| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta Kolsch, H., M. Ludwig, et al. (2001), J Neural Transm 108(4): 475-88. Abstract: 24-Hydroxycholesterol, the main cholesterol elimination product of the brain is increased in serum of Alzheimer patients. This oxysterol behaves neurotoxic towards the human neuroblastoma cell line, SH-SY5Y. Here we demonstrate, that 24-hydroxycholesterol-induced neurotoxicity in differentiated SH-SY5Y cells was due to apoptosis, as indicated by DNA-fragmentation, caspase-3 activation and a decrease of the mitochondrial membrane potential. Free radicals were generated, resulting in the death of 75% of the cells within 48h; neurotoxicity in differentiated SH-SY5Y cells was partially prevented by physiological concentrations of vitamin E (50-100 microM) in that 75% of the cells survived. Physiological concentrations of estradiol-17beta (1-100nM) elicited a protective effect in differentiated cells, which was not significant; however, in undifferentiated cells a significant protection was noted by this steroid hormone. Vitamin C and melatonin did not prevent 24-hydroxycholesterol-induced neurotoxicity. These in vitro data support the in vivo observed beneficial effects reported as circumstantial evidence of vitamin E and estradiol-17beta treatment in the prevention and therapy of neurodegenerative disease. |
| Neurotoxicity of 25-OH-cholesterol on NGF-differentiated PC12 cells Chang, J. Y., K. D. Phelan, et al. (1998), Neurochem Res 23(1): 7-16. Abstract: PC12 cells induced to differentiate with nerve growth factor were used to study the neurotoxicity of 25-OH-cholesterol. This agent induced a dose- and time-dependent cell death in neuronal PC12 cells. Cells treated with this agent showed condensed nuclei, a morphology similar to that of cells dying of programmed cell death. However, agents known to prevent neuronal programmed cell death (cyclic AMP, KCl, aurintricarboxylic acid, and cycloheximide) failed to prevent the 25-OH-cholesterol-mediated cytotoxicity. On the other hand, cell death induced by 25-OH-cholesterol was prevented by treatment with vitamin E and methyl-beta-cyclodextrin. In contrast to observations made in other cell types, whole-cell patch clamp recording of neuronal PC12 cells revealed that treatment with 25-OH-cholesterol did not significantly alter calcium influx through voltage-dependent channels. These results provide the first characterization of the toxicity of cholesterol oxides toward neuronal PC12 cells, which should be useful in future studies on the interactions between cholesterol oxides and cells from the nervous system. |
| Neurotoxicity of 25-OH-cholesterol on sympathetic neurons Chang, J. Y., K. D. Phelan, et al. (1998), Brain Res Bull 45(6): 615-22. Abstract: Cultured rat sympathetic neurons derived from postnatal rat superior cervical ganglia (SCG) were used to compare the neurotoxicity of several cholesterol oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH-, and 25-OH-cholesterol. These agents caused an acute as well as a delayed toxicity in sympathetic neurons with 25-OH-cholesterol appearing to be the most toxic. A time-dependent experiment indicated that 25-OH-cholesterol at 4 microg/ml (10 microM) was able to kill 50% of the cells in 36 h. Morphological studies indicate that most of the cells do not exhibit a structural change similar to that observed in neuronal programmed cell death. Whole-cell patch clamp recording of untreated controls and 25-OH-cholesterol (2 microg/ml)-treated cells indicated that this toxicity was not accompanied by significant changes in voltage-dependent calcium channel activity. A number of pharmacological agents including ethylene glycolbis (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), cycloheximide, KCl, vitamin E, and methyl-beta-cyclodextrin were able to prevent the 25-OH-cholesterol-induced cell death to various degrees. These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may induce neurotoxicity in sympathetic neurons. |
| Neurotoxicity of cholesterol oxides on cultured cerebellar granule cells Chang, J. Y. and L. Z. Liu (1998), Neurochem Int 32(4): 317-23. Abstract: Cultured rat cerebellar granule cells were used to determine the potential neurotoxicity of cholesterol oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH- cholesterol. Among them, 7-beta-OH- and 7-keto-cholesterol were the most efficacious in causing neuronal death such that 20 microg/ml (50 microM) of these agents killed more than 80% of cells in 2 days. 7-beta-OH-cholesterol at this concentration killed 50% of cells in approximately 7 h. A number of pharmacological agents were tested for their abilities to prevent neuronal death induced by cholesterol oxides. Among them, aurintricarboxylic acid, vitamin E and methyl-beta-cyclodextrin were able to prevent cholesterol oxide-induced neurotoxicity in a dose-dependent manner. These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may induce toxicity in neurons of the central nervous system. |
| Neutral lipid storage disease with ichthyosis: serum apolipoprotein levels and cholesterol metabolism in monocyte-derived macrophages Bergman, R., M. Aviram, et al. (1991), J Inherit Metab Dis 14(2): 241-6. Abstract: Neutral lipid storage disease with ichthyosis (NLSDI) is an inherited metabolic disorder characterized by accumulation of neutral lipids, in a wide variety of cells, by a still unknown mechanism. Previous studies have shown normal cholesterol content in NLSDI granulocytes, fibroblasts and skin cells. Monocyte-derived macrophages possess an additional pathway of cholesterol uptake, which is not shared by these cells and which is not regulated by intracellular cholesterol levels. This pathway is thought to play a role in the process of atherosclerosis. Three NLSDI patients were studied. The serum levels of triglycerides, cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A-I and B were within normal limits in all three patients. The intracellular levels of free and esterified cholesterol were measured in the monocyte-derived macrophages of one patient and found to be normal, while the triglyceride concentrations were twice as high as normal. The cholesterol esterification rates, which serve as a sensitive indicator of intracellular changes in cholesteryl ester levels, were normal in the monocyte-derived macrophages of all three patients. These findings provide further evidence that cholesterol metabolism is not disturbed in NLSDI, and it may be inferred that in this respect these patients are not at increased risk for atherosclerosis. |
| Neutral-lipid analysis reveals elevation of acylglycerols and lack of cholesterol esters in Plasmodium falciparum-infected erythrocytes Nawabi, P., A. Lykidis, et al. (2003), Eukaryot Cell 2(5): 1128-31. Abstract: Here we show that blood-stage Plasmodium falciparum organisms accumulate a high mass of triacylglycerol and diacylglycerol. However, we failed to detect cholesterol esters, a second neutral lipid species reported to be important for a related apicomplexan, Toxoplasma gondii. Evidence for P. falciparum and T. gondii homologues of acyl coenzyme A:diacylglycerol acyltransferase suggests that acylglycerols may be the conserved neutral lipids in apicomplexans. |
| New approach for lipids and its clinical significance. Part II. Remnant like particles cholesterol Fukuo, Y. and Y. Kobayashi (1994), Nippon Ika Daigaku Zasshi 61(5): 506-9. |
| New approach to assess the cholesterol distribution in the eye lens: confocal Raman microspectroscopy and filipin cytochemistry Duindam, H. J., G. F. Vrensen, et al. (1995), J Lipid Res 36(5): 1139-46. Abstract: Confocal Raman microspectroscopy (CRM) is a non-invasive, non-destructive, and sensitive analytical tool for the study of some aspects of the molecular organization of cells and tissues with high spatial resolution. Filipin, a polyene antibiotic, specifically binds to cholesterol, and its molecular structure predicts it to be Raman-active. The aim of the present study was to assess the potentialities of a combined CRM-filipin approach to study the distribution of cholesterol in the human eye lens. Paraformaldehyde-fixed human lenses were sliced (0.7 mm), incubated with filipin, and analyzed by CRM. Filipin proved to give a specific Raman signal at 1586 cm-1, hardly interfering with signals from lens proteins. The CRM-filipin approach proved to be extremely sensitive, allowing detection of cholesterol in the femtogram range. It has an excellent spatial resolution (0.2-0.5 micron 3) when using point measurements. Due to the intrinsic anisotropy of membranes in the eye lens and therefore of the cholesterol distribution, a line-scan approach has to be adopted when fiber-to-fiber changes in cholesterol are of interest. The distribution of filipin along the optical axis of four human eye lenses was compared with data from the literature. The combined CRM-filipin approach is a highly specific and sensitive method for the study of cholesterol within cells and tissues. The spatial resolution is high and can be adapted to the desired discriminative power. The gross distribution of filipin along the optical axis obtained in this study is similar to that found in biochemical studies. |
| New approach to study fast and slow motions in lipid bilayers: application to dimyristoylphosphatidylcholine-cholesterol interactions Le Guerneve, C. and M. Auger (1995), Biophys J 68(5): 1952-9. Abstract: Natural abundance 13C solid-state nuclear magnetic resonance spectroscopy was used to investigate the effect of the incorporation of cholesterol on the dynamics of dimyristoylphosphatidylcholine (DMPC) bilayers in the liquid-crystalline phase. In particular, the use of a combination of the cross-polarization and magic angle spinning techniques allows one to obtain very high resolution spectra from which can be distinguished several resonances attributed to the polar head group, the glycerol backbone, and the acyl chains of the lipid molecule. To examine both the fast and slow motions of the lipid bilayers, 1H spin-lattice relaxation times as well as proton and carbon spin-lattice relaxation times in the rotating frame were measured for each resolved resonance of DMPC. The use of the newly developed ramped-amplitude cross-polarization technique results in a significant increase in the stability of the cross-polarization conditions, especially for molecular groups undergoing rapid motions. The combination of T1 and T1 rho measurements indicates that the presence of cholesterol significantly decreases the rate and/or amplitude of both the high and low frequency motions in the DMPC bilayers. This effect is particularly important for the lipid acyl chains and the glycerol backbone region. |
| New approaches to raising the HDL cholesterol level Shinkai, H. (2002), Mini Rev Med Chem 2(3): 271-6. Abstract: Not only a high level of low-density lipoprotein (LDL) cholesterol, but also a low level of high-density lipoprotein (HDL) cholesterol, is a critical risk factor for atherosclerosis and coronary heart disease. Although fibrates and niacin can be used to improve low HDL cholesterol levels, their effect is not wholly satisfactory, so better drugs for the elevation of HDL cholesterol are desired. Among the many methods that may be used to raise HDL cholesterol levels, this review focuses on inhibitors of cholesteryl ester transfer protein (CETP) and on nuclear orphan receptor agonists that mediate the expression of ATP-binding cassette transporter 1 (ABC1). |
| New aspects of cholesterol in the central nervous system Claudepierre, T. and F. W. Pfrieger (2003), Med Sci (Paris) 19(5): 601-5. Abstract: Cholesterol is a multifacetted molecule, which serves as essential membrane component, as cofactor for signaling molecules and as precursor for steroid hormones. Despite intense research on the diverse aspects of cholesterol, the role of cholesterol in the nervous system is still little understood. Our recent studies on primary cultures of highly purified neurons from the rodent central nervous system (CNS) suggest that during development, neurons reduce or even abandon cholesterol synthesis and import cholesterol from astrocytes via lipoproteins. Neurons use the glia-derived cholesterol to form numerous and efficient synapses. This provokes new ideas about the role of astrocytes as cholesterol producers and about the function of cholesterol in the CNS and its involvement in neurodegenerative diseases. |
| New aspects of the interaction of cholesterol with dipalmitoylphosphatidylcholine bilayers as revealed by high-sensitivity differential scanning calorimetry McMullen, T. P. and R. N. McElhaney (1995), Biochim Biophys Acta 1234(1): 90-8. Abstract: We have investigated the effects of cholesterol on the thermotropic phase behavior of annealed and unannealed aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) using high-sensitivity differential scanning calorimetry (DSC), concentrating particularly on the cholesterol concentration range from 0 to 20 mol%. We find that the incorporation of cholesterol into low-temperature annealed DPPC bilayers decreases the enthalpy of the subtransition without affecting the transition temperature, such that the subtransition is abolished by 20 mol% cholesterol. Similarly, the incorporation of cholesterol progressively decreases the temperature and enthalpy of the pretransition and abolishes it entirely at cholesterol concentrations above 5 mol%. The incorporation of increasing quantities of cholesterol also alters the main or chain-melting phase transition. At cholesterol concentrations of 2 to 20 mol% cholesterol, the DSC endotherm arising from the main transition consists of superimposed sharp and broad components, the former due to the melting of cholesterol-poor and the latter to the melting of the cholesterol-rich DPPC domains. The temperature and cooperativity of the sharp component decreases slightly with increasing cholesterol concentration whereas the enthalpy decreases markedly, becoming zero at 20-25 mol% cholesterol. In contrast, the temperature and enthalpy of the broad component increases, and the cooperativity decreases markedly over this same range of cholesterol concentrations. An apparent increase in cooperativity of the overall DPPC endotherm at 7 mol% cholesterol is shown to arise because of a convergence in the transition temperatures of the sharp and broad components of the DSC endotherms. Some of our experimental findings, particularly the absence of any evidence for the existence of a triple point near 7.5 mol% cholesterol, do not accord with a recently proposed DPPC/cholesterol phase diagram derived from DSC and 2H-NMR data (see Vist, M.R. and Davis, J.H. (1990) Biochemistry 29, 451-464). In addition, we examined the effect of cholesterol on phosphatidylcholines (PCs) of different chain lengths and confirm that a eutectic point does not exist for any of these PC/cholesterol mixtures. We then propose a new, more complete DPPC/cholesterol phase diagram based on our high-sensitivity DSC data as well as some recent spectroscopic data on PC/cholesterol mixtures and explore some of its biological implications. |
| New aspects of the pathogenesis of cholesterol cholelithiasis Vitek, L. (2002), Cas Lek Cesk 141(19): 595-600. Abstract: During the last few years our knowledge of the pathogenesis of cholesterol gallstone disease has dramatically changed. Only a decade ago this topic was considered as already explored and scientifically not very interesting. However, with the progress in the field of lipid metabolism, the views on the aetiopathogenesis of cholelithiasis and particularly on its genetic aspects appear to be revolutionary. The predominant pathogenetic factor turned up to be the biliary cholesterol supersaturation, which is influenced by biliary secretion of the three major components of bile--cholesterol, phospholipids and bile salts. During the last years biliary secretion of these biliary lipids has been studied thoroughly and genetic mechanisms leading to the disorder of the biliary lipids homeostasis have been described. These novel aspects are discussed in the review article presented. |
| New cationic lipids for gene transfer with high efficiency and low toxicity: T-shape cholesterol ester derivatives Lee, Y., H. Koo, et al. (2004), Bioorg Med Chem Lett 14(10): 2637-41. Abstract: New degradable cationic ester lipids with 'T-shape' configurations were synthesized and tested for gene delivery carrier. Their transfection efficiency and toxicity were compared with commercially available cationic lipids, DOTMA, DOSPA, and DC-Chol. They showed efficient transfection activity and almost no toxicity on mammalian cell lines. Their ester bond degradation was monitored by (1)H NMR. |
| New cholesterol guidelines for the new millennium Clearfield, M. B. (2001), J Am Osteopath Assoc 101(6): 335, 363. |
| New cholesterol guidelines, new treatment challenges McKenney, J. M. (2002), Pharmacotherapy 22(7): 853-63. Abstract: Coronary heart disease (CHD) is the largest single killer of Americans. Epidemiologic trials have indicted low-density lipoprotein cholesterol (LDL) as directly correlating with CHD events, and clinical trials confirmed that lipid-lowering therapy decreases the risk of CHD events. The literature also indicates that only about 18% of these patients are treated to their goal LDL levels. New guidelines from the National Cholesterol Education Program extend the LDL-lowering recommendations, add a new non-high-density lipoprotein cholesterol (non-HDL) goal for patients with hypertriglyceridemia, and increase the number of drug-eligible patients from about 15 to 36 million. Most of those who are eligible for lipid-altering drug therapy have the highest CHD risk and require the most aggressive treatment to achieve goals. This presents a challenge to clinicians: how best to achieve LDL and non-HDL goals. Statins are the most effective agents for lowering LDL and one of the most effective for lowering non-HDL. This efficacy and the ability to reduce CHD risk were well documented in a number of randomized clinical trials. When statin monotherapy fails to achieve goals, a bile acid resin, niacin, or both may be added to lower LDL further, or a fibrate, niacin, or fish oils may be added to lower non-HDL further. Drugs are under development that may enhance our ability to reach LDL and non-HDL goals. Included are a group of so-called super statins, rosuvastatin and pitavastatin; agents that interfere with cholesterol or bile acid transport in the gut, such as ezetimibe; and dual peroxisome proliferator-activated receptor agonists that have both fibrate and thiazolidinedione-like effects. |
| New cholesterol guidelines: better, but harder to follow Mandell, B. (2001), Cleve Clin J Med 68(7): 579. |
| New clinical application of direct and chemical measurement of low density lipoprotein cholesterol-estimation of compositional changes in triglyceride-rich lipoprotein fraction Yoshino, G., T. Hirano, et al. (1999), Nippon Rinsho 57(12): 2745-53. Abstract: Recently several new direct assay systems for chemical measurement of LDL-cholesterol (Ch) have been developed. These systems allow us to estimate LDL-Ch value even in samples under non-fasting condition as well as samples from prominent hypertriglyceridemics without ultracentrifugation. Since it is possible that the difference between LDL-Ch value measured using new direct method and that calculated using Friedewald's formula can indicate compositional abnormalities of triglyceride-rich lipoprotein (TGRL) fraction (if VLDL-Ch equal to 1/5 of plasma triglyceride, this difference must always be zero), this difference (estimated remnant-Ch) may represent the presence of remnant or intermediate density lipoprotein (IDL) fraction. LDL-Ch is not detected by means of this direct method (LDL-EX, Denka Seiken Co.) in the eluate of the affinity column, which contains anti-apoA1 and anti-B100 antibody, indicating that RLP fraction can be excluded from the assay system. Estimated remnant-Ch correlated well with RLP-Ch, IDL-Ch and apoE. Furthermore, there is no significant correlation between LDL-Ch measured by LDL-EX and Lp(a), indicating that this direct assay system does not include Lp(a) in plasma. Thus, this new direct assay method for LDL-Ch enables us to measure LDL-Ch value with ease and also to estimate compositional abnormalities of TGRL fraction and/or appearance of remnant or IDL fraction without ultracentrifugation. |
| New concepts of mechanisms of intestinal cholesterol absorption Wang, D. Q. (2003), Ann Hepatol 2(3): 113-21. Abstract: The small intestine is a unique organ providing dietary and reabsorbed biliary cholesterol to the body. However, the molecular mechanisms whereby cholesterol is absorbed have not yet been fully understood. Recent research suggests that the newly identified ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 are apical cholesterol export pumps that promote partial efflux of cholesterol and nearly complete efflux of plant sterols from enterocytes into the intestinal lumen after their absorption. This provides an explanation why cholesterol absorption is a selective process in that plant sterols and other non-cholesterol sterols are absorbed poorly or not at all. Furthermore, a putative cholesterol import protein has been proposed, but remains uncharacterized. The identification of such a gene should yield new insights into the mechanisms that potentially regulate the influx of cholesterol across the apical brush border membrane of the enterocyte. Combination therapy using a novel and potent cholesterol absorption inhibitor (ezetimibe) and an HMG-CoA reductase inhibitor (statins) offers an efficacious new approach to the prevention and treatment of hypercholesterolemia. |
| New data on the total lipid, cholesterol and fatty acid composition of raw and grilled beef longissimus dorsi Bragagnolo, N. and D. B. Rodriguez-Amaya (2003), Arch Latinoam Nutr 53(3): 312-9. Abstract: Simultaneous analyses of total lipids, cholesterol and fatty acids were carried out on raw and grilled beef longissimus dorsi trimmed of external fat. Cholesterol was determined by high performance liquid chromatography and the fatty acids by gas chromatography. Mean total lipid (g/100 g) ranged from 2.1 to 2.6 for raw beef and 3.5 to 4.0 for grilled beef steaks. Cholesterol levels (mg/100 g) ranged from 40 to 43 for raw beef and 67 to 70 for grilled beef steaks. The main intramuscular fatty acids of the raw and grilled meat were 14:0, 16:0, 16:1n7, 18:0, 18:1n9, 18:1n7 and 18:2n6. Grilled lean beef steaks had significantly higher contents of the principal fatty acids and most of the minor fatty acids. The higher values for the three components in the grilled meat were due to loss of moisture during grilling. There was no significant difference between the apparent and true retentions values, both indicating no significant loss or degradation of total lipids, cholesterol and fatty acids during grilling. |