Cholesterol Journal Articles

Record 741 to 760

An inhibitor of squalene epoxidase, NB-598, suppresses the secretion of cholesterol and triacylglycerol and simultaneously reduces apolipoprotein B in HepG2 cells
Horie, M., M. Hayashi, et al. (1993), Biochim Biophys Acta 1168(1): 45-51.
Abstract: NB-598, a specific inhibitor of squalene epoxidase, suppressed the secretion of cholesterol and triacylglycerol from HepG2 cells into the medium. L-654,969, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibited the secretion of cholesterol as potently as NB-598, but did not suppress the secretion of triacylglycerol. Both compounds decreased the intracellular cholesterol content almost equally, and neither of the compounds reduced the intracellular triacylglycerol content. The suppression of lipid secretion by NB-598 was associated with a significant reduction in apolipoprotein (apo) B secretion into the medium. Therefore, the suppression of lipid secretion by NB-598 may be caused by a reduction in the number of triacylglycerol-rich lipoprotein particles. In contrast, the suppression of cholesterol secretion by L-654,969 may be due to a modulation of lipoprotein lipid composition, since this agent did not reduce the secretion of apo B or triacylglycerol. The secretion of apo A-I was unaffected by either NB-598 or L-654,969. Pulse chase studies using 35Smethionine showed that the suppression of apo B secretion by NB-598 depended on an enhancement of intracellular degradation of apo B. These results indicate that the secretion of apo B from HepG2 cells is not regulated by the lipid synthesis alone, and suggest that the mechanism of the hypolipidemic effect of NB-598 involves the suppression of triacylglycerol-rich lipoprotein secretion from the liver as well as an inhibition of cholesterol synthesis in the liver.

An interaction between the human cholesteryl ester transfer protein (CETP) and apolipoprotein A-I genes in transgenic mice results in a profound CETP-mediated depression of high density lipoprotein cholesterol levels
Hayek, T., T. Chajek-Shaul, et al. (1992), J Clin Invest 90(2): 505-10.
Abstract: We have previously described two transgenic mouse lines, one heterozygous for the human apo A-I gene and the other heterozygous for a human cholesteryl ester transfer protein (CETP) minigene driven by the mouse metallothionein-I gene promoter. In the current study, these two lines were crossed producing control, HuCETPTg, HuAITg, and HuAICETPTg mice to study the influence of CETP on HDL cholesterol levels, particle size distribution, and metabolism in animals with mouse and human-like HDL. In the HuCETPTg and HuAICETPTg animals, zinc induction approximately doubled plasma CETP activity, with no activity in plasma from the control and HuAITg animals. The only significant effect of CETP on lipoprotein subfraction cholesterol concentrations was for HDL-C. Compared to control animals, HuCETPTg animals had lower HDL-C, 20% before and 35% after Zn induction, and compared to HuAITg animals, HuAICETPTg animals had lower HDL-C, 35% before and 66% after Zn induction. Control and HuCETPTg HDL consist primarily of a single size population with a mean diameter of 10.00 +/- 0.10 nm and 9.71 +/- 0.05 nm, respectively. HuAITg HDL consists primarily of three distinct HDL size subpopulations with peak diameters of 10.35 +/- 0.08 nm, 8.80 +/- 0.06 nm, 7.40 +/- 0.10 nm, and HuAICETPTg HDL also consists primarily of three distinct HDL size subpopulations with peak diameters of 9.87 +/- 0.05 nm, 8.60 +/- 0.10 nm, 7.30 +/- 0.15 nm before, and 9.71 +/- 0.08 nm, 8.50 +/- 0.11 nm, 7.27 +/- 0.15 nm after zinc induction, respectively. Western blotting analysis of nondenaturing gradient gels of plasma with a monoclonal antibody to CETP indicated that in HuCETPTg and HuAICETPTg mice, 22 and 100%, respectively, of the CETP was HDL associated. Turnover studies with HDL doubly labeled with 125I apo A-I and 3H cholesteryl linoleate indicated that the CETP-induced fall in HDL-C was associated with increased HDL-cholesterol ester fractional catabolic rate in both the absence and presence of human apo A-I, suggesting CETP-mediated transfer of HDL-cholesterol ester to apo B-containing lipoproteins. In summary, these studies suggest that CETP has a much more profound effect on HDL cholesterol levels in transgenic animals expressing human apo A-I. This may be due to an enhanced interaction of CETP with human compared to mouse apo A-I or to the HDL particles they produce.

An interaction between the TaqIB polymorphism of cholesterol ester transfer protein and smoking is associated with changes in plasma high-density lipoprotein cholesterol levels in Turks
Hodoglugil, U., D. W. Williamson, et al. (2005), Clin Genet 68(2): 118-27.
Abstract: Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for atherosclerosis. We investigated the effects of the TaqIB polymorphism of cholesterol ester transfer protein (CETP) on CETP activity and plasma HDL-C levels in random nondiabetic and self-reported diabetic subjects in a population with very low HDL-C levels. The rare B2B2 genotype was associated with significantly higher HDL-C levels and lower CETP activity in random subjects and with higher HDL-C in diabetic subjects. After stratification of random subjects by smoking status, the common B1B1 genotype was associated with lower HDL-C levels than the B2B2 genotype. Although smoking was associated with lower HDL-C, especially in men, HDL-C levels between smokers and nonsmokers were not different in subjects with the B1B2 or B2B2 genotypes. However, smoking (20+ cigarettes/day) was associated with a marked reduction in HDL-C in the B1B1 subjects. The B1B1/smoking interaction was not reflected in a difference in CETP activity. High triglycerides and elevated body mass index (BMI) lower HDL-C. The B2B2 genotype was associated with the highest HDL-C levels, and these levels were significantly lower in the hypertriglyceridemic subjects (>or=50th percentile). The lowest HDL-C levels were seen in hypertriglyceridemic subjects with the B1B1 genotype. Although BMI (>or=50th vs<50th percentile) did not affect HDL-C in B2B2 subjects, a high BMI was associated with markedly lower HDL-C in B1B1 subjects. Thus, HDL-C levels in Turks may be modulated by an interaction between the CETP TaqIB polymorphism and smoking, as well as an interaction with hypertriglyceridemia and BMI.

An international perspective on the cholesterol debate
Rosser, W. W., W. H. Palmer, et al. (1993), Fam Pract 10(4): 431-8.
Abstract: For the past 5 years there has been an intensive debate and a number of conflicting guidelines suggesting what general practitioners (GPs) should do to screen and manage hyperlipidaemia. At a WONCA seminar in Vancouver in 1992, policies and guidelines from Canada, the UK, The Netherlands, New Zealand, Hong Kong and the USA were reviewed. It was concluded that cholesterol policy and guidelines tend to be influenced more by political and economic factors than by evidence of health benefit. International guidelines for cholesterol screening and management would be of minimal value, as GPs would have to interpret the epidemiological evidence of benefit from lipid screening and lipid lowering strategy in the context of each patient to arrive at optimum management.

An internist's update on cholesterol management
Holman, H. E., G. S. Hicks, et al. (2002), Am J Med Sci 324(4): 189-95.
Abstract: Coronary heart disease (CHD) remains the leading cause of death in the United States. It is now well established that cholesterol is an important, reversible risk factor for CHD. This article provides a brief background on classification of the dyslipidemias, then discusses current recommendations for the evaluation and treatment of hyperlipidemia. Other risk factors currently being investigated as they relate to the development of CHD are discussed.

An investigation of the relationship between estrogen, estrogen metabolites and blood cholesterol levels in ovariectomized rats
Liu, D. and K. A. Bachmann (1998), J Pharmacol Exp Ther 286(1): 561-8.
Abstract: 17 beta-Estradiol (E2) has long been known for protecting against coronary heart disease by lowering cholesterol levels in premenopausal women. A recent study in our laboratory suggested that two hydroxylated metabolites of E2 possess similar hypocholesterolemic effects in male rats. This effect has been further investigated with additional estrogen metabolites in ovariectomized rats with a view toward mimicking the true postmenopausal situation in humans. Their effects in reproductive tissues were also evaluated histologically. Fundamentally, the following issues were addressed: (1) Do oxidized metabolites of estradiol lower total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved without eliciting estrogenic activities on reproductive tissues? The results of this investigation showed that a number of oxygenated metabolites of estradiol can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a striking hypocholesterolemic effect and a substantial uterotropic effect. 2-Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2-meoE1) produced a significant decrease in cholesterol levels at doses that did not produce significant uterotropic effects.

An isocratic high-performance liquid chromatographic assay for CYP7A1-catalyzed cholesterol 7 alpha-hydroxylation
Waxman, D. J. and T. K. Chang (1998), Methods Mol Biol 107: 169-73.

An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women
Volek, J. S., M. J. Sharman, et al. (2003), J Nutr 133(9): 2756-61.
Abstract: Very low carbohydrate diets are popular, yet little is known about their effects on blood lipids and other cardiovascular disease risk factors. We reported previously that a very low carbohydrate diet favorably affected fasting and postprandial triacylglycerols, LDL subclasses and HDL cholesterol (HDL-C) in men but the effects in women are unclear. We compared the effects of a very low carbohydrate and a low fat diet on fasting lipids, postprandial lipemia and markers of inflammation in women. We conducted a balanced, randomized, two-period, crossover study in 10 healthy normolipidemic women who consumed both a low fat (<30% fat) and a very low carbohydrate (<10% carbohydrate) diet for 4 wk each. Two blood draws were performed on separate days at 0, 2 and 4 wk and an oral fat tolerance test was performed at baseline and after each diet period. Compared with the low fat diet, the very low carbohydrate diet increased (P

An often ignored complication of left heart catheterization: embolism of cholesterol crystals. Report of 9 cases
Mycinski, C., G. Doll, et al. (1990), Arch Mal Coeur Vaiss 83(11): 1643-50.
Abstract: Cholesterol embolism (CE) is caused by the migration of cholesterol crystals from severe atheromatous lesions. Until recently, this was considered to be a classical but rare complication of atheroma. With the upsurge in techniques of left heart catheterization there has been a regain of interest in this subject. Nine cases of cholesterol embolism occurring after left heart catheterisation are reported, 3 after coronary angioplasty, and 3 cases after associated thrombolytic therapy. Three patients developed cutaneous syndromes (livedo reticularis, the "purple toe syndrome") with a favorable outcome in a few weeks. Two patients developed segmental necrosis of the small bowel requiring surgical resection of the affected area. Finally, in 4 cases, the patients died 12 hours to 3 months after catheterization: 2 patients had polyvisceral involvement; one patient developed cardiogenic shock; one patient had intestinal necrosis involving 2/3 of the ileum and the right colon. The cases illustrate the variability of the presentation of CE and its potential gravity. At present, the only effective measures are prophylactic; curative treatment remains particularly disappointing.

An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets
Pedersen, A., M. W. Baumstark, et al. (2000), J Lipid Res 41(12): 1901-11.
Abstract: We investigated the effect of olive oil, rapeseed oil, and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses. Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3-week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets analysis of variance (ANOVA), P < 0.05. The size of IDL, VLDL, and LDL subfractions did not differ between the diets, whereas a significantly higher number (apolipoprotein B concentration) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets (ANOVA, P < 0.05). Total HDL cholesterol concentration did not differ significantly, but HDL(2a) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil (ANOVA, P < 0.05).In conclusion, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.

An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia
Calabresi, L., B. Villa, et al. (2004), Metabolism 53(2): 153-8.
Abstract: A remarkable reduction of plasma concentrations of high-density lipoproteins (HDL), especially of the HDL(2) subfraction, is one of the typical lipoprotein alterations found in patients with familial combined hyperlipidemia (FCHL). Fourteen FCHL patients received 4 capsules daily of Omacor (an omega-3 polyunsaturated fatty acid omega3 FA concentrate providing 1.88 g of eicosapentaenoic acid EPA and 1.48 g of docosahexaenoic acid DHA per day; Pronova Biocare, Oslo, Norway) or placebo for 8 weeks in a randomized, double-blind, crossover study. Plasma triglycerides were 44% lower, and LDL cholesterol and apoliporpotein (apo)B were 25% and 7% higher after Omacor than placebo. HDL cholesterol was higher (+8%) after Omacor than placebo, but this difference did not achieve statistical significance. Omacor caused a selective increase of the more buoyant HDL(2) subfraction; plasma HDL(2) cholesterol and total mass increased by 40% and 26%, respectively, whereas HDL(3) cholesterol and total mass decreased by 4% and 6%. Both HDL(2) and HDL(3) were enriched in cholesteryl esters and depleted of triglycerides after Omacor. No changes were observed in the plasma concentration of major HDL apolipoproteins, LpA-I and LpA-I:A-II particles, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP). The plasma concentration of the HDL-bound antioxidant enzyme paraoxonase increased by 10% after Omacor. Omacor may be helpful in correcting multiple lipoprotein abnormalities and reducing cardiovascular risk in FCHL patients.

An operative case of cholesterol granuloma of the petrous apex
Saino, M., T. Kayama, et al. (1996), No Shinkei Geka 24(11): 1041-4.
Abstract: A 59-year-old man presented with a rare cholesterol granuloma of the petrous apex manifesting as headache, left facial dysesthesia, diplopia, left hearing impairment, and left tinnitus. Neurological examination revealed dysesthesia of territory in all divisions of the left trigeminal nerve, left incomplete abducens nerve palsy, left mixed hearing impairment, and left tinnitus. Plain CT scan showed a smoothly marginated mass involving the left petrous apex. The mass was isodense with the brain parenchyma and not enhanced by contrast medium. The mass appeared heterogeneously slightly hyperintense on the T1-weighted MR image and homogeneously hyperintense on the T2-weighted MR image except for the peripheral portion. The mass was not enhanced after intravenous gadolinium DTPA administration. Surgery via a petrosal approach totally removed the mass in the intracranial, extradural space. Histological examination showed typical features of cholesterol granuloma, with cholesterin clefts, hemosiderin deposits, and erythrocytes in non-specific granulation tissue. Cholesterol granuloma most commonly occurs in the middle ear cavity, and rarely in the petrous apex. The characteristic hyperintense appearance of cholesterol granuloma on T1- and T2-weighted MR images is very useful for differentiation from other lesions of the petrous apex and the cerebellopontine angle such as cholesteatoma, mucocele, chordoma, and meningioma. Solid cholesterol granuloma of the petrous apex should be treated by total removal via craniotomy, not by drainage which is commonly performed by otorhinologists.

An overview of quality control practices in Ontario with particular reference to cholesterol analysis
Krishnan, S., S. Webb, et al. (1999), Clin Biochem 32(2): 93-9.
Abstract: BACKGROUND: The Laboratory Proficiency Testing Program (LPTP) assesses the analytical performance of all licensed laboratories in Ontario. The LPTP Enzymes, Cardiac Markers, and Lipids Committee conducted a "Patterns of Practice" survey to assess the in-house quality control (QC) practices of laboratories in Ontario using cholesterol as the QC paradigm. DESIGN AND METHODS: The survey was questionnaire-based seeking information on statistical calculations, software rules, review process and data retention, and so on. Copies of the in-house cholesterol QC graphs were requested. A total of 120 of 210 laboratories were randomly chosen to receive the questionnaires during 1995 and 1996; 115 laboratories responded, although some did not answer all questions. RESULTS: The majority calculate means and standard deviations (SD) every month, using anywhere from 4 to >100 data points. 65% use a fixed mean and SD, while 17% use means calculated from the previous month. A few use a floating or cumulative mean. Some laboratories that do not use fixed means use a fixed SD. About 90% use some form of statistical quality control rules. The most common rules used to detect random error are 1(3s)/R4s while 2(2s)/4(1s)/10x are used for systematic errors. About 20% did not assay any QC at levels >5.5 mmol/L. CONCLUSIONS: Quality control data are reviewed daily (technologists), weekly and monthly (supervisors/directors). Most laboratories retain their QC records for up to 3 years on paper and magnetic media. On some QC graphs the mean and SD, QC product lot number, or reference to action logs are not apparent. Quality control practices in Ontario are, therefore, disappointing. Improvement is required in the use of clinically appropriate concentrations of QC material and documentation on QC graphs.

An overview of reverse cholesterol transport
Tall, A. R. (1998), Eur Heart J 19 Suppl A: A31-5.
Abstract: Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver via the plasma compartment. Cellular cholesterol efflux is mediated by HDL, acting in conjunction with the cholesterol esterifying enzyme, lecithin: cholesterol acyltransferase. Cholesteryl ester accumulating in HDL can then follow a number of different fates: uptake in the liver in HDL containing apolipoprotein (particle uptake) by LDL receptors, selective uptake of HDL cholesteryl ester in liver or other tissues involving scavenger receptor B1, or transfer to triglyceride-rich lipoproteins as a result of the activity of cholesteryl ester transfer protein, with subsequent uptake of triglyceride-rich lipoprotein remnants in the liver. Recently, we and others have taken a molecular approach to analysing the different components of reverse cholesterol transport, by over- or under-expression of individual molecules in induced mutant mouse models, or by the study of human mutations involving molecules of reverse cholesterol transport. Such studies reveal that over-expression of the major HDL apoprotein, apolipoprotein A-I, is clearly anti-atherogenic. However, over- or under-expression of molecules such as cholesteryl ester transfer protein, which have opposite effects on HDL levels and reverse cholesterol transport, suggest that both HDL levels as well as the dynamics of cholesterol movement through HDL are involved in the anti-atherogenic actions of HDL.

An overview of trials of cholesterol lowering and risk of stroke
Hebert, P. R., J. M. Gaziano, et al. (1995), Arch Intern Med 155(1): 50-5.
Abstract: BACKGROUND: While blood cholesterol level predicts coronary heart disease, whether there is any association with the risk of stroke is unclear. Some, but not all, observational studies suggest that cholesterol level predicts risk of stroke, particularly ischemic stroke. This hypothesis is attractive because ischemic events constitute the vast majority of all strokes and, like coronary heart disease, involve atherogenic processes. METHODS: To investigate whether lipid lowering reduces the risk of stroke, we performed an overview of randomized trials that included more than 36,000 individuals. RESULTS: The mean reduction in cholesterol level in the treated as compared with the control subjects ranged from 6% to 23%. Those assigned to treatment experienced no significant reduction in all (fatal plus nonfatal) stroke (relative risk, 1.0; 95% confidence interval, 0.8 to 1.2) or fatal stroke (1.1; 0.8 to 1.6). CONCLUSIONS: The confidence interval for fatal stroke is wide, and alternative hypotheses, including either a small protective or harmful effect, cannot be excluded; however, the point estimates are compatible with no benefit of cholesterol lowering on the risk of stroke. Additional large-scale randomized trials assessing total mortality would more definitively address any benefits on stroke, as well as any excess nonvascular causes of mortality, for which risks of cholesterol lowering also remain uncertain.

An oxidized derivative of cholesterol increases the release of soluble vascular cell adhesion molecule-1 from human umbilical vein endothelial cells in culture
Tamasawa, N., H. Murakami, et al. (2001), Biochim Biophys Acta 1531(3): 178-87.
Abstract: Treatment of human umbilical vein endothelial cells (HUVECs) with 7-ketocholesterol resulted in an increased release of soluble vascular cell adhesion molecule-1 (VCAM-1) into culture medium. 7-Ketocholesterol did not enhance the expression of mRNA for VCAM-1. 7 beta-Hydroxy- or 25-hydroxycholesterol had no effect on soluble VCAM-1 levels. Western blot analysis revealed that soluble VCAM-1, in the conditioned medium of both 7-ketocholesterol-stimulated and control cells, had a molecular size of 100 kDa. Stimulation of the TNF-alpha-treated HUVECs with 7-ketocholesterol further increased the levels of soluble VCAM-1 in the culture medium. Again, 7-ketocholesterol did not affect the VCAM-1 mRNA level, which was enhanced by TNF-alpha. Pretreatment of the cells with tissue inhibitor of membrane metalloproteinase-2 (TIMP-2) completely inhibited the release of VCAM-1 in response to 7-ketocholesterol but TIMP-1 had no effect. Adherence of mononuclear cells to TNF-stimulated HUVEC monolayers was slightly inhibited by 7-ketocholesterol, but this oxysterol did not affect the basal adherence to non-stimulated HUVECs. Immunofluorescent staining of the cells confirmed diffuse perinuclear distribution of VCAM-1 in HUVECs treated with TNF-alpha, but 7-ketocholesterol did not affect the intensity or distribution of immunofluorescence. We conclude that 7-ketocholesterol releases VCAM-1 from the endothelium probably by a proteolytic process.

An update on cholesterol guidelines
Holcomb, S. S. (2005), Nurse Pract 30(3): 55-7.

An update on the pathogenesis and treatment of cholesterol gallstones
Portincasa, P., P. van de Meeberg, et al. (1997), Scand J Gastroenterol Suppl 223: 60-9.
Abstract: The primum movens in cholesterol gallstone formation is hepatic cholesterol hypersecretion and chronic supersaturation of bile. A cascade of events will then include: (i) multiple biochemical defects: increased total biliary proteins (and qualitative shift to cholesterol crystallization-promoting factors), increased proportions of hydrophobic bile salts, increased mucin secretion, and rapid nucleation/crystallization of cholesterol from cholesterol-enriched biliary vesicles; (ii) multiple motility defects: impaired gallbladder contractility in vitro and gallbladder stasis in vivo, delayed intestinal transit. A genetic predisposition (together with environmental factors) might also be important. Therapy should be offered to patients with symptomatic gallstones. Cholecystectomy remains the only radical therapy for cholelithiasis. For a subgroup of patients with symptomatic, uncomplicated cholesterol stones who are unwilling to undergo surgery, or who have a significant surgical risk, alternative non-invasive therapies include: (i) oral litholysis of small stones by bile salts, (ii) fragmentation of 1-3 medium-sized stones by extracorporeal shock-wave lithotripsy, and (iii) topical dissolution of multiple stones by methyl tertbutyl ether. A major disadvantage of all non-surgical therapies, however, is the 50% recurrence rate of stones at 5 years. A number of prokinetic agents can improve gallbladder and/or intestine transit, two important contributing factors in gallstone disease. In selected patients, administration of these agents might enhance the clearance of cholesterol crystals/gallstones or might impede/delay gallstone formation and recurrence.

Anaerobic oxidation of cholesterol by a denitrifying enrichment
Barrandeguy, E. and S. Tarlera (2001), Water Sci Technol 44(4): 145-50.
Abstract: Sterols (e.g. cholesterol) present in wool scouring effluent represent the most recalcitrant fraction in anaerobic treatment. This study was conducted to examine the feasibility of removal of this organic load through a denitrifying post-treatment stage. A stable cholesterol-denitrifying enrichment (CHOL-1) was obtained from sludge of a bench-scale upflow sludge bed (USB) denitrifying reactor integrated to a carbon and nitrogen removal system for sanitary landfill leachate. According to the amounts of cholesterol degraded and of nitrite and nitrogen gas formed, the capacity for complete cholesterol oxidation under anaerobic conditions by CHOL-1 can be assumed. Nitrite accumulation observed at a low C/N ratio outlines the importance of determining the optimal C/N ratio for adequate denitrifying reactor performance. The enrichment was partly identified with molecular analysis of cloned 16S rDNA sequences revealing the presence of two groups of bacteria belonging to the beta subclass of the Proteobacteria. According to analysis of sequences, it can be inferred that a yet uncultivated new bacterium is the one responsible for cholesterol oxidation. Results of this study suggest that sludge from a denitrifying reactor treating leachate is potentially useful in a combined anaerobic-anoxic system for degradation of cholesterol that remains after methanogenic treatment.

Analysis of a Chinese hamster ovary cell mutant with defective mobilization of cholesterol from the plasma membrane to the endoplasmic reticulum
Jacobs, N. L., B. Andemariam, et al. (1997), J Lipid Res 38(10): 1973-87.
Abstract: The factors involved in shuttling cholesterol among cellular membranes have not been defined. Using amphotericin B selection, we previously isolated Chinese hamster ovary cell mutants expressing defects in intracellular cholesterol transport. Complementation analysis among seven mutants identified one cell line, mutant 3-6, with a unique defect. The present analysis revealed three key features of mutant 3-6. First, the movement of cholesterol both from the endoplasmic reticulum and through lysosomes to the plasma membrane was normal. However, when intact 3-6 cells were treated with sphingomyelinase, movement of plasma membrane cholesterol to acyl CoA:cholesterol acyltransferase in the endoplasmic reticulum was defective. Cellular cholesterol was mobilized to this enzyme upon activation by 25-hydroxycholesterol. Second, mutant 3-6 did not utilize endogenously synthesized sterol or low density lipoprotein-derived cholesterol for growth as effectively as parental Chinese hamster ovary cells. Finally, despite normal movement of cholesterol to the plasma membrane, mutant 3-6 was amphotericin B resistant. The plasma membrane cholesterol content was normal as assessed by cholesterol oxidase treatment and Semliki Forest virus fusion, which suggests that the 3-6 mutation alters the organization of cholesterol in the plasma membrane. Our characterization of this mutant cell line should facilitate the identification of gene(s) required for this transport pathway.

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