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Modification of the core lipids of low density lipoproteins produces selective alterations in the expression of apoB-100 epitopes.

The conformation of the apolipoprotein B-100 associated with low density lipoproteins (LDL) is not fixed. Rather, the conformations of several regions are subject to alteration by a variety of metabolic and therapeutic perturbations that change either the lipid compositions and/or sizes of LDL particles. However, because these perturbations simultaneously alter several structural-compositional features of the particles it has been difficult to relate structural-compositional features of LDL to apoB-100 conformations. Furthermore, in in vivo studies several days pass between samplings, thus different sets of particles are studied before and after experimental perturbation. In the present experiments more discrete perturbations of LDL were obtained in vitro by incubating LDL with very low density lipoproteins (VLDL) in the presence of partially purified human plasma lipid transfer proteins. The conformations of apoB on the LDL particles then were examined a) by probing epitope expression and b) by examining interactions between LDL and LDL-receptors in cultured human fibroblasts. During incubations with VLDL and lipid transfer proteins, the diameters of LDL particles decreased; the percentage composition of LDL triglycerides increased three-to fivefold; concomitantly, cholesteryl esters decreased. Lipid transfer protein was required for the transfer to occur and the magnitude of the increase in LDL-triglycerides depended upon the duration of incubation, the ratio of VLDL/LDL, and unknown properties specific to the various LDL preparations. The fact that the triglyceride contents of all LDL preparations were not identically affected suggests that initial packaging of the core region may affect capacity for lipid exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein B-100↗

Modification of radiation induced lipid peroxidation by calmodulin antagonists.

It has been shown that calmodulin antagonists provide radio-protection in euoxic and sensitization in hypoxic conditions. This differential protection in euoxic conditions might have arisen from the interaction of calmodulin antagonists with oxygen free radicals. This possibility has been tested in the present communication. Radiation induced lipid peroxidation process in liposomes has been used for this purpose. Liposomes prepared from L-alpha-lecithin were irradiated with or without calmodulin antagonists. Calmodulin antagonists inhibited lipid peroxidation significantly. The inhibition was found to increase with increase in concentration of the drugs. These observations suggest that calmodulin antagonists have a capacity to scavenge oxygen free radicals involved in initiation and/or propagation of lipid peroxidation process. This may be the reason for their differential radioprotection in euoxic conditions in biological systems.

Calmodulin↗

Covalent modification of hepatic microsomal lipids of rats by carbon tetrachloride.

The present study was undertaken to isolate and identify various lipids bound to 14C label during hepatic microsomal metabolism of 14CCl4 in vitro under anaerobic conditions and in vivo in rats. The two major radioactive fractions identified by thin-layer chromatography each for neutral lipids and phospholipids from in vitro and in vivo experiments corresponded to fatty acids and triglycerides and to phosphatidylcholine (PC) and phosphatidylethanolamine (PE), respectively. Approximately 89% of the radioactivity associated with phospholipids was found in PC and PE fractions. Hydrolysis of PC and PE with phospholipase A2 (EC 3.1.1.4) released about 50% of the total radioactivity as lipid moieties corresponding to fatty acids. The radioactive neutral lipids and the lipid moieties hydrolyzed from PC and PE were methylated with boron trifluoride in methanol. These methylated lipids were separated by reversed-phase high-performance liquid chromatography (HPLC), and the elution profiles of 14C label found for the lipids obtained from in vitro experiments were similar to those from in vivo. The major radioactive fractions eluted immediately after methyl oleate were identified as trichloromethyloctadecenoic and trichloromethyleicosatrienoic acid methyl esters by chemical ionization mass spectrometry. The mass spectral analysis of these fractions also indicated the formation of dichlorocarbene adduct of oleic acid. However, similar mass spectrometric detection of trichloromethylated lipids was not evident in neutral lipids and phospholipids isolated from in vivo studies. The 14C-labeled lipids eluted as a nonpolar fraction exhibited a high molecular weight containing more than three chlorines. Dimerization and cross-linking of trichloromethylated lipids based on HPLC and mass spectral analysis are also discussed in this paper.

Animals↗

[Role of the nonspecific modification of erythrocyte membrane lipids during hibernation in the suslik Citellus parryi].

Studies have been made on the content of cholesterol, phospholipids, fatty acid composition, the intensity of lipid peroxidation, the activity of Na+, K+-ATPase, as well as on the peroxide hemolysis in the erythrocytes in prehibernating and hibernating ground squirrels. Changes in partial content of cholesterol and in fatty acid composition of membranes are presumably due to the excessive lipid peroxidation during hibernation resulting from the decrease in the activity of antioxidative enzymes, which also accounts for the increase in peroxide hemolysis of erythrocytes.

Animals↗

Modification of electrocyte membrane lipid composition induced by denervation.

1. We determined the effect of denervation on the lipid composition of the main electric organ and electrocyte postsynaptic membrane vesicles of Electrophorus electricus. 2. Lipid extracts of whole electric organ contain mainly cholesterol, triglycerides, phosphatidylcholine and phosphatidylethanolamine. After 30 days of denervation, the lipid composition of whole electric organ did not change appreciably. 3. Lipid extracts of the membrane vesicles were similar, except that they contained mainly free fatty acids rather than triglycerides. After 30 days of denervation, cholesterol concentration was increased and phospholipids were decreased in the membrane fraction, with higher relative concentrations of phosphatidylethanolamine and cerebrosides. 4. These results suggest that electrocyte membrane fluidity and permeability will change after 30 days of denervation.

Animals↗

Dietary modification of host blood lipids affect reproduction in the lone star tick, Amblyomma americanum(L.).

The feeding and reproductive performance of female lone star ticks (Amblyomma americanum (L.)) infesting guinea pigs on diets containing 15% fish oil (FO) or safflower oil (SO) were investigated. Replete ticks fed on FO-fed guinea pigs weighed approximately 30% less than those on the SO-fed guinea pigs. The lower engorged weight resulted in a similar decrease in the mass and number of eggs laid and number of larvae hatching. No effect of host dietary treatment was observed upon the reproductive efficiency index, egg weight, or hatchability. Guinea pig blood on the FO-diet contained high levels of eicosapentaenoic acid, which has previously been shown to inhibit the accumulation of arachidonic acid in the tick salivary gland. It is suggested that the ticks on the FO-fed guinea pigs have impaired production and secretion of dienoic prostaglandins in the saliva resulting in poorer feeding performance, possibly by altering the amount of host blood present in the feeding lesion.

Adipose Tissue↗

Inhibitory effects of Astragali Radix, a crude drug in Oriental medicines, on lipid peroxidation and protein oxidative modification by copper.

Effects of Astragali Radix, the root of Astragalus membrauaceus Bunge, were investigated on oxidative stress such as lipid peroxidation and protein oxidative modification by copper. The results showed that these effects are similar to those of mannitol and superoxide dismutase as a free radical scavenger. It was demonstrated that Astragali Radix have inhibitory effects on oxidative stress induced by copper.

Copper↗

Cyclosporine-induced insulin release in rats is related to an increase in plasma lipid levels.

We studied the modifications of plasma lipid levels induced by cyclosporine (CsA), streptozocin (STZ) or both drugs in rats. Male Wistar rats (RT1y) were administered i.p. with CsA or STZ or both at the dosage of 15 mg/kg daily for 8 days and were sacrificed on day 9. Total lipid, triglyceride and total cholesterol plasma levels were measured. The plasma total lipid content was significantly increased in CsA-treated and in CsA + STZ-treated rats with respect to controls (662 +/- 29 and 632 +/- 32, respectively, vs 472 +/- 27 mg/dl). The triglyceride content was significantly higher in CsA-treated and in CsA + STZ-treated animals than in controls (137 +/- 8.7 and 188 +/- 14.1, respectively, vs 79 +/- 7.7 mg/dl). The total cholesterol level was not significantly different in CsA- and STZ-treated rats with respect to controls. CsA-treated and STZ-treated rats concomitantly revealed a significant impairment of glucose tolerance. In fact, 150 min after orogastric administration of 350 mg glucose, glycaemia was significantly more elevated in treated animals than in controls. We conclude that the increase in lipid levels induced by CsA treatment could be related to drug-induced damage to the pancreas islets, as shown by the early insulin release and fatty tissue degeneration.

Animals↗

Comparative effects of prazosin and atenolol on plasma lipids in hypertensive patients.

Adverse modifications of blood lipid fractions are thought to be an additional risk factor in hypertensive patients treated with some antihypertensive drugs. The purpose of this study was to compare the changes in concentrations of lipid fractions in patients treated with either the cardioselective beta blocker atenolol or the selective alpha 1 blocker prazosin. When used in approximately equipotent doses for antihypertensive effect, prazosin and atenolol demonstrated different effects on lipid metabolism. Prazosin lowered total levels of cholesterol, low-density lipoprotein cholesterol and B-apolipoproteins, but increased the levels of high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol and A1-apolipoproteins. Changes opposite to those induced by prazosin were observed during atenolol therapy.

Adult↗

Age-associated alteration of lipid peroxidation and superoxide dismutase activity in CBA and AKR mice.

Oxidative modification of lipids, proteins and DNA by reactive oxygen species in the organism and imbalance between the concentrations of free radicals and the antioxidant defenses may be related to processes such as aging and diseases (cardiovascular, neurodegenerative, cancer, etc.). Although the relationship between oxidant status and antioxidant defence in aging of different species, organs or sexes has been investigated extensively, the studies have produced conflicting results. In order to determine the extent of age-associated alteration, oxidant production and antioxidant status were measured in tissues of CBA and AKR mice of both sexes. At the same time we will focus on lipid peroxidation (LPO) process and superoxide dismutase activity (SOD) of AKR mice related to ontogeny of thymic lymphoma in mice of different age and sex. Male and female CBA and AKR mice aged 3, 6, 12 or 18 months were used. Lipid-bound sialic acid (LSA) content was determined as a malignancy marker. LPO processes of CBA and AKR mice were monitored according to the presence of thiobarbituric acid reactive substances (TBARS) in liver and thymus, and antioxidant status as SOD activity in whole blood. TBARS concentration increased significantly with age in the liver of CBA and AKR mice of both sexes, but only in male thymuses of both strains. TBARS concentration in female thymuses of both strains was unchanged during aging. Thus, age-associated LPO processes of tumor-free mice of both strains were tissue-dependent. In the liver of tumor-bearing CBA and AKR mice as well as in thymuses of AKR mice, TBARS concentration significantly decreased and was neither sex nor tissue related. SOD activity was strain-dependent but independent of sex. However, SOD activity in mice with developed thymomas was drastically reduced in comparison to tumor-free mice. Our data indicate that age associated LPO processes in both strains are only tissue-dependent and SOD activity mainly strain-dependent in tumor-free mice. In tumor-bearing mice LPO processes and SOD activity were not tissue, sex or strain dependent.

Aging↗

Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria.

Regulated covalent modifications of lipid A are implicated in virulence of pathogenic Gram-negative bacteria. The Salmonella typhimurium PhoP/PhoQ-activated gene pagP is required both for biosynthesis of hepta-acylated lipid A species containing palmitate and for resistance to cationic anti-microbial peptides. Palmitoylated lipid A can also function as an endotoxin antagonist. We now show that pagP and its Escherichia coli homolog (crcA) encode an unusual enzyme of lipid A biosynthesis localized in the outer membrane. PagP transfers a palmitate residue from the sn-1 position of a phospholipid to the N-linked hydroxymyristate on the proximal unit of lipid A (or its precursors). PagP bearing a C-terminal His(6)-tag accumulated in outer membranes during overproduction, was purified with full activity and was shown by cross-linking to behave as a homodimer. PagP is the first example of an outer membrane enzyme involved in lipid A biosynthesis. Additional pagP homologs are encoded in the genomes of Yersinia and Bordetella species. PagP may provide an adaptive response toward both Mg(2+) limitation and host innate immune defenses.

Acylation↗

[The effects of short term comprehensive life style modification program on glycemic metabolism, lipid metabolism and body composition in type 2 diabetes mellitus].

PURPOSE: This study was to evaluate the effects of a short term comprehensive life style modification program on glycemic metabolism, lipid metabolism and body composition in type 2 diabetes mellitus patients. METHOD: A nonequivalent control group with a pre post test was designed. Data collection was done from October 2003 to June, 2004 at a hospital. Glycemic metabolism was measured by a.c., p.c. and HbA(1c), and lipid metabolism was measured by cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Body Composition was measured by body weight, body mass index, waist, measurement waist per hip ratio, body fat, muscle weight and abdominal fat tissue(intra abdominal distance). The Experimental group, which was composed of 29 participants, was educated based on a life style modification protocol at a weekly meeting for 12 weeks and carried out exercise, diet along individual parameters and self monitoring, while 24 participants in the control group received only diet education. RESULT: 1. The experimental group showed a significant lower a.c.(t=2.11, p=.04) and HbA(1c)(t=2.65, p=.01) compared to those of the control group. 2. The experimental group showed a significant lower LDL than the results of the control group(t=2.42, p=.02). 3. The experimental group showed a significant lower weight(t=3.09, p=.00), BMI(t=3.01, p=.00), body fat(t=2.94, p=.01) and abdominal fat tissue(t=3.05, p=.01) than those of the control group. CONCLUSION: The results provided evidence for the effectiveness of a short term comprehensive life style modification program composed of exercise, diet, support, self efficacy elevation and self monitoring in type 2 diabetes mellitus.

Adult↗

Thermal transition studies of a mature xanthelasma by differential scanning calorimetry.

A large xanthelasma which had been present for at least 5 years was removed surgically from a normolipaemic female age 54 years, and examined in the fresh state by differential scanning calorimetry. Thermal transitions recorded over the range 30-40 degrees C suggest that the lipid present, predominantly esterified cholesterol, is not bound to protein or other tissue components, and that the chronicity of mature xanthelasmata as with ectopic lipid deposits at other sites is enhanced by chemical modification of lipid and effects on component phase behaviour, which are significant at local skin temperature.

Calorimetry, Differential Scanning↗

Lipids in total parenteral nutrition solutions differentially modify lipids in piglet intestinal brush border and microsomal membranes.

BACKGROUND: Fats in the diet modify the lipid composition and function of the intestinal brush border membrane (BBM) as well as the enterocyte microsomal membrane (EMM). METHODS: This study was undertaken in pigs to establish the effect of 3 weeks of total parenteral nutrition (TPN) on the fatty acids in the major phospholipids, (phosphatidylcholine [PC] and phosphatidylethenolamine [PE] in the jejunal and ileal BBM and EMM. RESULTS: In a comparison of 21-day-old milk-fed piglets and newborn animals, there were differences in the major fatty acids (palmitic, 16:0; stearic, 18:0; oleic, 18:1 omega 9, and linoleic acid, 18:2 omega 6) in PC and PE in BBM and EMM. Age-matched (3-week-old) animals fed a lipid-free glucose-containing TPN solution had different membrane fatty acids than did milk-fed piglets, or animals given a soybean oil-containing TPN solution for 21 days. Substituting fish oil or fish oil plus soybean oil altered BBM and EMM fatty acids, compared with the soybean oil-based TPN solutions. These changes varied between the class of phospholipids (PC vs PE), between intestinal site (jejunum vs ileum), and between the type of membrane (BBM vs EMM). CONCLUSIONS: The jejunum and ileum have distinctive control mechanisms for varying their membrane lipids in response to TPN. There is some postmicrosomal modification of lipids between the EMM and BBM. It remains to be established whether the lipid content of the membranes of other organs, and therefore their function, is modified by the lipid composition of parenterally infused lipids.

Aging↗

[Lipid changes of fibrinogen and of platelet aggregation induced by etofibrate].

PURPOSE: To evaluate modifications on lipid profile, fibrinogen and platelet aggregation induced by etofibrate. METHODS: Twenty-one adult patients were studied. They all had primary hyperlipidemia and had already been on the AHA step I diet and placebo. Etofibrate (500mg/day) was administered for 60 days in the active phase, when lipid parameters, fibrinogen and platelet aggregation were measured. RESULTS: The % significant reductions were: total cholesterol (-9.50%), LDL-cholesterol (-7.88%), triglycerides (-19.07%), total cholesterol/HDL-cholesterol(-11.90%), LDL-cholesterol/HDL-cholesterol (-10.20%), fibrinogen (-12.79%), platelet aggregation with adrenaline (-24.02%), with ADP 1 mumol (-30.13%), and ADP 3 mumol (-24.51%). CONCLUSION: The beneficial effects of etofibrate were observed not only on the lipid profile but also on the thrombogenic parameters measured by fibrinogen and platelet aggregation.

Adult↗