerably inhibited by trishydroxymethyl-aminomethane(Tris)-HCl buffer. The (a3+, a3(2)+CO) spectrum appeared with maximal intensity at around pH 7. The pH-dependency of the intensity of the spectrum was not in parallel with the pH-dependent change of the polymerization state of the cytochrome oxidase preparation. On freezing to liquid nitrogen temperature, the (a3+, a3(2)+CO) complex prepared in usual solvent buffers was mostly converted to the oxidized form of cytochrome oxidase (a3+, a3(3)+. However, when prepared in the phosphate buffer, pH 8.0, containing 1.2% (w/v) sodium cholate and with 20% saturation with ammonium sulfate, the complex mostly remained unchanged after the freezing. Based on the results obtained, the stability of the juxta-heme structure of cytochrome a3 was also discussed.

Animals↗
PubMed2006

Chronic liver disease is triggered by taurine transporter knockout in the mouse.

Taurine is an abundant organic osmolyte with antioxidant and immunomodulatory properties. Its role in the pathogenesis of chronic liver disease is unknown. The liver phenotype was studied in taurine transporter knockout (taut-/-) mice. Hepatic taurine levels were ~21, 15 and 6 mumol/g liver wet weight in adult wild-type, heterozygous (taut+/-) and homozygous (taut-/-) mice, respectively. Immunoelectronmicroscopy revealed an almost complete depletion of taurine in Kupffer and sinusoidal endothelial cells, but not in parenchymal cells of (taut-/-) mice. Compared with wild-type mice, (taut-/-) and (taut+/-) mice developed moderate unspecific hepatitis and liver fibrosis with increased frequency of neoplastic lesions beyond 1 year of age. Liver disease in (taut-/-) mice was characterized by hepatocyte apoptosis, activation of the CD95 system, elevated plasma TNF-alpha levels, hepatic stellate cell and oval cell proliferation, and severe mitochondrial abnormalities in liver parenchymal cells. Mitochondrial dysfunction was suggested by a significantly lower respiratory control ratio in isolated mitochondria from (taut-/-) mice. Taut knockout had no effect on taurine-conjugated bile acids in bile; however, the relative amount of cholate-conjugates acid was decreased at the expense of 7-keto-cholate-conjugates. In conclusion, taurine deficiency due to defective taurine transport triggers chronic liver disease, which may involve mitochondrial dysfunction.

Animals↗
PubMed1974

Bile production in fasted and fed primates.

Previous experiments have suggested differences in the bile salt independent flow rate between monkeys and dogs, and in the ability of bile salt secretion to influence bile flow. The present study was performed to determine whether the availability of food could have influenced these results. Bile flow and bile salt secretion rates were studied in fasted and fed primates. In the fasting experiments, sodium cholate, sodium taurocholate, and monkey bile were infused into the duodenum; only sodium cholate was infused in the feeding experiments. The results showed that bile flow was linearly related to the bile salt secretion rate in both fasting and feeding animals. Bile salt independent flow is extremely variable during fasting and is increased and stabilized by feeding. These studies indicate that the differences found in previous experiments are probably attributable to variations in experimental design.

Animals↗
PubMed1984

Serum bile acid patterns determined by an enzymatic method and high-performance liquid chromatography in young infants with cholestasis.

Serum unconjugated and conjugated bile acids in young infants with intrahepatic cholestasis (idiopathic neonatal hepatitis syndrome, n = 8) or extra-hepatic cholestasis (preoperative extrahepatic biliary atresia, n = 8) were examined by an enzymatic procedure and high-performance liquid chromatography. In comparison with the mean level of total serum bile acid of controls having no liver or gastrointestinal diseases, those of each group markedly increased (15.6 +/- 5.1 vs. 120.9 +/- 64.0 and 161.8 +/- 54.2 nmol/ml), but those of unconjugated bile acid were almost unchanged (1.4 +/- 0.5 vs. 1.0 +/- 0.6 and 0.6 +/- 0.2 nmol/ml). The ratios of cholate to chenodeoxycholate and glycine- to taurine-conjugated bile acids (G/T) were not significantly different between the groups of intrahepatic and extrahepatic cholestasis. However, in the patients with intrahepatic cholestasis, the G/T ratio varied greatly and the quantitative determination of individual conjugated bile acids in serum revealed that a half of the patients examined had very low levels of taurine-conjugated cholate and chenodeoxycholate, suggesting a bile acid metabolism alternation specific for underlying intrahepatic cholestasis.

3-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Effect of infusion of bile salts into the mesenteric artery in situ on jejunal mucosal transport function in dogs.

We studied the effects of increased circulating levels of bile salts on jejunal mucosal function in dogs. In situ luminal perfusion of a 30-cm proximal jejunal segment was performed while deoxycholate, cholate, taurodeoxycholate, or taurocholate solutions were directly added to the mesenteric arterial supply, reaching the intestinal wall at successive concentrations of 5, 8, 12, and 22 mumol/L. The transport rates of water, sodium, glucose, fructose, glycine, and lysine were measured. The mucosa of the experimental loop was assayed for ATPase activity, and examined by light and electron microscopy. Deoxycholate at 8 microM in the blood supply of the perfused jejunal segment was associated with a significant (p less than 0.02) reduction in the absorption rates of water, sodium, glucose, and glycine, and inhibition of mucosal Na+, K+-ATPase. The absorption of fructose and lysine, and brush border enzyme activities, were not affected. Cholate had a similar effect at 12 microM. There were no obvious histological alterations, but electron microscopy showed swelling of mitochondria in the enterocytes. The reduction in mucosal transport, the inhibition of mucosal Na+, K+-ATPase, and the mitochondrial swelling were reversed after discontinuation of the bile salt infusion. The taurine conjugates at 22 microM depressed transport of water and sodium only, and did not inhibit Na+, K+-ATPase. Our study indicates that increased circulating concentrations of unconjugated bile salts, particularly deoxycholate, may impair Na+, K+-ATPase-related jejunal mucosal function.

Animals↗
PubMed2004

The P-407-induced murine model of dose-controlled hyperlipidemia and atherosclerosis: a review of findings to date.

We are continuing to both elucidate underlying mechanisms and identify clinical applications for a chemically induced murine model of dose-controlled hyperlipidemia and atherosclerosis. This murine model neither utilizes genetically modified mice nor a high-fat, cholate-containing diet, although simultaneous ingestion of a high-fat, cholate-enriched diet potentiates the hyperlipidemic response and the number and size of aortic atherosclerotic lesions formed in C57BL/6 mice. The chemical agent used to induce hyperlipidemia is poloxamer 407 (P-407), a nonionic surface-active-agent. To date, we have investigated the effect of P-407 on the biologic activity of a variety of key enzymes involved with lipid metabolism and transport. These enzymes include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LPL), cholesterol 7alpha-hydoxylase (C7alphaH), sterol 27-hydroxylase (S27H), lecithin cholesterol acyltransferase (LCAT), cholesteryl-ester-transfer-protein (CETP), hepatic lipase (HL), and endothelial lipase (EL). P-407 directly inhibits the heparin-releasable fraction of LPL and HL and indirectly increases the biologic activity of CETP and LCAT. Long-term (> 4 months) administration of P-407 to C57BL/6 mice appears to have no effect on the biologic activity of S27H and HMG-CoA reductase, but decreases the activity of C7alphaH. This would suggest that hypertriglyceridemia and hypercholesterolemia result from inhibition of LPL and C7alphaH, respectively, while the biologic activity of CETP and LCAT are indirectly increased to compensate for the increased cholesterol burden. The above model has proven useful for predicting the therapeutic efficacy of existing and possibly newer statin drugs, as well as evaluating the potential of one statin drug (atorvastatin calcium) to cause the regression of P-407-induced atherosclerotic lesions in mice. The P-407-induced murine model of atherogenesis represents an alternative to the use of either genetically modified or diet-induced models and may also prove beneficial for the evaluation of newer classes of antihyperlipidemic agents such as antioxidants, CETP inhibitors, and liver X receptor (LXR) agonists.

Animals↗
PubMed1986

A determinant of resistance of Neisseria gonorrhoeae to killing by human phagocytes: an outer membrane lipoprotein of about 20 kDa with a high content of glutamic acid.

A protein of about 20 kDa was extracted by sodium cholate (1%, w/v) from outer membranes of a strain of Neisseria gonorrhoeae, BS4 (agar), which is resistant to killing by human phagocytes. When the protein was purified by repeated fractionation on Sephadex G75, contamination with other outer-membrane proteins and lipopolysaccharide was negligible. The protein contained a full complement of amino acids, with high levels of glutamic acid. Carbohydrate, detected by the anthrone method and by sugar and hexosamine analysis, was present, but at very low levels. There was a significant content of fatty acids (about 5.7% of the protein), indicating a lipoprotein. The 20 kDa lipoprotein: (1) neutralized the ability of antiserum against whole organisms of BS4 (agar) to reduce the resistance of this strain to phagocyte killing; (2) evoked in mice an antiserum which reduced this resistance and immunoblotted only with 20 kDa lipoprotein in the cholate extract of outer membranes; and (3) promoted resistance to intracellular killing of an otherwise phagocyte susceptible gonococcal strain (BSSH). This is strong evidence that it is a determinant of gonococcal resistance to phagocyte killing.

Bacterial Outer Membrane Proteins↗