| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of breast feeding on the plasma cholesterol and growth of infants Jooste, P. L., L. J. Rossouw, et al. (1991), J Pediatr Gastroenterol Nutr 13(2): 139-42. Abstract: The effect of breast-feeding on plasma cholesterol, body weight, and body length was studied longitudinally in a large free-living cohort of infants (n = 512) from birth until the age of 1 year. Of the cohort, 21.4% were exclusively breast-fed for at least 3 months, 39.3% received bottle-feeding, and 39.3% received a combination of breast- and bottle-feeding. At birth the plasma cholesterol was similar in the three groups. After 3 months the mean plasma cholesterol and proportion of hypercholesterolemic infants in the breast-fed group were significantly (p less than 0.001) higher than that of the other two groups. These differences had disappeared at the age of 1 year. Breast-fed infants weighed less at 3 and 12 months, but body length was similar to those of the other groups. These results suggest that breast-feeding elevates plasma cholesterol by a direct mechanism and that the effect persists only as long as the breast-feeding is continued. |
| Effect of bulky lesions on DNA: solution structure of a DNA duplex containing a cholesterol adduct Gomez-Pinto, I., E. Cubero, et al. (2004), J Biol Chem 279(23): 24552-60. Abstract: The three-dimensional solution structure of two DNA decamers of sequence d(CCACXGGAAC)-(GTTCCGGTGG) with a modified nucleotide containing a cholesterol derivative (X) in its C1 '(chol)alpha or C1 '(chol)beta diastereoisomer form has been determined by using NMR and restrained molecular dynamics. This DNA derivative is recognized with high efficiency by the UvrB protein, which is part of the bacterial nucleotide excision repair, and the alpha anomer is repaired more efficiently than the beta one. The structures of the two decamers have been determined from accurate distance constraints obtained from a complete relaxation matrix analysis of the NOE intensities and torsion angle constraints derived from J-coupling constants. The structures have been refined with molecular dynamics methods, including explicit solvent and applying the particle mesh Ewald method to properly evaluate the long range electrostatic interactions. These calculations converge to well defined structures whose conformation is intermediate between the A- and B-DNA families as judged by the root mean square deviation but with sugar puckerings and groove shapes corresponding to a distorted B-conformation. Both duplex adducts exhibit intercalation of the cholesterol group from the major groove of the helix and displacement of the guanine base opposite the modified nucleotide. Based on these structures and molecular dynamics calculations, we propose a tentative model for the recognition of damaged DNA substrates by the UvrB protein. |
| Effect of calcium supplementation on serum cholesterol and blood pressure. A randomized, double-blind, placebo-controlled, clinical trial Bostick, R. M., L. Fosdick, et al. (2000), Arch Fam Med 9(1): 31-8; discussion 39. Abstract: OBJECTIVE: To test the effect of daily supplemental calcium on serum total and high-density lipoprotein cholesterol (HDL-C) levels and blood pressure in adults. DESIGN: Randomized, double-blind, placebo-controlled clinical trial; adjunct study to a trial of calcium and colon cell proliferation in patients with sporadic adenoma. SETTING: Outpatient clinic. PATIENTS: A total of 193 men and women, aged 30 to 74 years. INTERVENTION: Treatment with 1.0 and 2.0 g/d of elemental calcium vs placebo over a 4-month period for cholesterol determinations and 6 months for blood pressure. MAIN OUTCOME MEASURES: Serum total cholesterol and HDL-C levels, systolic and diastolic blood pressure. RESULTS: Because there were no apparent differences in responses between the 1.0-g and 2.0-g calcium groups, their data were combined and compared with those of the placebo group. Among all participants, the mean total cholesterol level dropped 0.07 mmol/L (2.9 mg/dL) (1.3%) (P =.43) more, and the mean HDL-C level dropped 0.01 mmol/L (0.4 mg/dL) (1.1%) (P =.71) less in the calcium group than in the placebo group. Among participants without a history of hypercholesterolemia, the mean total cholesterol level dropped 0.18 mmol/L (6.8 mg/dL) (3.3%) (P =.10) and the HDL-C level dropped 0.02 mmol/L (0.6 mg/dL) (1.5%) (P =.61) more in the calcium group than in the placebo group. Among all participants, there was no apparent change in blood pressure until 6 months, when the mean systolic blood pressure dropped 0.8 mm Hg (0.6%) (P =.85) and the mean diastolic blood pressure dropped 0.4 mm Hg (0.5%) (P =.80) more in the calcium group than in the placebo group. CONCLUSIONS: There were no substantial or statistically significant effects of calcium supplementation on total cholesterol or HDL-C levels or on blood pressure. There was a suggestion (not statistically significant) of a 0.07 to 0.18 mmol/L (3-7 mg/dL) or 2% to 4% drop in the total cholesterol level, a finding similar to that reported in other studies, which indicates the need for further study. |
| Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat Nicolle, C., N. Cardinault, et al. (2003), Eur J Nutr 42(5): 254-61. Abstract: BACKGROUND: Vegetables are major dietary sources of fibers and antioxidants such as carotenoids, polyphenols and vitamin C which contribute to explain their protective effects against cardiovascular diseases. AIM OF THE STUDY: We investigated in the rat the effects of a 3-week supplementation of the diet with carrot (15% dry matter) on lipid metabolism and antioxidant status. RESULTS: A significant decrease of cholesterol level in liver (-44%; P= 0.0007) was observed together with a reduction of the level of liver triglycerides (-40%; P= 0.0005). Fecal total steroids excretion increased by 30% upon feeding the carrot diet as compared to the control. The secretion of bile acids was maintained, whereas the cholesterol apparent absorption was reduced in rats fed carrot diet. Carrot consumption also improved the antioxidant status. It significantly decreased the urinary excretion of thiobarbituric acid reactive substances (TBARS), reduced the TBARS levels in heart, increased the vitamin E plasmatic level and tended to increase the ferric reducing ability of plasma (FRAP) as compared to the controls. The carrot diet provided carotenoid antioxidants: 5.1 mg beta-carotene, 1.6 mg alpha-carotene and 0.25mg lutein per 100 g diet. No carotenoids were found in plasma whereas the three carotenoids were detected in the plasma of the rats fed the carrot diet at 125, 41, 43 nmol/L respective concentrations. beta-Carotene was also detected in liver and heart. CONCLUSION: Carrot consumption modifies cholesterol absorption and bile acids excretion and increases antioxidant status and these effects could be interesting for cardiovascular protection. |
| Effect of castration and hormonal supplementation on cholesterol cholelithiasis in the male hamster Ohshima, A., B. I. Cohen, et al. (1996), Lipids 31(9): 945-8. Abstract: This study examined the effect of castration and dietary hormonal supplementation on cholesterol cholelithiasis in male hamsters. Animals fed a standard lithogenic diet developed cholesterol gallstones (17%) after 6 wk, while castrated hamsters did not form any stones. Addition of a synthetic androgen, methyltestosterone, to the lithogenic diet induced cholelithiasis in castrated animals (50%). The biles of normal and castrated-hormone supplemented hamsters had cholesterol saturation indices of 1.0 and 1.1, respectively, while the bile of the castrated animals remained unsaturated (0.6). The ratio of cholic acid/chenodeoxycholic acid in bile increased after castration, but returned to normal levels following hormonal supplementation. Biliary cholesterol carriers were separated by ultracentrifugation. Animals in the stone-forming groups (normal and castrated-hormone treated) had a significant proportion of their biliary cholesterol in vesicles (44 and 46%, respectively); castrated hamsters had less cholesterol in vesicle form (9%). The molar ratio of cholesterol/phospholipid in vesicles was reduced after castration (0.93 vs. 0.42) and increased by hormonal supplementation (1.89). In conclusion, when compared to normal male hamsters fed a standard lithogenic diet, castration reduced the cholesterol saturation of bile, lowered the vesicular/micellar ratio in bile, and inhibited cholesterol cholelithiasis. Dietary androgen supplementation increased the lithogenicity of bile, resulting in stone formation in castrated animals. |
| Effect of cationic cholesterol derivatives on gene transfer and protein kinase C activity Farhood, H., R. Bottega, et al. (1992), Biochim Biophys Acta 1111(2): 239-46. Abstract: Four different cationic derivatives of cholesterol were synthesized which contain either a tertiary or a quaternary amino head group, with and without a succinyl spacer-arm. Their ability to inhibit protein kinase C (PKC) activity was measured in a detergent mixed micellar solution. Derivatives containing a quaternary amino head group were effective inhibitors (Ki approx. 12 and 59 microM) of PKC and derivatives containing a tertiary amino head group were approx. 4-20-fold less inhibitory. Liposomes containing an equimolar mixture of dioleoylphosphatidylethanolamine (DOPE) and a cationic cholesterol derivative were tested for the DNA-mediated transfection activity in mouse L929 cells. Highest activity was found with the derivative with low PKC inhibitory activity and with a succinyl spacer-arm. The transfection activity of this tertiary amine derivative, N,N-dimethylethylenediaminyl succinyl cholesterol was dependent on DOPE as a helper lipid; liposomes containing dioleoylphosphatidylcholine and this derivative had little activity. The transfection protocol of this new cationic liposome reagent was optimized with respect to the ratio of liposome/DNA, dose of the complex and time of incubation with cells. Several adherent cell lines could be efficiently transfected with this liposome reagent without any apparent cytotoxicity. However, the transfection activity was strongly inhibited by the presence of serum components. |
| Effect of cerivastatin on serum cholesterol levels in patients with type 2 diabetes mellitus De Luis, D. A., E. Romero, et al. (2000), Clin Nutr 19(5): 367-70. Abstract: The incidence of coronary heart disease (CHD) is greatly increased in overweight diabetic patients. Modification of dietary intake and weight loss improve hypercholesterolaemia. However, cholesterol goal levels are not achieved in several patients under this treatment. The aim of our study was to evaluate the effect of Cerivastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in patients with type 2 diabetes mellitus. A population of 40 diabetic type 2 outpatients were analyzed in a prospective way. The mean+/-SD age was 60.7+/-11.6 years, with a diabetes duration of 8.5+/-6.6 years. All patients were treated with cerivastatin (0.2 mg once a day) for 6 months. Weight HbAlc fasting blood glucose, urine microalbuminuria, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were measured at the beginning of the study and again after 3 and 6 months of treatment with cerivastatin. An improvement in lipid levels was achieved, with a significant decrease in LDL-cholesterol (27.7%), total cholesterol (21.4%), triglycerides levels (10.4%) and a significant increase in HDL-cholesterol levels (8.3%) (P<0.05). Cardiovascular risk ratios such as; total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol improved during treatment, decreasing 11.3% and 30%, respectively (P<0.05). Low incidence of side effects was demonstrated. In summary, cerivastatin improved lipid control in patients with type 2 diabetes, with a low incidence of side effects. |
| Effect of certain toxicants on gonadotropin-induced ovarian non-esterified cholesterol depletion and steroidogenic enzyme stimulation of the common carp Cyprinus carpio in vitro Mukherjee, D., D. Guha, et al. (1992), Biomed Environ Sci 5(2): 92-8. Abstract: Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin-induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, delta 5-3 beta-HSD and 17 beta-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 microgram/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin-induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately. |
| Effect of chemical carcinogens on cholesterol biosynthetic pathways in the skin of mice Tanimoto, Y., K. Fukao, et al. (1990), Carcinogenesis 11(9): 1647-51. Abstract: The metabolism of zymosterol and mevalonic acid was studied in vitro using the skin homogenates of 3-methylcholanthrene (3MC), diazacholesterol-treated and untreated mice. In normal mouse skin only lathosterol was a major metabolite and the other metabolites, cholesta-5,7,24-trien-3 beta-ol, desmosterol, cholesterol and 7-dehydrocholesterol were much less abundant. However, in the skin homogenate of mice treated with 3MC lathosterol production was depressed, while the production of cholesta-5,7,24-trien-3 beta-ol and desmosterol was significantly increased, the cholesterol level being normal or a little higher. In contrast, in the skin homogenate of mice administered diazacholesterol the production of both lathosterol and cholesterol was almost completely blocked with the slightly increased production of cholesta-5,7,24-trien-3 beta-ol and desmosterol. The metabolism in vitro of 2-14C-mevalonic acid was quite similar to that of zymosterol, and no additional product which might possibly have been produced by the Kandutsch-Russell pathway was observed. Two pathways for cholesterol biosynthesis, therefore, may exist in mouse skin; the first is lanosterol----zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----lathosterol----7-dehydrocholesterol----cholesterol, and the second by Bloch: lanosterol----zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----cholesta-5,7,24-trien-3 beta-ol----desmosterol----cholesterol. When mouse skin is treated with 3-MC the former pathway is virtually blocked and the latter is stimulated, keeping the level of cholesterol in the tissue constant or a little higher than normal, which seems to be a significant change in the early stage of chemical carcinogenesis. |
| Effect of chenodeoxycholic acid and ursodeoxycholic acid administration on acyl-CoA: cholesterol acyltransferase activity in human liver Abate, N., F. Carubbi, et al. (1994), Ital J Gastroenterol 26(6): 287-93. Abstract: In order to investigate the relationship between bile acid pool composition and hepatic cholesterol metabolism in humans, we studied the effect of chronic feeding of chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) on the hepatic activity of acyl-CoA: cholesterol acyltransferase (ACAT) evaluated "in vitro". Twenty-eight gallstone patients were admitted to the study: 15 were untreated subjects, 8 were treated with UDCA (10 mg/kg/day for 15-20 days) and 5 were treated with CDCA (15 mg/kg/day for 15-20 days). A liver specimen and a bile sample were obtained during laparotomy for elective cholecystectomy. Untreated subjects had bile supersaturated with cholesterol (mean saturation index: 1.35 +/- 0.31) whereas subjects treated with either UDCA or CDCA had bile unsaturated with cholesterol (mean saturation index: 0.66 +/- 0.1 and 0.75 +/- 0.06 respectively). In all treated subjects the bile acid administered became predominant in bile. ACAT activity was 14% lower in subjects treated with UDCA and 16% lower in those treated with CDCA compared to controls; the differences did not achieve statistical significance. Microsomal cholesterol content did not differ between the groups (75.4 +/- 7.2 nmol/mg protein in control group; 86.5 +/- 7.0 nmol/mg protein in CDCA treated group; 83.4 +/- 7.0 nmol/mg protein in UDCA treated group). Our data show that the cholesterol esterifying activity of human liver is not affected by changes in bile acid pool composition. |
| Effect of cholesterol addition on growth kinetics and shear stress sensitivity of adherent mammalian cells Tomeczkowski, J., A. Ludwig, et al. (1993), Enzyme Microb Technol 15(10): 849-53. Abstract: The growth kinetics of adherent baby hamster kidney cells cultivated with additional cholesterol as well as the effect of cholesterol addition on shear stress sensitivity were investigated. The influence of various cholesterol preparations was tested, whereby dimethylsulfoxide and ethanol show negative effects at higher concentrations. With addition of cholesterol in the range of 90 micrograms ml-1, a positive effect on the shear stress resistance was achieved. |
| Effect of cholesterol and 7-beta hydroxycholesterol on glutathione status and nitric oxide production in murine peritoneal macrophages Bansal, M. P. and S. Shalini (2005), Indian J Exp Biol 43(6): 503-8. Abstract: Present study was conducted to observe the effect of cholesterol and oxidized cholesterol (7beta-hydroxycholesterol,7beta-OH) on the nitric oxide (NO) production and the redox ratio by lipopolysaccharide-stimulated macrophages. Dose-dependent decrease in NO levels was seen with both cholesterol and 7beta-OH at different incubation intervals (6,12,18,24 hr) and concentrations (2.5,5,7.5microg/ml). On comparison, a significant decrease in the NO was observed at 24 hr interval in 7beta-OH exposed cells with all respective concentrations of cholesterol. Incubation with 7beta-OH also resulted in significant increase in levels of oxidized glutathione (GSSG) and decrease in reduced glutathione (GSH), while cholesterol showed no effect on GSSG levels. Moreover, GSH levels were lowered only at highest concentration (7.5microg/ml), and at longer incubation intervals (18,24 hr) with cholesterol exposure. This altered the redox status in both cholesterol/7beta-OH treated macrophages. Increased redox ratio and decreased NO levels indicated increased oxidative stress and decreased vasodilation by 7beta-OH compared to cholesterol. |
| Effect of cholesterol and charge on pore formation in bilayer vesicles by a pH-sensitive peptide Nicol, F., S. Nir, et al. (1996), Biophys J 71(6): 3288-301. Abstract: The effect of cholesterol on the bilayer partitioning of the peptide GALA (WEAALAEALAEALAEHLAEALAEALEALAA) and its assembly into a pore in large unilamellar vesicles composed of neutral and negatively charged phospholipids has been determined. GALA undergoes a conformational change from a random coil to an amphipathic alpha-helix when the pH is reduced from 7.0 to 5.0, inducing at low pH leakage of contents from vesicles. Leakage from neutral or negatively charged vesicles at pH 5.0 was similar and could be adequately explained by the mathematical model (Parente, R. A., S. Nir, and F. C. Szoka, Jr., 1990. Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA. Biochemistry. 29:8720-8728) which assumed that GALA becomes incorporated into the vesicle bilayer and irreversibly aggregates to form a pore consisting of 10 +/- 2 peptides. Increasing cholesterol content in the membranes resulted in a reduced efficiency of the peptide to induce leakage. Part of the cholesterol effect was due to reduced binding of the peptide to cholesterol-containing membranes. An additional effect of cholesterol was to increase reversibility of surface aggregation of the peptide in the membrane. Results could be explained and predicted with a model that retains the same pore size, i.e., 10 +/- 2 peptides, but includes reversible aggregation of the monomers to form the pore. Resonance energy transfer experiments using fluorescently labeled peptides confirmed that the degree of reversibility of surface aggregation of GALA was significantly larger in cholesterol-containing liposomes, thus reducing the efficiency of pore formation. |
| Effect of cholesterol and dipalmitoyl phosphatidylcholine enrichment on the kinetics of Na-Li exchange of human erythrocytes Engelmann, B. and J. Duhm (1991), J Membr Biol 122(3): 231-8. Abstract: The effects of cholesterol loading and depletion and of a 10% replacement of native phosphatidylcholine by dipalmitoyl phosphatidylcholine (di 16:0-PC) on kinetic properties of human red cell Na-Li exchange have been studied. Compared to control erythrocytes (cholesterol/phospholipid ratio (C/P = 0.8-0.9, Vmax of phloretin-sensitive Li uptake and of Li efflux stimulated by extracellular Na (Nao) were reduced by 15-30% in cholesterol-loaded red cells (C/P = 1.05-1.33). The apparent Km values for external Li (Lio) and for internal Li (Lii) were decreased by about one-third in these cells. Cholesterol depletion (C/P = 0.7) exerted opposite effects on the kinetics of Nao-dependent Li efflux. On augmenting C/P from 0.66 to 1.0, Vmax of Nao-dependent Li efflux was reduced by about 30%; increasing C/P above 1.0 caused no further lowering of Vmax.Li leakage rates monotonically decreased over the whole range of C/P ratios examined (0.66-1.3). This indicates that Na-Li exchange and Li leak are differentially affected by cholesterol. Incorporation of di 16:0-PC (replacement of 3% of total red cell phospholipids) caused similar kinetic alterations of Na-Li exchange as a rise in membrane cholesterol by 20-50%. Notably, selective incorporation of di 16:0-PC into the outer monolayer increased both intra- and extracellular Li binding affinities of Na-Li exchange and lowered its maximum velocity. Thus, both di 16:0-PC enrichment and cholesterol loading exerted an uncompetitive type of transport inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes Lopez-Pinto, J. M., M. L. Gonzalez-Rodriguez, et al. (2005), Int J Pharm 298(1): 1-12. Abstract: The main objective of the present work was to compare the dermal delivery of minoxidil (Mx), a lipophilic drug from ethosomes versus classic liposomes, containing different cholesterol (CHOL) concentrations. All the systems were characterized for shape, lamellarity, particle size and entrapment efficiency percentage (EE), by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser diffraction and ultracentrifugation or dialysis methods, respectively. Multilamellar vesicles (MLVs) were obtained and one to six lamellae were visualized by CLSM. The presence of ethanol in the formulations affects the particle size in terms of reducing this parameter. In addition, it was possible to appreciate the influence of CHOL on the vesicle size, because it was increased, as CHOL concentration was higher. When the EE was determined by two different methods (ultracentrifugation and dialysis methods), a clear losing of entrapped drug by the ultracentrifugation method was observed, because the strong energy transmitted to the samples disrupted vesicles. Vesicles were non-occlusively applied on rat skin and the permeation pattern of the different systems, depth into the skin and the main permeation pathway were studied by using beta-carotene as a fluorescent probe. CLSM studies showed that ethosomal systems were much more efficient at delivering the fluorescent substance into the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solutions. |
| Effect of cholesterol and its autooxidation derivatives on endocytosis and dipeptidyl peptidases of aortic endothelial cells Fornas, E., F. Mayordomo, et al. (1992), Histol Histopathol 7(2): 163-8. Abstract: The effects of cholesterol (CHO) and cholesterol autooxidation derivatives (CAD) on the endocytosis of cationized ferritin (CF) by endothelial cells have been investigated. The effect of both substances on the activity of lysosomal enzymes dipeptidyl peptidase I (DPP I) and dipeptidyl peptidase II (DPP II) was also studied. Treatment of rats with CAD induced striking alterations in the ultrastructure of endothelial cells and makes it impossible to analyze the effect of this toxin on endocytosis processes. In contrast, CHO-treated cells displayed a good ultrastructural preservation and showed an increased ability to endocyte ferritin, as compared with controls. Both DPP I and DPP II activities increased after 3 weeks of CAD or CHO treatment. Our results indicate that although CHO damage endothelial cells, the most important effects could be attributed to CAD which usually accompanies CHO-supplemented diets. |
| Effect of cholesterol and lanosterol on the structure and dynamics of the cell membrane of Mycoplasma capricolum. Deuterium nuclear magnetic resonance study Huang, T. H., A. J. DeSiervo, et al. (1991), Biophys J 59(3): 691-702. Abstract: Deuterium nuclear magnetic resonance (NMR) techniques were employed to study the effect of sterols on the composition and dynamics of the membrane lipids of Mycoplasma capricolum, a natural fatty acid auxotroph that requires sterols for growth. The membrane lipids of cells grown in modified Edwards medium supplemented with cholesterol, oleic acid (OA), and palmitic acid (PA) were composed primarily of phosphatidylglycerol (PG) (60%) and cardiolipin (CL) (35%). The incorporation of cholesterol and the cellular OA/PA ratio increased nonlinearly with increases in exogenous cholesterol level, whereas the levels of phospholipid increased only slightly. At the growth temperature, 37 degrees C, the residual deuterium quadrupole splittings were found to be 43-46 kHz for cells grown with (7,7,8,8-2H4) PA and 1.25 micrograms/ml (30 mol%) to 10 micrograms/ml (50 mol%) cholesterol, respectively, similar to that found in the cholesterol/lecithin binary dispersions of similar cholesterol contents. Deuterium T2e of these samples were found to be 170 +/- 10 microseconds and were independent of cellular cholesterol content. In comparison, T2e of the corresponding lipid extracts were longer (320-420 microseconds) and dependent on cholesterol content. Thus, lipid-protein interactions in the cell membrane is the dominant mechanism responsible for the reduced T2e. At lower temperatures, spectra indicative of the coexistence of gel and liquid-crystalline states were observed for cells having low cholesterol levels. For both cell membrane and membrane lipid extract containing 50 mol% cholesterol, T2e was found to be constant at the temperature range from 15 to 40 degrees C. On the other hand, T2e of cell membrane containing 30 mol% cholesterol decreased linearly at 3.2 microseconds/degrees C. T2e of the corresponding lipid extract showed much stronger temperature variation. Cells containing 39 mol% lanosterol were found to have a quadrupole splitting of 39 kHz, broader than that of the cholesterol-free lecithin dispersion (less than 30 kHz) but less than that of cell membrane containing 30 mol% cholesterol (43 kHz). T2e of the lanosterol sample was found to be 130 +/- 10 microseconds which decreased linearly at a slope similar to that observed for the low cholesterol sample. Therefore, although lanosterol appeared to be capable of modulating cell membrane physical properties it is less effective than cholesterol. When growth rates were correlated with NMR parameters, we found that the membranes of faster growing cells were also more ordered. In contrast, the T2e of the cells of M. capricolum seemed to be maintained at a relatively constant value around 170 microseconds. |
| Effect of cholesterol and other sterols on human sperm acrosomal responsiveness Cross, N. L. (1996), Mol Reprod Dev 45(2): 212-7. Abstract: Human sperm become responsive to inducers of the acrosome reaction when they are washed free of seminal plasma and incubated in an appropriate medium. Previous work has shown that cholesterol-enriched medium prevents sperm from becoming responsive to the inducer, progesterone. Sperm that were incubated 24 hr in cholesterol-enriched medium and then treated with progesterone showed no evidence of membrane fusion, indicating that cholesterol acts at a stage before the earliest morphological change. Inhibition of acrosomal responsiveness by cholesterol was reversible. Among other sterols reported in mammalian sperm, desmosterol and cholesterol sulfate also inhibited sperm from becoming responsive, but cholesterol palmitate did not. Our results support a model in which sperm unesterified cholesterol, or a molecule in equilibrium with it, suppresses acrosomal responsiveness. Cholesterol-enriched medium also prevented sperm from becoming responsive to the calcium/proton exchanging ionophore, ionomycin, suggesting that cholesterol's effect may be, at least in part, at a point in the signal transduction pathway subsequent to the rise in intracellular-free calcium. |
| Effect of cholesterol and surfactant protein B on the viscosity of phospholipid mixtures Tolle, A., W. Meier, et al. (2002), Chem Phys Lipids 114(2): 159-68. Abstract: Low viscosity of the surface of alveolar fluid is mandatory for undisturbed surfactant function. Based on the known reduction of the viscosity of surfactant-like phospholipid (PL-) mixtures by plasmalogens, the effect of cholesterol and surfactant protein (SP-) B on surface viscosity of these lipid mixtures has been studied. Surface viscosity at the corresponding surface tension was measured with the oscillating drop surfactometer. We found that the viscosity was lowest in cholesterol-, followed by plasmalogen- and SP-B containing samples. Addition of SP-B to a plasmalogen-containing PL-mixture caused a further decrease in viscosity. However, in cholesterol containing mixtures, addition of SP-B led to a significant increase in viscosity, and the effect was reversed by further addition of plasmalogens. We conclude that SP-B, plasmalogens and cholesterol all affect the surface viscosity, thus synergistically regulate monolayer stability. This suggests that they are all needed in vivo for fine tuning of surface properties of pulmonary surfactant. |
| Effect of cholesterol content in activation of the classical versus the alternative pathway of rat complement system induced by hydrogenated egg phosphatidylcholine-based liposomes Ishida, T., K. Yasukawa, et al. (2001), Int J Pharm 224(1-2): 69-79. Abstract: Liposomes composed of hydrogenated egg phosphatidylcholine (HEPC) and cholesterol (CHOL) were found to activate the rat complement (C) system in a CHOL content-dependent manner. Liposomes containing 22 or 33 mol% CHOL activated the C system in a Ca(2+)-dependent manner, suggesting that C activation occurred via the classical pathway. Liposomes containing 44 mol% CHOL activated the C system in a Ca(2+) independent manner, suggesting that C activation occurred via the alternative pathway. The CHOL content appeared to dictate the pathway by which the C system was activated. This C activation was inhibited by removal of serum component(s), which adsorb to the liposomes. Activation of the alternative pathway, induced by the liposomes, was reduced by the depletion of IgG and IgM, whereas the classical pathway activation was reduced by the depletion of IgG, but not IgM. In addition, the removal of adsorbed serum component(s) by treatment with 44 mol% CHOL-containing liposomes decreased serum IgG and IgM levels that adsorb to the same liposomes, whereas the removal of adsorbed serum component(s) by treatment with 22 mol% CHOL-containing liposomes only slightly decreased serum IgG levels, which adsorbs to the same liposomes. Collectively, both IgG and IgM, which are specifically adsorbed to the liposomes in a CHOL-content dependent manner, were responsible for C activation via the alternative pathway induced by the 44 mol% CHOL containing liposomes. IgG alone would be partially responsible for C activation via the classical pathway induced by 22 or 33 mol% CHOL-containing liposomes. The discovery of this unique C-activating property of liposomes will be of value in attempts to decipher the underlying mechanism of C activation by providing a useful model membrane system. |