| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of cholesterol content in diet on capillary flow of rat erythrocytes. Part I: geometric and flow characteristics Abugo, O. O., R. R. Peddada, et al. (1997), Clin Hemorheol Microcirc 17(6): 437-43. Abstract: Four different groups of male Fisher rats were placed on one of the following diets for a period of one month: normal (control) diet, high cholesterol (HC) diet, high saturated fat (HF) diet and low fat (LF) diet. Subsequently, blood samples were drawn and washed in phosphate buffered saline (PBS), and the red cells were resuspended in the same buffer. These samples were introduced into a polycarbonate capillary flow system and their flow characteristics observed. In addition, the mean cell volumes (MCV) in isotonic PBS and the maximum swollen cell volume (MCVmax) in hypotonic PBS were determined using a Coulter counter. From these, the mean surface area (MSA) and the excess surface area (ESA) were calculated. It was found that rats on a high cholesterol diet develop erythrocyte geometric characteristics which should contribute to improved capillary flow, namely, a decreased mean cell volume and an increased excess surface area. Nevertheless, in these rats a decreased capillary flow was observed as indicated by an increase in mean cell transit time, MCTT, and an appreciable drop in the number of cells per second passing through the capillary flow system. The flow and geometric properties of the high saturated fat and low fat fed rats did not differ significantly from those of the control group. |
| Effect of cholesterol content in diet on capillary flow of rat erythrocytes. Part II: mechanical properties Peddada, R. R., O. O. Abugo, et al. (1997), Clin Hemorheol Microcirc 17(6): 445-57. Abstract: Erythrocytes from male Fisher 344 rats on a high cholesterol diet (HC) exhibited a decreased ability to flow through capillaries when compared with those on a normal diet (control), a phenomenon which could not be explained by changes in geometric characteristics. To explain these results, changes in capillary-dependent rheological characteristics and intrinsic mechanical properties of red blood cells (RBC) due to diet were calculated. The hematocrit deficit in the capillary with respect to the reservoir was greater in the high cholesterol diet fed rats than in the control ones. This was attributed to an overall decrease in red cell deformability which, in turn, was related to an increase in the membrane shear viscosity, the cytoplasmic viscosity, the membrane shear modulus of elasticity, and the membrane bending rigidity. By an independent calculation, we determined that the shear modulus of elasticity increased with a high cholesterol diet. The changes in both the capillary hematocrit deficit and the shear modulus of elasticity with a high cholesterol diet were found to be statistically significant (p < or = 0.05). |
| Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes Zhou, D., M. Mi, et al. (2001), Wei Sheng Yan Jiu 30(2): 83-5. Abstract: The mechanism of cholesterol deficiency on inhibiting the proliferation of T lymphocytes was investigated on cell membrane fluidity by using fluorescence polarization measurement, 3H-TdR incorporation test and flow cytometer analysis in Jurkat cells, in order to clarify the importance of cholesterol in maintaining the normal function of lymphocytes. The results showed that cell membrane fluidity was increased, cell proliferation was inhibited and blocked on G0/G1 phase in Jurkat cells after being cultured with lovastatin (an inhibitor of rate limiting enzyme for cholesterol synthesis) for 3 days. When the cells were treated with LDL. The changes could be partially buffered. These results suggest that the change of membrane fluidity may be caused by cholesterol deficiency on the proliferation of Jurkat cells. |
| Effect of cholesterol deprivation on piglet small intestine and serum lipids Engelhardt, E. L., M. Sankar, et al. (1991), J Pediatr Gastroenterol Nutr 12(4): 494-500. Abstract: Using the neonatal piglet, the effects of dietary cholesterol deprivation on growth, intestinal enzyme activity, intestinal and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and serum lipid were studied. Six litters of piglets were randomly assigned to one of two feeding regimens: restricted (800 ml of formula/24 h) versus unrestricted (1,200 ml of formula/24 h). Within litters, piglets were separated by sex, then randomly assigned to a formula containing low cholesterol (less than 2 mg/dl) or high cholesterol (145 mg/dl). Piglets were fed for 2 weeks. Male piglets in the restricted low cholesterol group gained significantly less weight per milliliter of formula than the restricted high cholesterol males. No effect was observed in the females. Microvillus membrane lactase activity was greater in males fed a high versus low cholesterol diet. Intestinal and hepatic HMG-CoA reductase activities and serum lipid profiles showed a trend toward compensation for dietary cholesterol deprivation but did not differ statistically between the cholesterol-fed versus -deprived groups. It is concluded that dietary cholesterol deprivation in the male neonatal pig causes alterations in growth, but no other statistically significant responses were detectable in this study. |
| Effect of cholesterol diet on reproductive function in male albino rats Bataineh, H. N. and M. K. Nusier (2005), Saudi Med J 26(3): 398-404. Abstract: OBJECTIVE: The present study was carried out to investigate the effect of cholesterol diet (400 mg/kg body weight) for 60 days on gonadal function in albino rats. METHODS: The study was conducted in the Animal House Unit at Jordan University of Science and Technology, School of Medicine, Irbid, Jordan between October 2003 and February 2004. Adult male and female albino rats of Sprague Dawley strain were raised under controlled temperature and light. Male rats were divided into: a) control group--rats receiving vehicle (olive oil) for 60 days and treatment group--rats receiving cholesterol diet for a reproductive cycle. Animals were weighed and autopsied 24 hours after the last dose. Biochemical and histological approaches were used to assess fertility in both groups. RESULTS: The treatment caused significant reduction (p < or = 0.001) in sperm motility and density in cauda epididymides and testes. A significant reduction (p < or = 0.001) in epithelial cell height of caput, cauda and seminal vesicle was also observed. In the treated group, there was a significant reduction (p<0.001) in seminiferous tubules diameter and Leydig cell nuclear diameter. Spermatocytes (primary and secondary) were significantly decreased (p < or = 0.01) and spermatids were significantly reduced (p < or = 0.001) in the treatment group. Whereas, the number of degenerating Leydig cells (interstitial cells) increased significantly (p < or = 0.001). Serum biochemistry reveals significant increase (p<0.001) in cholesterol and triglyceride levels. The intragastric administration of cholesterol diet to male rats for 60 days significantly reduced the number of females impregnated by these males. However, the number of implantations and number of viable fetuses were significantly (p<0.01) decreased in female rats impregnated by males that ingested cholesterol. On the other hand, the number of resorptions was significantly (p<0.01) increased in females impregnated by males that ingested cholesterol. The histometry and histology of reproductive organs confirm these results. CONCLUSION: Hyperlipidemia can cause alteration in the biochemistry and histometry of reproductive organs and can cause inhibition of spermatogenesis via the Leydig cell. |
| Effect of cholesterol feeding on DNA damage in male and female Syrian hamsters Turley, E., N. C. Armstrong, et al. (1999), Ann Nutr Metab 43(1): 47-51. Abstract: Cholesterol oxides are cytotoxic and have been implicated in many disease processes; however, it has been proposed that cholesterol oxides result from cholesterol acting as a sacrificial antioxidant. In this study, the effect of dietary cholesterol on DNA damage, assessed by the alkaline comet assay, was examined in male and female Syrian hamsters. Animals were fed ad libitum a modified AIN-76 diet (control) or a diet with 0.5% cholesterol for 10 weeks. Following the 10-week feeding period, there was no significant difference in body weight between cholesterol-fed and control animals. Cholesterol feeding resulted in significant liver hypertrophy, and increased plasma total and HDL cholesterol in both male and female animals compared with controls. There was no difference in liver cell DNA damage levels as measured by the comet assay. Heart cells from cholesterol-fed hamsters, however, showed a significant decrease in tail DNA (p = 0.050) indicating decreased damage compared with controls and a possible protective effect of cholesterol against DNA damage. |
| Effect of cholesterol feeding on the compositions of plasma lipoproteins and plasma lipolytic activities in SHRSP Ogawa, H., T. Nioshikawa, et al. (1991), Clin Exp Hypertens A 13(5): 999-1008. Abstract: By cholesterol feeding, atherogenic VLDL, beta-VLDL (IDL) and LDL increased more remarkably in SHRSP than in normotensive WKY, suggesting that hypertension may promote the productions of atherogenic lipoproteins. On the other hand, HDL significantly decreased in SHRSP, which was associated with the decrease in apoA-I and E in the HDL fraction. This indicates the decreases of two HDL subfractions, apoE HDL and apoA-I HDL, in SHRSP. These decreases of HDL subfractions in SHRSP may be closely related to the higher h-TGL activity in SHRSP than in WKY, and could be a trigger of the excess production of atherogenic lipoproteins. |
| Effect of cholesterol feeding on the susceptibility of lipoproteins to oxidative modification Nenseter, M. S., O. Gudmundsen, et al. (1994), Biochim Biophys Acta 1213(2): 207-14. Abstract: In previous studies we have shown that the liver endothelial and Kupffer cells in hypercholesterolemic rabbits are very active in endocytosis of low-density lipoprotein (LDL) and beta-very-low-density lipoprotein (beta-VLDL) (Nenseter et al. (1992) J. Lipid Res. 33, 867-877; Gudmundsen et al. (1993) J. Lipid Res. 34, 589-600). These data raised the question whether subfractions of LDL and beta-VLDL were modified in vivo to forms recognized by the scavenger/oxidized LDL receptors of the non-parenchymal liver cells. The purpose of the present study was to address this question by assessing the effect of cholesterol feeding on the susceptibility of the lipoproteins to oxidative modification in vitro. In addition, the effect of HDL on the lipid peroxidation of LDL was evaluated. LDL and beta-VLDL were isolated from rabbits given a diet supplemented with cholesterol (2% w/w) for 3 weeks. The extent of Cu(2+)-catalyzed oxidation of the lipoproteins was compared with that of LDL from control-fed rabbits. Extent of oxidation assessed by formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, relative electrophoretic mobility and uptake of lipoproteins by J774 macrophages suggested that LDL and beta-VLDL from the hypercholesterolemic rabbits were more susceptible to oxidation than LDL from normolipidemic rabbits. HDL protected LDL and beta-VLDL from lipid peroxidation in vitro. Taken together, the increased susceptibility of LDL and beta-VLDL to oxidative modification in vitro, combined with the low levels of alpha-tocopherol, and the reduced ratio of HDL to LDL cholesterol observed in the hypercholesterolemic rabbits, and the protective effect of HDL on the lipid peroxidation of LDL, support the probability that oxidative modification of LDL and beta-VLDL occur in vivo in the hypercholesterolemic rabbits. |
| Effect of cholesterol in bile on cholecystokinin receptor in the gallbladder Fu, H., W. Wu, et al. (2002), Zhonghua Wai Ke Za Zhi 40(10): 786-8. Abstract: OBJECTIVE: To assess the effect of cholesterol in bile on cholecystokinin receptor (CCK-R) in the gallbladder. METHODS: One hundred Guinea pigs were randomly divided into four groups, 25 animals for each. The control group was fed a standard diet, and the cholesterol group fed a diet containing 2% cholesterol. After taking the 2% cholesterol diet for two weeks, the natural group persisted on the standard diet, and the treated group was perfused by traditional Chinese medicine. Serum cholecystokinin (CCK) level in the portal vein and maximal binding capacity (B(max)) and Kd of CCK-R in the gallbladder were measured in the four groups by RIA and RBA, and the concentrations of cholesterol in bile were also observed. RESULTS: Compared with the control group, after high-cholesterol feeding for two weeks, the gallbladder emptying rate (65.83 +/- 7.32)% approximately (47.22 +/- 5.24)% and B(max) of CCK-R (60 +/- 27) approximately (32 +/- 13) fmol/mg protein and in decreased fasting gallbladder volume (FV) (0.89 +/- 0.26) approximately (1.34 +/- 0.61) cm(3) and concentration of cholesterol (0.44 +/- 0.11) approximately (0.60 +/- 0.13) mmol/L in bile increased, but no change was in the serum CCK level and Kd of CCK-R in the cholesterol group. Compared with the natural group, after two-week in take of herb decoction of qingre lidan and liqi huoxue, FV (1.27 +/- 0.60) approximately (0.90 +/- 0.27) cm(3), RV (0.85 +/- 0.45) approximately (0.32 +/- 0.12) cm(3), FB (0.92 +/- 0.35) approximately (0.73 +/- 0.21) cm(3), RB (0.76 +/- 0.34) approximately (0.29 +/- 0.08) cm(3) in the treated group decreased significantly; but gallbladder emptying rate (43.06 +/- 4.27)% approximately (67.01 +/- 6.82)% increased significantly. The concentration of cholesterol in bile was lower in the treated group than in the natural group (0.59 +/- 0.14) approximately (0.43 +/- 0.10) mmol/L, but no change was found in the serum CCK level. Bmax of CCK-R in the treated group increased significantly (39 +/- 19) approximately (59 +/- 11) fmol/mg protein, Kd of CCK-R showed no significant changes between the treated group and natural group. CONCLUSION: High cholesterol in gallbladder bile causes defective muscle contraction by down-regulating CCK-R in the gallbladder, so the reduction of cholesterol concentration of bile may contribute to gallbladder contraction. |
| Effect of cholesterol in various liposomal compositions on the in vivo toxicity, therapeutic efficacy, and tissue distribution of amphotericin B Ahmad, I., A. K. Sarkar, et al. (1990), Biotechnol Appl Biochem 12(5): 550-6. Abstract: The effect of cholesterol in neutral, positively and negatively charged liposomes on the toxicity, therapeutic efficacy, and alteration in the tissue distribution pattern of amphotericin B (Amp-B) in normal and infected mice was studied. It was observed that inclusion of cholesterol (CHOL) into egg phosphatidylcholine (EPC) liposomes increased the LD50 of Amp-B from 5.3 to 8.5 mg/kg body weight. In the case of phosphatidylserine (PS) liposomes as well as stearylamine (SA) liposomes, cholesterol incorporation had no effect in altering the toxicity of the drug. The survival pattern of animals with all types of liposomal formulation of Amp-B was similar. The tissue distribution studies indicated that in the case of normal mice, cholesterol inclusion in all types of liposomes increased the organ concentration of the drug in various tissues. In infected animals, the concentration of Amp-B in all organs was increased when cholesterol was included in EPC and EPC/PS liposomes. The organ concentration of Amp-B in lung and liver after 1 h of injection was the same in the case of EPC/SA and EPC/SA/CHOL liposomes. Considering the observations on toxicity, therapeutic efficacy, and tissue distribution, it was suggested that cholesterol had a beneficial therapeutic effect on neutral EPC liposomes. |
| Effect of cholesterol levels on villous histology in colonic adenomas Houghton, J., G. G. Lardieri, et al. (2000), Dig Dis Sci 45(5): 896-9. Abstract: To date no studies have examined the relationship between cholesterol levels and the occurrence of specific colonic polyp histologies. Villous histology has a greater predilection for subsequent malignancies than other histologies. Consequently, we examined the effect of cholesterol levels on the occurrence of villous adenomas. Just under one in 10 (9.5%, 15/158) patients had polyps with villous histologies. Cholesterol levels were positively and nonlinearly associated with a greater likelihood of villous histology, suggesting that a threshold exists for the effect of cholesterol level on the likelihood of having polyps with villous histology odds ratios (OR) for combined two variable quadratic effect: cholesterol OR, 1.18; 95% confidence interval (CI), 1.02-1.37 and cholesterol squared OR, 1.004; 95% CI, 1.00-1.02. Our data suggest that, in patients with polyps, higher cholesterol levels increase the likelihood of having polyps with villous histology, but that the effect of cholesterol level reaches a threshold. |
| Effect of cholesterol liposomes on calcium mobilization in muscle cells from the rabbit sphincter of Oddi Wang, X. J., J. G. Wei, et al. (2002), World J Gastroenterol 8(1): 144-9. Abstract: AIM: To analyze the influence of cholesterol liposome on the Ca2+ mobilization of cultured muscle cells in the rabbit sphincter of Oddi's. METHODS: New Zealand rabbit was sacrificed and the sphincter of Oddi (SO) segment was obtained aseptically. The SO segment was cut into pieces and cultured in DMEM solution. Then the smooth muscle cells were subcultured, and the 4th-7th passage cells were used for further investigation. The intracellular Ca2+ increase was measured under confocal microscope after the addition of 20 mmol x L(-1) KCl, 10(-7) mol x L(-1) acetylcholine and 10(-7) mol x L(-1) cholecystokinin, and different antagonists were added to analyze the Ca2+ mobilization pathway. After the cells were incubated with 1g x L(-1) cholesterol liposome (CL)(molar ratio was -2:1), the intracellular Ca2+ increase was measured again to determine the effect of CL on cellular Ca(2+) mobilization. RESULTS: The resting cellular calcium concentration of cultured SO cell was 108+/-21 nmol x L(-1).The intracellular Ca2+ increases induced by 20 mmol x L(-1) KCl, 10(-7) mol x L(-1) ACh and 10(-7) mol x L(-1) CCK were 183+/-56% 161+/-52% and 130+/-43%, respectively. When the extracellular Ca2+ was eliminated by 2 mmol x L(-1) EGTA and 5 micromol x L(-1) verapamil, the intracellular Ca2+ increases induced by KCl, ACh and CCK were 20+/-14%,82+/-21% and 104+/-23%, respectively. After the preincubation with heparin, the Ca2+ increases were 62+/-23% and 23+/-19% induced by ACh and CCK, as for preincubation with procaine they were 72+/-28% and 85+/-37% induced by ACh and CCK, respectively. Pretreatment with CL for 18 h, the resting cellular Ca2+ concentration elevated to 152+/-26 nmol x L(-1), however, the cellular Ca2+ increase percentages in response to these agonists were 67+/-32%,56+/-33% and 34+/-15%. CONCLUSION: KCl elicit the SO cellular Ca2+ increase depends on influx of extracellular Ca2+, ACh evoked the SO cellular Ca2+ increase is through the mobilization of intracellular Ca2+ pool and influx of extracellular Ca2+ as well, CCK excites the SO cells mainly through mobilization of intracellular IP3-sensitive Ca2+ store. After the incorporation with cholesterol liposome, KCl,ACh and CCK induced cellular Ca2+ increase percentages decreased. |
| Effect of cholesterol lowering and cardiovascular risk factors on the progression of aortoiliac arteriosclerosis: a quantitative cineangiography study Campeau, L., J. Lesperance, et al. (2005), Angiology 56(2): 191-9. Abstract: The post-Coronary Artery Bypass Graft (Post-CABG) trial has shown that aggressive compared to moderate lowering of low-density lipoprotein cholesterol (LDL-C) delayed the progression of obstructive disease in aortocoronary saphenous vein grafts and in the left main coronary artery. Patients had been allocated to high-and low-dose lovastatin therapy for a 4-5 year period. The present study evaluated the effect of LDL-C lowering and the role of cardiovascular risk factors on the progression of arteriosclerosis in the distal abdominal aorta and common iliac arteries. From one of the participating centers of the post-CABG trial, 145 patients who had adequate imaging of the aortoiliac arteries at baseline and follow-up were included. Angiographic outcomes, presumed to reflect progression of arteriosclerosis and obtained from lumen diameter (LD) measurements using quantitative cineangiography, were as follows: significant decrease of the minimum lumen diameter (LD) and increase of the maximum LD, percent lumen stenosis, and percent lumen dilatation. These outcomes were not significantly less frequent in patients randomly allocated to aggressive compared to moderate LDL-C lowering. Of 9 cardiovascular risk factors, only 2 were significantly related to progression of aortoiliac arteriosclerosis. Current smoking predicted both percent lumen stenosis increase and, to a lesser degree, percent lumen dilatation increase (p = 0.010 and p = 0.055, respectively). Abnormally high body mass index (BMI > or = 25 kg/m2) correlated with percent lumen dilatation increase (p = 0.006). Aggressive compared to moderate LDL-C lowering did not prevent or delay the progression of aortoiliac arteriosclerosis. Smoking predicted both lumen narrowing and dilatation presumably caused by arteriosclerosis. Abnormally high BMI, reflecting overweight or obesity, was strongly associated with vessel dilatation. |
| Effect of cholesterol lowering on intravascular pools of TFPI and its anticoagulant potential in type II hyperlipoproteinemia Hansen, J. B., K. R. Huseby, et al. (1995), Arterioscler Thromb Vasc Biol 15(7): 879-85. Abstract: Tissue factor pathway inhibitor (TFPI) inhibits the extrinsic coagulation system. A major pool of TFPI is associated with the vascular endothelium and can be mobilized into the circulation by heparin. In circulating blood, TFPI is mainly associated with LDL (80%), whereas 10% to 20% is carrier free. In this study, heparin administration caused a 2.2-fold and a 7.5-fold increase in TFPI activity and TFPI antigen, respectively, in 25 patients with phenotypes IIa and IIb hyperbetalipoproteinemia. Because the antigen determination of TFPI almost exclusively measures carrier-free TFPI, more than 90% of the heparin-induced increase in TFPI activity was caused by mobilization of carrier-free TFPI from the vascular endothelium. Therapeutic lowering of total cholesterol (a decrease of 31.1 +/- 11.6%, P <.001) by 40 mg/d lovastatin in 17 patients with hyperbetalipoproteinemia was accompanied by a parallel decrease in TFPI activity (of 27.7 +/- 24.2%, P <.001) because of a reduction in LDL-TFPI complexes. However, drug intervention did not affect carrier-free TFPI or the magnitude of the vascular pool of TFPI that could be mobilized into the circulation by heparin. Moreover, this reduction of LDL-TFPI complexes did not reduce the anticoagulant potency of TFPI in plasma or of the vascular endothelial pool. The results of this study may imply that the anticoagulant potency of TFPI is associated with its carrier-free form in plasma or on the endothelium and that downregulation of LDL affects neither the size nor the anticoagulant potency of the endothelial pool of TFPI. |
| Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms Mansur, A. P., C. V. Serrano, Jr., et al. (1999), Heart 82(6): 689-93. Abstract: AIM: To assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms. METHODS: 43 non-diabetic patients aged 43-61 years, with total serum cholesterol concentrations of more than 7.75 mmol/l, positive exercise tests, and normal coronary angiograms, were started on the American Heart Association step 1 diet. After 12 weeks these patients were randomly assigned to treatment for another 16 weeks with the diet alone (diet group, n = 20) or with the diet plus lovastatin or simvastatin (statin group, n = 23). After this 28 week run in period, statins were withdrawn and lipid profile tests and exercise tests were done and repeated 20 weeks later. RESULTS: At week 28, the statin group but not the diet group had significant reductions from baseline (week 12) in plasma total cholesterol (p < 0.0001), low density lipoprotein (p < 0.0001), and triglyceride (p < 0.0001). The number of patients with positive exercise tests decreased from 23 to three in the statin group and from 20 to 15 in the diet group (p = 0.01). After the final 20 weeks without statins, lipid profiles returned to baseline levels in all 17 patients remaining in the statin group, and exercise tests were again positive in 15 of these patients. CONCLUSIONS: In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing. |
| Effect of cholesterol on apolipoprotein A-I binding to lipid bilayers and emulsions Saito, H., Y. Miyako, et al. (1997), J Lipid Res 38(2): 287-94. Abstract: The effects of cholesterol (Chol) on the interaction of apolipoprotein A-I (apoA-I) with phospholipid bilayer vesicles and lipid emulsions were investigated. ApoA-I bound to phosphatidylcholine (PC) vesicles with higher affinity and lower capacity compared to triglyceride-PC emulsions. An increase in surface Chol in triglyceride-PC emulsions decreased the binding capacity without changing the binding affinity. In contrast, addition of Chol to PC vesicles caused a marked increase in capacity and decrease in affinity for apoA-I binding. ApoA-I caused a large release of entrapped aqueous dye, calcein, from PC vesicles, whereas this apoA-I-induced leakage was relatively small in the vesicles containing Chol. The incorporation of phosphatidylethanolamine into the vesicles also exerted effects similar to those of Chol on apoA-I binding and calcein leakage. The shifts of fluorescence emission maximum of dansyl lysine, probing the surface region of membranes, indicated that Chol as well as phosphatidylethanolamine increased the headgroup space of the vesicles. The binding maximum of apoA-I was closely correlated with the emission maximum of dansyl lysine, not with the fluorescence anisotropy of I-4-(trimethylamino)phenylphenylhexatriene, suggesting that the binding capacity of apoA-I to the bilayer surface was modulated by the headgroup space rather than the acyl chain fluidity. These results show that Chol affects the bilayer surface so as to allow more apoA-I to bind to bilayers and may suggest the possibility of the interaction of apoA-I with Chol-enriched membrane domains. |
| Effect of cholesterol on bilayer location of the class A peptide Ac-18A-NH2 as revealed by fluorescence resonance energy transfer Gorbenko, G., T. Handa, et al. (2003), Eur Biophys J 32(8): 703-9. Abstract: An amphipathic class A peptide, Ac-18A-NH(2), has been employed in modeling the alpha-helical lipid-binding site of apolipoprotein A-I (apoA-I). To gain insight into the nature of protein-lipid interactions responsible for the ability of apoA-I to promote the efflux of intracellular cholesterol, the peptide disposition in model membranes composed of phosphatidylcholine (PC) and its mixture with cholesterol (Chol) has been characterized. By examining resonance energy transfer between the peptide Trp as a donor and anthrylvinyl-labeled PC as an acceptor it was found that Chol inclusion is conducive to shallower bilayer location of the Ac-18A-NH(2) alpha-helix. The limits for the Trp distance from the membrane center were estimated to be 1.5-1.7 nm (PC) and 1.9-2.1 nm (PC:Chol), indicating that in the PC bilayer the Trp resides at the level of the glycerol backbone and carbonyl groups while the region of the phosphocholine moieties is preferable for Trp location in the PC:Chol bilayer. These findings suggest that Chol can modulate the interactions between apoA-I and membrane lipids via reducing the depth of alpha-helix bilayer penetration. |
| Effect of cholesterol on egg yolk phosphatidylcholine peroxidation in multilamellar liposomes Filipek, J., D. Uhrikova, et al. (2001), Pharmazie 56(12): 953-7. Abstract: Lipid peroxidation of aerated multilamellar liposomes composed of egg yolk phosphatidylcholine (EYPC) and cholesterol (CHOL) at molar ratios CHOL:EYPC = 0, 0.1, 0.2, 0.3, 0.4, 0.6 and 1.0 was studied during autooxidation and during Fe2+/H2O2-induced peroxidation by following the formation of conjugated diene and thiobarbituric acid reactive substances. The presence of cholesterol in the fluid lipid bilayers has an inhibiting effect on the EYPC peroxidation in the propagation phase of both the autooxidation and Fe(2+)-induced peroxidation free radical chain reactions. This inhibiting effect increases with the increase in CHOL:EYPC molar ratio. The inhibition of EYPC peroxidation by cholesterol probably originates a) from the increased lateral separation of polyunsaturated EYPC acyl chains caused by insertion of cholesterol between EYPC molecules, b) from the increased molecular packing of both the bilayer polar and hydrophobic regions due to the reduced bilayer hydration, and c) from the antioxidant properties of cholesterol. |
| Effect of cholesterol on interaction of dibucaine with phospholipid vesicles: a fluorescence study Mondal, M., K. Mukhopadhyay, et al. (2001), Biochim Biophys Acta 1511(1): 146-55. Abstract: Interaction of the local anesthetic dibucaine with small unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) and dioleoyl phosphatidylcholine (DOPC) containing different mol percents of cholesterol has been studied by fluorescence spectroscopy. Fluorescence measurements on dibucaine in presence of phospholipid vesicles containing various amounts of cholesterol yielded a pattern of variation of wavelength at emission maximum and steady-state anisotropy which indicated that the microenvironment of dibucaine is more polar and flexible in membranes that contain cholesterol than in membranes without cholesterol. Experiments on quenching of fluorescence from membrane-associated dibucaine by potassium iodide showed a marked increase in quenching efficiency as the cholesterol content of the vesicles was increased, demonstrating increased accessibility of the iodide quenchers to dibucaine in the presence of cholesterol, when compared to that in its absence. Total emission intensity decay profiles of dibucaine yielded two lifetime components of approximately 1 ns and approximately 2.8--3.1 ns with mean relative contributions of approximately 25 and approximately 75%, respectively. The mean lifetime in vesicles was 20--30% smaller than in the aqueous medium and showed a moderate variation with cholesterol content. Fluorescence measurements at two different temperatures in DMPC SUVs, one at 33 degrees C, above the phase transition temperature and another at 25 degrees C, around the main phase transition, indicated two different mode of dibucaine localization. At 25 degrees C dibucaine partitioned differentially in presence and absence of cholesterol. However, at 33 degrees C the apparent partition coefficients remained unaltered indicating differences in the microenvironment of dibucaine in presence and absence of cholesterol in the phospholipid membranes. |
| Effect of cholesterol on miscibility and phase behavior in binary mixtures with synthetic ceramide 2 and octadecanoic acid. Infrared studies Chen, H., R. Mendelsohn, et al. (2001), Biochim Biophys Acta 1512(2): 345-56. Abstract: The three main lipid components of the stratum corneum, namely ceramides, free fatty acids and cholesterol, play a fundamental role in the maintenance of the skin barrier. The current investigation is aimed toward understanding the miscibility and intermolecular interactions of these lipids. Toward this end, Fourier transform infrared spectroscopic studies of the three possible equimolar binary mixtures of cholesterol, a synthetic non-hydroxylated fatty acid N-acyl sphingosine with a C18 chain length (N-stearoylsphingosine, approximating human ceramide 2), and stearic acid were undertaken. The thermotropic responses of the methylene stretching and scissoring vibrations were used to evaluate chain conformation and packing respectively. Selective perdeuteration, of either the stearic acid or the ceramide acid chains, permitted separate and simultaneous evaluation of the conformational order and packing properties of the sphingosine chain, the amide linked fatty acid chains and/or the stearic acid chain. Whereas cholesterol mixed well with ceramide at physiological temperatures, the stearic acid was miscible with the cholesterol only at relatively high temperatures where the fatty acid is disordered. A complex interaction between stearic acid and ceramide was detected. A separate fatty acid-rich phase persisted until at least 50 degrees C, whereas at higher temperatures the components appear to be quite miscible. However, a preferential association of the fatty acid with the ceramide base chain is indicated. None of the binary systems studied exhibit miscibility and interactions resembling those in the ternary mixtures of these substances, which is widely used to model stratum corneum. The role of cholesterol in controlling the miscibility characteristics in the ternary system is evident. |