| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol and sphingomyelin syntheses are regulated independently in cultured human intestinal cells, CaCo-2: role of membrane cholesterol and sphingomyelin content Chen, H., E. Born, et al. (1993), J Lipid Res 34(12): 2159-67. Abstract: There is a presumed association between cellular cholesterol and sphingomyelin metabolism. To study this relationship in the intestine, the activity of the rate controlling enzyme of sphingolipid synthesis, serine palmitoyltransferase (SPT), and the biosynthesis of long-chain bases were characterized in cultured human intestinal cells, CaCo-2. Cells were then incubated with substances known to alter cholesterol biosynthesis, and the effect of these mediators on SPT activity and long-chain base synthesis was determined and compared with their effects on HMG-CoA reductase activity and cholesterol synthesis. The polar sterol, 25-hydroxycholesterol, the squalene epoxide inhibitor, U18666A, and the inhibitor of HMG-CoA reductase, lovastatin, all significantly inhibited the synthesis of cholesterol without altering either SPT activity or long-chain base synthesis. Mevalonate, which increased cholesterol production 3-fold, also had no affect on SPT activity or sphingoid base synthesis. Serine, which significantly increased the synthesis of long-chain bases, did not alter cholesterol biosynthesis. Moreover, the suicide inhibitors of SPT, beta-chloroalanine and cycloserine, did not alter cholesterol synthesis while markedly decreasing long chain base synthesis. Cells were incubated with palmitic, oleic, linoleic, and eicosapentaenoic acids. Only palmitic acid, the preferred substrate for SPT, increased the production of long-chain bases. Both palmitic and oleic acids, however, increased the synthesis of cholesterol. Cells enriched in sphingomyelin had higher rates of synthesis of both cholesterol and long-chain bases compared to their controls. In contrast, cholesterol and long-chain base syntheses were significantly decreased in cells enriched in cholesterol. Control cells incubated with phospholipid liposomes alone had higher rates of synthesis of both lipids.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol and statins Ferrari, M. (1997), G Ital Cardiol 27(5): 499-500. |
| Cholesterol and steroid hormones: modulators of oxytocin receptor function Gimpl, G., V. Wiegand, et al. (2002), Prog Brain Res 139: 43-55. Abstract: The function and physiological regulation of the oxytocin-receptor system is strongly steroid-dependent. This is, unexpectedly, only partially reflected by the promoter sequences in the oxytocin receptor and favors the idea that posttranscriptional mechanisms may also play a significant role for the physiological regulation of the oxytocin-receptor system. Our data indicate that cholesterol acts as an allosteric modulator of the oxytocin receptor and stabilizes both membrane-associated and solubilized OT receptors in a high-affinity state for agonists and antagonists. Moreover, high-affinity OT receptors are 2-fold enriched in cholesterol-rich plasma membrane domains in HEK293 fibroblasts stably expressing the human OT receptor. Biochemical data suggest a direct and cooperative molecular interaction of cholesterol molecules with OT receptors. To localize the cholesterol interacting domain of the oxytocin receptor the C-terminal part including the last two transmembrane domains have been exchanged by the corresponding sequences of the cholecystokinin type B receptor, which is functionally not dependent on cholesterol. Concerning its ligand-binding behavior this chimeric receptor protein showed the same dependence on cholesterol and its analogues as the wild type oxytocin receptor. From mutagenesis experiments and studies with receptor chimera between the OTR and cholecystokinin type B receptor, we conclude that a major part of the cholesterol interacting domain may be localized in the first part of the oxytocin receptor, possibly in a domain nearby the agonist binding site. Progesterone is considered to be essential to maintain the uterine quiescence. High concentrations of progesterone (> 10 microM) attenuate or block the signaling of several GPCRs, including the OT receptor via a fast, reversible and non-genomic pathway. Progesterone is known to inhibit both cholesterol biosynthesis and the intracellular trafficking of cholesterol. We therefore test the hypothesis that progesterone affects the signal transduction and subdomain localization of receptors via its influence on cholesterol trafficking. Since cholesterol-rich subdomains (rafts) are considered to be organization centers for cellular signal transduction, changes of the level or distribution of cholesterol may have profound effects on receptor-mediated signaling in general. Using fluorescence recovery after photobleaching (FRAP) measurements with GFP-tagged oxytocin receptors the influence of steroids on the mobility and distribution of the oxytocin receptor in the plasma membrane was analyzed. Progesterone had no effect on the lateral mobility of the oxytocin receptor, but it led to marked inhibition of cellular motility such as vesicle trafficking and movements of filopodia. Non-genomic effects of progesterone and estradiol with respect to receptor signaling as well as the influence of cholesterol on signal transduction will be discussed in more detail. |
| Cholesterol and steroid synthesizing smooth endoplasmic reticulum of adrenocortical cells contains high levels of translocation apparatus proteins Black, V. H., A. Sanjay, et al. (2002), Endocr Res 28(4): 425-30. Abstract: Steroid-secreting cells possess abundant smooth endoplasmic reticulum whose membranes contain many enzymes involved in sterol and steroid synthesis. In this study we demonstrate that adrenal smooth microsomal subfractions enriched in these membranes also possess high levels of proteins belonging to the translocation apparatus, proteins previously assumed to be confined to morphologically identifiable rough endoplasmic reticulum (RER). We further demonstrate that these smooth microsomal subfractions are capable of effecting the functions of these protein complexes: co-translational translocation, signal peptide cleavage and N-glycosylation of newly synthesized polypeptides. We hypothesize that these elements participate in regulating the levels of ER-targeted membrane proteins involved in cholesterol and steroid metabolism in a sterol-dependent and hormonally-regulated manner. |
| Cholesterol and steroids action on aminopeptidases Martinez, J. M., I. Prieto, et al. (1997), Biochem Soc Trans 25(1): 113S. |
| Cholesterol and stroke risk: a role for statins? Devuyst, G. and J. Bogousslavsky (2000), Schweiz Med Wochenschr 130(33): 1157-63. Abstract: Atherosclerosis is the most common cause of vascular diseases, but the relevance of cholesterol has only been definitely associated with coronary artery disease and peripheral vascular disease. In comparison, the role of cholesterol in stroke is, while a tempting assumption, subject to controversy in the literature. The crucial question--is cholesterol a risk factor for stroke?--remains open. Recent trials with statin drugs, such as 4 S, CARE, LIPID and WOSCOP, have created a new wave of enthusiasm by showing decreased risk of stroke in the statin-treated patients. However, these trials are most often designed for patients with a known history of coronary artery disease. In contrast, studies investigating the impact of statins in the secondary prevention of stroke are still lacking. Moreover, the beneficial effects of statins on clinical events may involve non-cholesterol mechanisms. In regard to stroke prevention, there is no absolute evidence to recommend the use of statin drug therapy. |
| Cholesterol and tau protein--findings in Alzheimer's and Niemann Pick C's disease Ohm, T. G., S. Treiber-Held, et al. (2003), Pharmacopsychiatry 36 Suppl 2: S120-6. Abstract: Niemann Pick C (NPC), a fatal autosomal-recessive neurovisceral lipid storage disorder, is a juvenile dementia with massive nerve-cell loss and cytoskeletal abnormalities in cerebral neurons. These abnormalities consist of tangles of tau protein, which is otherwise highly soluble and usually stabilizes the microtubules. Immunologically and ultrastructurally similar tangles are seen some decades later in patients with Alzheimer's disease (AD). There is evidence that tangle-bearing cells in both diseases show higher levels of free (i. e. filipin-positive) cholesterol than adjacent tangle-free nerve cells. The cholesterol accumulates either in a more diffuse way (mainly in AD) or in granule-like accumulations (mainly in NPC). In NPC, neuron cholesterol may originate from sources other than the alimentary tract. Experiments with a NPC mouse model revealed that even in pure neuron cultures, the NPC -/- neurons accumulate free cholesterol in contrast to NPC-wt littermates, suggesting that the cholesterol is either synthesized by the neurons or liberated from degenerated ones before being taken up by the endosomal/lysosomal pathway. The accumulation of free cholesterol in the somata of NPC neurons is associated with a decrease of cholesterol levels in myelin sheaths. In terms of tau protein, NPC -/- mice exhibit higher levels of AT8-positive tau, suggesting that the phosphorylation-dependent mAb AT8 has detected a tau-epitope in a state considered to represent early stages of tangle formation. Concomitantly to the increase in free intracellular cholesterol, the rate-limiting enzyme in cholesterol and isoprenoid biosynthesis, HMG-CoA reductase, was found to be significantly reduced. Experimental blockade of the enzyme's activity by application of the lipid-lowering drug lovastatin showed subcellular shifts in tau phosphorylation as monitored with mAbs AT8, 12E8 and others. In summary, the data showed interesting similarities between NPC and AD suggesting some pathological metabolic pathway in common. |
| Cholesterol and the activity of bacterial toxins Palmer, M. (2004), FEMS Microbiol Lett 238(2): 281-9. Abstract: Cholesterol may affect the activity of microbial toxins in a direct, specific way, or it may exert indirect effects because of its role in membrane fluidity, membrane line tension, and in the stabilization of rafts in the cytoplasmic membrane. The thiol-activated toxins of gram-positive bacteria, and the cytolysin of Vibrio cholerae are presented as examples of specific toxin-cholesterol interaction. Several mechanisms of indirect effects of cholesterol are discussed using examples such as Staphylococcus aureus alpha-hemolysin, aerolysin, and diphtheria toxin. |
| Cholesterol and the biology of Alzheimer's disease Wolozin, B. (2004), Neuron 41(1): 7-10. Abstract: Recent results implicating cholesterol metabolism in the pathophysiology of Alzheimer's disease (AD) bring cholesterol to the forefront of AD research. Research from genetics, epidemiology, and cell biology all converge, suggesting that cholesterol plays a central role in the biology of amyloid precursor protein and the toxic peptide generated by its cleavage, beta-amyloid (Abeta). The ability of cholesterol to modulate Abeta production suggests opportunities for therapeutic intervention, although the functional significance underlying the connection between cholesterol and Abeta remains to be investigated. |
| Cholesterol and the coronary endothelium Knight, C. J. and J. B. Warren (1995), J Cardiovasc Risk 2(3): 180-8. Abstract: The root causes of atherosclerosis lie in cellular events that precede the clinical presentation of the disease by many years. The initiating events centre around the response of endothelial cells to chronic injury, such as that sustained in hypercholesterolaemia. These responses involve the activation, attachment and migration of leucocytes and platelets. |
| Cholesterol and the Golgi apparatus Bretscher, M. S. and S. Munro (1993), Science 261(5126): 1280-1. |
| Cholesterol and the older adult Kaiser, F. E. (1993), South Med J 86(10): 2S11-4. Abstract: The National Cholesterol Education Program and physician/patient awareness of the risks of hypercholesterolemia have resulted in aggressive screening and treatment of elevated cholesterol levels. The "one size fits all" concept has been used as the criterion for intervention. However, this has been promulgated without convincing evidence that levels of cholesterol are as important in older individuals as in those of middle age. Clearly, cholesterol is not the only contributor to cardiovascular risk, and other risk factors such as smoking, hypertension, diabetes, and obesity should not be ignored. To prevent unnecessary intervention, overzealous interpretation of cholesterol values should be avoided. |
| Cholesterol and the risk of ischemic stroke Bowman, T. S., H. D. Sesso, et al. (2003), Stroke 34(12): 2930-4. Abstract: BACKGROUND AND PURPOSE: Large epidemiological studies have not established cholesterol levels as a risk factor for ischemic stroke, but recent clinical trials have demonstrated a reduction in the ischemic stroke rate for patients taking HMG-CoA reductase inhibitors ("statins"). The goal of this study was to evaluate whether total cholesterol (TC), high-density lipoprotein (HDL), triglycerides, and the TC:HDL ratio are risk factors for ischemic stroke in apparently healthy men enrolled in the Physicians' Health Study. METHODS: We used a nested case-control study design and matched 296 ischemic stroke cases with an equal number of controls on age, tobacco use, and follow-up time. At baseline, TC, HDL, and triglyceride levels were measured. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using conditional logistic regression, adjusting for major risk factors for ischemic stroke. RESULTS: Compared with the reference lowest quartile, the highest quartile for TC had an adjusted OR of 1.56 (95% CI, 0.84 to 2.92), the highest quartile of HDL had an adjusted OR of 0.75 (95% CI, 0.43 to 1.30), and the highest quartile of triglycerides had an adjusted OR of 1.07 (95% CI, 0.63 to 1.82). Although the highest quartile of the TC:HDL ratio had an adjusted OR of 1.62 (95% CI, 0.93 to 2.82), the risk of ischemic stroke was not a linear relationship. CONCLUSIONS: After adjustment, TC, HDL, and triglycerides were not significantly associated with ischemic stroke risk, and for the TC:HDL ratio, a suggestion of increased risk of ischemic stroke was limited to those with the highest levels. |
| Cholesterol and the risk of renal dysfunction in apparently healthy men Schaeffner, E. S., T. Kurth, et al. (2003), J Am Soc Nephrol 14(8): 2084-91. Abstract: Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as /= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval CI, 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl. |
| Cholesterol and total mortality: need for larger trials Collins, R., A. Keech, et al. (1992), Bmj 304(6843): 1689. |
| Cholesterol and triacylglycerols in human breast milk before and after nursing Hromadova, M., J. Ponec, et al. (1991), Endocr Regul 25(1-2): 70-3. Abstract: Cholesterol and triacylglycerols concentrations were estimated in human breast milk taken before and after nursing at the period of 1 week, 3 months, and 6 months after delivery. In all postfeeding samples significantly higher concentration of cholesterol and triacylglycerols was found as compared with the appropriate samples obtained before the feeding. In cholesterol concentration such difference was most remarkable in the milk of mothers who were breast feeding their infants over 6 months. The highest cholesterol concentrations were found during the first week after the delivery, whereas the highest concentrations of triglycerides were found 6 months after the delivery. The elevations of the lipid levels were not associated with changes of osmolality and/or electrolytes (Na+, K+, Ca2+) during the nursing. |
| Cholesterol and triglyceride concentration as risk factors for myocardial infarction and death in women, with special reference to influence of age Lindquist, P., C. Bengtsson, et al. (2002), J Intern Med 251(6): 484-9. Abstract: OBJECTIVE: To evaluate the importance of serum cholesterol and triglyceride concentrations as predictors of myocardial infarction and death in women of different ages. DESIGN: Prospective observational study, initiated in 1968-69. Setting. Gothenburg, Sweden, with about 430 000 inhabitants. SUBJECTS: A population-based sample of 1462 women aged 38, 46, 50, 54 and 60 years at start of the study, followed up for 24 years. Main outcome measures. Within each age group, myocardial infarction and death were predicted by serum cholesterol and triglyceride concentrations and smoking in a multivariate model. RESULTS: In the total population only serum triglyceride concentration was a strong independent risk factor for both end-points studied. Serum triglyceride concentration measured in 38- and 46-year-old women had no predictive value with respect to 24-year incidence of myocardial infarction or death. In 50-, 54- and 60-year-old women, high serum triglyceride concentration consistently predicted myocardial infarction and total mortality. Serum cholesterol concentration, on the other hand, showed evidence of direct association for 24-year all-cause mortality in the younger premenopausal group. Serum cholesterol had no predictive value for myocardial infarction or mortality in the peri- and postmenopausal ages. CONCLUSIONS: There appears to be age-specificity in association between serum lipids and these end-points in women, serum cholesterol concentration being more important for younger women and serum triglyceride concentration more important for postmenopausal women as risk factors, observations which need further attention. |
| Cholesterol and triglyceride concentrations, birthweight and central obesity in pre-school children. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood Cowin, I. and P. Emmett (2000), Int J Obes Relat Metab Disord 24(3): 330-9. Abstract: OBJECTIVE: To investigate the relationship between blood cholesterol and triglyceride, birthweight and central obesity in pre-school children, after controlling for height and body mass index. METHODS: This was a longitudinal population-based study in south-west England. Research clinics were held when the children were 31 and 43 months of age, where anthropometric measurements were made and a non-fasting blood sample was taken and analysed for triglyceride, total cholesterol and high-density lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL) cholesterol values were calculated using the Friedewald equation. Central obesity was estimated using the ratio of waist circumference:arm circumference (WC:AC). RESULTS: Complete blood lipid and anthropometric data were available for 385 children at 31 months and 470 children at 43 months. Height was negatively associated with the concentration of triglyceride, and total and LDL cholesterol. There was little evidence for a relationship between body mass index (BMI) and blood lipids at either 31 or 43 months. The only significant relationship between birthweight and blood lipids was a negative association with HDL (and consequently a positive association with the ratio of total:HDL cholesterol) in boys at 43 months. Adjustment for current height and BMI had little effect on the associations between birthweight and blood lipid concentrations. WC:AC was positively associated with triglycerides and negatively associated with HDL values in boys, and had a quadratic relationship with LDL concentrations among girls. These relationships were unchanged or became stronger on adjustment for current height and body mass index. CONCLUSION: In the pre-school child, central obesity has a relationship with triglyceride and HDL concentrations that is independent of current height and BMI. We have found no evidence that increasing birthweight is associated with a more favourable blood lipid profile at 31 and 43 months. |
| Cholesterol and triglyceride content in lipoprotein fractions of rats treated with bovine serum albumin Pejovic, M. D., V. B. Djordjevic, et al. (1996), Nephron 73(4): 713. |
| Cholesterol and triglyceride fatty acid synthesis in apolipoprotein E2-associated hyperlipidemia Jones, P. J., S. M. Dendy, et al. (1992), Arterioscler Thromb 12(1): 106-13. Abstract: To investigate whether increased endogenous lipogenesis contributes to elevated plasma lipid levels in individuals with apolipoprotein (apo) E2-associated hyperlipidemia (E2-HL), plasma pool cholesterol and triglyceride fatty acid syntheses were measured in subjects with E2-HL and in those with normal lipid levels. Subjects were given a priming dose of deuterium oxide (D2O) followed by maintenance doses over 48 hours. During the first 24 hours, subjects consumed prepared meals, whereas during the 24-48 hour interval, they consumed water only. Blood samples were drawn every 12 hours, and cholesterol and triglyceride fatty acid formation rates were determined from the change in deuterium enrichment. The free cholesterol fractional synthesis rate over 0-24 hours of E2-HL subjects (0.057 +/- 0.010 day-1, mean +/- SEM) was not significantly different from that of normolipidemics (0.075 +/- 0.005 day-1). Calculated cholesterol net synthesis was not different between the two groups (0.56 +/- 0.07 and 0.75 +/- 0.05 g/day, respectively). Mean free cholesterol synthesis for all subjects was higher in the fed (0-24 hour) compared with the fasted (24-48-hour) condition. Initial 12-hour triglyceride fatty acid fractional synthesis was significantly (p less than 0.01) increased in E2-HL subjects (0.143 +/- 0.012 day-1) compared with controls (0.082 +/- 0.0013 day-1). These findings suggest that in E2-HL, elevated plasma cholesterol levels are due to factors other than increased sterol synthesis, while higher de novo fatty acid synthesis contributes to the observed hypertriglyceridemia. |