| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Ordered distribution of membrane-associated dense plaques in intact quail gizzard smooth muscle cells revealed by freeze-fracture following treatment with cholesterol probes Davis, E. C. and R. R. Shivers (1992), Anat Rec 232(3): 385-92. Abstract: The surface distribution of membrane-associated dense plaques in intact quail gizzard smooth muscle cells was investigated by freeze-fracture. Replicas of fractured smooth muscle cell plasma membrane showed caveola-free regions with few intramembrane particles, interspersed with caveola-populated areas with a higher intramembrane particle density. Electron microscopy of thin sections of quail gizzard smooth muscle revealed the regions free of caveolae to be occupied by membrane-associated dense plaques; anchoring sites for the contractile filaments of the cell. Demarcation between the caveola-populated and caveola-free regions on the relicated intramembrane surface was not clear and thus provided little information concerning the distribution of dense plaque sites. However, treatment of the smooth muscle tissue with the cholesterol-binding agents filipin or tomatin prior to freeze-fracture allowed the dense plaque sites to be easily observed as the sites remained free of the membrane deformations characteristic of these agents. The dense plaque sites consist of caveola-free oval areas juxtaposed in regular bands that traverse the long axis of the cell. The dense plaque sites on the freeze-fracture replica were confirmed by electron microscopy of thin sections of filipin-treated quail gizzard smooth muscle cells, which showed the plasma membrane associated with the dense plaques to be unaffected by the actions of filipin, whereas that of the caveola-populated region was severely deformed. The observations presented in this study provide evidence for a highly ordered distribution of dense plaques at the cell surface of intact quail gizzard smooth muscle cells and thus corroborate existing evidence for an organized substructure of smooth muscle cells. |
| Organization and interaction of cholesterol and phosphatidylcholine in model bilayer membranes Hyslop, P. A., B. Morel, et al. (1990), Biochemistry 29(4): 1025-38. Abstract: The molecular organization of sterols in liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at 37 degrees C is examined by utilizing the fluorescent analogue of cholesterol cholesta-5,7,9-trien-3 beta-ol (cholestatrienol). (1) Cholestatrienol is shown to be indistinguishable from native cholesterol in terms of its ability to condense POPC, as determined by (i) pressure/area studies of mixed-lipid monolayers and (ii) its ability to increase the order of POPC bilayers (determined by electron spin resonance studies) whether on its own or admixed with cholesterol at various ratios. (2) By analysis of the perturbation of the absorption spectra, cholestatrienol was found to be freely miscible in aggregates of cholesterol in buffer. In contrast, a lack of any detectable direct interaction of the sterol molecules in POPC bilayers was detected. (3) Fluorescence intensity and lifetime measurements of POPC/sterol (1:1 mol/mol) at various cholesterol/cholestratrienol molar ratios (0.5:1 up to 1:1 cholestatrienol/POPC) confirmed that sterol molecules in the membrane matrix were not associated to any great degree. (4) A quantitative estimate of how close sterol molecules approach each other in the membrane matrix was evaluated from the concentration dependence of the steady-state depolarization of fluorescence and was found to be 10.6 A. From geometrical considerations, the sterol/phospholipid phase at 1:1 mol/mol is depicted as each sterol having four POPC molecules as nearest neighbors. We term this arrangement of the lipid matrix an "ordered bimolecular mesomorphic lattice". (5) The concentration dependence of depolarization of fluorescence of cholestatrienol in POPC liposomes in the absence of cholesterol yielded results that were consistent with the cholestatrienol molecules being homogeneously dispersed throughout the phospholipid phase at sterol/POPC ratios of less than 1:1. (6) From qualitative calculations of the van der Walls' hydrophobic interactions of the lipid species, the phospholipid condensing effect of cholesterol is postulated to arise from increased interpenetration of the flexible methylene segments of the acyl chains, as a direct result of their greater mutual attraction compared to their attraction for neighboring sterol molecules. (7) The interdependence of the ordered bimolecular mesomorphic lattice and the acyl chain condensation is discussed in an effort to understand the ability of cholesterol to modulate the physical and mechanical properties of biological membranes. |
| Organization in lipid membranes containing cholesterol Veatch, S. L. and S. L. Keller (2002), Phys Rev Lett 89(26): 268101. Abstract: A fundamental attribute of raft formation in cell membranes is lateral separation of lipids into coexisting liquid phases. Using fluorescence microscopy, we observe spontaneous lateral separation in free-floating giant unilamellar vesicles. We record coexisting liquid domains over a range of composition and temperature significantly wider than previously reported. Furthermore, we establish correlations between miscibility in bilayers and in monolayers. For example, the same lipid mixtures that produce liquid domains in bilayer membranes produce two upper miscibility critical points in the phase diagrams of monolayers. |
| Organization of skin stratum corneum extracellular lamellae: diffraction evidence for asymmetric distribution of cholesterol McIntosh, T. J. (2003), Biophys J 85(3): 1675-81. Abstract: Lipid suspensions containing 2:1:1 skin ceramides:palmitic acid:cholesterol, similar to the lipid composition found in the extracellular matrix of skin stratum corneum, were analyzed by X-ray diffraction methods. These suspensions gave a sharp wide-angle reflection at 4.1 A, indicating tight hydrocarbon chain packing that would function as a water barrier, and low-angle lamellar diffraction with a repeat period near 130 A, similar to that previously recorded from intact stratum corneum. The lamellar repeat increased from 121 A at pH 6 to 133 A at pH 8.5, allowing phase angles of the lamellar data to be obtained by a sampling theorem "swelling" analysis. Electron density profiles showed that each repeating unit contained two asymmetric bilayers, with a fluid space on one side of the bilayer that increased with increasing pH, due to electrostatic repulsion between bilayers because of ionization of the palmitic acid. Profiles obtained from lamellae with cholesterol sulfate partially substituted for cholesterol showed large density increases on that same side of the bilayer, indicating that cholesterol is asymmetrically distributed in each bilayer. A molecular model was developed postulating that this asymmetry is due to the exclusion of cholesterol from lipid monolayers containing the ester-linked unsaturated (linoleic) hydrocarbon chain of skin ceramide 1. This model can explain the altered organization of extracellular lamellae in epidermal cysts (P. W. Wertz, D. C. Swartzendruber, K. C. Madison, D. T. Downing. 1987. J. Invest. Dermatol. 89:419-425) where the ester-linked chains have a higher percentage of saturated fatty acids than found in normal epidermis. |
| Organization of water molecules by adhering to oriented layers of dipalmitoylphosphatidyl serine in the presence of varying concentrations of cholesterol Miller, I. R. and D. Bach (2000), Biochim Biophys Acta 1468(1-2): 199-202. Abstract: About seven water molecules adhere to one molecule of dipalmitoylphosphatidyl serine (DPPS) in an oriented surface layer as inferred from the increase of the dichroic ratio R of their OH stretching vibration band (3400 cm(-1)) from 2 in the random bulk state to about 2.8 when adhering to DPPS. In DPPS-cholesterol mixtures the number of water molecules adhering to the phospholipid molecules and oriented by them increases as cholesterol content increases. This increase is very steep between molar fractions of cholesterol X(chol)=0.2-0.4 and at X(chol)=0.6 about 13 water molecules adhere and are oriented by one DPPS molecule. |
| Origin of cholesterol and bile acids in the diverted bile of two patients with total small bowel resection Ferezou, J., P. Beau, et al. (1991), Adv Exp Med Biol 285: 183-7. |
| Origin of cholesterol in myelin Morell, P. and H. Jurevics (1996), Neurochem Res 21(4): 463-70. Abstract: We review some of the older literature concerning metabolic turnover of cholesterol in the nervous system. The overall picture is that incorporation of radioactive precursors into brain cholesterol is roughly proportional to the rate of myelination and that, once incorporated, radioactive cholesterol is relatively stable metabolically. We outline a strategy for demonstrating the source (local synthesis or uptake from circulation) of cholesterol in brain. The experimental design involves determining the rate of accumulation of cholesterol; this is calculated as the increasing amounts of sterol in brain at successive time intervals during development. The rate of appearance of newly synthesized cholesterol is determined from incorporation of radioactivity from 3H20 (injected i.p. several hours prior to sacrifice) into cholesterol. The radioactivity associated with the sterol fractions and the specific activity of body water determined from the serum can be used to calculate the absolute amount of sterol newly synthesized during the time when 3H20 was present. The results obtained demonstrated that all of the bulk cholesterol accumulating in brain can be accounted for by newly synthesized cholesterol. None of the radioactive cholesterol came from the circulation, since cholesterol feeding suppressed cholesterol biosynthesis in the liver and specific radioactivity of circulating cholesterol was negligible. Thus, almost all cholesterol accumulating in brain during development is locally synthesized. |
| Origin of cholesterol in the fetal golden Syrian hamster: contribution of de novo sterol synthesis and maternal-derived lipoprotein cholesterol Woollett, L. A. (1996), J Lipid Res 37(6): 1246-57. Abstract: A fetal hamster increases in mass almost 100-fold in the third trimester of gestation. During this 5.5-day period, the acquisition of over 4 mg of cholesterol is required for normal development. The purpose of the present studies was to determine the potential source(s) of this fetal sterol. Rates of cholesterol synthesis in the whole fetus were measured initially. Synthesis rates in the whole fetus increased linearly from 10 days (approximately 25 nmol sterol/h) through 13.5 days of gestation (approximately 400 nmol sterol/h). During the last 1.5 days of intrauterine development, rates remained constant. Even though the synthesis rates were relatively elevated, as compared to those in an adult, the amount of cholesterol synthesized was about half of that accrued. When synthesis rates in all of the fetal tissues were summed, however, a majority of the sterol in the fetus could now be accounted for. During this same time when the fetus was accumulating 4 mg of cholesterol, the placenta and yolk sac increased in cholesterol content by 2.5 mg, indicating the need for a second source of sterol for fetal tissue development. Two other sources of sterol for these tissues were found to be maternal low density and high density lipoprotein (LDL and HDL, respectively). In fact, more than 0.9 mg of cholesterol was taken up during the third trimester as LDL. To summarize, a majority of cholesterol in the fetus could be accounted for by synthesis in all fetal tissues. Additionally, a significant amount of cholesterol was taken up as maternal-derived LDL and HDL by these same tissues. |
| Orlistat inhibits dietary cholesterol absorption Mittendorfer, B., R. E. Ostlund, Jr., et al. (2001), Obes Res 9(10): 599-604. Abstract: OBJECTIVE: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration. RESEARCH METHODS AND PROCEDURES: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of intravenous ((2)H(6) cholesterol) and oral ((2)H(5) cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption. RESULTS: In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01). DISCUSSION: These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself. |
| ORP2, a homolog of oxysterol binding protein, regulates cellular cholesterol metabolism Laitinen, S., M. Lehto, et al. (2002), J Lipid Res 43(2): 245-55. Abstract: Oxysterol binding protein (OSBP) related proteins (ORPs) constitute a family that has at least 12 members in humans. In the present study we characterize one of the novel OSBP homologs, ORP2, which we show to be expressed ubiquitously in mammalian tissues. The ORP2 cDNA encodes a deduced 55 kDa protein that lacks a pleckstrin homology (PH) domain, a feature found in the other family members. Sucrose gradient centrifugation analysis of Chinese hamster ovary (CHO) cell post-nuclear supernatant demonstrated that ORP2 is distributed in soluble and membrane-bound fractions. Immunofluorescence microscopy of the endogenous and overexpressed ORP2 in CHO cells suggested that the membrane-bound fraction of the protein localizes to the Golgi apparatus. Stably transfected CHO cells that overexpress ORP2 showed an increase in 14Ccholesterol efflux to serum, apolipoprotein A-I (apoA-I), and phosphatidyl choline vesicles. The proportion of cellular 14Ccholesterol that is esterified and the ACAT activity measured as 14Coleyl-CoA conversion into cholesteryl 14Coleate by the cellular membranes, were markedly decreased in the ORP2 expressing cells. Transient high level overexpression of ORP2 interfered with the clearance of a secretory pathway protein marker from the Golgi complex. The results implicate ORP2 as a novel regulator of cellular sterol homeostasis and intracellular membrane trafficking. |
| 'Orphans' meet cholesterol Tall, A. R., P. Costet, et al. (2000), Nat Med 6(10): 1104-5. |
| Oryzanol decreases cholesterol absorption and aortic fatty streaks in hamsters Rong, N., L. M. Ausman, et al. (1997), Lipids 32(3): 303-9. Abstract: Oryzanol is a class of nonsaponifiable lipids of rice bran oil (RBO). More specifically, oryzanol is a group of ferulic acid esters of triterpene alcohol and plant sterols. In experiment 1, the mechanisms of the cholesterol-lowering action of oryzanol were investigated in 32 hamsters made hypercholesterolemic by feeding chow-based diets containing 5% coconut oil and 0.1% cholesterol with or without 1% oryzanol for 7 wk. Relative to the control animals, oryzanol treatment resulted in a significant reduction in plasma total cholesterol (TC) (28%, P < 0.01) and the sum of IDL-C, LDL-C, and VLDL-C (NON-HDL-C) (34%, P < 0.01). In addition, the oryzanol-treated animals also exhibited a 25% reduction in percent cholesterol absorption vs. control animals. Endogenous cholesterol synthesis, as measured by the liver and intestinal HMG-CoA reductase activities, showed no difference between the two groups. To determine whether a lower dose of oryzanol was also efficacious and to measure aortic fatty streaks, 19 hamsters in experiment 2 were divided into two groups and fed for 10 wk chow-based diets containing 0.05% cholesterol and 10% coconut oil (w/w) (control) and the control diet plus 0.5% oryzanol (oryzanol). Relative to the control, oryzanol-treated hamsters had reduced plasma TC (44%, P < 0.001), NON-HDL-C (57%, P < 0.01), and triglyceride (TG) (46%, P < 0.05) concentrations. Despite a 12% decrease in high density lipoprotein cholesterol (HDL-C) (P < 0.01), the oryzanol-treated animals maintained a more optimum NON-HDL-C/HDL-C profile (1.1 +/- 0.4) than the control (2.5 +/- 1.4; P < 0.0075). Aortic fatty streak formation, so defined by the degree of accumulation of Oil Red O-stained macrophage-derived foam cells, was reduced 67% (P < 0.01) in the oryzanol-treated animals. From these studies, it is concluded that a constituent of the non-saponifiable lipids of RBO, oryzanol, is at least partially responsible for the cholesterol-lowering action of RBO. In addition, the cholesterol-lowering action of oryzanol was associated with significant reductions in aortic fatty streak formation. |
| OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation Wang, P. Y., J. Weng, et al. (2005), Science 307(5714): 1472-6. Abstract: Oxysterol-binding protein (OSBP) is the founding member of a family of sterol-binding proteins implicated in vesicle transport, lipid metabolism, and signal transduction. Here, OSBP was found to function as a cholesterol-binding scaffolding protein coordinating the activity of two phosphatases to control the extracellular signal-regulated kinase (ERK) signaling pathway. Cytosolic OSBP formed a approximately 440-kilodalton oligomer with a member of the PTPPBS family of tyrosine phosphatases, the serine/threonine phosphatase PP2A, and cholesterol. This oligomer had dual specific phosphatase activity for phosphorylated ERK (pERK). When cell cholesterol was lowered, the oligomer disassembled and the level of pERK rose. The oligomer also disassembled when exposed to oxysterols. Increasing the amount of OSBP oligomer rendered cells resistant to the effects of cholesterol depletion and decreased the basal level of pERK. Thus, cholesterol functions through its interaction with OSBP outside of membranes to regulate the assembly of an oligomeric phosphatase that controls a key signaling pathway in the cell. |
| Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins Luegmayr, E., H. Glantschnig, et al. (2004), Cell Death Differ 11 Suppl 1: S108-18. Abstract: Osteoporosis is associated with both atherosclerosis and vascular calcification. No mechanism yet explains the parallel progression of these diseases. Here, we demonstrate that osteoclasts (OCL) depend on lipoproteins to modulate cellular cholesterol levels and that this controls OCL formation and survival. Removal of cholesterol in OCL via high-density lipoprotein or cyclodextrin treatment dose-dependently induced apoptosis, with actin disruption, nuclear condensation and caspase-3 activation. One mechanism linked to the induction of OCL apoptosis was the cell-type-specific failure to induce HMG-CoA reductase mRNA expression, suggesting an absence of feedback regulation of de novo cholesterol biosynthesis. Furthermore, cyclodextrin treatment substantially suppressed essential M-CSF and RANKL-induced survival signaling pathways via Akt, mTOR and S6K. Consistent with these findings, cholesterol delivery via low-density lipoprotein (LDL) significantly increased OCL viability. Interestingly, OCLs from the LDL receptor (LDLR)-/- mouse exhibited reduced size and lifespan in vitro. Remarkably, LDLR+/+ OCL in lipoprotein-deficient medium phenocopied LDLR-/- OCL, while fusion and spreading of LDLR-/- OCL was rescued when cholesterol was chemically delivered during differentiation. With hyperlipidemia being associated with disease of the vascular system and bone, these findings provide novel insights into the selective lipoprotein and cholesterol dependency of the bone resorbing cell.Cell Death and Differentiation (2004) 11, S108-S118. doi:10.1038/sj.cdd.4401399 Published online 12 March 2004 |
| Osteopontin transgenic mice fed a high-cholesterol diet develop early fatty-streak lesions Isoda, K., Y. Kamezawa, et al. (2003), Circulation 107(5): 679-81. Abstract: BACKGROUND: Osteopontin (OPN) is a noncollagenous adhesion protein found at the site of atherosclerotic lesions. However, it has not yet been clarified whether or not OPN can promote atherosclerotic lesions. METHODS AND RESULTS We investigated the contribution of OPN to atherosclerosis by evaluating aortic sinus lesions of both OPN transgenic (Tg) and non-Tg mice fed an atherogenic diet (1.25% cholesterol) for 16 weeks. The atherosclerotic lesions were found to be significantly larger in OPN-Tg compared with those in non-Tg (17,859+/-2010 versus 6469+/-485 micro m(2), P<0.01). The lesions in both mice were fatty-streak lesions with an accumulation of mononuclear cells and lipids. We next investigated the production of interleukin (IL)-10 by macrophages from both mice. Compared with the non-Tg mice, a 42% (P<0.01) and 73% (P<0.001) decrease in the IL-10 production was identified in the OPN-Tg mice either without or with lipopolysaccharide. CONCLUSIONS: The expression of OPN induces fatty-streak lesion formation in mice fed an atherogenic diet and inhibits IL-10 production by macrophages, thus suggesting that OPN plays an important role in the development of fatty-streak lesions in vivo. |
| Ostreolysin, a pore-forming protein from the oyster mushroom, interacts specifically with membrane cholesterol-rich lipid domains Sepcic, K., S. Berne, et al. (2004), FEBS Lett 575(1-3): 81-5. Abstract: Ostreolysin, a 15 kDa pore-forming protein from the edible oyster mushroom (Pleurotus ostreatus), is lytic to membranes containing both cholesterol and sphingomyelin. Its cytotoxicity to Chinese hamster ovary cells correlates with their cholesterol contents and with the occurrence of ostreolysin in the cells detergent resistant membranes. Moreover, ostreolysin binds to supported monolayers and efficiently permeabilizes sonicated lipid vesicles, only if cholesterol is combined with either sphingomyelin or dipalmitoylphosphatidylcholine. Addition of mono- or di-unsaturated phosphatidylcholine to the cholesterol/sphingomyelin vesicles dramatically reduces the ostreolysin's activity. It appears that the protein recognizes specifically a cholesterol-rich lipid phase, probably the liquid-ordered phase. |
| Outcome of cholesterol screening in a community pharmacy Ibrahim, O. M., P. N. Catania, et al. (1990), Dicp 24(9): 817-21. Abstract: The purpose of our study was to determine if a community pharmacist could affect total blood cholesterol (TBC) of ambulatory patients by a program of education, consultation, and cholesterol screening. Of 241 initially screened individuals, 57 patients with TBC greater than 5.17 mmol/L (greater than 200 mg/dL) met the inclusion criteria of this six-month study. Of these, 51 completed the study. Outcome was determined by changes in TBC measured during the initial screening and after two follow-up visits. Pharmacist intervention included obtaining TBC concentrations and reporting the results to patients, teaching patients about the role of cholesterol in illness and health, explaining risk factors associated with cardiovascular disease, and providing follow-up communication with patients. Data were analyzed using ANOVA, Mann-Whitney, and chi-square. The mean TBC was 5.84 mmol/L (225.7 mg/dL) for the study group and 4.23 mmol/L (163.8 mg/dL) for participants with TBC less than 5.17 mmol/L (less than 200 mg/dL (p less than 0.0001). There was a significant difference (p = 0.0124) in mean age for the study group (36.4 years) versus other participants (30.0 years) but no difference in distribution by gender (p = 0.18). ANOVA showed significant differences in TBC during the three visits (p less than 0.0001). There was a significant decrease in mean TBC concentrations between visits 1 and 2 and between visits 1 and 3 (p less than 0.0001), but no difference between visits 2 and 3 (p = 0.48). Compared with mean baseline values, 81.4 and 72.6 percent of the patients had a decline in TBC at visits 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Outcomes of a cardiovascular nutrition counseling program in African-Americans with elevated blood pressure or cholesterol level Kumanyika, S. K., L. Adams-Campbell, et al. (1999), J Am Diet Assoc 99(11): 1380-91. Abstract: OBJECTIVE: To evaluate a cardiovascular nutrition education package designed for African-American adults with a wide range of literacy skills. DESIGN: Comparison of a self-help group and a full-instruction group; each group received nutrition counseling and clinical monitoring every 4 months. SUBJECTS: Three hundred thirty African-American adults, aged 40 to 70 years, with elevated cholesterol level or high blood pressure were randomly assigned to the self-help or full-instruction group; 255 completed the 12-month follow-up. INTERVENTIONS: Counseling to reduce intake of dietary fat, cholesterol, and sodium was based on Cardiovascular Dietary Education System (CARDES) materials, which included food-picture cards, a nutrition guide (self-help and full-instruction group), a video and audiotape series, and 4 classes (full-instruction group only). MAIN OUTCOME MEASURES: Changes in lipid levels and blood pressure after 12 months. STATISTICAL ANALYSES PERFORMED: Primary analyses consisted of repeated-measures analysis of variance to examine effects of time and randomization group on outcomes. RESULTS: Total cholesterol and low-density lipoprotein cholesterol level decreased by 7% to 8% in the self-help and full-instruction groups of men and women (P <.01). The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) decreased in both groups of women and in the men in the full-instruction group (P <.01). In full-instruction and self-help participants with elevated blood pressure at baseline, systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg (P <.01). Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES materials. APPLICATIONS/CONCLUSIONS: These results suggest that periodic nutrition counseling based on CARDES materials used for home study can enhance management of lipid levels and blood pressure in African-American outpatients. |
| Outcomes of a worksite cholesterol education program over a 5-year period Perovich, S. J. and W. M. Sandoval (1995), J Am Diet Assoc 95(5): 589-90. |
| Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? Pfrieger, F. W. (2003), Bioessays 25(1): 72-8. Abstract: Brain function depends on the cooperation between highly specialized cells. Neurons generate electrical signals and glial cells provide structural and metabolic support. Here, I propose a new kind of job-sharing between neurons and astrocytes. 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 to save energy and import cholesterol from astrocytes via lipoproteins. The cholesterol shuttle may be restricted to compartments distant from the soma including synapses and may be regulated by electrical activity. Testing these hypotheses will help to improve our still insufficient understanding of brain cholesterol metabolism and its role in neurodegeneration. |