| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues, StarD5 and StarD6 Soccio, R. E., R. M. Adams, et al. (2002), Proc Natl Acad Sci U S A 99(10): 6943-8. Abstract: Using cDNA microarrays, we identified StarD4 as a gene whose expression decreased more than 2-fold in the livers of mice fed a high-cholesterol diet. StarD4 expression in cultured 3T3 cells was also sterol-regulated, and known sterol regulatory element binding protein (SREBP)-target genes showed coordinate regulation. The closest homologues to StarD4 were two other StAR-related lipid transfer (START) proteins named StarD5 and StarD6. StarD4, StarD5, and StarD6 are 205- to 233-aa proteins consisting almost entirely of START domains. These three constitute a subfamily among START proteins, sharing approximately 30% amino acid identity with one another, approximately 20% identity with the cholesterol-binding START domains of StAR and MLN64, and less than 15% identity with phosphatidylcholine transfer protein (PCTP) and other START domains. StarD4 and StarD5 were expressed in most tissues, with highest levels in liver and kidney, whereas StarD6 was expressed exclusively in the testis. In contrast to StarD4, expression of StarD5 and MLN64 was not sterol-regulated. StarD4, StarD5, and StarD6 may be involved in the intracellular transport of sterols or other lipids. |
| The class B, type I scavenger receptor promotes the selective uptake of high density lipoprotein cholesterol ethers into caveolae Graf, G. A., P. M. Connell, et al. (1999), J Biol Chem 274(17): 12043-8. Abstract: The uptake of cholesterol esters from high density lipoproteins (HDLs) is characterized by the initial movement of cholesterol esters into a reversible plasma membrane pool. Cholesterol esters are subsequently internalized to a nonreversible pool. Unlike the uptake of cholesterol from low density lipoproteins, cholesterol ester uptake from HDL does not involve the internalization and degradation of the particle and is therefore termed selective. The class B, type I scavenger receptor (SR-BI) has been identified as an HDL receptor and shown to mediate selective cholesterol ester uptake. SR-BI is localized to cholesterol- and sphingomyelin-rich microdomains called caveolae. Caveolae are directly involved in cholesterol trafficking. Therefore, we tested the hypothesis that caveolae are acceptors for HDL-derived cholesterol ether (CE). Our studies demonstrate that in Chinese hamster ovary cells expressing SR-BI, >80% of the plasma membrane associated CE is present in caveolae after 7.5 min of selective cholesterol ether uptake. We also show that excess, unlabeled HDL can extract the radiolabeled CE from caveolae, demonstrating that caveolae constitute a reversible plasma membrane pool of CE. Furthermore, 50% of the caveolae-associated CE can be chased into a nonreversible pool. We conclude that caveolae are acceptors for HDL-derived cholesterol ethers, and that caveolae constitute a reversible, plasma membrane pool of cholesterol ethers. |
| The clinical evaluation of the hypocholesterolemic effects of an inhibitor of cholesterol synthesis: mevalonic acid Del Nero, E., N. Aloe, et al. (1992), Clin Ter 141(7): 47-50. Abstract: Twenty eight patients with heterozygous familial hypercholesterolemia were treated with mevalonic acid (an inhibitor of cholesterol synthesis) for 45 days. Patients received a daily dose of 750 to 1500 mg mevalonic acid depending on plasma cholesterol levels. Results showed a significant reduction in cholesterol values whereas no significant difference was observed in HDL cholesterol and triglyceride levels. |
| The clustered Fcgamma receptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner Kwiatkowska, K. and A. Sobota (2001), Eur J Immunol 31(4): 989-98. Abstract: Phosphorylation of clustered Fcgamma receptor II (FcgammaRII) by Src family tyrosine kinases is the earliest event in the receptor signaling cascade. However, the molecular mechanisms for the interaction between FcgammaRII and these kinases are not elucidated. To asses this problem we isolated high molecular weight complexes of cross-linked FcgammaRII from non-ionic detergent lysates of U937 monocytic cells. CD55, a glycosylphosphatidylinositol-anchored protein, a ganglioside GM1 and Lyn, a Src family tyrosine kinase, were also located in these complexes. Gradient centrifugation demonstrated that the complexes containing cross-linked FcgammaRII displayed a low buoyant density. The FcgammaRII present in the complexes underwent tyrosine phosphorylation. Cross-linked FcgammaRII and Lyn occupied common 100-200 nm detergent-resistant membrane fragments, as demonstrated by immunoprecipitation and microscopy studies. Pretreatment of the cells with beta-cyclodextrin, a cholesterol acceptor, depleted membrane cholesterol and released CD55, GM1 and Lyn from the detergent-resistant complexes. In parallel, the association of Lyn with cross-linked FcgammaRII was disrupted and phosphorylation of the receptor inhibited. Reincorporation of cholesterol evoked the relocation of Lyn into the detergent-resistant membrane fraction and restored both Lyn association with cross-linked FcgammaRII and tyrosine phosphorylation of the receptor. Our data demonstrate that cholesterol-enriched membrane rafts can facilitate tyrosine phosphorylation of clustered FcgammaRII by Lyn kinase. |
| The combined effects of apolipoprotein E polymorphism and low-density lipoprotein cholesterol on cognitive performance in young adults Puttonen, S., M. Elovainio, et al. (2003), Neuropsychobiology 48(1): 35-40. Abstract: This study examined the relations of apolipoprotein E (ApoE) genotype and the low-density lipoprotein (LDL) cholesterol level to cognitive performance of 57 randomly selected healthy young adults. From the ongoing population-based study of Cardiovascular Risk in Young Finns, 25 men and 32 women were ApoE genotyped and participated in mental arithmetic and reaction time tasks. In contrast to findings obtained from studies with elderly subjects, ApoE4 polymorphism was associated with better cognitive performance. In addition, LDL cholesterol moderated this association. In the ApoE4 genotype group, low LDL cholesterol was associated with good performance in the mental arithmetic test, whereas for those without ApoE4 genotype, low LDL cholesterol was associated with poor performance. Performance in the reaction time task did not differ between the ApoE groups. In conclusion, assessment of the influence of ApoE on cognitive performance may require taking additional physiological factors, such as the level of cholesterol, into account. |
| The combined use of cholesterol-lowering drugs and cholesterol-lowering bread spreads: health behavior data from Finland de Jong, N., M. Simojoki, et al. (2004), Prev Med 39(5): 849-55. Abstract: BACKGROUND: Cholesterol-lowering drugs may metabolically interact with cholesterol-lowering bread spreads. This study analyses the prevalence of use of drugs, bread spreads or the combination of both in people aware of their high/elevated cholesterol level, and compares users of the three therapies on health behavior and demographics. METHODS: Participants (9581, 25-74 years) from The National FINRISK 2002 Study filled out a questionnaire on demographics and health (related) issues. Blood samples, blood pressure, body weight and height were measured. RESULTS: Of those who reported to have a high cholesterol level (31% of the study population), 19% used cholesterol-lowering drugs, 11% used cholesterol-lowering bread spreads and 5% combined both therapies. On a population level, only 1% jointly used a drug and bread spread therapy. The combination was used by especially highly educated people and those having a healthy diet. CONCLUSION: Combining a cholesterol-lowering drug with a bread spread regimen is relatively rare, even among those being aware of their high cholesterol levels. The combined usage was most frequent among 'the better off'. Public health risks of a metabolic interaction between both therapies may not be of major importance yet, but future follow-up is recommended. |
| The comparative potency of cholesterol crystallization-effector proteins in supersaturated model bile systems: association with vesicle transformation Hattori, Y., S. Tazuma, et al. (1998), J Gastroenterol Hepatol 13(11): 1161-70. Abstract: Various proteins which affect cholesterol crystallization are known to be present in bile, although the relative potency of their action is yet to be established. In this study, we evaluated the comparative potency of nucleating-effector proteins using a recently developed method for quantitative assessment of vesicle transformation in supersaturated model bile systems, to partially characterize mechanisms of their action. Concanavalin A-bound glycoproteins isolated from human gall-bladder bile shortened cholesterol crystallization time by 40% and increased cholesterol growth rate and final crystal mass by 161 and 19%, respectively, when compared to the control. In addition, immunoglobulins isolated from human gall-bladder bile increased cholesterol growth rate by 9%, but showed no significant effect on cholesterol crystallization time and final crystal mass. In contrast, human serum apolipoproteins A-I and B reduced cholesterol growth rate by 26 and 31% and reduced final crystal mass by 12 and 21%, but did not affect cholesterol crystallization time. Gel permeation chromatography revealed that proteins were distributed to both vesicles and bile salt micelles, but that no marked redistribution of lipids was caused by addition of these proteins. Furthermore, no significant difference in crystal structure was observed by video-enhanced contrast microscopy. These results indicate that nucleating-effector substances tested in this study may modulate vesicular cholesterol-holding capacity, thus affecting cholesterol crystallization. Such modulation is based upon the protein-vesicle association which defines the physico-chemical metastability of vesicular cholesterol. |
| The condensing effects of egg lecithin and cholesterol on triolein monolayers are inhibited by substitution of one saturated acyl chain in the triacylglycerol Redgrave, T. G., M. G. Ivanova, et al. (1994), Biochim Biophys Acta 1211(2): 229-33. Abstract: Previous work showed that the clearance from plasma of chylomicron-like emulsions injected intravenously was affected by the acyl chains of the constituent triacylglycerols. Compared with emulsions containing triolein (OOO) as the only triacylglycerol, clearances were decreased by a single saturated chain in emulsions containing 1,3-dioleoyl-2-stearoyl-sn-glycerol (OSO), 1,2-dioleoyl-3-stearoyl-sn-glycerol (OOS) or 1-stearoyl-2,3-dioleoyl-sn-glycerol (SOO). The differences in clearance may reflect physical differences at the oil-water interface related to chain interactions of the triacylglycerol structures with other lipid components. In the present work lipid monomolecular films at the air-water interface were used to establish the capacity of OOO to interact with the pure synthetic triacylglycerols OOS and SOO, and the capacity of OOS and SOO to co-exist in monolayers of lecithin and of cholesterol was compared with OOO. Substituting one oleoyl chain by a stearoyl chain induced a 20% condensation in monomolecular films of the pure triacylglycerols. Mixtures of OOO with either pure egg yolk phosphatidylcholine or cholesterol also showed substantial condensing effects. In contrast substituting one oleoyl chain by a stearoyl chain substantially lessened the condensing effects. At surface pressures above the collapse pressure of the pure triacylglycerols, substantially more OOO than OOS or SOO was retained in mixed monolayers with phosphatidylcholine. These differences could underlie the effects on metabolism of saturated chains in emulsion triacylglycerols. |
| The conflicting role of brain cholesterol in Alzheimer's disease: lessons from the brain plasminogen system Ledesma, M. D. and C. G. Dotti (2005), Biochem Soc Symp(72): 129-38. Abstract: Retrospective clinical studies indicate that individuals chronically treated with cholesterol synthesis inhibitors, statins, are at lower risk of developing AD (Alzheimer's disease). Moreover, treatment of guinea pigs with high doses of simvastatin or drastic reduction of cholesterol in cultured cells decrease Abeta (beta-amyloid peptide) production. These data sustain the concept that high brain cholesterol is responsible for Abeta accumulation in AD, providing the scientific support for the proposed use of statins to prevent this disease. However, a number of unresolved issues raise doubts that high brain cholesterol is to blame. First, it has not been shown that higher neuronal cholesterol increases Abeta production. Secondly, it has not been demonstrated that neurons in AD have more cholesterol than control neurons. On the contrary, the brains of AD patients show a specific down-regulation of seladin-1, a protein involved in cholesterol synthesis, and low membrane cholesterol was observed in hippocampal membranes of ApoE4 (apolipoprotein E4) AD cases. This effect was also evidenced by altered cholesterol-rich membrane domains (rafts) and raft-mediated functions, such as diminished generation of the Abeta-degrading enzyme plasmin. Thirdly, numerous genetic defects that cause neurodegeneration are due to defective cholesterol metabolism. Fourthly, in female mice, the most brain-permeant statin induces neurodegeneration and high amyloid production. Altogether, this evidence makes it difficult to accept that statins are beneficial through acting as brain cholesterol-synthesis inhibitors. It appears more likely that their advantageous role arises from improved brain oxygenation. |
| The conjoint trait of low high-density lipoprotein cholesterol and high triglycerides in adolescent black and white males Morrison, J. A., B. A. Barton, et al. (1998), Metabolism 47(5): 514-21. Abstract: To evaluate the interrelationships among body composition, blood pressure, and lipid phenotypes in adolescent black and white boys, we assessed racial distributions of lipids, blood pressure, and obesity and their joint occurrence in black and white boys aged 10 to 15 years. Subjects were recruited from Cincinnati (OH) schools. Because the differences in high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) are the most profound coronary heart disease (CHD) risk factor differences between black and white males, we assigned subjects to one of four low-HDL-C and high-TG categories (normal and increased risk) using the age/race-specific 25th (HDL-C) and 75th (TG) percentiles. We then assessed racial distributions of lipids, blood pressure, and obesity by these phenotypes. Age differences between the black and white participants were significant, with the former about 3 months younger (P=.03), but black boys were more mature and were significantly taller and heavier and had a greater body mass index (BMI weight in kilograms divided by height in centimeters squared). Differences in the sum of the triceps, subscapular, and suprailiac skinfolds were not significant. Blacks had significantly higher HDL-C, lower TG, and higher diastolic blood pressure (DBP), but differences in systolic blood pressure (SBP) were not significant. In both racial groups, the body composition measures were significantly correlated with HDL-C, TG, and blood pressure levels; the correlations between HDL-C and both weight and BMI were significantly stronger in white boys. The proportion of boys of each race with low HDL-C and high TG was similar by design. In both racial groups, subjects with the conjoint trait had a significantly greater BMI, triceps skinfold, and sum of skinfolds than subjects in the other phenotypic groups. For white boys, participants with the conjoint trait had the highest SBP and DBP; differences in SBP were significant for comparisons to the normal- and high-TG group alone, and differences in DBP were significant for the comparison between normal and low HDL-C alone. For black boys, subjects with both normal HDL-C and TG had significantly lower SBP than boys with either the conjoint trait or high TG alone; none of the group differences in DBP were significant. Black had significantly less dense LDL (more LDL-C per apolipoprotein apo B). In each racial group, boys with the conjoint trait had the most dense LDL, significantly more dense than in any of the other phenotypes in black boys and significantly more dense than in boys with low HDL-C alone and normal boys in the white group. In both racial groups, the occurrence of no risk factors (>75th percentile TG, BMI, SBP, and DBP or <25th percentile HDL-C) and three or more risk factors was greater than expected by chance alone, and the occurrence of exactly one risk factor and two factors was less. When examined by phenotypic groups within race, boys in each racial group with the normal phenotype had a greater than expected percentage with no risk factors, and white boys with the conjoint trait were more likely to have a marked increase in multiple risk factors. Possible mechanisms for this clustering of risk factors and for the racial differences in the patterns are discussed. |
| The continuing debate on the treatment of hypercholesterolemia in the primary prevention of coronary disease. What did cholesterol do to deserve that? Ros Rahola, E. (1997), Med Clin (Barc) 109(14): 542-5. |
| The contribution of lipoprotein cholesterol to hepatic precursor pools for bile acid synthesis Bravo, E., G. Ortu, et al. (1992), Biochem Soc Trans 20(4): 338S. |
| The contribution of newly synthesized cholesterol to bile salt synthesis in rats quantified by mass isotopomer distribution analysis Bandsma, R. H., F. Kuipers, et al. (2000), Biochim Biophys Acta 1483(3): 343-51. Abstract: A new stable isotope procedure has been developed and validated in rats, applying 1-(13)Cacetate infusion to quantify the production of bile salts from de novo synthesized cholesterol making use of the mass isotopomer distribution analysis (MIDA) principle. Ions (m/z) 458-461, 370-373 and 285-288 were monitored by GC/MS (EI-mode) for the methyl trimethylsilylether derivatives of cholate, chenodeoxycholate and beta-muricholate, respectively. Rats with intact exteriorized enterohepatic circulation and rats with chronic bile diversion were infused with 1-(13)Cacetate for up to 14 h. After 10 h of infusion the enterohepatic circulation of the intact group was interrupted to deplete the existing bile salt pool (acute bile diversion). The fractions of biliary cholesterol and individual bile salts derived from newly synthesized cholesterol were determined by MIDA at t=14 h. In rats with acute bile diversion, these fractions were 20, 25, 27 and 23% for biliary cholesterol, cholate, chenodeoxycholate and beta-muricholate, respectively. After bile diversion for 8 days to induce hepatic cholesterol and bile salt synthesis, these fractions increased significantly to 32, 47, 41 and 47%, respectively. Calculated enrichments of the acetyl-CoA precursor pools were similar for all bile salts and biliary cholesterol within the two rat groups. However, chronic enterohepatic interruption decreased the acetyl-CoA pool size almost two-fold. We conclude that MIDA is a validated new stable isotope technique for studying the synthetic pathway from acetyl-CoA to bile salts. This technique provides an important new tool for studying bile salt metabolism in humans using stable isotopes. |
| The contribution of newly synthesized cholesterol to biliary cholesterol in healthy humans Scheibner, J., K. Lange, et al. (1997), Z Ernahrungswiss 36(4): 368-71. Abstract: Hypersecretion of biliary cholesterol appears to be the key defect in the pathogenesis of cholesterol gallstones, and this may be due to an enhanced synthesis of cholesterol. To measure fractional syntheses of biliary and plasma cholesterol, five male and 3 female healthy humans with an intact enterohepatic circulation were infused intravenously with 1-13Cacetate for 15 h. Samples of duodenal bile and blood were taken hourly and an enteral formula diet was given. Free cholesterol mass distribution was analyzed by gas chromatography mass spectrometry. The Mass Isotopomer Distribution Analysis (MIDA) technique allowed to calculate fractional synthesis. After 6 hours of infusion, the 13Clabel of the cytosolic acetate pool reached a plateau of approximately 12%. Individual fractional cholesterol synthesis is plasma and bile correlated significantly (6-15 h) and amounted to 4.2% and 5.3% after 15 h, respectively. It may be concluded from this study, that newly synthesized cholesterol is secreted into bile to a higher extent than into plasma. |
| The control by angiotensin II of cholesterol supply for aldosterone biosynthesis Capponi, A. M. (2004), Mol Cell Endocrinol 217(1-2): 113-8. Abstract: In the adrenal glomerulosa cell, aldosterone is synthesized from cholesterol, which is supplied to the cell and stored under the form of cholesterol esters, then hydrolyzed to be transferred to the mitochondrial outer membrane and finally transported to the inner membrane where the P450 side-chain cleavage enzyme will convert it to pregnenolone. Angiotensin II (AngII), one of the major physiological regulators of mineralocorticoid synthesis, appears to affect most of the steps along this cascade and thus to exert a powerful control over the use of cholesterol for aldosterone production. |
| The control of cholesterol by diet Stoy, D. B. (1990), Servir 38(6): 286-90. |
| The control of cholesterol by drugs Stoy, D. B. (1990), Servir 38(6): 291-6. |
| The control of cholesterol in the prevention of coronary cardiopathy Vintro, I. B. (1995), Rev Esp Salud Publica 69(6): 439-43. |
| The control of cholesterol metabolism and plasma lipid levels in infant rats Hahn, P. and L. Mahler (1992), Physiol Res 41(6): 407-10. Abstract: Infant rats received an i.p. injection of insulin, anti-insulin serum, streptozotocin, antiglucagon serum or dexamethasone. All substances except the antiinsulin serum, raised the plasma triglyceride level. Both antisera decreased plasma cholesterol levels, while streptozotocin, insulin and dexamethasone caused an increase. The activity of 3-hydroxy-3-glutaryl CoA reductase in liver and brown adipose tissue changed inversely to the cholesterol level. However, small intestinal enzyme activity was increased by insulin administration inspite of the rise in plasma cholesterol. |
| The correlation between serum total cholesterol and some trace elements in serum, liver and heart of rats fed high cholesterol diet Abu-el-Zahab, H. S., W. E. Abdel Aal, et al. (1991), Nahrung 35(8): 827-34. Abstract: The work indicates the link between the serum cholesterol, atherosclerosis and certain metal metabolism. 122 adult albino rats were used in this study and classified into 5 groups: Control group, 29 rats fed the stock diet; group I, 32 rats fed the stock diet with 1% cholesterol for 6 weeks; group II, 36 rats fed the stock diet with 1% cholesterol for 8 weeks; group IIIA, 17 rats fed the stock diet and 0.2 ml oil/day orally for 8 weeks and group IIIB, 18 rats fed the stock diet and 0.2 ml oil with cholesterol daily (50 mg cholesterol/1 ml oil) for 8 weeks. The results obtained showed that: 1. A positive correlation was found between serum total cholesterol and serum copper, cadmium and Cd/Zn ratio, whereas a negative correlation occurred between serum total cholesterol and serum Zinc and Zn/Cu ratio. 2. A positive correlation was found between serum total cholesterol and cadmium, Zn/Cu and Cd/Zn ratio in liver. On the other hand, a negative correlation occurred between serum total cholesterol and copper in liver. 3. A positive correlation was found between serum total cholesterol and Zn/Cu ratio in heart which was negative in heart copper, cadmium and Cd/Zn ratio. Histopathological examination of liver sections of animals treated with cholesterol revealed the presence of mild degree of fatty change, while the kidney tissues showed glomerular lesion in the form of obliteration of Bowman's capsule with increased cellularity inside, beside degenerated tubules and interstitial fibrosis. |