| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver Shimomura, I., Y. Bashmakov, et al. (1997), Proc Natl Acad Sci U S A 94(23): 12354-9. Abstract: Cholesterol feeding reduces the mRNAs encoding multiple enzymes in the cholesterol biosynthetic pathway and the low density lipoprotein receptor in livers of hamsters. Here we show that cholesterol feeding also reduces the levels of the nuclear NH2-terminal domains of sterol regulatory element binding proteins (SREBPs), which activate transcription of sterol-regulated genes. We show that livers of hamsters, like those of mice and humans, predominantly produce SREBP-2 and the 1c isoform of SREBP-1. Both are produced as membrane-bound precursors that must be proteolyzed to release the transcriptionally active NH2-terminal domains. Diets containing 0.1% to 1.0% cholesterol decreased the amount of nuclear SREBP-1c without affecting the amount of the membrane precursor or its mRNA, suggesting that cholesterol inhibits the proteolytic processing of SREBP-1 in liver as it does in cultured cells. Cholesterol also appeared to reduce the proteolytic processing of SREBP-2. In addition, at high levels of dietary cholesterol the mRNA encoding SREBP-2 declined and the amount of the precursor also fell, suggesting that cholesterol accumulation also may inhibit transcription of the SREBP-2 gene. The high-cholesterol diets reduced the amount of low density lipoprotein receptor mRNA by 30% and produced a more profound 70-90% reduction in mRNAs encoding 3-hydroxy-3-methylglutaryl CoA synthase and reductase. Treatment with lovastatin and Colestipol, which increases hepatic demands for cholesterol, increased the amount of SREBP-2 mRNA as well as the precursor and nuclear forms of the protein. This treatment caused a reciprocal decline in SREBP-1c mRNA and protein. Considered together, these data suggest that SREBPs play important roles in controlling transcription of sterol-regulated genes in liver, as they do in cultured cells. |
| Cholesterol flux between lipid vesicles and apolipoprotein AI discs of variable size and composition Toledo, J. D., M. A. Tricerri, et al. (2000), Arch Biochem Biophys 380(1): 63-70. Abstract: Reconstituted discoidal high-density lipoproteins (rHDLs) of apolipoprotein AI are able to induce leakage of the internal aqueous space of lipid vesicles (A. Tricerri et al., 1998, Biochim. Biophys. Acta 1391, 67-78) and such interaction depends on the cholesterol content of vesicles and rHDL as well as the rHDL size. With the aim of knowing if this rHDL/vesicle interaction plays some role in the cholesterol exchange, the time course for bidirectional radiolabeled cholesterol transfer between 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) vesicles and different sized rHDLs was measured. The results show that size increase in the rHDL decreases the rate constant for cholesterol transfer from POPC/cholesterol vesicles and that the initial presence of cholesterol in the vesicles results in an increased rate constant for cholesterol transfer from the rHDLs. This cannot be explained by a simple aqueous diffusion mechanism. The existing correlation between rHDL/vesicle interaction and cholesterol transfer rate suggests that besides the aqueous diffusion, another mechanism involving the binding or interaction between donor and acceptor may occur. This fact may be of physiological relevance since the relative high affinity of small cholesterol-poor discs for cell membranes could facilitate the cholesterol efflux, while the decreased membrane affinity as a consequence of cholesterol enrichment and increase in size would decrease the rate of transfer in the opposite direction. |
| Cholesterol flux in cholesterol ester-loaded macrophages in an in vitro perfusion system Michishita, I. and G. R. Thompson (1991), Atherosclerosis 88(2-3): 203-11. Abstract: Cholesterol ester-loaded J774 macrophages attached to microcarrier beads were perfused or incubated with lipoproteins in vitro. Cholesterol influx was reduced by decreasing LDL cholesterol, efflux was promoted by increasing HDL cholesterol or by adding apolipoprotein A-I/phosphatidylcholine complexes to the perfusate or incubation medium. Addition of sera obtained from patients after LDL apheresis or plasma exchange resulted in much smaller increments in cell cholesterol than pretreatment sera, due to decreased influx, but efflux was unchanged despite the reduction in HDL cholesterol by plasma exchange. These data suggest that extracorporeal cholesterol removal promotes mobilization of intracellular cholesterol ester mainly by reducing cholesterol influx. |
| Cholesterol for synthesis of myelin is made locally, not imported into brain Jurevics, H. and P. Morell (1995), J Neurochem 64(2): 895-901. Abstract: We examined whether cholesterol needed for myelin formation is locally synthesized or whether it comes from the circulation. The experimental design was to inject 3Hwater and to use incorporation of label into brain cholesterol as a measure of the rate of accumulation of newly synthesized cholesterol in brain. The contribution of the circulation to this labeled cholesterol pool was minimized by repressing liver synthesis of cholesterol with a high cholesterol diet. The rate of accumulation of total cholesterol was calculated from the increasing amounts of sterol in brain regions at successive time intervals during development. Thus, accumulating cholesterol not explained as being newly synthesized (radioactive) could be assumed to have come from the circulation. Long-Evans rats, ranging in age from birth to 35 days, were injected intraperitoneally with 3Hwater (0.3-1.0 mCi/g of body weight) and killed 2 h later. The brain was dissected into brainstem, cerebellum, and cerebral hemispheres, and total lipids were extracted. Cholesterol and its precursors were quantified by HPLC. The radioactivity associated with the sterol fractions and the specific activity of body water determined from serum were used to calculate the absolute amount of newly synthesized sterol. The rates of cholesterol synthesis were compared with the rates of accumulation of total cholesterol in each brain region. The rate of accumulation of total sterol (cholesterol and desmosterol) closely followed that of newly synthesized total sterol in all brain regions from the second through the fifth postnatal weeks.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol fractions and apolipoproteins during endometriosis treatment by a gonadotrophin releasing hormone (GnRH) agonist implant or by danazol Lemay, A., N. A. Brideau, et al. (1991), Clin Endocrinol (Oxf) 35(4): 305-10. Abstract: OBJECTIVE: The evaluation of cholesterol fractions and apoproteins during ovarian suppression by a GnRH agonist implant vs danazol in the treatment of endometriosis. DESIGN: A randomized study in 33 patients comparing goserelin (3.6 mg/4 weeks s.c., n = 20) with danazol (2 x 400 mg/day p.o., n = 13) in patients with a laparoscopic diagnosis of endometriosis and treated for 6 months. MEASUREMENTS: Triglycerides, cholesterol (C), LDL-C, HDL-C subfractions and apoproteins A-1 and B were measured at admission, at months 2, 4 and 6 of treatment and at month 2 post-treatment. RESULTS: After 1 month of therapy, serum oestradiol levels were maintained in the menopausal range with goserelin and in the early follicular phase range with danazol. Goserelin induced a significant elevation in HDL-C (by 31.4%), in HDL2-C (24.6%) and in HDL3-C (45.7%) but no significant change in LDL-C or in ApoA-1 and ApoB. By contrast, danazol caused significant diminutions in HDL-C (23.9%), HDL2-C (56.6%) and ApoA-1 (35.6%). Moreover, danazol increased LDL-C (10.5%) and ApoB (29.0%, P less than 0.05). The lipoprotein changes during goserelin had a favourable effect on the atherogenic index (cholesterol/HDL-C) and ApoA-1/ApoB ratio whereas those of danazol had opposite effects. These changes reverted 2 months after danazol while HDL was still elevated after goserelin. CONCLUSIONS: In relation to cholesterol, goserelin is a safe medication. The significance of temporary adverse changes in cholesterol fractions due to danazol is still unknown. |
| Cholesterol from degenerating nerve myelin becomes associated with lipoproteins containing apolipoprotein E Goodrum, J. F. (1991), J Neurochem 56(6): 2082-6. Abstract: Apolipoprotein E is synthesized and secreted by rat sciatic nerve consequent to several types of injury. It has been proposed that endoneurial apolipoprotein E, in analogy to its role in systemic cholesterol transport, is involved in the salvage and reutilization of myelin cholesterol during degeneration and regeneration. To test this hypothesis, nerve lipids were prelabeled via intraneural injection of 3Hacetate. Four weeks later the nerves were crushed. From 1 to 12 weeks later, crushed nerves were examined for extracellular lipoprotein-bound cholesterol label. By 2 weeks after injury, 10% of the endoneurial lipid label was in a soluble form that was releasable into incubation medium. This released fraction was enriched in labeled cholesterol, and its labeled lipid composition was constant, in contrast to the changing distribution of label in the nerve with time after injury. On a KBr gradient, the released lipid label cofractionated with the released apolipoprotein E at densities similar to that of lipoproteins. These data indicate that at least some myelin cholesterol in injured nerve becomes associated with apolipoprotein E-containing lipoproteins and thus is available for reutilization via the hypothesized model. |
| Cholesterol gallstone formation in man and potential treatments of the gallbladder motility defect Portincasa, P., M. F. Stolk, et al. (1995), Scand J Gastroenterol Suppl 212: 63-78. Abstract: Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed. |
| Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk Bouchard, G., D. Johnson, et al. (2002), J Lipid Res 43(7): 1105-13. Abstract: The relationship between obesity and cholesterol cholelithiasis is not well understood at physiologic or genetic levels. To clarify whether obesity per se leads to increased prevalence of cholelithiasis, we examined cholesterol gallstone susceptibility in three polygenic (KK/H1J, NON/LtJ, NOD/LtJ) and five monogenic carboxypeptidase E (Cpe (fat)), agouti yellow (A(y)), tubby (tub), leptin (Lep(ob)), leptin receptor (Lepr (db)) murine models of obesity during ingestion of a lithogenic diet containing dairy fat, cholesterol, and cholic acid. At 8 weeks on the diet, one strain of polygenic obese mice was resistant whereas the others revealed low or intermediate prevalence rates of cholelithiasis. Monogenic obese mice showed distinct patterns with either high or low gallstone prevalence rates depending upon the mutation. Dysfunction of the leptin axis, as evidenced by the Lep(ob) and the Lepr (db) mutations, markedly reduced gallstone formation in a genetically susceptible background strain, indicating that in mice with this genetic background, physiologic leptin homeostasis is a requisite for cholesterol cholelithogenesis. In contrast, the Cpe (fat) mutation enhanced the prevalence of cholelithiasis markedly when compared with the background strain. Since CPE converts many prohormones to hormones, a deficiency of biologically active cholecystokinin is a likely contributor to enhanced susceptibility to cholelithiasis through compromising gallbladder contractility and small intestinal motility. Because some murine models of obesity increased, whereas others decreased cholesterol gallstone susceptibility, we establish that cholesterol cholelithiasis in mice is not simply a secondary consequence of obesity per se. Rather, specific genes and distinct pathophysiological pathways are responsible for the shared susceptibility to both of these common diseases. |
| Cholesterol gallstone formation. 1. Physical-chemistry of bile and biliary lipid secretion Carey, M. C. and J. T. Lamont (1992), Prog Liver Dis 10: 139-63. |
| Cholesterol gallstone formation. 2. Pathobiology and pathomechanics Lamont, J. T. and M. C. Carey (1992), Prog Liver Dis 10: 165-91. |
| Cholesterol gallstone formation: supersaturation, nucleation and gallbladder motility Duellberg, S. H., A. L. Werneck-Silva, et al. (1996), Rev Hosp Clin Fac Med Sao Paulo 51(5): 198-202. |
| Cholesterol gallstone induction in hamsters reflects strain differences in plasma lipoproteins and bile acid profiles Trautwein, E. A., J. Liang, et al. (1993), Lipids 28(4): 305-12. Abstract: Because different strains of hamsters vary in their susceptibility to gallstones, the relationship between plasma lipoproteins, hepatic cholesterol, bile lipids and bile acid profile was examined during gallstone induction in strains of male Syrian hamsters from Charles River Lakeview (CHR), Biobreeder F1B (BIO) and Harlan Sprague-Dawley (HAR). Gallstones were induced by feeding a purified diet containing 0.4 or 0.8% cholesterol for 5 wk. Basal plasma total cholesterol was similar, but the hypercholesterolemia induced by dietary challenge was significantly lower in CHR than in HAR and BIO hamsters. Cholesterol-fed CHR hamsters transported cholesterol mainly in HDL (47%), whereas VLDL-C + IDL-C predominated in BIO and HAR hamsters, and their HDL transported only 28 and 38%, respectively. HAR hamsters accumulated the most hepatic cholesterol, revealed the highest cholate/cheno ratio, the lowest glycine/taurine ratio and hydrophobicity index. HAR also developed the fewest cholesterol gallstones (23%), while 64% of CHR and 58% of BIO hamsters had cholesterol gallstones and 34% of BIO hamsters developed pigment stones. Doubling dietary cholesterol from 0.4 to 0.8% doubled the incidence of cholesterol gallstones but exerted minimal impact on other parameters compared to strain differences. Thus, different strains of hamsters vary considerably with respect to biliary cholesterol, bile acid profile and formation of cholesterol gallstones associated with differences in plasma lipoprotein profiles. |
| Cholesterol gallstones and aspirin Mendez-Sanchez, N., J. Lizardi-Cervera, et al. (1992), Gastroenterology 103(4): 1369-70. |
| Cholesterol gallstones: a fellow traveler with metabolic syndrome? Grundy, S. M. (2004), Am J Clin Nutr 80(1): 1-2. |
| Cholesterol gallstones: from epidemiology to prevention Acalovschi, M. (2001), Postgrad Med J 77(906): 221-9. |
| Cholesterol gallstone--symptoms, diagnosis and treatments Abei, M. and N. Tanaka (1996), Ryoikibetsu Shokogun Shirizu(9): 400-3. |
| Cholesterol goals established for patients with diabetes and metabolic syndrome Haffner, S. M. (2002), Am J Manag Care Suppl: 6-7. |
| Cholesterol granuloma (Xanthomatous metritis) in the uterus of a cat Zanghi, A., P. A. Nicotina, et al. (1999), J Comp Pathol 121(3): 307-10. Abstract: A case of uterine cholesterol granuloma in a 12-year old mixed breed cat is reported. The lesions were found in the endometrium of the left uterine horn as scattered, raised nodules or foci. Histologically, mononuclear cell infiltrates were seen to surround cholesterol crystals, in both the endometrium and the smooth muscle layer, reaching the serosa. The findings support the role of haemorrhage in promoting chronic inflammatory reactions around interstitial cholesterol ester precipitates. |
| Cholesterol granuloma Biller, J. A. and F. H. Linthicum, Jr. (2001), Otol Neurotol 22(4): 569-70. |
| Cholesterol granuloma DeGuine, C. and J. L. Pulec (1996), Ear Nose Throat J 75(4): 190. |