| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol superlattice modulates the activity of cholesterol oxidase in lipid membranes Wang, M. M., M. Olsher, et al. (2004), Biochemistry 43(8): 2159-66. Abstract: Here, the interplay between membrane cholesterol lateral organization and the activity of membrane surface-acting enzymes was addressed using soil bacteria cholesterol oxidase (COD) as a model. Specifically, the effect of the membrane cholesterol mole fraction on the initial rate of cholesterol oxidation catalyzed by COD was investigated at 37 degrees C using cholesterol/1-palmitoyl-2-oleoyl-l-alpha-phosphatidylcholine (POPC) large unilamellar vesicles (LUVs, approximately 800 nm in diameter). In the three concentration ranges examined (18.8-21.2, 23.6-26.3, and 32.2-34.5 mol % cholesterol), the initial activity of COD changed with cholesterol mole fraction in a biphasic manner, exhibiting a local maximum at 19.7, 25.0, and 33.4 mol %. Within the experimental errors, these mole fractions agree with the critical cholesterol mole fractions (C(r)) (20.0, 25.0, and 33.3) theoretically predicted for maximal superlattice formation. The activity variation with cholesterol content was correlated well with the area of regular distribution (A(reg)) in the plane of the membrane as determined by nystatin fluorescence. A similar biphasic change in COD activity was detected at the critical sterol mole fraction 20 mol % in dehydroergosterol (DHE)/POPC LUVs (approximately 168 nm in diameter). These results indicate that the activity of COD is regulated by the extent of sterol superlattice for both sterols (DHE and cholesterol) and for a wide range of vesicle sizes (approximately 168-800 nm). The present work on COD and the previous study on phospholipase A(2) (sPLA(2)) Liu and Chong (1999) Biochemistry 38, 3867-3873 suggest that the activities of some surface-acting enzymes may be regulated by the extent of sterol superlattice in the membrane in a substrate-dependent manner. When the substrate is a sterol, as it is with COD, the enzyme activity reaches a local maximum at C(r). When phospholipid is the substrate, the minimum activity is at C(r), as is the case with sPLA(2). Both phenomena are in accordance with the sterol superlattice model and manifest the functional importance of membrane cholesterol content. |
| Cholesterol supplementation attenuates the hypocholesterolemic effect of rice bran oil in rats Koba, K., J. W. Liu, et al. (2000), J Nutr Sci Vitaminol (Tokyo) 46(2): 58-64. Abstract: Rice bran oil (RBO), when blended with safflower oil (SFO) at the ratio of 7 to 3, has been shown to lower serum cholesterol in humans consuming cholesterol. The mechanism as to how this oil blend exerts its effect is not yet clear. This study examined the effect of cholesterol supplementation on the cholesterol-lowering ability of different RBO/SFO blends. Male Sprague Dawley rats (4 wk old) were fed purified diets containing 10% fat with or without the addition of 0.5% cholesterol for 3 wk. The fat was either SFO or RBO alone, or the mixture of these two oils at the ratio of 7: 3 (7S/3R), 5:5 (5S/5R), or 3:7 (3S/7R). Without cholesterol supplementation, there were no significant differences in the serum and liver total cholesterol levels among different dietary fats. However, the HDL cholesterol level of rats fed the RBO-containing diets (especially in rats fed the 3S/7R diet) was higher than that of rats fed the diet containing SFO alone. This resulted in an increase in the ratio of HDL/total cholesterol-a desirable outcome. Supplementation of the diets with 0.5% cholesterol significantly increased the cholesterol level in both the serum and the liver. Increasing the proportion of RBO in the diet further raised the total cholesterol level in the serum whereas it reduced liver cholesterol. Then, the specific effect of the 3S/7R mixture on the ratio of HDL/total cholesterol disappeared. These findings suggest that cholesterol supplemented at the level of 0.5% in this study masked the cholesterol-lowering effect of RBO. Smaller percentages of polyunsaturated fatty acid (i.e., 18:2n-6) in the RBO-containing diets than in the SFO diet might have reduced their ability to dispose the circulating serum cholesterol into the liver. |
| Cholesterol supplementation does not improve developmental progress in Smith-Lemli-Opitz syndrome Sikora, D. M., M. Ruggiero, et al. (2004), J Pediatr 144(6): 783-91. Abstract: OBJECTIVE: Smith-Lemli-Opitz syndrome (SLOS) results in multiple malformations, growth deficiency, and mental retardation. Cholesterol supplementation has been used for several years to treat symptoms of SLOS. We assessed the developmental progress of children and adolescents with SLOS over a 6-year period. STUDY DESIGN: Patients with SLOS (n=14) received continuous cholesterol supplementation as part of a longitudinal study. Assessment of their developmental progress in the areas of cognitive, motor, and adaptive skills occurred every 6 to 12 months. The progress of each subject over time and the progress of the group as a whole were analyzed by using a repeated-measures design and multiple t tests. RESULTS: Developmental quotients did not improve over time for children with SLOS receiving cholesterol. In addition, baseline cholesterol levels, rather than age when supplementation began or increase in cholesterol levels, best predicted developmental outcome. CONCLUSIONS: These results suggest that cholesterol supplementation in its current form does not improve the developmental progress of children and adolescents with SLOS. |
| Cholesterol supplementation in Smith-Lemli-Opitz syndrome Abuelo, D. N. (1998), Am J Med Genet 78(4): 378-80. |
| Cholesterol supplementation objectively reduces photosensitivity in the Smith-Lemli-Opitz syndrome Azurdia, R. M., A. V. Anstey, et al. (2001), Br J Dermatol 144(1): 143-5. Abstract: Smith-Lemli-Opitz (SLO) affected children have multiple congenital physical and mental abnormalities; photosensitivity to ultraviolet A (UVA) has recently become a recognized feature. We present a patient with SLO and prominent photosensitivity in whom detailed phototesting has been performed at baseline and following 6 months of cholesterol supplementation. There was significant improvement in the symptoms of photosensitivity, confirmed objectively by phototesting and accompanied by partial correction of the biochemical abnormalities seen in SLO. This case report is the first to show that cholesterol supplementation in SLO can lead to an objective improvement in the associated photosensitivity. |
| Cholesterol supplementation prevents necrosis and inflammation but enhances fibrosis in alcoholic liver disease in the rat Nanji, A. A., A. Rahemtulla, et al. (1997), Hepatology 26(1): 90-7. Abstract: Based on studies that show a role for the low-density lipoprotein (LDL)-receptor in arachidonic acid delivery and eicosanoid synthesis in macrophages, the present study investigated the effect of cholesterol supplementation on pathological changes and thromboxane (TX) synthesis in alcoholic liver injury. Male Wistar rats were intragastrically fed ethanol with either corn oil or fish oil for 1 month. Control rats received isocaloric amounts of dextrose instead of ethanol. An additional group of rats fed either ethanol or dextrose with fish oil or corn oil were supplemented with 1% cholesterol. At the time of killing, all rats had the following evaluated: liver histopathology, lipid peroxidation, liver and plasma thromboxane levels, plasma endotoxin and messenger RNA (mRNA) levels of LDL-receptor, tumor necrosis factor alpha (TNF-alpha), cyclooxygenase (Cox)-1 and -2, and transforming growth factor beta (TGF-beta). Rats fed ethanol with either fish oil or corn oil developed fatty liver, necrosis, inflammation, and central vein collagen deposition. Cholesterol supplementation enhanced the degree of fibrosis but prevented necrosis and inflammation. These alterations in pathological changes by cholesterol were accompanied by absent TNF-alpha and Cox-2 mRNAs, decreased thromboxane levels, decreased lipid peroxidation, and increased TGF-beta mRNA. Cholesterol enrichment of the diet thus decreases proinflammatory components, but enhances fibrosis in ethanol-fed rats. |
| Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome Linck, L. M., D. S. Lin, et al. (2000), Am J Med Genet 93(5): 360-5. Abstract: Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition comprising multiple malformations, mental retardation, and growth failure, results from reduced activity of the final enzyme in cholesterol biosynthesis, 7-dehydrocholesterol Delta(7)-reductase (DHCR7). Reduced plasma and tissue cholesterol concentrations and accumulation of cholesterol precursors including 7-dehydrocholesterol (7-DHC) are characteristic biochemical abnormalities. While it is still unclear what role these potentially toxic precursors have in the pathogenesis of this disorder, the accumulation of 7-DHC in the brain has been associated with impaired learning in rats and oxidized 7-DHC has been shown to induce growth retardation in cultured rat embryos. We hypothesized that supplemental dietary cholesterol would increase plasma cholesterol levels and suppress synthesis of 7-DHC and other abnormal sterols in individuals with SLOS. After baseline sterol levels were obtained, patients were provided supplemental cholesterol as egg yolk. Plasma sterols were analyzed by capillary-column gas chromatography over time in four children with SLOS. When evaluated at 4-8 weeks after the initiation of cholesterol supplementation, there was a marked increase in mean plasma cholesterol, from 53 mg/dl to 82 mg/dl. While the percent of total sterols as 7-DHC decreased from 15% to 10%, there was no change in total plasma 7-DHC levels. However, when evaluated 35-90 weeks after the institution of cholesterol supplementation, mean plasma 7-DHC decreased, from 11.3 mg/dl to 3.5 mg/dl (-67%, P < 0.05), along with an increase in mean plasma cholesterol from 53 mg/dl to 114 mg/dl (+116%, P < 0.05). These results support the hypothesis that over time dietary cholesterol supplementation from egg yolk increases the plasma cholesterol levels and decreases levels of 7-DHC which may be toxic. These data have important therapeutic implications in the management of SLOS. |
| Cholesterol synthesis and absorption by 2H2O and 18O-cholesterol and hypocholesterolemic effect of soy protein Wong, W. W., D. L. Hachey, et al. (1995), J Nutr 125(3 Suppl): 612S-618S. Abstract: The kinetic behavior of orally ingested 18O-cholesterol was compared with that of orally ingested 13C5-cholesterol in two normocholesterolemic men and the hypocholesterolemic effect of soy protein was demonstrated in 12 hypercholesterolemic men. Our results indicated no difference in the metabolism of orally ingested 18O- and 13C5-cholesterol. The use of 18O-cholesterol and 13C5-cholesterol also allowed simultaneous estimation of fractional rates of cholesterol synthesis using the 2H2O method, which were calculated to be 5.76 and 8.17%/d for the two normocholesterolemic subjects. The percent reduction in plasma cholesterol levels were found to be greater when the hypercholesterolemic men were placed on a soy protein diet than on an animal protein diet. |
| Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup Miettinen, T. A. and H. Gylling (2003), Atherosclerosis 168(2): 343-9. Abstract: We assumed that assaying serum cholesterol precursors (synthesis markers) and plant sterols and cholestanol (absorption markers of cholesterol) reveals differences in cholesterol synthesis and absorption in the Finnish 4S subgroup divided in high triglyceride-low HDL cholesterol (lipid triad=HTG) and isolated high LDL cholesterol (ILDL) groups. Serum squalene and non-cholesterol sterol ratios to cholesterol were measured with gas-liquid chromatography at baseline, 6 weeks, 1 year, and 5 years on simvastatin. Patients with HTG (n=135) exhibited features of metabolic syndrome and, in spite of similar serum total and LDL cholesterol levels, ratios of synthesis markers were higher and those of absorption markers lower than in ILDL (n=133). The latter patients accumulated to a subgroup shown earlier to be clinical non-responders to simvastatin in 4S. Serum cholesterol reduction by simvastatin only tended to be higher in HTG than ILDL. The synthesis marker ratios were markedly reduced, and more effectively in HTG than ILDL, while the absorption marker ratios were increased, and for plant sterols more in ILDL than HTG. In conclusion, HTG is associated with high synthesis and low absorption of cholesterol, these events being opposite in ILDL. Synthesis is more effectively reduced by simvastatin in HTG than ILDL in spite of similar reduction in serum cholesterol. Patients defined by highest baseline absorption marker ratios in ILDL group are poor coronary event-reducers on regular simvastatin treatment. |
| Cholesterol synthesis and accretion within various tissues of the fetal and neonatal rat Haave, N. C. and S. M. Innis (2001), Metabolism 50(1): 12-8. Abstract: The rate of cholesterol synthesis is reported to be higher in fetal relative to adult rats. Along with the observation that maternal diets high in fat and cholesterol are unable to alter the rate of cholesterol synthesis in the fetus, this has been taken as indirect evidence that the fetal rat meets its cholesterol needs through de novo synthesis. This study quantified the rates of cholesterol synthesis and accumulation in the liver, brain, intestine, and carcass of the fetal and neonatal rat and the placenta to determine whether these developing tissues are able to support their own cholesterol needs without the uptake of plasma lipoprotein cholesterol. The rate of cholesterol synthesis was determined in vivo using 3Hwater. The rate of cholesterol accumulation was determined by calculating the difference in tissue cholesterol content between 2 subsequent days of development. Total fetal body cholesterol synthesis was sufficient to support the rate of cholesterol accumulation. Fetal and neonatal liver synthesized cholesterol at a rate in excess of cholesterol accumulation, suggesting hepatic secretion of cholesterol into the plasma. Before the onset of suckling, the rates of de novo cholesterol synthesis in the intestine, brain, and carcass were also sufficient but not higher than the need for cholesterol accretion. After the establishment of suckling, the rate of cholesterol accumulation in the intestine and carcass was in excess of synthesis, suggesting that neonatal tissues derive some of their cholesterol from dietary milk or liver. These studies suggest that the perinatal rat does not require exogenous cholesterol to support tissue cholesterol accretion. However, the fetal liver may support cholesterol accretion in other tissues through rates of synthesis in excess of accumulation and secretion into plasma. The placenta may derive some cholesterol from the maternal and/or fetal plasma. |
| Cholesterol synthesis and de novo lipogenesis in premature infants determined by mass isotopomer distribution analysis Renfurm, L. N., R. H. Bandsma, et al. (2004), Pediatr Res 56(4): 602-7. Abstract: Premature infants change from placental supply of mainly carbohydrates to an enteral supply of mainly lipids earlier in their development than term infants. The metabolic consequences hereof are not known but might have long-lasting health effects. In fact, knowledge of lipid metabolism in premature infants is very limited. We have quantified de novo lipogenesis and cholesterogenesis on d 3 of life in seven premature infants (birth weight, 1319 +/- 417 g; gestational age, 30 +/- 2 wk). For comparison, five healthy adult subjects were also studied. All subjects received a 12-h 1-(13)C acetate infusion, followed by mass isotopomer distribution analysis (MIDA) on lipoprotein-palmitate and plasma unesterified cholesterol. The fraction of lipoprotein-palmitate synthesized at the end of the infusion period was 5.4 +/- 3.9% in infants, which was in the same range as found in adult subjects on a normal diet, suggesting that hepatic de novo lipogenesis is not a major contributor to fat accumulation in these premature neonates. The fractional contribution of newly synthesized cholesterol to plasma unesterified cholesterol was 7.4 +/- 1.3% after a 12-h infusion. The calculated rate of endogenous cholesterol synthesis was 31 +/- 7 mg/kg/d, a value approximately three times higher than that found in adult subjects (10 +/- 6 mg/kg/d). These results indicate that the cholesterol-synthesizing machinery is well developed in premature infants. |
| Cholesterol synthesis and degradation in normal rats fed a cholesterol-free diet with excess cystine Aoyama, Y., N. Amano, et al. (1999), Lipids 34(6): 583-9. Abstract: Feeding a diet with excess cystine to rats resulted in hypercholesterolemia. To understand the mechanism of the hypercholesterolemia, cholesterol synthesis and degradation, bile acid content of bile, and fecal steroids were determined. The in vivo incorporation of tritiated water into hepatic cholesterol, and activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase in rats fed a high-cystine diet were significantly higher than those in rats fed a control diet. The activity of hepatic cholesterol 7 alpha-hydroxylase was similar between two groups. Little effect of cystine supplementation was found on fecal sterol excretion although there were some changes in biliary excretion of cholic acid derivatives. These results indicate that hypercholesterolemia caused by feeding of a high-cystine diet may be due to the stimulation of hepatic cholesterol synthesis. |
| Cholesterol synthesis and esterification in isolated enterocytes: regulation by cholesterol and cholestyramine feeding Iglesias, J., D. Gonzalez-Pacanowska, et al. (1993), Lipids 28(6): 549-53. Abstract: The purpose of the present study was to investigate the physiological control of the main regulatory enzymes of cholesterol metabolism in isolated enterocytes obtained from chick duodenum, jejunum and ileum. Cholesterol feeding resulted in an inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase and mevalonate 5-pyrophosphate decarboxylase, while cholestyramine feeding increased reductase activity in all the regions studied and decarboxylase activity only in duodenum. Cholesterol feeding markedly increased acyl-CoA:cholesterol acyltransferase, but the effects of cholestyramine were less clear. The effects on transferase activity cannot be due to differences in the availability of acyl-CoA as exogenous substrate as no significant differences were found in acyl-CoA hydrolase activity after any of the dietary treatments. The effects of cholesterol feeding were related to changes in the cholesterol content of epithelial cells, whereas in the case of cholestyramine this relationship was less apparent. |
| Cholesterol synthesis and high density lipoprotein uptake are regulated independently in rat small intestinal epithelium Lutton, C. and G. Champarnaud (1994), Gut 35(3): 343-6. Abstract: The rates of high density lipoprotein HDL uptake and cholesterol synthesis were compared in the normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rat intestine. The RICO rat has a hyperintestinal cholesterol synthesis. 14C sucrose, a marker which becomes irreversibly entrapped within the cells, was used to measure total rat HDL uptake over 24 hours in the various cells of the small intestinal mucosa. The rates of sterol synthesis were estimated in vivo with 1-14C acetate, as previously validated. The rates of HDL uptake in the upper villus cells were similar along the length of the small intestine in both types of rat, but the rates of sterol synthesis varied up to eightfold. When the mucosal epithelium was divided along the villus/crypt axis, HDL uptake increased two to threefold and cholesterol synthesis two to fivefold in the upper villus compared with the crypt cells in both SW and RICO rats. The high cholesterogenesis in the mucosal cells of the RICO rat is not related to a modified HDL cholesterol uptake. Thus, cholesterol synthesis and HDL uptake seem to be regulated independently in the rat small intestinal mucosa. |
| Cholesterol synthesis and import contribute to protective cholesterol increments in acute myeloid leukemia cells Banker, D. E., S. J. Mayer, et al. (2004), Blood 104(6): 1816-24. Abstract: Cholesterol levels are abnormally increased in many acute myeloid leukemia (AML) samples exposed in vitro to chemotherapy. Blocking these acute cholesterol responses selectively sensitizes AML cells to therapeutics. Thus, defining the molecular mechanisms by which AML cells accomplish these protective cholesterol increments might elucidate novel therapeutic targets. We now report that the levels of mRNAs encoding the cholesterol synthesis-regulating enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and the cholesterol-importing low-density lipoprotein (LDL) receptor were both increased by daunorubicin (DNR) or cytarabine (ARA-C) treatments in almost three fourths of cultured AML samples. However, less than one third of AML samples significantly increased LDL accumulation during drug treatments, suggesting that de novo synthesis is the primary mechanism by which most AML cells increase cholesterol levels during drug exposures. LDL increments were not correlated with cholesterol increments in ARA-C-treated AML samples. However, LDL and cholesterol increments did correlate in DNR-treated AML samples where they were measured, suggesting that a subset of AMLs may rely on increased LDL accumulation during treatment with particular drugs. Our data suggest that cholesterol synthesis inhibitors may improve the efficacy of standard antileukemia regimens, but that for maximum benefit, therapy may need to be tailored for individual patients with leukemia. |
| Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats Poirier, J., A. Baccichet, et al. (1993), Neuroscience 55(1): 81-90. Abstract: Apolipoprotein E is synthesized and secreted by astrocytes in the hippocampus following lesions of the entorhinal cortex. It was proposed that apolipoprotein E, by analogy to its role in cholesterol transport in circulation, could be involved in the salvage and reutilization of non-esterified cholesterol released during terminal breakdown. The salvaged cholesterol could then be transported to neurons by apolipoprotein E-complexes and taken up via the apolipoprotein E/apolipoprotein B (low-density lipoprotein) receptor. To test this hypothesis, we have examined low-density lipoprotein receptor binding in brain sections of rats undergoing hippocampal reinnervation. The number of neuronal cells labelled by fluorescent Dil-low-density lipoprotein as well as the density of 125Ilow-density lipoprotein binding sites in the dentate gyrus were found to increase in parallel with the extent of cholinergic reinnervation occurring in the deafferented hippocampus. In contrast, hippocampal cholesterol synthesis fell by more than 60% at eight days post-lesion, but eventually returned to control levels at 30 days post-lesion. The transient loss of cholesterol synthesis coincided with a peak in hippocampal apolipoprotein E expression. A concomitant accumulation of sudanophilic lipids (cholesterol esters and phospholipids) was detected in the outer molecular layer of the dentate gyrus and in the hilar region. The present findings suggest that non-esterified cholesterol released during terminal breakdown is esterified, transported via the apolipoprotein E transport system to neurons undergoing reinnervation, and take-up through the low-density lipoprotein receptor pathway where it is presumably used as a precursor molecule for the synthesis of new synapses and terminals. |
| Cholesterol synthesis and skeletal formation Gibson, K. M. (2000), Pediatr Res 47(3): 289. |
| Cholesterol synthesis in mice is suppressed but lipofuscin formation is not affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard and n-6 fatty acid-enriched oils Du, C., A. Sato, et al. (2003), Biol Pharm Bull 26(6): 766-70. Abstract: Hypocholesterolemic activity of dietary polyunsaturated fatty acids is observed after relatively short-term but not long-term feedings, and their long-term feedings are suspected to accelerate aging through tissue accumulation of lipid peroxides and age pigments (lipofuscin). To define the long-term effects of fats and oils in more detail, female mice were fed a conventional basal diet supplemented with lard (Lar), high-linoleic (n-6) safflower oil (Saf), rapeseed oil (Rap), high-alpha-linolenic (n-3) perilla oil (Per), or a mixture of ethyl docosahexaenoate and soybean oil (DHA/Soy) from 17 weeks to 71 weeks of age. The DHA/Soy and Per groups had decreased serum cholesterol levels compared with the Lar and Saf groups, but the difference between the Lar and Saf groups was not significant. The 3-hydroxy-3-methyglutary-CoA (HMG-CoA) reductase activity in the liver was also significantly lower in the Per and DHA/Soy groups. However, no significant difference in lipofuscin contents in the brain and liver was observed among the 5 dietary groups, despite significant differences in peroxidizability indices of the dietary and/or tissue lipids. These results indicate that n-3 fatty acid-rich oils are hypocholesterolemic by suppressing hepatic HMG-CoA reductase activity compared with animal fats and high-linoleic (n-6) oil, but tissue lipofuscin contents are not affected by a long-term feeding of fats and oils with different degree of unsaturation in mice. |
| Cholesterol synthesis in patients with glutathione deficiency Gustafsson, J., B. Carlsson, et al. (1990), Eur J Clin Invest 20(4): 470-4. Abstract: 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate-limiting step in cholesterol synthesis. Glutathione (GSH) has been postulated to be an important activator of HMG-CoA reductase in vivo. HMG-CoA reductase activity was assayed in cultured fibroblasts from healthy children. Solubilized enzyme preparations were prepared by ultracentrifugation after freezing and thawing of fibroblasts. Such treatment increased the relative enzyme activity markedly. Enzymological assay conditions were established. Addition of GSH stimulated the reaction, whereas there was inhibition after addition of glutathione disulphide (GSSG). The inhibitory effect of GSSG could be reversed by the addition of excess GSH. Fibroblast preparations, deficient in GSH, were obtained from children with glutathione synthetase deficiency or from normal subjects after the growth of fibroblasts in the presence of buthionine sulphoximine. Solubilized enzyme preparations from GSH-deficient fibroblasts had HMG-CoA reductase activities lower than or comparable with those of control preparations. The results indicate only some reduction in the capacity for cholesterol synthesis in subjects with glutathione deficiency. The existence of additional activation mechanisms in vivo, alternative to GSH, for thiol-dependent modulation of HMG-CoA reductase activity seems likely. |
| Cholesterol synthesis in regenerating peripheral nerve is not influenced by serum cholesterol levels Goodrum, J. F. (1993), J Neurochem 60(4): 1564-6. Abstract: Following a nerve crush, cholesterol from degenerating myelin is retained within the nerve and reutilized for new myelin synthesis during nerve regeneration, apparently via a lipoprotein-mediated process. Because at least some serum components have access to the endoneurium of injured nerve, it has been suggested that serum lipoproteins are also significant contributors of cholesterol to Schwann cells during nerve regeneration. To test this hypothesis, serum cholesterol levels were reduced by > 90% with 4-aminopyrazolopyrimidine, followed by measurement of the activity of the key regulatory enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase. Treatment with 4-aminopyrazolopyrimidine caused a sevenfold increase in 3-hydroxy-3-methylglutaryl-CoA reductase activity in kidney but had no effect on the activity of this enzyme in either intact or regenerating sciatic nerve. These data indicate that serum-derived cholesterol is neither necessary for nor contributes significantly to myelin synthesis in regenerating nerve. |