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Results for “Lipid modification”

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PubMed1991

Modification of lipid peroxidation by some known substituted imidazole derivatives. An attempt to correlate their antioxidant activity with lipophilicity.

The antioxidant activity of two antiallergic agents, oxatomide, astemizole and two neuroleptic drugs, penfluridol, pimozide, structurally related, was tested, using heat-inactivated rat hepatic microsomal fraction and linoleic acid. Lipid peroxidation was induced by Fe2+/ascorbic acid and Fe2+, respectively, and evaluated spectrophotometrically as 2-thiobarbituric acid reactive material. It was found that these compounds inhibited significantly the peroxidation of microsomal membranes in a concentration-dependent manner, as well as the peroxidation of linoleic acid. The lipophilicity of the tested compounds, expressed as RM values derived from reversed phase thin layer chromatography (RPTLC), was determined and the relationship between antioxidant activity and lipophilicity was discussed.

Animals↗
PubMedDate not supplied

[The modification of lipids in a secondary prevention program by general practice physicians].

This study follows a cognitive investigation about risk factor for ischemic heart disease performed in 1990 by a group of general practitioners in Pistoia, Italy. From this investigation we selected subjects with hypercholesterolemia; we also considered the association with other risk factors for ischemic heart disease. According to the frequency of risk factors subjects received a low-fat diet or diet plus cholesterol-lowering drug therapy (simvastatin). We describe changes on total cholesterol and its fractions by these therapeutic regimens.

Adult↗
PubMed1994

Acetylated low density lipoprotein reduces its ligand activity for the scavenger receptor after interaction with reconstituted high density lipoprotein.

Complexes of apolipoprotein A-I (apoA-I) with phospholipids are known to induce cholesterol efflux from cells. In a cholesteryl ester accumulation system in which rat peritoneal macrophages were incubated with acetylated low density lipoprotein (acetyl-LDL) and either dimyristoylphosphatidylcholine complexes (DMPC/apoA-I) or native high density lipoprotein (HDL), DMPC/apoA-I exhibited a much stronger effect than native HDL in preventing cholesteryl ester accumulation. The mechanism for this phenomenon was investigated in the present study. After 18 h incubation with DMPC/apoA-I in a cell-free system, acetyl-LDL was re-isolated from DMPC/apoA-I by Sephacryl S-300 gel filtration chromatography. Re-isolated acetyl-LDL exhibited an increase in its phospholipid content by 86% as well as a reduction in the electrophoretic mobility. Its endocytic degradation by macrophages was reduced by 60% when compared with control acetyl-LDL, suggesting a significant reduction in the ligand activity for the macrophage scavenger receptor. Transfer of apolipoproteins between acetyl-LDL and DMPC/apoA-I did not occur. These results indicate that transfer of DMPC from DMPC/apoA-I to acetyl-LDL weakens the ligand activity for the scavenger receptor due probably to a decrease in net negative charge. This study demonstrated for the first time that lipid modification (change in the lipid moiety) of acetyl-LDL can induce alteration in its apolipoprotein moiety, leading to a significant loss of its biological activity. Because discoidal HDLs are known to occur in vivo, this phenomenon may explain one of the anti-atherogenic functions of HDL in vivo.

Animals↗
PubMed2006

The plasma membrane lipid composition affects fusion between cells and model membranes.

Investigations were carried out on the effect of plasma membrane lipid modifications on the fusogenic capacity of control and ras-transformed fibroblasts. The plasma membrane lipid composition was modified by treatment of cells with exogenous phospholipases C and D, sphingomyelinase and cyclodextrin. The used enzymes hydrolyzed definite membrane lipids thus inducing specific modifications of the lipid composition while cyclodextrin treatment reduced significantly the level of cholesterol. The cells with modified membranes were used for assessment of their fusogenic capacity with model membranes with a constant lipid composition. Treatment with phospholipases C and D stimulated the fusogenic potential of both cell lines whereas the specific reduction of either sphingomyelin or cholesterol induced the opposite effect. The results showed that all modifications of the plasma membrane lipid composition affected the fusogenic capacity irrespective of the initial differences in the membrane lipid composition of the two cell lines. These results support the notion that the lipid composition plays a significant role in the processes of membrane-membrane fusion. This role could be either direct or through modulation of the activity of specific proteins which regulate membrane fusion.

Animals↗
PubMed1991

Effects of life-style modification on serum lipids.

Life-style modification has been recommended by the National Cholesterol Education Program as the first approach to reduce serum lipid values and the risk for coronary heart disease. Presented are data from 4587 adults who attended a 3-week residential, life-style modification program consisting of a high-complex-carbohydrate, high-fiber, low-fat, and low-cholesterol diet combined with daily aerobic exercise, primarily walking. Total cholesterol values were reduced by 23%, from 6.06 to 4.66 mmol/L (234 to 180 mg/dL). Low-density cholesterol (LDL-C) values were also reduced by 23%, from 3.9 to 3.0 mmol/L (151 to 116 mg/dL), with most of the change occurring during the first 2 weeks. Male subjects showed a greater reduction in total cholesterol (24.4% vs 20.8%) and LDL-C (25% vs 19.4%) values compared with female subjects. Follow-up studies for 18 months on a small group showed that, in most cases, continued compliance with the program maintained total cholesterol values well below 5.18 mmol/L (200 mg/dL), the level recommended by the National Cholesterol Education Program. High-density cholesterol (HDL-C) was reduced by 16%, but the ratio of total cholesterol to HDL-C was reduced by 11%. Female subjects showed a greater drop in HDL-C values than did male subjects (19.4% vs 11.6%). Serum triglyceride values were reduced by 33%, from 2.29 to 1.54 mmol/L (200 to 135 mg/dL); again, male subjects showed a greater reduction than the did female subjects (37.9% vs 22.5%). Body weight was also significantly reduced, 5.5% for male subjects and 4.4% for female subjects. These results show that most adults can significantly reduce serum lipid values and the risk for atherosclerosis and its clinical sequelae through life-style modification consisting of diet and exercise.

Adult↗
PubMed1999

Coronary artery surgery is associated with different forms of atherogenic lipoprotein modifications.

BACKGROUND: Increasing evidence shows that thrombogenicity and atherogenicity of lipoproteins are related to modifications involving oxidative, enzymatic, or physical alterations of these molecules. Findings on lipid peroxidation associated with cardiopulmonary bypass are conflicting, and the possible other forms of atherogenic lipid modification are unknown. The various forms of lipoprotein modifications including lipid peroxidation, desialylation, and leukocytic elastase activity after coronary artery bypass graft operations are examined. METHODS: In patients undergoing coronary artery bypass graft operations, plasma total lipid hydroperoxides (n = 102), plasma leukocytic elastase activity (n = 125), free radical formation (n = 30), low-density lipoprotein oxidation, and sialic acid content before operation and at 2, 24, 48, and 72 hours after cardiopulmonary bypass and 3 months after operation were measured. RESULTS: Preoperative plasma lipid peroxide concentration (2.2 micromol/L) increased after cardiopulmonary bypass (peak, 7.5 micromol/L; p<0.001) and remained significantly elevated at 3 months after surgery (4.2 micromol/L; p<0.01). There was a significant correlation between increased free radical generation and lipid peroxide levels in blood at all postoperative intervals. Low-density lipoprotein separated from plasma samples showed increased oxidation 48 hours after bypass. Sialic acid content of low-density lipoprotein was significantly reduced 48 hours after bypass. Plasma elastase activity increased significantly at all postoperative intervals. CONCLUSIONS: Coronary artery bypass graft operation is associated with generation of sustained blood levels of modified lipoproteins. These thrombogenic and atherogenic particles may play an important role in hemostatic and arteriosclerotic complications of coronary artery bypass graft operations.

Adult↗
PubMed1994

Effect of dithiothreitol on lipid peroxidation induced modification of NMDA receptor in fetal guinea pig brain.

The present study examines if the NMDA receptor modification induced by lipid peroxidation is mediated through its redox site and is therefore reversible by dithiothreitol (DTT) by performing [3H]MK-801 binding in the fetal guinea pig brain. P2 membrane fractions were prepared from fetal guinea pig brains and were peroxidized in vitro by 100 microM ascorbate and 25 microM ferric chloride for 20 min. Control and peroxidized membranes were then incubated with 100 microM DTT for 30 min at 37 degrees C. [3H]MK-801 binding was performed in DTT treated and untreated membranes in the presence of 100 microM each of glutamate and glycine. In addition, to study the glutamate- and glycine-dependent activation, [3H]MK-801 binding was determined in the absence (basal) and presence (activated) of glutamate and glycine. Bmax (number of binding sites) and Kd (affinity) of the binding sites were used as indices of NMDA receptor modification and its reversibility by DTT. After lipid peroxidation, the Kd value increased from 4.44 +/- 0.12 in control to 10.39 +/- 1.78 nM (P < 0.01) suggesting decreased affinity following lipid peroxidation. Following treatment with DTT, there was no significant change in Kd, but Bmax was significantly (P < 0.007) decreased in the peroxidized membrane. This suggests that DTT did not improve the affinity of the NMDA receptor of the lipid peroxidized membrane but may have a deleterious effect by reducing the number of binding sites. However, in the control membrane DTT significantly increased the affinity (P < 0.004) and the Bmax (P < 0.01) of the NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Modulation of neuronal protein trafficking and function by palmitoylation.

Modification of proteins with the lipid palmitate regulates targeting to specific vesicular compartments and synaptic membranes. Mounting evidence indicates that this lipid modification modulates diverse aspects of neuronal development and synaptic transmission. In particular, palmitoylation regulates the function of proteins that control neuronal differentiation, axonal pathfinding and filopodia formation. In addition, trafficking of numerous proteins associated with synaptic vesicle release machinery requires protein palmitoylation. Remarkably, reversible palmitoylation of specific scaffolding proteins and signaling molecules dynamically regulates ion channel clustering and synaptic strength. The recent discovery of enzymes that palmitoylate specific subsets of synaptic proteins suggests that this process is tightly controlled in neurons.

Animals↗