| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of gemfibrozil in men with primary isolated low high-density lipoprotein cholesterol: a randomized, double-blind, placebo-controlled, crossover study Miller, M., P. S. Bachorik, et al. (1993), Am J Med 94(1): 7-12. Abstract: PURPOSE: To evaluate the efficacy of gemfibrozil in men with primary isolated low high-density lipoprotein cholesterol (HDL-C) levels. PATIENTS AND METHODS: Fourteen men with low levels of HDL-C but desirable total cholesterol levels received gemfibrozil in a randomized, double-blind, placebo-controlled, crossover trial. The men were placed on a National Cholesterol Education Program Step-Two Diet. They were randomly assigned to receive placebo and gemfibrozil each for 3 months, with a 1-month washout period between phases. RESULTS: Overall, gemfibrozil increased the total HDL-C concentration by 9.2% (p = 0.001), reduced triglyceride (TG) levels by 38% (p < 0.01), and significantly lowered the total cholesterol:HDL-C ratio (p = 0.01). Those with fasting TG levels of 1.07 mmol/L (95 mg/dL) or greater had a significant elevation in the HDL-C level (14.6%, p = 0.005) and a reduction in TG levels (50%, p = 0.002) with gemfibrozil; those with fasting TG levels less than 1.07 mmol/L had a smaller increase in the HDL-C level (4.1%, p > 0.05) and a smaller reduction in TG levels (15%, p = 0.02). There were no significant differences in the plasma levels of low density lipoprotein-cholesterol, HDL2-C, apolipoproteins (apo) A-I and B, or Lp(a). HDL3-C and apo A-II levels rose slightly. The adverse effects attributable to gemfibrozil were minimal. CONCLUSION: In men with desirable total cholesterol levels, gemfibrozil raises HDL-C and lowers TG levels to a similar extent as reported for hyperlipidemic men in the Helsinki Heart Study. These lipid-altering effects were most pronounced in those with the highest fasting TG levels. |
| Effect of germinated and heated soybean meals on plasma cholesterol and triglycerides in rats Chandrasiri, V., H. M. Bau, et al. (1990), Reprod Nutr Dev 30(5): 611-8. Abstract: Soybean may be useful in diets for the prevention of cardiovascular disease and the treatment of type II hyperlipoproteinemia as it lowers blood cholesterol levels. However, unpleasant organoleptic qualities and the presence of antinutritional substances hinder its use. Some of these problems may be partially solved by germinating the seeds or heating the meals. The effects of the duration of soybean germination and of heating the meal were studied in Wistar rats. Dietary meal composition, plasma cholesterol and triglyceride levels were evaluated after feeding rats with various soybean meal or casein diets containing 10% protein for 6 weeks. Plasma cholesterol and triglyceride levels were 0.81 +/- 0.11 and 0.82 +/- 0.23 g/l respectively after the casein diet and 0.90 +/- 0.10 and 0.51 +/- 0.17 g/l after the raw soybean diet. Soybean germination had a hypercholesterolemic effect (1.05 +/- 0.11 g/l after 5 d). Heating the raw meal or germinated soybean meal did not affect cholesterol levels, though it suppressed the hypotriglyceridemic effect. The triglyceride-lowering effect of soybean was probably caused by the presence of thermolabile substances or by the quantity of food ingested. The unexpected increase in blood cholesterol levels may have been due to the effect of the low dietary protein levels. |
| Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults Beentjes, J. A., A. van Tol, et al. (2000), J Lipid Res 41(6): 925-32. Abstract: The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are unknown. We carried out a 6 months study in 24 GH-deficient adults who were randomized to placebo (n = 8), low dose GH (1 U daily, n = 8), and high dose GH (2 U daily, n = 8), followed by a 6 months open extension study with high dose GH (1 drop-out). No significant changes in plasma lipoproteins, LCAT, CETP, and PLTP activities, cholesterol esterification (EST) and cholesteryl ester transfer (CET) were observed after placebo. After 6 months of GH (combined data, n = 24), very low + low density lipoprotein (VLDL + LDL) cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) decreased, whereas HDL cholesterol and HDL cholesteryl ester increased (P < 0. 05). Prolonged treatment showed comparable effects. Plasma apolipoprotein A-I and Lpa remained unchanged. Plasma LCAT (P < 0. 01) and CETP activities (P < 0.01), as well as EST (P < 0.01) and CET decreased (P < 0.01) after 12 months of GH (n = 15), but PLTP activity did not significantly change. Changes in EST and CET after 12 months of treatment were independently related to changes in plasma LCAT (P = 0.001 and CETP activity (P = 0.01). In conclusion, GH replacement therapy improves the lipoprotein profile in GH-deficient adults. Chronic GH replacement lowers plasma LCAT and CETP activities, contributing to a decrease in cholesterol esterification and cholesteryl ester transfer. These effects may have consequences for HDL metabolism and reverse cholesterol transport. |
| Effect of habitual physical activity on physical fitness and serum cholesterol in middle-aged male workers Kushima, K., M. Ohtaki, et al. (1994), Nippon Koshu Eisei Zasshi 41(4): 341-51. Abstract: The effects of habitual physical activity on physical fitness parameters and serum cholesterol profile were studied in middle-aged male workers. The subjects were 3376 middle-aged men (age: 30-59 yrs) who worked at two enterprises in HIROSHIMA Prefecture. As for physical fitness parameters, grip strength, vertical jump, side step, and step test scores were measured. Atherogenic index was calculated as (total Chol-HDL Chol)/(HDL Chol). Because daily physical activity mainly consists of physical activities during leisure time and working time, by using a questionnaire, physical activity during leisure time was assessed and categorized by frequency into three categories: 'frequently', 'sometimes', and 'seldom': and physical activity during work was categorized as 'high' or 'low' according to the average walking time per day during work. The effect of these physical activities on physical fitness parameters and serum cholesterol profile was evaluated by analysis of covariance (PC-SAS: GLM procedure) adjusting for several confounding factors such as age, body mass index, type of job, smoking and drinking habits. The main results are summarized as follows: 1) Physical activity during leisure time was positively related to vertical jump, side step, and step test score, independent of physical activity during working time, and 2) physical activity during leisure time was negatively associated to LDL-C and AI in the group with 'low' physical activity during work. These results show that in middle-aged male workers, even moderate or light physical activity during leisure time has some beneficial health promoting effects through changes in physical fitness and serum cholesterol profile. |
| Effect of Helicobacter pylori eradication on high-density lipoprotein cholesterol Scharnagl, H., M. Kist, et al. (2004), Am J Cardiol 93(2): 219-20. Abstract: We examined the effect of Helicobacter pylori (H. pylori) eradication on lipids and apolipoproteins in 87 patients with duodenal ulcers. A significant increase was observed in high-density lipoprotein (HDL) cholesterol (+24.7%, p <0.001), apolipoprotein AI (+9.0%, p <0.001), and apolipoprotein AII (+11.7%, p <0.001) after eradication. Minor increases occurred in total cholesterol, triglycerides, and apolipoprotein B, whereas low-density lipoprotein cholesterol remained unchanged. Our results suggest that chronic H. pylori infection reduces plasma levels of HDL cholesterol and that eradication improves the lipoprotein pattern. |
| Effect of high dietary cholesterol on gentamicin-induced nephrotoxicity in rabbits Abu-Spetan, K. A. and A. A. Abdel-Gayoum (2001), Arch Toxicol 75(5): 284-90. Abstract: Administration of gentamicin to rabbits intramuscularly at a dose of 80 mg/kg per day for 5 days induced nephrotoxicity exhibited by significantly (P < 0.001) elevated serum urea and creatinine levels and a significant (P < 0.001) decrease in renal cortical alkaline phosphatase (ALP) activity, in addition to tubular necrosis revealed by the histopathological examination of the kidney cortices. The deranged parameters returned to normal within 1 week of drug withdrawal, except the cortical ALP activity, which was still significantly lower compared to control. In contrast, feeding of 2% cholesterol-supplemented diet (CSD) to the rabbits for 15 days did not produce any nephrotoxic effects. However, the concurrent feeding of CSD for 15 days and gentamicin treatment at a dose of 80 mg/kg per day for 5 days, starting from day 10 of feeding, resulted in extensive nephrotoxic effects which were more severe than those observed with the gentamicin alone, with delayed recovery of the injured kidney following drug withdrawal. Gentamicin treatment produced significant elevation in serum total cholesterol, which was greater in animals fed with CSD. The serum triglyceride levels in the groups injected with gentamicin were also significantly greater than their respective controls. However, the serum phosphlipids were significantly reduced with gentamicin treatment and this reduction was greater in animals fed with cholesterol and treated with the drug. The liver cholesterol contents in animals fed with the CSD were significantly higher than those fed with the plain diet. However, the kidney cortices of the animals injected with the gentamicin showed significantly increased total phospholipid contents compared to their respective controls. On the other hand, the liver function was not altered in any of the experimental groups. In summary, the present results suggest that cholesterol feeding exacerbated the gentamicin-induced nephrotoxicity. Moreover, it delayed the period required by the injured kidney to recover back to normal. However, neither gentamicin treatment nor cholesterol feeding, or both together, had any injurious effects on the liver. |
| Effect of high fat diets with and without cholesterol on erythrocyte and tissue fatty acids in rats Hariharan, K. and P. L. Raina (1996), Nahrung 40(6): 325-30. Abstract: Male weanling wistar rats were fed synthetic diets containing 20% safflower oil (SFO) or palm oil (PO) with and without cholesterol for a period of six weeks. Erythrocyte membranes were isolated and their fatty acid composition were determined at the end of the experiment. Besides the fatty acid composition of the kidney and spleen lipids were also determined. Erythrocyte membrane, kidney fatty acids of rats fed safflower oil (SFO) had in the majority of variants a higher level of n-6 fatty acids when compared to palm oil group. However, in the spleen, the level of n-6 fatty acids in the palm oil groups were higher than in the safflower oil group. In general the arachidonic acid 20:4 (n-6) levels were higher in the spleen and erythrocytes particularly in the cholesterol fed groups when compared to the kidney levels. Palm oil fed rats had a higher level of palmitic (16:0) and oleic 18:1 (n-9) acids. Rats fed diets containing cholesterol significantly reduced the level of stearic (18:0) but increased the level of oleic 18:1 (n-9), linoleic 18:2 (n-3), and arachidonic acids 20:4 (n-6). The ratios such as 18:1 (n-9)/18:2 (n-6), 18:1 (n-9)/18:0, 18:2 (n-6)/20:4 (n-6) and 20:4 (n-6)/18:2 (n-6) are all indicative of the normal activity of enzymes involved in the desaturation and elongation. Thus these studies indicate that addition of cholesterol can modify the fatty acid composition in erythrocytes, kidney and spleen lipids. |
| Effect of high glucose concentration on collagen synthesis and cholesterol level in the phenotypic modulation of aortic cultured smooth muscle cells of sand rat (Psammomys obesus) Aouichat Bouguerra, S., Y. Benazzoug, et al. (2004), Exp Diabesity Res 5(3): 227-35. Abstract: To simulate diabetic conditions, the effects of high glucose concentration on collagen synthesis and cholesterol level in cultured aortic smooth muscle cells of Psammomys were investigated. For collagen biosynthesis, smooth muscle cells (SMCs) were incubated in synthetic proliferative phase and in postconfluent phase with 3H-proline. Cellular cholesterol was determined by enzymatic method. Under high glucose concentration, the results showed morphological modifications characterized by morphometric cellular, nuclear, and nucleolar changes. In biochemical studies, the authors observed an increase of free and esterified cellular cholesterol as well as of total proteins, collagen biosynthesis, and alpha1 (I+III) and alpha2 (I) chains of collagen contained in the SMCs and in the extracellular matrix. These results showed the sensitivity of Psammomys aortic SMCs to high glucose concentration and would constitute an interesting cellular model to study atherosclerosis pathogeny in experimental diabetes. |
| Effect of high plant sterol-enriched diet and cholesterol absorption inhibitor, SCH 58235, on plant sterol absorption and plasma concentrations in hypercholesterolemic wild-type Kyoto rats Batta, A. K., G. Xu, et al. (2005), Metabolism 54(1): 38-48. Abstract: BACKGROUND AND AIMS: Plant sterols are widely distributed in human diet but are poorly absorbed so that their plasma levels are very low. However, when fed in large amounts, they lower plasma cholesterol levels by interfering with cholesterol absorption. We have studied the effect of 4 weeks of feeding a chow diet supplemented with 1% plant sterols brassicasterol (6.3%), campesterol (28.5%), stigmasterol (15.6%) and sitosterol (49.6%), with or without SCH 58235 (a derivative of ezetimibe), 30 mg/kg per day, known to suppress intestinal cholesterol absorption, on plasma, tissue, biliary, and fecal sterols in Wistar and wild-type Kyoto (WKY) rats, and their metabolism by intestinal bacteria. METHODS: After 2 weeks of feeding control or experimental diet, rats were given 3alpha-(3)Hsitosterol intravenously and 4-(14)Csitosterol by mouth, and blood was collected after 1, 2, 3, and 5 days after labeling to determine sitosterol absorption. Feces were collected during the last 3 days and freeze dried. At the end of feeding, bile fistulas were created in 3 rats of each strain and bile was collected for 1 hour. All rats were then sacrificed and plasma and liver were collected for sterol measurements and activities of hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and cholesterol 27-hydroxylase. RESULTS: Wild-type Kyoto rats were hypercholesterolemic compared to Wistar rats and had increased plant sterols in the plasma. Plasma cholesterol tended to be lower in WKY rats after feeding with plant sterol-enriched diet whereas plant sterol levels rose to approximately 31% of plasma sterols in WKY and 14% in Wistar rats. However, brassicasterol and stigmasterol, with a double bond at C-22, constituted less than 3.5% of total plasma plant sterols. After feeding, biliary plant sterols increased 2.25-fold in Wistar and 1.5-fold in WKY rats, suggesting less hepatic clearance in WKY rats. SCH 58235 feeding significantly increased plasma as well as biliary cholesterol levels in both the untreated and plant sterol-fed WKY rats, and the plasma plant sterols showed a tendency to increase but did not reach significant level. Intestinal bacteria in both rat strains metabolized all plant sterols to mainly the 5beta-H-stanols. However, the C-22 double bond was stable to bacterial degradation. Intestinal absorption of sitosterol and cholesterol was increased 1.5- and 1.3-fold, respectively, in the WKY rats as compared to the Wistar rats, and plant sterol feeding lowered absorption of these sterols in both strains. Absorption of both these sterols was also lowered in SCH 58235-treated rats in both strains and was further lowered when SCH 58235 and plant sterols were simultaneously fed. The activity of the rate-limiting enzyme, HMG-CoA reductase, was increased 1.57-fold in Wistar rats and 1.27-fold in WKY rats that were fed plant sterols as compared to untreated rats. CONCLUSIONS: (1) Plant sterol absorption was increased whereas hepatic elimination of all sterols was diminished in WKY rats accounting for elevated cholesterol and plant sterol levels. (2) The 1% plant sterol-enriched diet tended to lower plasma cholesterol levels whereas SCH 58235 feeding significantly increased plasma cholesterol levels in the WKY rats. (3) Intestinal absorption of sterols with C-22 double bond is diminished and the side-chain double bond is resistant to intestinal bacteria. |
| Effect of high-density lipoprotein cholesterol levels on carotid artery geometry in a Mediterranean female population De Michele, M., A. Iannuzzi, et al. (2004), Eur J Cardiovasc Prev Rehabil 11(5): 403-7. Abstract: BACKGROUND: Controversy remains on the relationship between high-density lipoprotein cholesterol (HDL-C) and atherosclerotic cerebrovascular disease. METHODS: Over 5000 women living in the area of Naples, Southern Italy, were recruited for a prospective study on the etiology of cardiovascular disease in the female population (the 'Progetto ATENA' study). A sample of 310 participants underwent high-resolution B-mode ultrasound examination and the intima-media thickness and diameters of common carotid artery were measured. In addition to routine biochemical tests, these women also had oxidation markers determined. RESULTS: Women in the upper HDL-C quartile (HDL-C>1.89 mmol/L) had significantly lower body mass index and waist-to-hip ratio values, and triglycerides concentrations when compared with women in the first three quartiles. A linear negative association was found between HDL-C and carotid intima-media thickness (1.07+/-0.16 mm for the IV quartile versus 1.10+/-0.20 mm for the III quartile, 1.15+/-0.26 mm for the II quartile and 1.19+/-0.23 mm for the I quartile; P<0.01 by ANOVA). No difference was found between groups with regard to carotid diameters and oxidation markers. After adjustment for other cardiovascular risk factors, women in the highest quartile of HDL-C had a decreased risk of carotid intima-media thickening (OR 0.42, 95%CI 0.23-0.94). CONCLUSIONS: In asymptomatic middle-aged women, HDL-C levels were independently and negatively associated with preclinical atherosclerotic changes of the carotid artery wall. |
| Effect of high-fat cholesterol enriched diets on hypolipemic action of Oenothera paradoxa oil in rats. Part 1. Blood serum and liver lipids Biernat, J. and H. Grajeta (1997), Nahrung 41(1): 46-9. Abstract: The effect on Oenothera paradoxa oil on blood serum and liver lipids metabolism in rats fed a semisynthetic high-fat cholesterol enriched diets was investigated. The source of fats was sunflower oil or lard in 15% quantities and the source of protein was soybean protein isolate in 27% quantity. The diets were enriched with 0.5% cholesterol. This dietary experiment was carried on for 8 weeks. For the first 4 weeks rats were fed standard diet and for the next 4 weeks Oe. paradoxa oil (300 mg/day/rat) was additionally given by stomach-tube. At the end of experiment the contents of total cholesterol, HDL-cholesterol, triglycerides and free fatty acids in blood serum as well as cholesterol and triglycerides level in liver were determined. It was found that the addition of cholesterol to the diet decreased the hypocholesterolemic and hypotriglyceridemic effects of Oe. paradoxa oil both in blood serum and liver. It have not had any significant effect on the free fatty acid concentration in blood serum decrease by Oe. paradoxa oil intake. |
| Effect of high-fat cholesterol enriched diets on hypolipemic action of Oenothera paradoxa oil in rats. Part 2. Blood serum and liver fatty acids Grajeta, H. and J. Biernat (1997), Nahrung 41(1): 50-2. Abstract: The effect of Oenothera paradoxa oil on blood serum and liver fatty acids composition in rats was studied. Rats were fed high-fat diets containing 15% of lard or sunflower oil with or without 0.5% of cholesterol. Soybean protein isolate (27%) was the source of proteins. Intake of Oe. paradoxa oil resulted in increase of levels of gamma-linolenic acid (GLA) and linoleic acid (LA) in blood serum and liver of experimental animals. The effect of Oe. paradoxa oil on blood serum and liver fatty acids composition depended mainly on the type and to the lower degree on the amount of fat in a diet. The addition of cholesterol did not change the influence of examined oil on the composition of fatty acids. |
| Effect of homocysteine and cholesterol in raising plasma homocysteine, cholesterol and triglyceride levels Zulli, A., B. Buxton, et al. (1998), Life Sci 62(24): 2191-4. Abstract: A high plasma homocysteine level is a newly regarded risk factor for coronary artery disease. We report a synergistic effect of homocysteine plus cholesterol feeding on further raising total plasma homocysteine, cholesterol and triglycerides levels than each agent alone, which further enhances the risk of coronary artery disease. |
| Effect of human biliary immunoglobulins on the nucleation of cholesterol Upadhya, G. A., P. R. Harvey, et al. (1993), J Biol Chem 268(7): 5193-200. Abstract: We have previously identified that either biliary immunoglobulin IgA or IgM is a pronucleating protein which can accelerate the precipitation of cholesterol from bile. In this study we purified the biliary immunoglobulins (IgA, IgG, and IgM) to homogeneity by affinity chromatography to investigate the relative cholesterol nucleating potency of each immunoglobulin. Each immunoglobulin was added to slow nucleating heated abnormal biles in a dose-response manner to give a final concentration of protein in the range of 62.5-625 micrograms/ml bile. Cholesterol-nucleating activity was measured by noting the first day of cholesterol crystal formation as well as the number of crystals formed over the observation period. Biliary IgM and IgG appear to be more potent pronucleators than IgA. Isolated serum IgM from patients with Waldenstrom's macroglobulinemia as well as serum IgG from patients with and without cholesterol gallstones were shown to have pronucleating activity and acted in a dose-response manner. Commercial IgG unlike commercial IgM retains nucleating activity. The concentration of biliary immunoglobulins was measured by an enzyme-linked immunoassay (ELISA) in the gallbladder bile of patients with and without cholesterol gallstones. Biliary IgG concentrations in bile were higher in cholesterol gallstones patients than in pigmented gallstone patients and controls. We conclude that immunoglobulins particularly IgG and IgM are important pronucleating proteins and could play a role in the pathogenesis of cholesterol gallstones. |
| Effect of human plasma HDL on the HDL receptors of plasma membranes of cholesterol-fed rabbit Wu, X., M. Fu, et al. (1999), Hua Xi Yi Ke Da Xue Xue Bao 30(4): 370-2. Abstract: Atherosclerosis(As) rabbit model was developed by high-cholesterol feeding for 12 weeks. The rabbits were injected intravenously with human plasma HDL preparation per week, and then the effects of HDL on the lipids contents of serum, liver and bile nd the activity of HDL receptors on liver plasma membranes of cholesterol-fed rabbit were investigated. The results showed that HDL preparation had no effect on decreasing the lipids contents of serum, but it could low down the lipid depositions in liver, and promote the excretion of lipids from bile. The value of Bmax of HDL receptor showed decreasing trendy and the value of Kd showed increasing trendy in cholesterol-fed rabbits. In HDL-treated rabbits, the value of Bmax increased significantly as compared with that of normal group(P < 0.05), but the value of Kd showed no difference. The results suggested that human plasma HDL could enhance the activity of HDL receptors on the liver plasma membranes of cholesterol-fed rabbit. |
| Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on cholesterol levels and atherosclerosis in ApoE-deficient mice Van Eck, M., M. P. De Winther, et al. (2000), Arterioscler Thromb Vasc Biol 20(12): 2600-6. Abstract: In the arterial wall, scavenger receptor class A (SRA) is implicated in pathological lipid deposition. In contrast, in the liver, SRA is suggested to remove modified lipoproteins from the circulation, thereby protecting the body from their pathological action. The role of SRA on bone marrow-derived cells in lipid metabolism and atherogenesis was assessed in vivo by transplantation of bone marrow cells overexpressing human SRA (MSR1) to apoE-deficient mice. In vitro studies with peritoneal macrophages from the transplanted mice showed that macrophage scavenger receptor function, as measured by cell association and degradation studies with acetylated LDL, was approximately 3-fold increased on overexpression of MSR1 in bone marrow-derived cells as compared with control mice. Despite the increased macrophage scavenger receptor function in vitro, no significant effect of MSR1 overexpression in bone marrow-derived cells on the in vivo atherosclerotic lesion development was found. In addition to arterial wall macrophages, liver sinusoidal Kupffer cells also overexpress MSR1 after bone marrow transplantation, which may scavenge atherogenic particles more efficiently from the blood compartment. Introduction of bone marrow cells overexpressing human MSR1 in apoE-deficient mice induced a significant reduction in serum cholesterol levels of approximately 20% (P:<0.001, 2-way ANOVA) as the result of a decrease in VLDL cholesterol. It is suggested that the reduction in VLDL cholesterol levels is due to increased clearance of modified lipoproteins by the overexpressed MSR1 in Kupffer cells of the liver, thereby protecting the arterial wall against the proatherogenic action of modified lipoproteins. |
| Effect of hydrostatic pressure and cholesterol depletion on the expression of a tumor-associated antigen Gesmundo, N., N. Calonghi, et al. (1993), Eur J Biochem 217(1): 337-43. Abstract: The molecular events related to the expression of three tumor-associated epitopes, Ca-MOv17, Ca-MOv18 and Ca-MOv19 have been addressed. The epitopes are carried by a 38-kDa glycoprotein (gp38), recently cloned and identified as a human folate-binding protein. They were found to be coexpressed on the surface of the ovarian carcinoma cell line OVCA432, while they are not coordinately expressed on other adenocarcinoma cell lines (IGROV1, HT-29). This lack of coexpression was investigated from a molecular point of view. We studied three carcinoma cell lines, characterized by a different reactivity with the three relevant monoclonal antibodies MOv17, MOv18 and MOv19. The epitope expression was examined after modifying the membrane properties by using hydrostatic pressure and/or the variation of cholesterol content. Measurement of the expression after cell labelling by mAbs was performed by indirect immunofluorescence, using both fluorescence microscopy and flow cytometry. At variance with HT-29 cells, treatment of ovarian carcinoma IGROV1 cells with hydrostatic pressure failed to exert any effect. On IGROV1, instead, cholesterol depletion affected the expression Ca-MOv17, increasing, in the indirect immunofluorescence tests, the proportion of positive cells from 0 to 66 +/- 9%. Moreover, restoring the cholesterol content of the plasma membrane did not reverse the induced epitope expression. In parallel, immunoprecipitation experiments confirmed that, on IGROV1 surface, gp38 was recognized by all three mAbs. The data presented suggest that in IGROV1 cells the selective lacking of the epitope expression is related to the physical state of the plasma membrane. An explanation is provided by the model of membrane microdomains in which epitope expression may be influenced by the cholesterol level of different plasma membrane regions. |
| Effect of hydrostatic pressure on water penetration and rotational dynamics in phospholipid-cholesterol bilayers Bernsdorff, C., A. Wolf, et al. (1997), Biophys J 72(3): 1264-77. Abstract: The effect of high hydrostatic pressure on the lipid bilayer hydration, the mean order parameter, and rotational dynamics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) cholesterol vesicles has been studied by time-resolved fluorescence spectroscopy up to 1500 bar. Whereas the degree of hydration in the lipid headgroup and interfacial region was assessed from fluorescence lifetime data using the probe 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), the corresponding information in the upper acyl chain region was estimated from its effect on the fluorescence lifetime of and 3-(diphenylhexatrienyl)propyl-trimethylammonium (TMAP-DPH). The lifetime data indicate a greater level of interfacial hydration for DPPC bilayers than for POPC bilayers, but there is no marked difference in interchain hydration of the two bilayer systems. The addition of cholesterol at levels from 30 to 50 mol% to DPPC has a greater effect on the increase of hydrophobicity in the interfacial region of the bilayer than the application of hydrostatic pressure of several hundred to 1000 bar. Although the same trend is observed in the corresponding system, POPC/30 mol% cholesterol, the observed effects are markedly less pronounced. Whereas the rotational correlation times of the fluorophores decrease in passing the pressure-induced liquid-crystalline to gel phase transition of DPPC, the wobbling diffusion coefficient remains essentially unchanged. The wobbling diffusion constant of the two fluorophores changes markedly upon incorporation of 30 mol% cholesterol, and increases at higher pressures, also in the case of POPC/30 mol% cholesterol. The observed effects are discussed in terms of changes in the rotational characteristics of the fluorophores and the phase-state of the lipid mixture. The results demonstrate the ability of cholesterol to adjust the structural and dynamic properties of membranes composed of different phospholipid components, and to efficiently regulate the motional freedom and hydrophobicity of membranes, so that they can withstand even drastic changes in environmental conditions, such as high external hydrostatic pressure. |
| Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages Kafonek, S. D., I. Raikhel, et al. (1993), Atherosclerosis 102(1): 23-36. Abstract: Hyperapobetalipoproteinemia (hyperapo B), a common disorder associated with coronary artery disease, is characterized by an increased number of small, dense, low density lipoprotein (LDL) particles. The cellular mechanisms responsible for early atherosclerosis in hyperapo B are unknown. We tested the hypothesis that hyperapo B LDL may be preferentially metabolized through an LDL receptor independent pathway promoting the accumulation of cellular cholesteryl ester (CE). THP-1 macrophages have little inducible LDL receptor activity after differentiation with phorbol esters and are, therefore, suitable for assessing non-LDL receptor mediated uptake of lipoproteins. LDL isolated from hyperapo B donors was found to have significantly lower total cholesterol to protein ratio (P = 0.03), higher average density (P = 0.0001) and smaller particle diameter (P = 0.016) compared with normal (control) LDL. LDL (250 micrograms lipoprotein-protein/ml) from normal (n = 11) and hyperapo B (n = 18) subjects were incubated for 24 h with THP-1 macrophages. The mean (S.D.) CE accumulation was 6.2 (3.6) for the normal and 6.4 (2.6) for the hyperapo B LDL (P = 0.84). CE accumulation in cells incubated with malondialdehyde modified (MDA) LDL, or without added lipoprotein, was 18.2 (2.0) and 0.6 (0.7), respectively. CE mass accumulation was significantly correlated with time (6-48 h) of incubation and concentration (100-500 micrograms/ml) of LDL protein (P < 0.05); no differences were observed between normal and hyperapo B LDL. Similarly, when the major LDL species was isolated by density gradient ultracentrifugation, mean (S.D.) CE was similar for the normal and hyperapo B LDL (8.7 (1.2) vs. 6.9 (1.5)). There were no differences in the mean (S.D.) incorporation of 14Coleate into CE (nmol/mg cell protein per 6 h) in THP-1 macrophages incubated with normal or hyperapo B LDL (0.238 (0.045) vs. 0.211 (0.046)); results were comparable in human monocyte-derived (HMD) macrophages (0.298 (0.037) vs. 0.258 (0.022)). Also, mean (S.D.) cellular uptake and degradation (ng 125I/mg cell protein per h) in THP macrophages of normal and hyperapo B LDL were similar (uptake: 18 (14) vs. 12 (6.0); degradation: 58 (32) vs. 44 (8)). In summary: (1) hyperapo B LDL did not stimulate the accumulation of cellular CE via LDL receptor independent pathways in THP-1 macrophages, (2) normal and hyperapo B LDL stimulation of CE synthesis is similar in THP-1 and HMD macrophages and (3) no differences in cellular uptake and degradation of normal and hyperapo B LDL were observed in THP macrophages. |
| Effect of hyperoxia on the composition of the alveolar surfactant and the turnover of surfactant phospholipids, cholesterol, plasmalogens and vitamin E Tolle, A., I. Kolleck, et al. (1997), Biochim Biophys Acta 1346(2): 198-204. Abstract: Experimental and clinical studies have provided evidence for the involvement of oxygen free radicals in development of acute and chronic lung diseases. Hyperoxia is very often an indispensable therapeutic intervention which seems to impose oxidative stress on lung tissue. We measured the effect of hyperoxia (80% O2 for 20 h) (1) on the lipid composition of pulmonary surfactant treated in vitro, (2) on surfactant lipid synthesis and secretion of type II pneumocytes in primary culture, (3) on the lipid composition and on the SP-A content of rat lung lavages and (4) on the turnover of phospholipids, cholesterol, plasmalogens and vitamin E in type II pneumocytes, lamellar bodies and lavages of adult rat lungs. (1) Hyperoxia of lung lavages in vitro reduces the vitamin E content significantly but does not change the relative proportion of PUFA or the content of plasmalogens. (2) Hyperoxia does not affect the biosynthesis or secretion of surfactant lipids and plasmalogens by type pneumocytes in primary culture. (3) Hyperoxic treatment of rats increases the SP-A content and reduces the vitamin E content significantly but does not change the concentration of other lipid components of lung lavage. (4) The vitamin E turnover, measured in type II pneumocytes, lamellar bodies and lung lavages, is increased 2-fold in these fractions. In contrast, the turnover of surfactant cholesterol and surfactant lipids does not change. (5) Hyperoxia caused an increase of the vitamin E uptake by type II pneumocytes resulting in a vitamin E enrichment of lamellar bodies. From these results we conclude that type II pneumocytes are able to regulate the turnover of lipophilic constituents of the alveolar surfactant independently of each other. Hyperoxia caused type II pneumocytes to increase the vitamin E content of lamellar bodies. The lipid and SP-A content of alveolar fluid can be regulated independently each other. |