| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Monensin and brefeldin A inhibit high density lipoprotein-mediated cholesterol efflux from cholesterol-enriched cells. Implications for intracellular cholesterol transport Mendez, A. J. (1995), J Biol Chem 270(11): 5891-900. Abstract: Mechanisms and pathways of excess cholesterol removal from intracellular sites of accumulation to extracellular cholesterol acceptors remain poorly defined. To gain further insights, compounds known to affect cellular protein transport pathways were tested for their effects on high density lipoprotein (HDL)-mediated cholesterol efflux from cultured cells enriched with cholesterol. Monensin, nigericin, and brefeldin A inhibited the ability of HDL to decrease cellular cholesterol esterification, stimulate sterol biosynthesis, and promote the efflux of labeled cholesterol and cholesterol mass from fibroblasts and smooth muscle cells. HDL-mediated decrease in cell cholesterol esterification was inhibited up to 80% by these compounds compared with control incubations over an HDL concentration of 5-100 micrograms/ml and up to 18 h of incubation. Up-regulation of sterol biosynthesis after depletion of cell cholesterol by HDL increased over 10-fold; however, inclusion of monensin or brefeldin A during the incubation completely prevented the increase of sterol biosynthesis by HDL. Efflux of 3Hcholesterol to HDL from prelabeled cells was inhibited up to 40% by these compounds, and this effect persisted when cholesterol esterification was blocked. Similarly, monensin and brefeldin A inhibited up to 50% of HDL-mediated cholesterol mass efflux relative to controls. Treatment of cells with cholesterol oxidase demonstrated an increase of intracellular cholesterol after exposure to monensin or nigericin and to a lesser extent with brefeldin A. These data show that monensin, nigericin, and brefeldin A sequester cholesterol from sites normally available for efflux by HDL. Since these compounds act by disruption of Golgi complex structure and function, a role for this intracellular organelle in transport of cholesterol between intracellular sites and the plasma membrane for eventual removal by extracellular acceptors such as HDL is suggested. |
| Monitoring cholesterol autoxidation processes using multideuteriated cholesterol Wasilchuk, B. A., P. W. Le Quesne, et al. (1992), Anal Chem 64(10): 1077-87. Abstract: Deuterium-labeled cholesterol is used to monitor for artifactually produced cholesterol oxidation products during analysis. 2H9Cholesterol, labeled on the side chain, is added to the sample immediately upon isolation, and the ratios of labeled to unlabeled oxides and of labeled to unlabeled cholesterol are monitored by capillary gas chromatography-mass spectrometry. The analytical methodology involves an initial solvent extraction followed by silica gel LC and reversed-phase HPLC to isolate and concentrate the oxide fraction. The feasibility of the technique for analysis of cholesterol oxides in foods and biological samples at the part per million level with an accuracy of better than +/- 5% is demonstrated. |
| Monitoring cholesterol crystallization from lithogenic model bile by time-lapse density gradient ultracentrifugation Konikoff, F. M., H. Laufer, et al. (1997), J Hepatol 26(3): 703-10. Abstract: BACKGROUND/AIMS: Cholesterol crystallization in a dilute, bile salt-rich model bile is a multiphase process in which early filamentous crystals gradually transform to classical cholesterol monohydrate plates. The pertinence of similar transformations in more complex model systems or native bile is, however, unclear. The aim of the present study was to characterize and monitor cholesterol crystallization in a model bile of physiological relevance. METHODS: A supersaturated model bile was prepared with a lipid composition (18 mM cholesterol, 37 mM lecithin, 120 mM taurocholate) that was derived from analyzing 10 gallbladder biles from cholesterol gallstone patients. Cholesterol crystallization was followed by light and electron microscopy, and sequential density gradient analysis of cholesterol-containing precipitates. RESULTS: During cholesterol crystallization a reproducible sequence of events was recorded. First (T<18 h), cholesterol-rich vesicular and multilamellar structures (density 1.005-1.015 g/ml) were observed. Later, (T>60 h) filamentous, helical, tubular (density 1.015-1.04 g/ml) and plate-like (density 1.04-1.06 g/ml) cholesterol crystals appeared. The concentration of crystals increased gradually, while bilayer structures became desaturated with cholesterol and disappeared, and early crystal forms were replaced by plates. Eventually (T>25 days) only classical plate-like cholesterol monohydrate crystals were present. Exposure of cholesterol-containing precipitates to micellar (100 mM) deoxycholate dissolved the bilayer structures but not the crystals. CONCLUSIONS: These data demonstrate that cholesterol crystallization in a physiologically relevant model bile is a multiphase process consisting of a sequence of transitions from vesicular and multilamellar structures to early crystal forms and to classical plate-like cholesterol monohydrate crystals. These transitions are associated with increasing density and decreasing phospholipid content of cholesterol precipitates. We suggest that time-lapse density gradient ultracentrifugation is a useful method for investigating and quantitating the process of cholesterol crystallization and factors that influence this process in bile. |
| Monitoring cholesterol organization in membranes at low concentrations utilizing the wavelength-selective fluorescence approach Mukherjee, S. and A. Chattopadhyay (2005), Chem Phys Lipids 134(1): 79-84. Abstract: We previously showed using a fluorescent analogue of cholesterol (NBD-cholesterol, or 25-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-methylamino-27-norcholesterol), that cholesterol may exhibit local organization at low concentrations in membranes by the formation of transbilayer tail-to-tail dimers of cholesterol (Rukmini, R., Rawat, S.S., Biswas, S.C., Chattopadhyay, A., 2001. Biophys. J. 81, 2122-2134). In this report, we have monitored the microenvironmental features of cholesterol monomers and dimers utilizing wavelength-selective fluorescence spectroscopy. Our results utilizing red edge excitation shift (REES) and wavelength-dependent change in fluorescence anisotropy show that the microenvironment around the NBD moieties in the dimer form is more rigid possibly due to steric constraints imposed by the dimer conformation. These results provide new information and are relevant in understanding the organization of cholesterol in membranes at low concentrations. |
| Monitoring the fat and cholesterol intake of children and adolescents McCabe, E. M. (1993), J Pediatr Health Care 7(2): 61-70. Abstract: Nurse practitioners and other health care providers play vital roles in the health education of their clients. A health professional should be able to understand the interplay of diet, education, and exercise in a healthy existence. This article reviews the recommendations offered by the National Cholesterol Education Program (1991) on testing and managing cholesterol levels in children and adolescents. The program recommends a strategy combining two complementary approaches: a population approach and an individual approach. By evaluating these approaches, the timing and rationale for lowering fat and cholesterol are discussed and recommendations are made to health care providers about identifying children at risk. Health care providers should work to promote a physically conscious generation that is well-versed in health maintenance, to identify "high-risk" individuals, and to update their own knowledge of national recommendations for managing fat and cholesterol levels in their clients' diets. |
| Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking Kruth, H. S., I. Ifrim, et al. (2001), J Lipid Res 42(9): 1492-500. Abstract: The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The cholesterol microdomains were visualized with a monoclonal antibody that specifically detects ordered cholesterol arrays. These unique cholesterol microdomains were induced on macrophages and fibroblasts when they were enriched with cholesterol in the presence of an ACAT inhibitor, to block esterification of excess cellular cholesterol. Induction of the plasma membrane cholesterol microdomains could be blocked by agents that inhibit trafficking of cholesterol to the plasma membrane and by cholesterol acceptors that remove cholesterol from the plasma membrane. In addition, plasma membrane cholesterol microdomains did not develop in mutant Niemann-Pick type C fibroblasts, consistent with the defect in cholesterol trafficking reported for these cells.The induction of plasma membrane cholesterol microdomains on inhibition of ACAT helps explain how ACAT inhibition promotes cholesterol efflux from cells in the presence of cholesterol acceptors such as HDL. The anti-cholesterol monoclonal antibody also detected extracellular cholesterol-containing particles that accumulated most prominently during cholesterol enrichment of less differentiated human monocyte-macrophages. For the first time, cholesterol microdomains have been visualized that function in cholesterol trafficking to and from the plasma membrane. |
| Monoclonal antibody recognition of cholesterol monohydrate crystal faces Perl-Treves, D., N. Kessler, et al. (1996), Chem Biol 3(7): 567-77. Abstract: BACKGROUND: The immune system can elicit antibodies against a wide variety of antigens. We have proposed that crystal surfaces may also operate as antigens, binding specific antibodies. Here we exploit the crystal surfaces of cholesterol monohydrate to investigate antibody-surface recognition at the molecular level. RESULTS: Four monoclonal antibodies were selected. Two specifically interact with cholesterol monohydrate crystals, and one with 1,4-dinitrobenzene crystals. The fourth interacts nonselectively with various solid substrates. The relative reactivities of the four antibodies to the different surfaces of cholesterol monohydrate and to other surfaces were compared. The nonspecific antibody adsorbs mainly at imperfections. Of the two specific antibodies, one shows a clear preference for one set of faces, relative to others, the second adsorbs selectively at one face of cholesterol monohydrate crystals. CONCLUSIONS: Monoclonal antibodies can be selected that specifically bind to the crystal surfaces of cholesterol monohydrate. The binding sites of such antibodies appear to recognize a number of molecular moieties, exposed at the surface in a specific structural organization. Different antibodies recognize different structural organizations with varying degrees of selectivity. Antibody-crystal surface interactions may serve as convenient models for studies aimed at an understanding of the molecular bases of antibody recognition. |
| Monoconjugated bilirubin as a possible factor in cholesterol gallstone pathogenesis Lesma, A., D. Monti, et al. (1997), Minerva Chir 52(6): 771-5. Abstract: HPLC determination of bilirubin conjugates in bile demonstrated a subgroup of patients with cholesterol gallstones who have more monoconjugated than diconjugated bilirubin in their gallbladder bile. None of the patients had abnormal liver function tests nor hemolysis. It was shown that this is not due to differences in liver secretion of the conjugates. In these patients, the more insoluble monoconjugated bilirubin might have provided the nucleus for the subsequent crystallization of cholesterol leading to the formation of cholesterol gallstones. |
| Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyte-derived macrophages Ishibashi, S., T. Inaba, et al. (1990), J Biol Chem 265(24): 14109-17. Abstract: We have investigated effects of monocyte colony-stimulating factor (M-CSF) on the uptake of acetylated low density lipoproteins (acetyl-LDL) and the activity of cholesterol esterification in human monocyte-derived macrophage. The cells were cultured with M-CSF for 10 days and then incubated with acetyl-LDL for 24 h. M-CSF (128 ng/ml) enhanced the uptake and degradation of 10 micrograms/ml of 125I-acetyl LDL 7.5-fold (n = 6) and the effect of M-CSF was dose-dependent at the concentrations of 0.5-32 ng/ml. The binding experiments at 4 degrees C demonstrated that the number of acetyl-LDL receptor was increased by the addition of M-CSF. Supporting this, ligand blotting analysis revealed a significant increase in a receptor protein for acetyl-LDL (240 kDa). Binding of LDL was also enhanced by M-CSF but less significantly than that of acetyl-LDL. Cellular cholesterol esterification in the presence of 10 micrograms/ml acetyl-LDL was enhanced 24.1-fold (n = 13) by 128 ng/ml M-CSF. It was evident that M-CSF enhanced cholesterol esterification to a greater extent than the cellular uptake of acetyl-LDL (24.1- versus 7.5-fold). Cholesterol esterification was also enhanced by the addition of granulocyte-macrophage colony-stimulating factor and interleukin 1. We conclude that M-CSF enhances the uptake of both acetyl-LDL and LDL by increasing their receptor number, and further enhances the process of cholesterol esterification, resulting in a remarkable increase in cholesterol esterification in macrophages. These findings strongly suggest the significant involvement of cytokines such as M-CSF in cholesterol metabolism of macrophages. |
| Monogenic disorders that cause LDL cholesterol to accumulate in plasma Desjeux, J. F. (2001), J Pediatr Gastroenterol Nutr 33(2): 119-21. |
| Monomer-monomer interactions drive the prepore to pore conversion of a beta-barrel-forming cholesterol-dependent cytolysin Hotze, E. M., A. P. Heuck, et al. (2002), J Biol Chem 277(13): 11597-605. Abstract: Perfringolysin O (PFO), a cholesterol-dependent cytolysin, forms large oligomeric pore complexes comprised of up to 50 PFO molecules. In the present studies a mutant of PFO (PFO(Y181A)) has been identified that traps PFO in a multimeric prepore complex that cannot insert its transmembrane beta-hairpins and therefore cannot form a pore. Remarkably, PFO(Y181A) can be induced to insert its transmembrane beta-hairpins if functional PFO is incorporated into the PFO(Y181A) oligomeric prepore complex. Furthermore, the transition from prepore to pore appears to be an "all or none" process; partial insertion of the transmembrane beta-barrel does not occur. Therefore, cooperative interactions between the monomers of the prepore drive the prepore to pore conversion that results in the formation of the transmembrane beta-barrel. |
| Monosegmented flow-analysis of serum cholesterol Araujo, A. N., J. A. Catita, et al. (1999), Farmaco 54(1-2): 51-5. Abstract: A monosegmented flow system is designed for enzymatic spectrophotometric determination of cholesterol in blood serum. The sample (4.5 microliters), enzymatic reagent (150 microliters) and an air plug (100 microliters) are simultaneously inserted into a carrier stream buffered to pH 7.4 (potassium dihydrogenphosphate). In order to avoid the step of air removal, a relocating detector was used. This system handles about 42 samples per hour, yielding precise results (R.S.D. usually < 3.0%). Sensitivity is 46 mAU 1/mmol (mAU stands for milliabsorbance units), being the method linear up to 10.3 mmol/l cholesterol. Accuracy was assessed by running 30 samples already analysed by a conventional procedure: no statistical difference between methods was found at the 95% confidence level. |
| Monosialoganglioside containing cationic liposomes with a cationic cholesterol derivative promote the efficiency of gene transfection in mammalian culture cells Kawaura, C., S. Hasegawa, et al. (2000), Biol Pharm Bull 23(6): 778-80. Abstract: We have studied the effects of monosialoganglioside (GM1)-containing cationic liposomes with a cationic cholesterol on the liposome-mediated gene transfection into mammalian culture cells. The results showed that both cationic liposomes with either a cationic cholesterol derivative of a hydrophobic amino head group (I) and a hydrophilic amino head group (II) promoted the transfection of luciferase plasmids (pGL3) into HeLa and CHO-K1 cells more than the control cationic liposomes without GM1. In addition, we found that cationic liposomes with a cationic cholesterol derivative (II) were about ten times as effective as that by commercially available cationic liposome Lipofectin. Confocal fluorescence microscopy showed that the liposome/DNA complex was transferred more efficiently into the target cells by the GM1-containing liposomes than by the liposomes without GM1. In proportion to the above results, free antisense DNAs were also more efficiently transferred into the nucleus of the target cells by the GM1-containing liposomes. When there was 100 mM galactose in the transfection medium, the luciferase activity by the GM1-containing liposomes was reduced to the level of the control liposomes. The results suggest that GM1-containing cationic liposomes with a cationic cholesterol derivative of a hydrophobic amino head group or a hydrophilic amino head group should significantly increase the transfection efficiency of plasmid DNAs and antisense DNAs by galactose receptor-mediated endocytosis. This means that the GM1-containing liposomes described here should be very promising for gene transfection in vitro. |
| Monounsaturated oils do not all have the same effect on plasma cholesterol Truswell, A. S. and N. Choudhury (1998), Eur J Clin Nutr 52(5): 312-5. Abstract: Evidence assembled here indicates that when olive oil forms a major part of dietary fat in controlled human experiments, total and LDL-cholesterols are somewhat higher than when the same amount of fat is one of the modern predominantly monounsaturated oils: low erucic rapeseed or high oleic sunflower oil. Oils rich in monounsaturated fatty acids thus do not all have the same effect on plasma cholesterol. This phenomenon is explicable by consideration of the content of other fatty acids and the non-saponifiable fractions of the different monounsaturated oils. It helps to explain the discrepancy that has existed between the classic experiments (using olive oil), which found monounsaturated oils 'neutral', and some of the more recent experiments which found them more cholesterol-lowering than carbohydrates. Four published meta-analyses are reviewed. The three which included most of the published experiments show that monounsaturated fatty acids (MUFA) have less plasma cholesterol-lowering effect than polyunsaturated fatty acids. |
| Monounsaturated PE does not phase-separate from the lipid raft molecules sphingomyelin and cholesterol: role for polyunsaturation? Shaikh, S. R., M. R. Brzustowicz, et al. (2002), Biochemistry 41(34): 10593-602. Abstract: We investigated interactions of the lipid raft molecules sphingomyelin (SM) and cholesterol (CHOL) in monolayers and bilayers composed of 1-palmitoyl-2-oleoyl-sn-glycerophosphatidylethanolamine (POPE) or 1-palmitoyl-2-docosahexaenoyl-sn-glycerophosphatidylethanolamine (PDPE) at 35 degrees C. Techniques employed were pressure-area (pi-A) isotherms generated from Langmuir-Blodgett films, solid-state (2)H and (31)P NMR spectroscopies, and differential scanning calorimetry (DSC). Condensation calculated from pi-A isotherms and reduction in the enthalpy of the gel-liquid-crystalline transition in DSC scans showed CHOL has a strong affinity for POPE, comparable to that observed between SM-CHOL. Order parameters derived from (2)H NMR spectra of the perdeuterated sn-1 chain of POPE-d(31) increased by >50% upon addition of equimolar CHOL to POPE-d(31)/SM (1:1 mol) bilayers. Close proximity of CHOL to POPE even in the presence of SM is indicated. Chemical shift anisotropy (Deltasigma(csa)) measured from (1)H-decoupled (31)P NMR spectra also implied intimate lipid mixing in POPE/SM/CHOL (1:1:1 mol). In contrast, pi-A isotherms and corroborating DSC studies of PDPE/SM (1:1 mol) indicate phase separation between SM and PDPE, which was maintained in the presence of CHOL. The cholesterol-associated increase in order of the perdeuterated sn-1 chain of PDPE determined by (2)H NMR was 2-fold less for PDPE-d(31)/SM/CHOL (1:1:1 mol) than POPE-d(31)/SM/CHOL (1:1:1 mol). Our findings support the notion that acyl chain dependent lateral phase separation occurs in the presence of a docosahexaenoic acid (DHA)-containing phospholipid (PDPE), but not an oleic acid-containing phospholipid (POPE). We propose that monounsaturated lipids do not promote formation of stable lipid rafts and that polyunsaturation may be important for raft stability. |
| MooPoong (Gye Young Jeong) increases HDL-cholesterol but decreases LDL cholesterol and body-weight Chung, H. S., S. H. Hong, et al. (2004), Immunopharmacol Immunotoxicol 26(2): 225-32. Abstract: MooPoong (MP, Gye Young Jeong), a Korean traditional wine, has been used as a prevention and treatment agent of blood circulatory trouble. To evaluate such an effect of MP, we analyzed whether the plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body weight change after rats were fed on high fat diet with MP for 8 weeks. Plasma LDL cholesterol level decreased by 5.6% in 0.128% MP treated group and by 11.1% in 0.640% MP treated group. However, HDL cholesterol was increased by 6.7% in 0.128% MP diet group and 33.3% in 0.640% MP diet group. In addition, there was a significant weight loss in the MP treated group compared with the high-fat diet group (P < 0.05). Our findings indicate that MP may contain compounds with actions which can treat blood circulatory trouble as well as overweight. |
| Morbidity and mortality in rural community-dwelling elderly with low total serum cholesterol Ives, D. G., P. Bonino, et al. (1993), J Gerontol 48(3): M103-7. Abstract: BACKGROUND. Low serum cholesterol has been associated with morbidity and mortality in the elderly. This study compared the health, functional status, and two-year mortality rates of community-dwelling rural elderly with serum cholesterol < 150 mg/dl to age- and sex-matched controls with serum cholesterol 200-240 mg/dl. METHODS. Self-reported disease history, disability, health habits, and cognitive function data were collected at a health risk appraisal interview. A single blood sample was also collected and analyzed for total serum cholesterol at a central lab. RESULTS. Of the 3,874 participants, 109 (2.8%) had total cholesterol levels < 150 mg/dl. Seventy-five percent of the low cholesterol group were male compared to 44% in the main study population. The low cholesterol group had significantly greater smoking history, current cigarettes smoked, diabetes history, angina and COPD symptoms, and assistance needed for heavy and light work. Men in the low cholesterol group had significantly lower blood pressure. After two years, 14 (12.8%) of the low cholesterol group had died vs 16 (7.3%) in the control group. There was no relationship to specific causes of death and cholesterol level. CONCLUSION. A very low cholesterol level in older individuals should be evaluated carefully to determine whether it is due to genetic or life-style factors such as diet or, more likely, is a marker of disease. |
| More on chewing the fat. The good fat and the good cholesterol Sacks, F. M. and W. W. Willett (1991), N Engl J Med 325(24): 1740-2. |
| More on cholesterol Kalant, N. (1993), Cmaj 149(1): 17; author reply 17-8. |
| More on cholesterol Masse, J. (1993), Cmaj 149(1): 17; author reply 17-8. |