| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Alcohol use and mortality from coronary heart disease: the role of high-density lipoprotein cholesterol. The Multiple Risk Factor Intervention Trial Research Group Suh, I., B. J. Shaten, et al. (1992), Ann Intern Med 116(11): 881-7. Abstract: OBJECTIVE: To study the association between alcohol consumption and death from coronary heart disease and to determine the extent to which the association can be explained by the high-density lipoprotein (HDL) cholesterol level. DESIGN: A cohort study involving men enrolled in the Multiple Risk Factor Intervention Trial (MRFIT). SETTING: Community-based study. PARTICIPANTS: Men (n = 11,688) at high risk for developing coronary heart disease but without clinical evidence of it. More than 90% of the men were white, and the average age was 46 years. Five percent of the men abstained from alcohol during the trial, 81% consumed fewer than 21 alcoholic drinks per week, and 14% consumed more than 21 alcoholic drinks per week. MEASUREMENTS: Average alcohol intake over 7 years was calculated for MRFIT participants who were alive at the end of the trial and who had at least three follow-up records of alcohol consumption. Post-trial mortality during a 3.8-year period was assessed. RESULTS: The adjusted relative risk for death from coronary heart disease for each increase of 7 drinks per week was 0.89 (95% CI, 0.80 to 1.00), with an apparent dose-response relationship. The average HDL level was associated with the average alcohol intake in a least-squares regression model (beta = -0.0074; P less than 0.01). When the average HDL level was included in the proportional hazards model for mortality from coronary heart disease, the absolute value of the coefficient for average drinks per week declined 45%, yielding an adjusted relative risk for each additional 7 drinks per week of 0.94 (CI, 0.84 to 1.05). CONCLUSION: In middle-aged men who are light to moderate drinkers, the inverse association between alcohol consumption and death from coronary heart disease can be explained, in large part, by the HDL cholesterol level, which increases with alcohol consumption. However, alcohol consumption cannot be recommended because of the known adverse effects of excess alcohol use. |
| Algorithm of channel gating and its allosteric regulation by membrane cholesterol Nakaya, J. (1999), Hokkaido Igaku Zasshi 74(5): 357-66. Abstract: A method for quantitative analysis of channel kinetics was established with the use of histograms of channel events. In this system, channel kinetics was expressed as an exponential function of temperatures. The two factors in this exponential function were independently regulated: one was the progressive index number, controlled by membrane cholesterol, and the other was the coefficient, directed by channel gramicidin. Mean frequencies of channel opening decreased depending on cholesterol concentrations in the membrane. Its sigmoidal nature suggested that cholesterol regulated the channel characteristics in allosteric manner. The theoretical formula to analyze channel kinetics from the exponental as a function of temperatures, channel and membrane cholesterol concentrations was confirmed to be valid by comparison with experimental results. |
| Alleles of the cholesterol 7 alpha-hydroxylase (CYP7) gene in pigs selected for high or low plasma total cholesterol Davis, A. M., W. G. Pond, et al. (1998), Proc Soc Exp Biol Med 217(4): 466-70. Abstract: Crossbred pigs were selected for high (HTC) or low (LTC) plasma total cholesterol (TC). Pigs from the seventh (n = 51) and eighth (n = 92) generations were used to determine restriction fragment length polymorphisms (RFLP). Using TaqI restriction enzyme digestion, the frequencies of two alleles (2.8- or 5.0-kb fragments) of the cholesterol 7 alpha-hydroxylase (CYP7) gene were determined in the two populations as a potential indicator of TC concentration at 8 weeks of age. Only the 2.8-kb fragment allele was present in the 26 HTC pigs tested in Generation 7. In the LTC pigs both the 2.8- and 5.0-kb alleles were present in 12 pigs, and only the 5.0-kb allele was present in 13 pigs. The allele frequencies of the 2.8 and 5.0 fragments, respectively, were.26 and.74 in LTC pigs and 1.00 and 0 in HTC pigs. There was an association (P <.001) between the 5.0- and 2.8-kb CYP7 alleles, respectively, and low and high TC concentrations. In Generation 8, all HTC pigs were homozygous for the 2.8-kb allele. The 5.0 kb allele was present in all LTC pigs tested and was homozygous in 57% of LTC pigs. Mean plasma TC was 105.0 mg/dl in 30 pigs homozygous for the 2.8-kb allele in Generation 8; means for LTC pigs were 53.5 and 60.4 mg/dl in 35 pigs homozygous for the 5.0-kb allele and in 27 heterozygous pigs, respectively. High TC was associated with the presence of the 2.8-kb allele, and low TC was associated with the presence of the 5.0-kb allele in both Generations 7 and 8. We conclude that TaqI RFLP analysis of the CYP7 gene is a reliable indicator for TC in these swine. |
| Allicin release under simulated gastrointestinal conditions from garlic powder tablets employed in clinical trials on serum cholesterol Lawson, L. D., Z. J. Wang, et al. (2001), Planta Med 67(1): 13-8. Abstract: The failure of five recent clinical trials to show significant reduction in elevated serum cholesterol by a single brand of allicin-standardized garlic powder tablets is in contrast to many prior positive studies with the same brand. The hypocholesterolemic activity of garlic is mainly due to allicin, a compound that is produced by the acid-sensitive garlic enzyme, alliinase, only after tablet consumption. Therefore, the allicin-releasing ability of ten lots of these tablets--manufactured over the same years that the positive and negative clinical trials were conducted (1989-1997)--was determined under simulated gastrointestinal dissolution conditions, as defined by U.S. Pharmacopeia Method 724A. It was found that the older lots were more resistant to acid-disintegration (2.5 h vs. 1.3 h, P < 0.001) and that they released three times as much allicin (44% vs. 15 % of their potential, P < 0.001) as the newer lots. A second brand of tablets employed in a recent negative trial released no detectable amount of allicin, while a third set of tablets with high allicin release was used in a trial that gave positive effects. Hence, the persons involved in the recent negative clinical trials probably received considerably less allicin than did those in the older positive studies, possibly accounting for much of the discrepancy in the outcomes. In conclusion, clinical trials using garlic powder tablets to assess any effect of garlic that might be related to allicin, as most are, cannot be considered valid for garlic when the trial shows no effect, unless the expected allicin release from the tablets has at least been determined under standardized drug release conditions (USP 724A). |
| Allicin-induced decrease in formation of fatty streaks (atherosclerosis) in mice fed a cholesterol-rich diet Abramovitz, D., S. Gavri, et al. (1999), Coron Artery Dis 10(7): 515-9. Abstract: BACKGROUND: Garlic (Allium sativum) has been considered to exhibit therapeutic features for many years. The effects of garlic on levels of serum lipids and on atherosclerosis have been investigated extensively. We have previously demonstrated that allicin, an active component of garlic, exerts a beneficial effect on lipid profile in hyperlipidemic rabbits. OBJECTIVE: To investigate the effects of allicin on formation of fatty streaks (atherosclerosis) and lipid profile in mice. METHODS: Allicin was extracted from garlic and kept in a buffer citrate solution at 4 degrees C. Sixty C57BL/6 mice were fed Paigen diet (17% fat, 1.25% cholesterol) for 15 weeks. Thirty randomly selected animals were administered allicin solution (9 mg/kg) and 30 were administered placebo. Blood lipid profile was evaluated five times during the study. At the end of the 15-week period, the animals were killed and the aortic sinus was evaluated for formation of fatty streaks (atherosclerosis). RESULTS: We observed no statistically significant differences between blood lipid profiles of groups. Microscopic evaluation of aortic sinus formation of fatty streaks (atherosclerosis), however, showed that values for mice in the allicin-treated group were significantly lower: areas of formation of fatty streaks (atherosclerosis) were 13,440 +/- 3310 and 23,410 +/- 3723 micron 2, respectively, for allicin-treated and control mice (means +/- SEM; P = 0.023). CONCLUSIONS: These results indicate that allicin reduces formation of fatty streaks (atherosclerosis) in hyperlipidemic mice. These changes do not seem to occur through an alteration in blood lipid profile. |
| Allylic nitration of 3 beta-sitosterol and cholesterol acetate: preparation of 7-nitro derivatives Jimenez-Estrada, M., M. O. Garcia, et al. (1997), Steroids 62(6): 500-3. |
| Alpha linolenic acid in cholesterol esters: a marker of alphalinolenic acid intake in newborns Babin, F., A. Rodriguez, et al. (2000), Eur J Clin Nutr 54(11): 840-3. Abstract: OBJECTIVE: To evaluate alpha-linolenic acid (ALA) (18∶3 n-3) and linolenic acid (LA) (18∶2 n-6) in cholesterol esters (CE) as markers of ALA and LA dietary intakes in preterm infants. SUBJECTS: Forty-five preterm infants: two groups fed different formulas, the third fed human milk. DESIGN: ALA and LA dietary intakes were precisely recorded in each infant to accurately determine the cumulative amount of ingested ALA and LA during two intervals: (i) between the second day after the first significant formula intake (D0) and the fifteenth day (D15); and (ii) between D0 and the first day of the 37th week of post-conception age (W37). The corresponding amounts of ingested ALA and LA were related to ALA and LA levels determined by capillary column gas-liquid chromatography in plasma cholesterol esters at D15 and W37, respectively. RESULTS: ALA in CE was very significantly correlated to D0-D15 and D0-W37 ALA intakes (0.66; P=0.0001 and 0.70; P=0.0001), respectively. LA in CE was weakly correlated to D0-D15 LA intakes (0.03; P=0.01) and whatever the group (human milk or enriched formula) the correlation was lost at W37. CONCLUSION: In preterm infants, ALA in CE can be considered as representative of ALA dietary intakes, whereas LA in CE appears as a poor marker of LA intakes. |
| Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats Rodriguez-Paez, L., M. Juarez-Sanchez, et al. (2003), Phytomedicine 10(5): 397-404. Abstract: Our results showed that alpha-asarone was an inhibitor of hepatic HMG-CoA reductase and that the administration of alpha-asarone at 80 mg/kg body wt. for 8 days decreased serum cholesterol by 38% (p < 0.001) in hypercholesterolemic rats. This alpha-asarone treatment affected mainly the serum LDL-cholesterol levels, leaving serum HDL-cholesterol lipoproteins unaffected, with a consequent decrease of 74% in the LDL/HDL ratio. In addition, alpha-asarone especially stimulated bile flow in hypercholesterolemic rats (60%), increasing the secretion of bile salts, phospholipids and bile cholesterol. The drug also reduced the cholesterol levels of gallbladder bile, whereas the concentration of phospholipids and bile salts increased only slightly, leading to a decrease in the cholesterol saturation index (CSI) of bile in the hypercholesterolemic rats. This CSI decrease and the increase in bile flow induced by alpha-asarone may account for the cholelitholytic effect of alpha-asarone. It seems that alpha-asarone induced clearance of cholesterol from the bloodstream and that the excess of hepatic cholesterol provided by LDL-cholesterol is diverted to bile sterol secretion via a bile choleresis process. The inhibition of HMG-CoA reductase and the increase in bile flow induced by alpha-asarone, as well as the decrease in the CSI, could then explain the hypocholesterolemic and cholelitholytic effects of alpha-asarone. |
| Alpha-hydroxylation at C-15 and C-16 in cholesterol: synthesis of (25R)-5alpha-cholesta-3beta,15alpha,26-triol and (25R)-5alpha-cholesta-3beta,16alpha,26-triol from diosgenin Williams, J. R., H. Gong, et al. (2004), Org Lett 6(2): 269-71. Abstract: reaction: see text (25R)-5alpha-cholesta-3beta,16alpha,26-triol 7b and (25R)-5alpha-cholesta-3beta,15alpha,26-triol 10b were synthesized, via (25R)-5alpha-cholesta-3beta,16beta,26-triol 5a, from diosgenin 3 in 52% yield over six steps and 47% yield over eight steps, respectively. An efficient method for inversion of a C-16beta hydroxyl to the C-16alpha position and a short method for transposition of a C-16beta hydroxyl to the C-15alpha position via the unexpected beta-reduction of a C-15 ketone in a steroid are reported. |
| Alpha-linolenic acid and metabolism of cholesterol and long-chain fatty acids Garg, M. L. and M. T. Clandinin (1992), Nutrition 8(3): 208-10. Abstract: Animal studies have demonstrated that dietary 18:3n-3 reduces 20:4n-6 content in plasma and tissue lipids. At megadose levels of 18:3n-3, the reduction in phospholipid 20:4n-6 is brought about by a combination of inhibition of desaturase activities and redistribution of 20:4n-6 from phospholipids to neutral lipid pools. The shifting phenomenon is not apparent when the dietary level of 18:3n-3 is low. Dietary 18:3n-3 reduces cholesterol levels in blood and liver tissue; however, the mechanism by which this effect is mediated is not known. Further studies are warranted to investigate the role of dietary 18:3n-3 on cholesterol biosynthesis, storage, and mobilization into and from the tissues and on the secretion of cholesterol into bile. The effect of the ratio of dietary 18:2n-6 to SFA as a determinant of 20:4n-6 and lipid-lowering effects should be further explored in human subjects. It is important to elucidate whether dietary 18:3n-3 interacts with other nutrients to modulate the parameters implicated in the pathogenic processes. The optimum level of dietary 18:3n-3 required to obtain health beneficial effects needs to be determined. Specific effects of dietary 18:3n-3 on low- and high-density lipoprotein cholesterol levels also deserves further investigation before any recommendation to achieve health benefits can be made. |
| Alpha-sialyl cholesterol increases laminin in Schwann cell cultures and attenuates cytostatic drug-induced reduction of laminin Konings, P. N., R. L. Philipsen, et al. (1994), Brain Res 654(1): 118-28. Abstract: Schwann cells play an important role in peripheral nerve regeneration. Here, we report the effect of alpha-sialyl cholesterol (alpha-SC), a derivative of the sialic acid-containing natural gangliosides, and the cytostatic agents, cisplatin, taxol and vincristine on the laminin production in Schwann cell cultures isolated from rat sciatic nerves. Laminin, one of several extracellular matrix components produced by Schwann cells, is known to potentiate axonal outgrowth. Laminin content was increased by alpha-SC, starting at 7.0 micrograms/ml with a maximal effect at 22.4 micrograms/ml (30%, P < 0.001). The three cytostatic drugs, dose-dependently reduced laminin content in Schwann cell cultures: (1) cisplatin at a threshold dose of 2 micrograms/ml (-26.4%, P < 0.001); (2) taxol, starting at a dose of 1 ng/ml (-8.0%, P < 0.05); and (3) vincristine, starting at 0.5 ng/ml (-5.9%, P < 0.05). Cultured Schwann cells were incubated with cytostatic drugs in combination with increasing amounts of alpha-SC and it was found that, depending on the cytostatic drug concentration used, alpha-SC could reduce or completely prevent the cytostatic drug-induced reduction of laminin in Schwann cell cultures. Co-treatment with alpha-SC also reduced part of the morphological changes caused by the cytostatic drugs. alpha-SC did not counteract the anti-proliferative effect of the cytostatic drugs on K-562 human erythroleukemia cells. In conclusion, alpha-SC increased laminin content in Schwann cell cultures and protected Schwann cell cultures against the decrease of laminin by cytostatic drugs without interfering with the anti-proliferative potential, suggesting that alpha-SC may have clinical use in protecting cancer patients against the neurotoxic effects of cytostatic drugs. |
| Alpha-sialyl cholesterol reverses AF64A-induced deficit in passive avoidance response and depletion of hippocampal acetylcholine in mice Abe, E., S. Murai, et al. (1993), Br J Pharmacol 108(2): 387-92. Abstract: 1. The effect of alpha-sialyl cholesterol (alpha-SC; alpha-D-N-acetylneuraminyl cholesterol) on disturbances of the central cholinergic system induced by ethylcholine mustard aziridinium ion (AF64A) and by scopolamine were studied by means of a step-down passive avoidance response and locomotor activities in mice. The levels of acetylcholine (ACh) in certain regions of the brain were measured to assess the neurochemical recovery promoted by alpha-SC. 2. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) impaired the 24 h retention latencies of animals in a dose-dependent manner, and scopolamine (0.5 mg kg-1, i.p.) also impaired the retention performance. Administration of alpha-SC (1 and 4 mg kg-1, p.o.) once daily for 13 days improved the retention performance in AF64A-treated animals in a dose-dependent manner, but not in the scopolamine-treated animals. 3. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) and scopolamine (0.5 mg kg-1, i.p.) increased vertical and horizontal locomotor activities. alpha-SC dose-dependently attenuated the increase in locomotor activities induced by 2.5 nmol of AF64A, but not the locomotor activities caused by 5 or 10 nmol of AF64A, or scopolamine (0.5 mg kg-1, i.p.). 4. The deficit retention performance of AF64A-treated animals was associated with depletion of ACh levels in the hippocampus, but not in the septum or cerebral cortex. Administration of alpha-SC to AF64A-treated animals dose-dependently reversed the depletion of ACh levels in the hippocampus. 5. The results indicate that alpha-SC had significant effects after oral administration of AF64A-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Alteration of a macrophages inflammatory protein-related protein-2 (MRP-2) response by high fat and cholesterol diet in mice Yu, R., J. S. Park, et al. (2002), Life Sci 70(21): 2535-45. Abstract: Macrophage inflammatory protein-related protein-2 (MRP-2) is a new member of the CC chemokine family that is recently identified in murine macrophages. MRP-2 is involved in leukocyte trafficking and activation, which can be implicated in inflammatory diseases including atherosclerosis. Little is known about the involvement of this novel chemokine MRP-2 in the pathogenesis of atherosclerosis. To explore the possible association of the MRP-2 with atherosclerosis, we investigated the effects of atherogenic diet on MRP-2 expression in mice. Male C57BL/6 mice were fed a high fat and cholesterol diet (20% fat and 1.5% cholesterol) or a control diet based on AIN-76 for 5, 10, or 14 weeks. The levels of total cholesterol, LDL cholesterol, and F2-isoprostanes in plasma were measured using appropriate enzymatic assays. Tumor necrosis factor alpha (TNF alpha) and MCP-1 release by peritoneal macrophages was determined by ELISA. The mRNA expression level of the MRP-2 was measured by RT-PCR. The levels of total cholesterol, LDL-cholesterol, and 8-iso-prostaglandin F2 alpha in plasma, well-known indexes of atherosclerosis, were significantly increased in the high fat and cholesterol diet group compared to those in the control. A significant increase in the TNF alpha and MCP-1 production by macrophages was also observed in the group fed high fat and cholesterol diet. The mRNA expression of MRP-2 was upregulated by oxLDL treatment in vitro and feeding a high fat and cholesterol diet in vivo at the late stage of atherosclerosis. These results suggest that MRP-2 may be an important contributing factor in the development of atherosclerosis. |
| Alteration of acidic lipids in human sera during the course of pregnancy: characteristic increase in the concentration of cholesterol sulfate Lin, B., K. Kubushiro, et al. (1997), J Chromatogr B Biomed Sci Appl 704(1-2): 99-104. Abstract: In this study, we determined the concentrations of acidic lipids, including cholesterol sulfate (CS), sulfatide and GM3 ganglioside, in human sera of non-pregnant state and during the course of pregnancy. In human sera of non-pregnant women, GM3 was present at a concentration of 8 nmol/ml and the concentrations of CS and sulfatides were less than 20% of that of GM3. The concentration of sulfatides in sera at the second trimester of gestation was decreased, but CS gradually increased from the first to the third trimester of gestation with a correlation coefficient of 0.66, and a correlation between the concentration of CS and weeks of gestation (p<0.01). CS was also contained in the placental villi, and its concentration increased from the first to the third trimester of gestation, suggesting that placental CS is one of the source of CS in the blood by shedding. |
| Alteration of substrate affinity of Streptomyces cholesterol oxidase for application to the rate assay of cholesterol in serum Nishiya, Y. and N. Hirayama (1999), Clin Chim Acta 287(1-2): 111-22. Abstract: The Streptomyces cholesterol oxidase (ChoA) can not be adopted for the rate assay, because the Km value of the enzyme for cholesterol is very small. The choA gene was subjected to random mutagenesis in vivo, and a mutant ChoA (designated E-ChoA) that showed altered substrate affinity was obtained by screening. The Km value of E-ChoA was approximately ten times larger than that of the wild type. Unexpectedly, the thermal stability was also improved. The amino acid substitutions of E-ChoA were identified to be the valine to glutamate at position 145, which has been previously identified as one of the thermostable mutations, and the glycine to serine at position 405. The mutational effects on the structure of E-ChoA are discussed on the basis of a three-dimensional model. E-ChoA has been successfully applied to the rate assay of cholesterol in serum. |
| Alteration of the myometrial plasma membrane cholesterol content with beta-cyclodextrin modulates the binding affinity of the oxytocin receptor Klein, U., G. Gimpl, et al. (1995), Biochemistry 34(42): 13784-93. Abstract: To investigate the effect of cholesterol on the oxytocin receptor function in myometrial membranes, we developed a new method to alter the membrane cholesterol content. Using a methyl-substituted beta-cyclodextrin, we were able to selectively deplete the myometrial plasma membrane of cholesterol. Vice versa, incubating cholesterol-depleted membranes with a preformed soluble cholesterol-methyl-beta-cyclodextrin complex restored the cholesterol content of the plasma membrane. Binding experiments showed that, with the removal of cholesterol from the membrane, the dissociation constant for 3Hoxytocin is enhanced 87-fold (from Kd = 1.5 nM to Kd = 131 nM), therefore shifting the oxytocin receptor from high to low affinity. Increasing the cholesterol content of the cholesterol-depleted membrane again restored the high-affinity binding (Kd = 1.2 nM). The presence of 0.1 mM GTP gamma S did not significantly change the number of high-affinity binding sites for 3Hoxytocin in native plasma membranes, in membranes depleted of cholesterol, and in plasma membranes with restored cholesterol content. The number of high-affinity binding sites for the oxytocin antagonist 3HPrOTA was dependent in the same way on the cholesterol content as for 3Hoxytocin. Substitution of the membrane cholesterol with other steroids showed a strong dependence of the oxytocin receptor function on the structure of the cholesterol molecule. The detergent-solubilized oxytocin receptor was not saturable with 3Hoxytocin even at concentrations up to 10(-6) M of radioligand. Addition of the cholesterol-methyl-beta-cyclodextrin complex to the detergent-solubilized oxytocin receptor induced a saturation of the solubilized binding sites (Bmax = 0.98 pmol/mg) for oxytocin (Kd = 16 nM).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Alterations in carbohydrate and lipid metabolism induced by a diet rich in coconut oil and cholesterol in a rat model Zulet, M. A., A. Barber, et al. (1999), J Am Coll Nutr 18(1): 36-42. Abstract: OBJECTIVE: The type of dietary fat as well as the amount of cholesterol occurring in the diet have been associated with several metabolic disorders. Thus, the aim of the present study was to investigate the influence of a hypercholesterolemic diet enriched with coconut oil and cholesterol on carbohydrate and lipid metabolism in a rat model. METHODS: Twenty male Wistar rats weighing about 190 g were assigned to two dietary groups. One group received a semipurified control diet and the other was given a diet enriched in coconut oil (25% by weight) and cholesterol (1% by weight) for 26 days. RESULTS: Our results indicated a significant increase in serum total cholesterol (+285%; p<0.001), low-density lipoproteins (+154%; p<0.01), liver cholesterol (+1509%; p<0.001), as well as a significant increase in liver weight (+46%; p<0.001) in those rats fed the hypercholesterolemia-inducing diet as compared to controls. Moreover, a significant decrease in serum high-density lipoproteins (-67%; p<0.001), triacylglycerols levels (-33%; p<0.05), and abdominal fat weight (-39%; p<0.01) were found. The observed alterations in serum lipid and lipoprotein profile resembled a situation of type IIa hyperlipidemia in humans. Measurement of several enzymes concerned with lipid utilization revealed a significant increase in 3-hydroxy-3-methylglutaryl-CoA reductase activity (+68%; p<0.01) in the liver of animals fed the hypercholesterolemic diet, while a significant reduction in plasma lecithin-cholesterol acyltransferase activity (-66%; p<0.001) was found. The situation of hypoglycemia (-18%; p<0.05) was accompanied by lower levels of serum insulin (-45%; p<0.01) and liver glycogen (-30%; p<0.05) in the hypercholesterolemic rats. Furthermore, glucose utilization was altered since lower glucose-6-Pase (-33%; p<0.05) and increased glucokinase (+212%; p<0.001) activities in the liver were found in the rat model of hypercholesterolemia. CONCLUSION: These results provide new evidence that a diet-induced hypercholesterolemia in rats is associated with several adaptative changes in carbohydrate metabolism. These findings may be of importance not only considering the role of western diets on cholesterogenesis, but also in other metabolic disturbances involving lipid and carbohydrate metabolism. |
| Alterations in cell cholesterol content modulate Ca(2+)-induced tight junction assembly by MDCK cells Stankewich, M. C., S. A. Francis, et al. (1996), Lipids 31(8): 817-28. Abstract: Transepithelial electrical resistance (TER), a measure of tight junction (TJ) barrier function, develops more rapidly and reaches higher values after preincubation of MDCK cells for 24 h with 2 microM Lovastatin (lova), an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase. While this effect was attributed to a 30% fall in cholesterol (CH), possible effects of lova on the supply of prenyl group precursors could not be excluded. In the current study, strategies were devised to examine effects on TER of agents that simultaneously lower CH and increase the flux of intermediates through the CH biosynthetic pathway. Zaragozic acid, 20 microM, an inhibitor of squalene synthase known to increase the synthesis of isoprenoids and levels of prenylated proteins, lowered cell CH by 30% after 24 h, while accelerating development of TER in the same manner as lova. TER was also enhanced, despite a 23% increase in the rate of 3Hacetate incorporation into CH, when total CH was reduced by 45% during a 2-h incubation with 2 mM methyl beta-cyclodextrin (MBCD), an agent that stimulates CH efflux from cells. The fact that the rate of TER development was diminished when cell CH content was elevated by incubation with a complex of CH and MBCD is further evidence that this sterol modulates development of the epithelial barrier. Cell associated CH derived from the complex was similar to endogenous CH with respect to its accessibility to cholesterol oxidase. Lova's effect on TER was diminished when 5 micrograms/mL of CH was added to the medium during the last 11 h of incubation with lova. |
| Alterations in cellular cholesterol metabolism following administration of 6-hydroxydopamine to rabbits O'Meara, N. M., R. A. Devery, et al. (1992), Br J Pharmacol 105(2): 495-9. Abstract: 1. The role of adrenergic mechanisms in the regulation of cholesterol metabolism was investigated by studying the effects of 6-hydroxydopamine (6-OHDA) on serum cholesterol levels and on the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-O-acyl-transferase (ACAT) in the livers and intestines, and cholesterol 7 alpha-hydroxylase in the livers of male New Zealand White rabbits. 2. Total serum cholesterol levels were significantly reduced (P less than 0.01) in 6-OHDA-treated animals. This was reflected in the very low density lipoprotein, low density lipoprotein and high density lipoprotein fractions. The reduction in lipoprotein cholesterol levels reflected reduced cholesterol proportions in the lipoprotein fractions. 3. The 6-OHDA-treated animals also had significantly lower activities of intestinal (P less than 0.001) and hepatic (P less than 0.01) HMGCoA reductase. The specific activities of intestinal ACAT, hepatic ACAT and cholesterol 7 alpha-hydroxylase were comparable in both groups. 4. In contrast to the results observed in vivo, 6-OHDA did not have any in vitro effect on cholesterol biosynthesis in cultured human leucocytes. 5. This latter finding suggests that the effects of 6-OHDA on cellular cholesterol biosynthesis in vivo are indirect, possibly resulting from the known toxic effect of this drug in sympathetic nerve terminals, and imply a potential role for the sympathetic nervous system in the regulation of cellular cholesterol biosynthesis in vivo. |
| Alterations in cholesterol metabolism in the genetically hypercholesterolemic RICO rat: an overview Ouguerram, K., T. Magot, et al. (1991), Adv Exp Med Biol 285: 257-74. |