| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Decreasing cholesterol is life extending Heinzl, S. (1994), Med Monatsschr Pharm 17(12): 357. |
| Decreasing dietary fat saturation lowers HDL-cholesterol and increases hepatic HDL binding in hamsters Terpstra, A. H., P. van den Berg, et al. (2000), Br J Nutr 83(2): 151-9. Abstract: In order to study the mechanism by which increasing unsaturation of dietary fat lowers HDL-cholesterol levels, we studied various measures of HDL metabolism in hamsters fed with fats with different degrees of saturation. Hamsters were fed on a cholesterol-enriched (1 g/kg) semipurified diet containing 200 g/kg of maize oil, olive oil, or palm oil for 9 weeks. Increasing saturation of dietary fat resulted in increasing concentrations of total plasma cholesterol (4.29 (SD 0.51), 5.30 (SD 0.67) and 5.58 (SD 0.76) mmol/l respectively, n 12) and HDL-cholesterol (3.31 (SD 0.50), 3.91 (SD 0.12) and 3.97 (SD 0.43) mmol/l) and these concentrations were significantly higher (P < 0.05) in the palm-oil and olive-oil-fed hamsters compared with the maize-oil group. Total plasma triacylglycerol levels also increased with increasing fat saturation (1.01 (SD 0.59), 1.56 (SD 0.65) and 2.75 (SD 1.03) mmol/l) and were significantly higher (P < 0.05) in the palm-oil group compared with the olive-oil and maize-oil-fed hamsters. The three diets did not have differential effects on plasma activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). Levels of phospholipid transfer protein (PLTP) tended to be higher with increasing fat saturation but this effect was not significant. The capacity of liver membranes to bind human HDL3 was significantly higher (P < 0.05) in the hamsters fed with maize oil (810 (SD 100) ng HDL3 protein/mg membrane protein, n 4) compared with those fed on palm oil (655 (SD 56) ng/mg), whereas the olive-oil group had intermediate values (674 (SD 26) ng/mg). The affinity of HDL3 for the binding sites was not affected by the type of dietary fat. Hepatic lipase (EC 3.1.1.3) activity, measured in liver homogenates, increased with increasing fat saturation. We conclude that dietary maize oil, when compared with either olive oil or palm-oil, may lower HDL-cholesterol concentrations by enhancing HDL binding to liver membranes. |
| Deduced amino acid sequence of heme binding region of chicken cholesterol side chain cleavage cytochrome P450 Mathew, P. A., N. Kagawa, et al. (1990), Protein Seq Data Anal 3(4): 323-5. Abstract: The primary structure of the carboxy terminal 296 amino acids of chicken cholesterol side chain cleavage cytochrome P450 (P450scc) was deduced from a partial cDNA clone isolated from a chicken ovarian cDNA library. The sequence contained putative steroid binding and heme binding regions. Comparison of this sequence with the corresponding sequences of three mammalian forms of P450scc shows greater than 50% homology. The heme binding region of the avian P450scc shows 76% homology with the heme binding regions of rat and human P450scc and 81% homology with that of bovine P450scc. |
| Defatted avocado pulp reduces body weight and total hepatic fat but increases plasma cholesterol in male rats fed diets with cholesterol Naveh, E., M. J. Werman, et al. (2002), J Nutr 132(7): 2015-8. Abstract: The potential use of avocado as a fiber source was evaluated. The total dietary fiber content of fresh avocado fruit of the Ettinger variety was 5.2 g/100 g. Approximately 75% was insoluble, and 25% soluble. The water-holding capacity of dry defatted avocado pulp was similar to that of cellulose, and trypsin inhibitors were not detected. The dietary and metabolic consequences of the avocado pulp were studied in male rats fed normal and hypercholesterolemic diets. Rats consumed semipurified diets containing either avocado pulp as the dietary fiber source or cellulose (control) with or without 10 g/kg cholesterol and 5 g/kg cholic acid. Food consumption and body weight gain were lower in rats fed avocado compared with those fed cellulose. Relative cecum weight was higher in avocado-fed rats. Plasma and hepatic cholesterol levels did not differ in rats fed diets without cholesterol, but plasma cholesterol was greater in avocado-fed than in cellulose-fed rats that consumed cholesterol. Regardless of dietary cholesterol, hepatic total fat levels, as evaluated histologically, but not directly, were lower in avocado-fed rats. These data suggest the presence of an appetite depressant in avocado and that avocado pulp interferes with hepatic fat metabolism. |
| Defect of receptor-G protein coupling in human gallbladder with cholesterol stones Xiao, Z. L., Q. Chen, et al. (2000), Am J Physiol Gastrointest Liver Physiol 278(2): G251-8. Abstract: Human gallbladders with cholesterol stones (ChS) exhibit an impaired muscle contraction and relaxation and a lower CCK receptor-binding capacity compared with those with pigment stones (PS). This study was designed to determine whether there is an abnormal receptor-G protein coupling in human gallbladders with ChS using (35)S-labeled guanosine 5'-O-(3-thiotriphosphate) ((35)SGTPgammaS) binding, (125)I-labeled CCK-8 autoradiography, immunoblotting, and G protein quantitation. CCK and vasoactive intestinal peptide caused significant increases in (35)SGTPgammaS binding to Galpha(i-3) and G(s)alpha, respectively. The binding was lower in ChS than in PS (P < 0.01). The reduced (35)SGTPgammaS binding in ChS was normalized after the muscles were treated with cholesterol-free liposomes (P < 0.01). Autoradiography and immunoblots showed a decreased optical density (OD) for CCK receptors, an even lower OD value for receptor-G protein coupling, and a higher OD for uncoupled receptors or Galpha(i-3) protein in ChS compared with PS (P < 0.001). G protein quantitation also showed that there were no significant differences in the Galpha(i-3) and G(s)alpha content in ChS and PS. We conclude that, in addition to an impaired CCK receptor-binding capacity, there is a defect in receptor-G protein coupling in muscle cells from gallbladder with ChS. These changes may be normalized after removal of excess cholesterol from the plasma membrane. |
| Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome Tint, G. S., M. Irons, et al. (1994), N Engl J Med 330(2): 107-13. Abstract: BACKGROUND. The Smith-Lemli-Opitz syndrome (frequency, 1:20,000 to 1:40,000) is defined by a constellation of severe birth defects affecting most organ systems. Abnormalities frequently include profound mental retardation, severe failure to thrive, and a high infant-mortality rate. The syndrome has heretofore been diagnosed only from its clinical presentation. METHODS. Using capillary-column gas chromatography-mass spectrometry, we measured the sterol composition of plasma, erythrocytes, lens, cultured fibroblasts, and feces from five children with the syndrome (three girls and two boys). RESULTS. Plasma cholesterol levels were abnormally low (8 to 101 mg per deciliter 0.20 to 2.60 mmol per liter) in every patient, being well below the 5th percentile for age- and sex-matched controls. Concentrations of the cholesterol precursor 7-dehydrocholesterol (cholesta-5,7-dien-3 beta-ol), which was not detectable in most of our controls, were elevated (11 to 31 mg per deciliter) more than 2000-fold above normal and were similar to the levels of cholesterol in all tissues from all patients. An isomeric dehydrocholesterol with a structure similar to that of 7-dehydrocholesterol was also detected. CONCLUSIONS. The combination of abnormally low plasma cholesterol levels and a high concentration of the cholesterol precursor 7-dehydrocholesterol points to a major block in cholesterol biosynthesis at the step in which the C-7(8) double bond of 7-dehydrocholesterol is reduced, forming cholesterol. The block may be sufficient to deprive an embryo or fetus of cholesterol and prevent normal development, whereas the incorporation of 7-dehydrocholesterol into all membranes may interfere with proper membrane function. |
| Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome Irons, M., E. R. Elias, et al. (1993), Lancet 341(8857): 1414. |
| Defective cholesterol efflux in Werner syndrome fibroblasts and its phenotypic correction by Cdc42, a RhoGTPase Zhang, Z., K. Hirano, et al. (2005), Exp Gerontol 40(4): 286-94. Abstract: Werner syndrome (WS) is characterized by the early onset of senescent phenotypes including premature atherosclerotic cardiovascular diseases, although the underlying molecular mechanism for atherosclerosis has not been fully understood yet. Cholesterol efflux from the cells is the initial step of reverse cholesterol transport, a major protective system against atherosclerosis. The aim of the present study was to determine whether this crucial step may be altered in WS. We examined intracellular lipid transport and cholesterol efflux and the expression levels of its related molecules in skin fibroblasts obtained from patients with WS. Cholesterol efflux was markedly reduced in the WS fibroblasts in association with increased cellular cholesterol. Fluorescent recovery after photobleaching (FRAP) technique revealed that intracellular lipid transport around Golgi apparatus was markedly reduced when using a C6-NBD-Ceramide as a tracer. Cdc42 protein and its GTP-bound form were markedly reduced in the WS fibroblasts. The complementation of wild-type Cdc42 corrected cholesterol efflux, intracellular lipid transport, and cellular cholesterol levels in the WS fibroblasts. These data indicated that the reduced expression of Cdc42 may be responsible for the abnormal lipid transport, which in turn might be related to the cardiovascular manifestations in WS. |
| Defective conversion of 7-dehydrocholesterol to cholesterol in cultured skin fibroblasts from Smith-Lemli-Opitz syndrome homozygotes Honda, A., G. S. Tint, et al. (1995), J Lipid Res 36(7): 1595-601. Abstract: The Smith-Lemli-Opitz syndrome is a common birth defect syndrome characterized biochemically by low plasma cholesterol levels and high concentrations of the cholesterol precursor 7-dehydrocholesterol. The present study was undertaken to prove that the enzyme defect is at the step in which 7-dehydrocholesterol is converted into cholesterol and to establish a new biochemical method for the diagnosis of this disease. We assayed the latter part of the cholesterol biosynthetic pathway by incubating 3Hlathosterol (the immediate precursor of 7-dehydrocholesterol) with cultured skin fibroblasts from 15 homozygous patients, 14 obligate heterozygous parents, and 8 controls, and measuring its conversion to 7-dehydrocholesterol and cholesterol. The formation of cholesterol from lathosterol in parents was not significantly different from that in controls. In contrast, cells from patients made very little cholesterol (P < 0.0001, patients vs. parents or vs. controls) but readily converted lathosterol to 7-dehydrocholesterol. The defect was especially profound in a subgroup of 8 of the most severely clinically affected patients, as virtually no label was detected in the cholesterol fraction. These results provide compelling evidence that 1) this disease is caused by a primary defect in 7-dehydrocholesterol delta 7-reductase, an essential enzyme in the biosynthesis of cholesterol; 2) the most clinically severe form of the syndrome may be associated with the most inhibited enzyme; and 3) the enzyme lathosterol 5-desaturase that converts lathosterol to 7-dehydrocholesterol is fully intact. The present method using fibroblast and amniocyte cultures establishes it as a useful procedure for the biochemical diagnosis of this syndrome. |
| Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier Disease Francis, G. A., R. H. Knopp, et al. (1995), J Clin Invest 96(1): 78-87. Abstract: Tangier disease is a rare genetic disorder characterized by extremely low plasma levels of HDL and apo A-I, deposition of cholesteryl esters in tissues, and a high prevalence of cardiovascular disease. We examined the possibility that HDL apolipoprotein-mediated removal of cellular lipids may be defective in Tangier disease. With fibroblasts from normal subjects, purified apo A-I cleared cells of cholesteryl esters, depleted cellular free cholesterol pools available for esterification, and stimulated efflux of radiolabeled cholesterol, phosphatidylcholine, and sphingomyelin. With fibroblasts from two unrelated Tangier patients, however, apo A-I had little or no effect on any of these lipid transport processes. Intact HDL also was unable to clear cholesteryl esters from Tangier cells even though it promoted radiolabeled cholesterol efflux to levels 50-70% normal. Passive desorption of radiolabeled cholesterol or phospholipids into medium containing albumin or trypsinized HDL was normal for Tangier cells. Binding studies showed that the interaction of apo A-I with high-affinity binding sites on Tangier fibroblasts was abnormal. These results indicate that apo A-I has an impaired ability to remove cholesterol and phospholipid from Tangier fibroblasts, possibly because of a defective interaction of apo A-I with cell-surface binding sites. Failure of apo A-I to acquire cellular lipids may account for the rapid catabolism of nascent HDL particles and the low plasma HDL levels in Tangier disease. |
| Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport Munn, N. J., E. Arnio, et al. (2003), J Lipid Res 44(1): 182-92. Abstract: Plasmalogens are a major sub-class of ethanolamine and choline phospholipids in which the sn-1 position has a long chain fatty alcohol attached through a vinyl ether bond. These phospholipids are proposed to play a role in membrane fusion-mediated events. In this study, we investigated the role of the ethanolamine plasmalogen plasmenylethanolamine (PlsEtn) in intracellular cholesterol transport in Chinese hamster ovary cell mutants NRel-4 and NZel-1, which have single gene defects in PlsEtn biosynthesis. We found that PlsEtn was essential for specific cholesterol transport pathways, those from the cell surface or endocytic compartments to acyl-CoA/cholesterol acyltransferase in the endoplasmic reticulum. The movement of cholesterol from the endoplasmic reticulum or endocytic compartments to the cell surface was normal in PlsEtn-deficient cells. Also, vesicle trafficking was normal in PlsEtn-deficient cells, as measured by fluid phase endocytosis and exocytosis, as was the movement of newly-synthesized proteins to the cell surface. The mutant cholesterol transport phenotype was due to the lack of PlsEtn, since it was corrected when NRel-4 cells were transfected with a cDNA encoding the missing enzyme or supplied with a metabolic intermediate that enters the PlsEtn biosynthetic pathway downstream of the defect. Future work must determine the precise role that plasmalogens have on cholesterol transport to the endoplasmic reticulum. |
| Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice Willner, E. L., B. Tow, et al. (2003), Proc Natl Acad Sci U S A 100(3): 1262-7. Abstract: Deficiency of acyl CoA:cholesterol acyltransferase 2 (ACAT2) in mice results in a reduction in cholesterol ester synthesis in the small intestine and liver, which in turn limits intestinal cholesterol absorption, hepatic cholesterol gallstone formation, and the accumulation of cholesterol esters in the plasma lipoproteins. Here we examined the contribution of ACAT2-derived cholesterol esters to atherosclerosis by crossing ACAT2-deficient (ACAT2(-/-)) mice with apolipoprotein (apo) E-deficient (ApoE(-/-)) mice, an atherosclerosis-susceptible strain that has impaired apoE-mediated clearance of apoB-containing lipoproteins. ACAT2(-/-) ApoE(-/-) mice and ACAT2(+/+) ApoE(-/-) (control) mice had similar elevations of plasma apoB and total plasma lipids; however, the lipid cores of the apoB-containing lipoproteins in ACAT2(-/-) ApoE(-/-) mice contained primarily triglycerides rather than cholesterol esters. At 30 wk of age, only the control mice had significant atherosclerosis, which was nearly absent in ACAT2(-/-) ApoE(-/-) mice. ACAT2 deficiency in the apoE-deficient background also led to a compensatory increase in the activity of lecithincholesterol acyltransferase, the major plasma cholesterol esterification enzyme, which increased high-density lipoprotein cholesterol esters. Our results demonstrate the crucial role of ACAT2-derived cholesterol esters in the development of atherosclerosis in mice and suggest that triglyceride-rich apoB-containing lipoproteins are not as atherogenic as those containing cholesterol esters. Our results also support the rationale of pharmacological inhibition of ACAT2 as a therapy for atherosclerosis. |
| Deficiency of interleukin-1 receptor antagonist deteriorates fatty liver and cholesterol metabolism in hypercholesterolemic mice Isoda, K., S. Sawada, et al. (2005), J Biol Chem 280(8): 7002-9. Abstract: Although the anti-inflammatory effect of interleukin-1 (IL-1) receptor antagonist (IL-1Ra) has been described, the contribution of this cytokine to cholesterol metabolism remains unclear. Our aim was to ascertain whether deficiency of IL-1Ra deteriorates cholesterol metabolism upon consumption of an atherogenic diet. IL-1Ra-deficient mice (IL-1Ra(-/-)) showed severe fatty liver and portal fibrosis containing many inflammatory cells following 20 weeks of an atherogenic diet when compared with wild type (WT) mice. Expectedly, the levels of total cholesterol in IL-1Ra(-/-) mice were significantly increased, and the start of lipid accumulation in liver was observed earlier when compared with WT mice. Real-time PCR analysis revealed that IL-1Ra(-/-) mice failed to induce mRNA expression of cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, with concurrent up-regulation of small heterodimer partner 1 mRNA expression. Indeed, IL-1Ra(-/-) mice showed markedly decreased bile acid excretion, which is elevated in WT mice to maintain cholesterol level under atherogenic diet feeding. Therefore, we conclude that the lack of IL-1Ra deteriorates cholesterol homeostasis under atherogenic diet-induced inflammation. |
| Deficiency of PPARalpha disturbs the response of lipogenic flux and of lipogenic and cholesterogenic gene expression to dietary cholesterol in mouse white adipose tissue Islam, K. K., B. L. Knight, et al. (2005), Biochim Biophys Acta 1734(3): 259-68. Abstract: PPARalpha-deficiency in mice fed a high-carbohydrate, low-cholesterol diet was associated with a decreased weight of epididymal adipose tissue and an increased concentration of adipose tissue cholesterol. Consumption of a high (2% w/w) cholesterol diet resulted in a further increase in the concentration of cholesterol and a further decrease in epididymal fat pad weight in PPARalpha-null mice, but had no effect in the wild-type. These reductions in fat pad weight were associated with an increase in hepatic triacylglycerol content, indicating that both PPARalpha-deficiency and cholesterol altered the distribution of triacylglycerol in the body. Adipose tissue de novo lipogenesis was increased in PPARalpha-null mice and was further enhanced when they were fed a cholesterol-rich diet; no such effect was observed in the wild-type mice. The increased lipogenesis in the chow-fed PPARalpha-null mice was accompanied paradoxically by lower mRNA expression of SREBP-1c and its target genes, acetyl-CoA carboxylase and fatty acid synthase. Consumption of a high-cholesterol diet increased the mRNA expression of these genes in the PPARalpha-deficient mice but not in the wild-type. De novo cholesterol synthesis was not detectable in the adipose tissue of either genotype despite a relatively high expression of the mRNA's encoding SREBP-2 and 3-hydroxy-3-methylglutaryl Coenzyme A reductase. The mRNA expression of these genes and of the LDL-receptor in adipose tissue of the PPARalpha-deficient mice was lower than that of the wild-type and was not downregulated by cholesterol feeding. The results suggest that PPARalpha plays a role in adipose tissue cholesterol and triacylglycerol homeostasis and prevents cholesterol-mediated changes in de novo lipogenesis. |
| Deficient ileal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in sitosterolemia: sitosterol is not a feedback inhibitor of intestinal cholesterol biosynthesis Nguyen, L. B., G. Salen, et al. (1994), Metabolism 43(7): 855-9. Abstract: We correlated the activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, with the sterol content and composition of mucosal cells from the ileum of three homozygous sitosterolemic subjects and one control subject. In this inherited disease, whole-body cholesterol biosynthesis is decreased and increased amounts of sitosterol are absorbed from the intestine and deposited in tissues. For comparison, similar measurements were obtained in the ileal mucosa of sitosterol-fed rats where sitosterol accounted for 11% of enterocyte sterols. In the three sitosterolemic homozygotes, sitosterol represented 9% to 11% of the total microsomal sterols in the intestinal mucosa, although normal architecture for both crypts and villi is observed. The mean ileal microsomal HMG-CoA reductase activity in the three homozygotes was less than half of control values. In the ileum of sitosterol-fed rats with increased mucosal sitosterol concentrations, microsomal HMG-CoA reductase activity was not inhibited. These results show that in three sitosterolemic homozygotes, abnormally low HMG-CoA reductase activity was detected in the ileum, as previously demonstrated in mononuclear leukocytes and liver. The failure of the increased tissue sitosterol pool to inhibit HMG-CoA reductase in rat ileum suggests that deficient cholesterol biosynthesis in homozygous sitosterolemia is inherited and is not due to feedback inhibition by tissue sitosterol. |
| Defining specific goals of therapy in treating dyslipidemia in the patient with low high-density lipoprotein cholesterol Belalcazar, L. M. and C. M. Ballantyne (1998), Prog Cardiovasc Dis 41(2): 151-74. Abstract: Because patients with low high-density lipoprotein (HDL) cholesterol (HDL-C) are at high risk for clinical coronary artery disease (CAD) events, these patients require aggressive treatment with lifestyle modifications-increased exercise, smoking cessation, and weight loss in overweight patients-and available pharmacological agents. Drugs that raise HDL-C include nicotinic acid, fibric acid derivatives, estrogens, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), alpha-blockers, and alcohol. However, all agents that increase HDL-C may not have the same clinical benefit, just as, as shown in genetic studies in humans and mice, genetic causes of high HDL-C do not always protect against CAD, nor do genetic causes of low HDL-C always increase risk for CAD. Better understanding of the complexities of HDL metabolism and the mechanisms by which HDL protects against CAD is needed to enable the development of new therapeutic strategies--novel drugs or gene delivery systems--to increase HDL-C and reduce CAD events. The statins are the agents with the greatest evidence for slowing progression of CAD and reducing clinical events in patients with low HDL-C, but additional research is needed to determine the potential benefits of additional interventions that increase HDL-C, including combination therapy, which may provide greater improvements in the entire lipid profile. |
| Definition and application of the discretionary screening indicators according to the National Cholesterol Education Program for Children and Adolescents Diller, P. M., G. A. Huster, et al. (1995), J Pediatr 126(3): 345-52. Abstract: OBJECTIVES: (1) To propose definitions for the discretionary screening indicators described by the National Cholesterol Education Program for Children and Adolescents (NCEP-Peds); (2) to examine the relative prevalence of major screening indicators (family history of premature heart disease and parental plasma cholesterol concentration > or = 6.21 mmol/L (240 mg/dl)) and discretionary screening indicators (excessive consumption of fat or cholesterol or both, smoking, diabetes, hypertension, and steroid use) in a family population; and (3) to evaluate the relative value of the major and the discretionary indicators in detecting high serum levels of low-density lipoprotein-cholesterol (LDL-C) (> or = 3.36 mmol/L (> or = 130 mg/dl)). DESIGN: Control cohort from a case-control study. SETTING: Lipid research clinic. PARTICIPANTS: White children and adolescents < 20 years of age from 232 nuclear families who participated in the Cincinnati Myocardial Infarction Hormone Study. MAIN OUTCOME MEASURES: (1) Number of children who have major and discretionary screening indicators; (2) sensitivity and specificity of the major and the discretionary screening indicators in identifying children with LDL-C concentrations > 3.36 mmol/L (130 mg/dl) (high LDL-C). RESULTS: With cutoff points of the 90th percentile for blood pressure, the 85th percentile for obesity, and the 80th percentile for dietary fat and cholesterol, and self-report for diabetes, smoking, and corticosteroid use, 54% of the 232 children in the cohort had one or more discretionary indicators. Additionally, applying the major screening indicators raised the percentage of children identified to 74%. Twenty-eight percent had both major and discretionary indicators. Having a discretionary screening indicator did not increase the probability of having a major indicator. Applying both discretionary and major screening indicators to the cohort identified 96% of the children who had a high concentration of LDL-C; 30% of the children with high LDL-C levels were discovered solely by the discretionary indicators. Similar sensitivity and specificity were noted between the major and the discretionary indicators. Children with high LDL-C concentrations were more likely to have multiple screening indicators. CONCLUSION: Discretionary and major screening indicators suggested by the National Cholesterol Education Program for Children and Adolescents identify different subsets of children at risk of having premature cardiovascular disease. Both major and discretionary indicators contribute to the identification of children with high LDL-C concentrations. |
| Degradation of cholesterol by Bacillus subtilis SFF34 isolated from Korean traditional fermented flatfish Kim, K. P., C. H. Rhee, et al. (2002), Lett Appl Microbiol 35(6): 468-72. Abstract: AIMS: To examine cholesterol degradation by Bacillus subtilis SFF34. METHODS AND RESULTS: Cholesterol degradation and cholesterol oxidase production by B. subtilis SFF34 were investigated in a medium containing 0.2% cholesterol. In addition, the oxidized product of cholesterol by the purified cholesterol oxidase was detected using a gas chromatograph. Cholesterol oxidase production reached its maximal level (3.14 U ml(-1) after 24 h of incubation in the cholesterol medium. The residual cholesterol content reduced to 0.98 mg g(-1) after 60 h of cultivation in the cholesterol medium. Two cholesterol oxidases were purified from the culture supernatant fluid and their reaction product against cholesterol was identified as 4-cholesten-3-one. CONCLUSIONS: B. subtilis SFF34 degraded cholesterol and produced a high level of extracellular cholesterol oxidase. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus subtilis will be very useful for the reduction of cholesterol in many fermented foods and as a source of cholesterol oxidase. |
| Degradation of HMG-CoA reductase in rat liver is cholesterol and ubiquitin independent Ness, G. C. and R. C. Holland (2005), FEBS Lett 579(14): 3126-30. Abstract: In contrast with the accelerated degradation observed in tumor cells in response to sterols, hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase turnover in whole animals was not increased by dietary cholesterol. Furthermore, treating rats with lovastatin to lower hepatic cholesterol levels did not decrease the rate of degradation. The half-life remained in the 6 h range. Co-immunoprecipitation studies revealed that the amount of ubiquitin associated with the reductase was entirely dependent upon the amount of microsomal protein subjected to immunoprecipitation. The results indicate that in liver, neither the rate of reductase protein degradation nor the ubiquitin-proteasome system appear to play roles in mediating changes in HMG-CoA reductase protein levels in response to dietary cholesterol. |
| Degradation of low density lipoprotein cholesterol esters by lysosomal lipase in vitro. Effect of core physical state and basis of species selectivity Lusa, S. and P. Somerharju (1998), Biochim Biophys Acta 1389(2): 112-22. Abstract: The effect of the physical state of low density lipoprotein (LDL) core and the selectivity of the degradation of LDL cholesterol esters (CEs) by the lysosomal acid lipase (LAL) in vitro were investigated. The physical state of LDL was modulated by varying temperature or the triglyceride content of the core. Normal LDL showed an abrupt increase of CE hydrolysis at 24 degrees C and another deviation occurred close to 36 degrees C. 1H-NMR measurements showed that these temperatures coincide with the onset and end temperatures of the LDL core lipid transition, respectively. Enrichment of LDL with triglycerides abolished the abrupt changes both in the CE hydrolysis and in the physical state of LDL lipids. These findings show that there is a correlation between the physical state of LDL lipids and the rate of LAL-mediated hydrolysis of the CEs in the particle. The relative rates of hydrolysis of different CE species were also compared. With native LDL, increasing the length of a saturated acyl chain from 14 to 20 carbons reduced the rate of degradation of CE modestly, while increasing acyl chain unsaturation increased the rate of degradation markedly. However, cholesterol oleate was hydrolyzed more slowly than cholesterol stearate. Essentially the same order of hydrolytic susceptibility was observed when the CE species were incorporated into triglyceride-enriched LDL, reconstituted high density lipoprotein particles or in detergent/phospholipid micelles. These results indicate that the selective hydrolysis of CE species in LDL is determined mainly by the ease with which the CE molecule can emerge from the surface layer reach the active site of LAL. Slower degradation of the more saturated CEs by LAL could lead, under certain conditions, to their accumulation in lysosomes and eventually, to cell death, lysis and deposition of crystalline, poorly mobilizable lipids to the arterial intima. |