|For medical practitioners and the general public - Cholesterol Journal Article Catalog.|
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| A 13C and 2H nuclear magnetic resonance study of phosphatidylcholine/cholesterol interactions: characterization of liquid-gel phases
Huang, T. H., C. W. Lee, et al. (1993), Biochemistry 32(48): 13277-87.
Abstract: A detailed study on the structure, dynamics, and thermodynamic behavior of phosphatidylcholine/cholesterol (PC/CHOL) mixtures was undertaken using differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance (NMR) spectroscopy. DSC thermograms of mixtures of cholesterol (CHOL) with 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC), 1,2-distearoyl-sn-phosphatidylcholine (DSPC), and 1,2-diarachidoyl-sn-phosphatidylcholine (DAPC) showed a broadening of the first-order gel-->liquid crystalline transition and a decrease in the transition enthalpy, indicating a gradual loss of cooperativity for high CHOL concentrations. DPPC and DSPC were labeled with 13C at the carbonyl group of the sn-2 chain and 2H was introduced into the middle of the sn-2 chain at the 6- and 12-position for DPPC and DSPC, respectively. The 13C and 2H NMR spectra of each labeled lipid were studied as a function of temperature and CHOL concentration. The residual quadrupole splitting in the 2H NMR spectra, delta nu Q perpendicular, was analyzed as a function of temperature and composition. For CHOL concentrations less than 30 mol %, a precipitous change in delta nu Q perpendicular occurs near the chain melting temperature of the phospholipid. Further increases in CHOL concentration broaden the transition and shift the midpoint to higher temperature, indicating the presence of a new phase at higher CHOL contents. Moreover, at a given temperature, delta nu Q perpendicular increases with increasing cholesterol content, which indicates a more ordered structure. The 13C NMR spectra in the gel state consisted of a superposition of two components which can be attributed to both gel-like and fluid phospholipid domains in the bilayer. This two-component spectrum can be simulated quantitatively with a two-parameter chemical exchange model, which permits the fraction of each form and the exchange rate to be determined as a function of temperature and composition. At high CHOL contents the line width of the fluid component broadens, suggesting an increase in the exchange rate between the domains. These results were interpreted in terms of a temperature composition diagram with one region L beta', two regions LGI and LGII, and one liquid crystalline region L alpha, with LG denoting "liquid-gel" type phases. Liquid-gel phases correspond to phases with increased order in the hydrocarbon chains (in comparison to that of the pure PC bilayer in the L alpha phase) combined with fast limit axial diffusion that averages the 13C NMR spectrum to a "fluidlike" line.(ABSTRACT TRUNCATED AT 400 WORDS)
| A 25-hydroxycholesterol-resistant cell line deficient in acyl-CoA: cholesterol acyltransferase
Metherall, J. E., N. D. Ridgway, et al. (1991), J Biol Chem 266(19): 12734-40.
Abstract: We describe a line of mutant Chinese hamster ovary cells, SRD-4 cells, that lacks acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and fails to synthesize cholesteryl esters when stimulated with 25-hydroxycholesterol or low density lipoprotein. The cells also have a partial defect in their ability to repress transcription of three sterol-regulated genes, 3-hydroxy-3-methylglutaryl-coenzyme A synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and the low density lipoprotein receptor. The cells were selected by mutagenesis followed by growth in the presence of 25-hydroxycholesterol, which kills the parental cells by cholesterol depletion, owing to an inhibition of cholesterol synthesis and a stimulation of cholesterol esterification. Treatment of parental cells with compound 58-035 (3-(decyldimethylsilyl)-N-2-(4-methylphenyl)-1- phenylethylpropanamide), an inhibitor of ACAT, abolished cholesterol esterification but did not reproduce the defect in gene repression seen in the SRD-4 cells, and it only partially reproduced the resistance to the killing effect of 25-hydroxycholesterol. We conclude that the SRD-4 cells most likely have two independent defects, one in ACAT and the other in a factor that mediates sterol-dependent transcriptional repression. The SRD-4 cells thus resemble a line of hamster cells previously isolated (Cadigan, K.M., Heider, J.G., and Chang, T.-Y. (1988) J. Biol. Chem. 263, 274-282), which has similar independent defects. The results raise the possibility that a partial resistance to sterol repression provides a growth advantage to cells that lack ACAT.
| A 2H solid-state NMR spectroscopic investigation of biomimetic bicelles containing cholesterol and polyunsaturated phosphatidylcholine
Minto, R. E., P. R. Adhikari, et al. (2004), Chem Phys Lipids 132(1): 55-64.
Abstract: Deuterium solid-state NMR spectroscopy was used to qualitatively study the effects of both 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLiPC) and cholesterol on magnetically aligned phospholipid bilayers (bicelles) as a function of temperature utilizing the chain-perdeuterated probe 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC-d54) in DMPC/dihexanoylPC (DHPC) phospholipid bilayers. The results demonstrate that polyunsaturated PC and cholesterol were successfully incorporated into DMPC/DHPC phospholipid bilayers, leading to a bicelle that will be useful for investigations of eukaryotic membrane protein-lipid interactions. The data indicate that polyunsaturated PC increases membrane fluidity and decreases the minimum magnetic alignment temperature for DMPC/DHPC bicelles. Conversely, the introduction of cholesterol into aligned DMPC/DHPC bilayers decreases fluidity in the membrane and increases the minimum temperature necessary to magnetically align the phospholipid bilayers. Finally, the addition of Tm3+ to magnetically aligned DMPC/DMPC-d54/PLiPC/DHPC bilayers doubles the quadrupolar splittings, indicating that this unique bicelle system can be aligned with the bilayer normal parallel to the static magnetic field.
| A 3D model of the peripheral benzodiazepine receptor and its implication in intra mitochondrial cholesterol transport
Bernassau, J. M., J. L. Reversat, et al. (1993), J Mol Graph 11(4): 236-44, 235.
Abstract: A three-dimensional (3D) model of the peripheral benzodiazepine receptor (PBR) has been built using molecular dynamics simulations. The transmembrane domain of the receptor has been modeled as five alpha-helices, which are not long enough to cross the entire bilayer membrane but correspond approximately to only one phospholipid layer. The receptor model has also been tested as a cholesterol carrier, and molecular dynamics simulations have shown that it could indeed accommodate a cholesterol molecule within the five helices. All three known PBR sequences have been modeled, and no significant difference has been found between them.
| A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study
Olsson, A. G., M. Eriksson, et al. (2003), Clin Ther 25(1): 119-38.
Abstract: BACKGROUND: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. OBJECTIVE: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C
| A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men
Nestel, P., M. Cehun, et al. (2004), Eur J Clin Nutr 58(3): 403-8.
Abstract: OBJECTIVE: To determine whether the two major isoflavones in red clover differ in their effect on low-density lipoprotein cholesterol (LDL-C). DESIGN: A randomised, placebo-controlled, double-blind trial; two parallel groups taking one of the two isoflavones within which treatment and placebo were administered in a crossover design. SETTING: Free-living volunteers. SUBJECTS: A total of 46 middle-aged men and 34 postmenopausal women. INTERVENTION: Two mixtures of red clover isoflavones enriched in either biochanin (n=40) or formononetin (n=40) were compared. Placebo and active treatment (40 mg/day) were administered for 6 weeks each in a crossover design within the two parallel groups. MAIN OUTCOME MEASURES: Plasma lipids were measured twice at the end of each period. RESULTS: Baseline LDL-C concentrations did not differ significantly between men (n=46) and women (n=34), nor between those randomised to biochanin or formononetin. Interaction between time and treatments, biochanin, formononetin and corresponding placebos (two-way ANOVA) on LDL-C showed a significant effect of biochanin treatment alone. The biochanin effect was confined to men; median LDL-C was 3.61 (3.05-4.14) mmol/l with biochanin and 3.99 (3.16-4.29) mmol/l with the corresponding placebo (RM ANOVA with Dunnett's adjustment P<0.05). The difference between placebo and biochanin effects on LDL-C was 9.5%. No other lipid was affected and women failed to respond significantly to treatment. CONCLUSION: Isolated isoflavones from red clover enriched in biochanin (genistein precursor) but not in formononetin (daidzein precursor), lowered LDL-C in men. This may partly explain the previous failure to demonstrate cholesterol-lowering effects with mixed isoflavones studied predominantly in women. SPONSORSHIP: Novogen Ltd, North Ryde NSW, Australia, provided partial support including provision of tablets and outside monitoring.
| A biotinylated perfringolysin O derivative: a new probe for detection of cell surface cholesterol
Iwamoto, M., I. Morita, et al. (1997), Biochim Biophys Acta 1327(2): 222-30.
Abstract: theta-Toxin is a cholesterol-binding, pore-forming cytolysin of Clostridium perfringens. To detect cell surface cholesterol, we prepared a theta-toxin derivative, BC theta by biotinylation of a protease-nicked theta-toxin, which has the same binding affinity for cholesterol as theta-toxin without cytolytic activity. Human erythrocytes, V79 cells and human umbilical vein endothelial cells (HUVEC), were stained with BC theta coupled with FITC-avidin, and then the cells were analyzed by either flow cytometry or laser confocal microscopy. The fluorescence intensity increased in both intact and briefly fixed cells when treated with BC theta. BC theta-treated V79 cells were stained by neither trypan blue nor propidium iodide, indicating that BC stained just the outer surface of the plasma membrane of vital cells. Treatment of the cells with digitonin, a cholesterol-sequestering reagent, decreased the fluorescence intensity to the background level, indicating that BC theta staining is specific for cholesterol. The fluorescence intensity of erythrocytes pre-permeabilized with a small amount of theta-toxin increased more than ten-fold, suggesting higher cholesterol contents in the inner layer of the plasma membrane. When cells were cultured with cholesterol-depleted medium, the fluorescence intensity stained by BC theta decreased remarkably in V79 cells, but did not change in HUVEC. This indicates that cell surface cholesterol may be provided in different ways with these two cell lines. These results suggest that BC theta can be a useful probe for visualizing cell surface cholesterol and for evaluating the effects of cellular events on the topology and distribution of cholesterol.
| A biphasic response of hepatobiliary cholesterol metabolism to dietary fat at the onset of obesity in the mouse
Roy, S., H. Hyogo, et al. (2005), Hepatology 41(4): 887-95.
Abstract: Human obesity is associated with abnormal hepatic cholesterol homeostasis and resistance to leptin action. Because leptin administration to rodents promotes the biliary elimination of plasma cholesterol, this study was designed to elucidate a pathophysiological role for leptin during the development of obesity. We fed mice diets containing high or low saturated fat contents. Before and after the onset of obesity, we measured downstream targets of leptin action and evaluated plasma, hepatic, and biliary cholesterol metabolism. Although not obese at 28 days, mice fed a high fat diet became hyperleptinemic. Sensitivity to leptin was evidenced by downregulation of both hepatic stearoyl CoA desaturase-1 and fatty acid synthase. Due principally to upregulation of adenosine triphosphate-binding cassette proteins A1 and G5, plasma high density lipoprotein (HDL) cholesterol concentrations increased, as did relative secretion rates of biliary cholesterol. A smaller, more hydrophilic bile salt pool decreased intestinal cholesterol absorption. In this setting, hepatic cholesterol synthesis was downregulated, indicative of increased uptake of plasma cholesterol. After 56 days of high fat feeding, obesity was associated with leptin resistance, as evidenced by marked hyperleptinemia without downregulation of stearoyl CoA desaturase-1 or fatty acid synthase and by upregulation of hepatic cholesterol and bile salt synthesis. Hypercholesterolemia was attributable to overproduction and decreased clearance of large HDL(1) particles. In conclusion, before the onset of obesity, preserved leptin sensitivity promotes biliary elimination of endogenous cholesterol in response to dietary fat. Leptin resistance due to obesity leads to a maladaptive response whereby newly synthesized cholesterol in the liver is eliminated via bile.
| A bivariate genetic analysis of HDL- and LDL-cholesterol incorporating measured covariates: a Gibbs sampling application
Mack, W. J., W. J. Gauderman, et al. (1993), Genet Epidemiol 10(6): 623-8.
Abstract: We analyzed HDL- and LDL-cholesterol levels as a bivariate phenotype in 27 families as a function of major genes, polygenes, and measured covariates using a Monte Carlo sampling technique called Gibbs sampling. Major genes and polygenes exhibited strong effects, when considered separately. While a major gene versus polygene model could not be clearly differentiated for HDL-C, polygenes appeared to play a stronger role than a major gene for LDL-C. There was no evidence of linkage between the two major genes for HDL- and LDL-C, and the correlation in polygenes was negative. The analysis illustrate the potential applicability of Gibbs sampling to such complex problems as the multivariate analysis of continuous phenotypes.
| A brief dietary assessment to guide cholesterol reduction in low-income individuals: design and validation
Ammerman, A. S., P. S. Haines, et al. (1991), J Am Diet Assoc 91(11): 1385-90.
Abstract: Low-income Americans are at greatest risk for coronary heart disease. Dietary assessment methods are needed that can efficiently and effectively guide diet counseling to reduce serum cholesterol in this population. The Dietary Risk Assessment is a brief food frequency questionnaire designed to guide an intervention program for cholesterol reduction. It can easily be administered and scored in 10 to 15 minutes by persons who are not trained in nutrition. The assessment is culturally specific for a low-income southern population, identifies positive as well as problematic dietary behaviors, is easily interpreted, and measures potential barriers to dietary change. The assessment was validated against 3 days of dietary recall data in a sample of 42 low-income individuals recruited from the waiting room of an ambulatory care clinic. A Keys score, which measures the serum-cholesterol-raising potential of the diet, was calculated for each patient from their recall data. The Keys and Dietary Risk Assessment scores were significantly correlated (r =.60, P less than.001). We conclude that the Dietary Risk Assessment can rank individuals by level of dietary atherogenic risk adequately to guide a dietary treatment program for low-income patients, an underserved population with a high prevalence of diet-induced elevations in serum cholesterol.
| A buckwheat protein product suppresses gallstone formation and plasma cholesterol more strongly than soy protein isolate in hamsters
Tomotake, H., I. Shimaoka, et al. (2000), J Nutr 130(7): 1670-4.
Abstract: This study was conducted to investigate the effects of a buckwheat protein product (BWP) on plasma cholesterol, gallbladder bile composition and fecal steroid excretion in hamsters fed diets with 5 g/kg cholesterol. Diets also contained 200 g/kg of casein, soy protein isolate (SPI) or BWP as protein sources. After 2 wk, plasma and liver concentrations of cholesterol in the hamsters fed BWP were significantly lower than those in the hamsters fed casein and SPI. The molar proportion of cholesterol in gallbladder bile was significantly lower in the BWP group than in the other groups, whereas that of bile acids was slightly higher in the BWP group (P = 0.05), resulting in the lowest lithogenic index in the BWP group. None of the hamsters fed BWP had gallstones, whereas they were present in some of the hamsters fed other proteins. Compared with casein intake, BWP intake resulted in significantly higher ratios of cholic acid to chenodeoxycholic acid and of cholic acid to lithocholic acid in the gallbladder bile. The excretions of fecal neutral and acidic steroids were markedly higher in the BWP group compared with the other groups (P = 0.05). SPI intake also significantly lowered cholesterol level in gallbladder bile and caused higher fecal bile acids compared with casein intake, but the effects were significantly less than those of BWP (P = 0.05). The results suggest that BWP suppresses gallstone formation and cholesterol level more strongly than SPI by enhancing bile acid synthesis and fecal excretion of both neutral and acidic steroids.
| A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster
Lilja, H. E., A. Soro, et al. (2002), Atherosclerosis 164(1): 103-11.
Abstract: In patients with premature coronary heart disease, the most common lipoprotein abnormality is high-density lipoprotein (HDL) deficiency. To assess the genetic background of the low HDL-cholesterol trait, we performed a candidate gene study in 25 families with low HDL, collected from the genetically isolated population of Finland. We studied 21 genes encoding essential proteins involved in the HDL metabolism by genotyping intragenic and flanking markers for these genes. We found suggestive evidence for linkage in two candidate regions: Marker D1S2844, in the apolipoprotein A-II (APOA2) region, yielded a LOD score of 2.14 and marker D11S939 flanking the apolipoprotein A-I/C-III/A-IV gene cluster (APOA1C3A4) produced a LOD score of 1.69. Interestingly, we identified potential shared haplotypes in these two regions in a subset of low HDL families. These families also contributed to the obtained positive LOD scores, whereas the rest of the families produced negative LOD scores. None of the remaining candidate regions provided any evidence for linkage. Since only a limited number of loci were tested in this candidate gene study, these LOD scores suggest significant involvement of the APOA2 gene and the APOA1C3A4 gene cluster, or loci in their immediate vicinity, in the pathogenesis of low HDL.
| A carrageenan hydrogel stabilized colloidal gold multi-enzyme biosensor electrode utilizing immobilized horseradish peroxidase and cholesterol oxidase/cholesterol esterase to detect cholesterol in serum and whole blood
Crumbliss, A. L., J. G. Stonehuerner, et al. (1993), Biosens Bioelectron 8(6): 331-7.
Abstract: The preparation of two immobilized enzyme electrodes is described. One electrode contains horseradish peroxidase absorbed to colloidal gold and deposited on a glassy carbon electrode along with cholesterol oxidase entrapped in a carrageenan hydrogel. The second electrode also includes cholesterol esterase entrapped in the carrageenan. The incorporation of ferrocene or ferrocenecarboxylic acid mediator is brought about by either evaporation on the glassy carbon electrode or, in the latter case, entrapment in the carrageenan hydrogel. Amperometric signal generation results from the HRP catalyzed turnover of H2O2, a secondary product of the cholesterol oxidase catalyzed oxidation of cholesterol. Use of these enzyme electrodes makes cholesterol detection possible in human serum, low density lipoprotein, and whole blood.
| A case of breast cholesterol granuloma accompanied by cancer
Furuhira, C., A. Ohshima, et al. (2004), Breast Cancer 11(2): 210-3.
Abstract: Cholesterol granuloma of the breast is a very rare benign disease with clinical and imaging features that are often indistinguishable from cancer preoperatively. We report a case of breast cholesterol granuloma accompanied by cancer. The patient was a 78-year-old woman who complained of a lump in her right breast. Mammography and ultrasonography showed a well-circumscribed mass. Fine needle aspiration cytology showed many cholesterol crystals and inflammatory cells without malignancy. With a diagnosis of cholesterol granuloma, tumor extirpation was performed. Histopathologic examination revealed cholesterol granuloma together with breast cancer, and additional partial mastectomy was subsequently performed. It is noted that breast cholesterol granuloma could be accompanied by cancer.
| A case of cholesterol granuloma with hematoma of tunica albuginea
Doi, H., Y. Naka, et al. (1993), Hinyokika Kiyo 39(2): 193-5.
Abstract: A case of cholesterol granuloma with hematoma of the tunica albuginea is reported. A 52-year-old man complained of a painless mass in the left scrotum. The mass was 50 x 25 x 30 mm in size. An operation was performed. Macroscopically the mass originated from the tunica albuginea and was a cystic lesion with a thick fibrous capsule. The cystic lesion was filled with an old hematoma. An extirpation was performed. Microscopically, the sections showed fibrogranulomatous tissue containing innumerable cholesterol clefts and numerous foreign body giant cells. The histological diagnosis was cholesterol granuloma with hematoma. This is the sixth case of cholesterol granuloma of the external genitalia, and is the first case of cholesterol granuloma with hematoma of the tunica albuginea in the literature.
| A case of 'crouching' triglyceride and 'hidden' cholesterol
Mak, C. M., R. W. Pang, et al. (2004), Br J Biomed Sci 61(3): 152-3.
| A case of gallbladder adenoma based on cholesterol polyp
Yoshikawa, K., S. Yamamoto, et al. (1994), Nippon Shokakibyo Gakkai Zasshi 91(8): 1365-8.
| A case of heterotopic pancreas in the liver with primary cholesterol hepatolithiasis
Fukueda, M., N. Hamada, et al. (2000), Nippon Shokakibyo Gakkai Zasshi 97(8): 1057-61.
| A case of intrahepatic cholesterol gallstone associated with various hepatic inflammatory granulation
Akiyama, T., Y. Kojima, et al. (1993), Nippon Shokakibyo Gakkai Zasshi 90(11): 2940-4.
| A case of intrahepatic cholesterol stone complicated with atrophy of the anterior superior ventral and anterior superior lateral subsegments (S8ab) of the liver
Kin, Y., Y. Nimura, et al. (1992), Nippon Geka Gakkai Zasshi 93(5): 550-2.
Abstract: A 61-year-old male patient with intrahepatic cholesterol stone is reported. Stones were detected in the anterior superior lateral subsegment (S8ab) of the right lobe with bile duct stenosis, the lateral anterior segment (S3) of the left lobe, and the left caudate lobe (S11). Partial hepatectomy including S8ab, S3 and S11 was performed to remove all stones. Atrophy of S8ab was diagnosed by CT, and PTP clarified the patency of the subsegmental portal vein (P8ab). This is a rare case with cholesterol intrahepatic stone with regional bile duct stenosis and subsegmental atrophy of S8ab of the liver.