Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lipid modification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1992

Adaptive changes of membrane lipid composition in humans living in the north.

Some parameters of red cell membrane lipid composition as well as intensiveness of lipid peroxidation and activity of its regulatory factors were assessed in northern aborigines, newcomers and alcohol abusers. It is proposed that the increased lipid peroxidation is responsible for the cholesterol and monoenic fatty acid accumulation in membranes of all groups studied. The data obtained make it possible to consider the lipid peroxidation as a mechanism for adaptive membrane lipid modification in humans.

Adaptation, Physiological↗
PubMed1987

Lipid changes associated with erythroid differentiation of Friend erythroleukemia cells.

Friend erythroleukemia cells were induced to differentiate by dimethyl sulfoxide (DMSO) and hexamethylene-bis-acetamide (HBMA) in order to investigate whether their lipid characteristics, common to other systems of transformed cells, revert to a normal differentiation pattern. DBA/2 mouse erythrocytes were examined as a model of terminal differentiation in erythroid lineage. Variants of erythroleukemia cells not inducible to erythroid differentiation by DMSO and HMBA were also used in this study, in order to test whether lipid modifications occurring in differentiated erythroleukemia cells were related to the differentiation process or caused by specific effects of the inducers. Friend erythroleukemia cells showed the same lipid characteristics as those found in other transformed cell types. That is, a high level of ether-linked lipids and low percentages of long chain polyunsaturated fatty acids along with an accumulation of monoenoic fatty acids in phospholipids. These lipid characteristics remained unchanged when erythroleukemia cells were induced to differentiation by either DMSO or HMBA. However, other lipid components of erythroleukemia cells, e.g., phosphatidylethanolamine and triglycerides, were affected by erythroid differentiation. There were also changes of some lipid components of erythroleukemia cells, such as cholesteryl esters, which were related to specific effects of the inducers. Both DMSO- and HMBA-resistant variants differed from the inducible erythroleukemia cells, mainly in their ether-linked phospholipid pattern.

Acetamides↗
PubMed2006

Type-2 diabetes mellitus related cardiovascular risk: new options for interventions to reduce risk and treatment goals.

Diabetes represents a state of accelerated cardiovascular risk with data from longitudinal studies suggesting that in patients with well established diabetes the risk is equivalent to those with existing cardiovascular disease. In addition, the prognosis of patients with diabetes who suffer cardiovascular disease (CVD) is much worse. There are therefore dual imperatives for all physicians, particularly those in primary care, to focus on strategies to reduce vascular risk in their patients with diabetes. There are, in parallel, background issues that make this risk modification in diabetes a priority, with the rising prevalence of disease, driven at least in part by the rising tide of obesity, and the rising cost (42% of total expenditure) of treating CVD in diabetics. Evidence for interventions that modify the CVD risk in diabetes is now strong, with unequivocal data to support multifactorial risk modification, particularly for the effective targeting of glycaemia and blood pressure (with primary evidence for bp targets below standard care) from studies such as Steno2 and UKPDS, and lipid modification through the use of statins in both secondary (HPS) and primary (CARDS) prevention of CVD in diabetes. Knowledge of these interventions is high in primary care, but implementation is variable. This is probably at least in part because primary care physicians appear to consider risk factor modification within single risk strategies, rather than adopting lifestyle and therapeutic interventions that influence multiple risks in a systematic package of care and patient follow up.

Cardiovascular Diseases↗
PubMed2001

Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal.

One of the most dominant influences in the patterning of multicellular embryos is exerted by the Hedgehog (Hh) family of secreted signaling proteins. Here, we identify a segment polarity gene in Drosophila melanogaster, skinny hedgehog (ski), and show that its product is required in Hh-expressing cells for production of appropriate signaling activity in embryos and in the imaginal precursors of adult tissues. The ski gene encodes an apparent acyltransferase, and we provide genetic and biochemical evidence that Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification. Our results suggest that ski encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh, and further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal.

Acylation↗
PubMed1989

Characterization of lipid-modified immunogenic proteins of Treponema pallidum expressed in Escherichia coli.

This study describes the sequence of the immunodominant Treponema pallidum surface protein TpD and its expression in Escherichia coli. The translated TpD DNA sequence revealed the presence of a putative site for lipid-modification downstream from the signal sequence of this membrane protein. Growth of TpD-expressing E. coli in the presence of radioactive palmitic acid revealed that TpD was lipid-modified. Three other, previously characterized cloned proteins of T. pallidum were also lipid-modified. The N-termini of two of three sequenced T. pallidum proteins contain a tetrapeptide sequence characteristic for lipoproteins in Gram-negative bacteria: Leu-X-Y-Cys. Only TpD differed from this consensus sequence in the substitution of the first residue by Phe. The apparent high incidence of lipoproteins among E. coli recombinants expressing T. pallidum antigens suggest an important role of lipoproteins in the induction of humoral immunity during syphilitic infection.

Amino Acid Sequence↗
PubMed2000

Bioorganic synthesis of lipid-modified proteins for the study of signal transduction.

Biological membranes define the boundaries of the cellular compartments in higher eukaryotes and are active in many processes such as signal transduction and vesicular transport. Although post-translational lipid modification of numerous proteins in signal transduction is crucial for biological function, analysis of protein-protein interactions has mainly focused on recombinant proteins in solution under defined in vitro conditions. Here we present a new strategy for the synthesis of such lipid-modified proteins. It involves the bacterial expression of a carboxy-terminally truncated non-lipidated protein, the chemical synthesis of differently lipidated peptides representing the C terminus of the proteins, and their covalent coupling. Our technique is demonstrated using Ras constructs, which exhibit properties very similar to fully processed Ras, but can be produced in high yields and are open for selective modifications. These constructs are operative in biophysical and cellular assay systems, showing specific recognition of effectors by Ras lipoproteins inserted into the membrane surface of biosensors and transforming activity of oncogenic variants after microinjection into cultured cells.

Animals↗
PubMedDate not supplied

Underidentification and undertreatment issues.

Despite the Adult Treatment Panel (ATP) guidelines and strong evidence that reduction of blood cholesterol levels favorably decreases the morbidity and mortality associated with coronary heart disease (CHD), a significant number of patients remain undiagnosed and untreated. With the aggressive detection and evaluation methods ATP III advocates, more than 65 million Americans are now eligible for lipid modification through lifestyle changes and/or drug therapy. Recent data suggest, however, that as many as 50% of all patients do not have their cholesterol assessed and less than 45% receive lipid-modifying therapy. Additionally, more than 75% of patients who receive therapy fail to achieve their National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol goal. Persistence with therapy is another challenge, as less than 30% of patients continue with therapy beyond one year. If a realistic attempt is to be made to reduce the CHD risk among Americans, diagnosis of dyslipidemia and treatment to therapeutic targets must be improved.

Anticholesteremic Agents↗
PubMed2004

Utility of currently available modes of therapy in reaching lipid goals.

The National Cholesterol Education Program Adult Treatment Panel III lipid management guidelines emphasize the importance of matching the intensity of lipid modification therapy to each patient's risk of coronary heart disease. For many patients who are at low risk, nonpharmacologic interventions such as diet, exercise, and smoking cessation can be effective lipid-lowering strategies. However, many patients require the addition of drug therapy to achieve lipid targets. Currently available lipid-modifying drugs include bile acid sequestrants, fibrates, nicotinic acid, cholesterol absorption inhibitors, and statins. In addition, nonprescription agents such as plant stanols and sterols are available to modify plasma lipid levels. These agents can be used individually or coadministered to achieve lipid goals.

Anticholesteremic Agents↗
PubMed2003

The national cholesterol education program adult treatment panel ill guidelines.

Coronary heart disease (CHD) remains the leading cause of death in the United States with more than 40% of all deaths each year directly attributed to the disease. Current evidence suggests that early identification and aggressive modification of risk factors offer the most promising approach to reducing the burden of CHD. Dyslipidemia has been identified as the primary risk factor leading to the development of CHD. It is estimated that nearly 65 million Americans require some form of lipid-modification therapy. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) set of guidelines released in May 2001 provides physicians with evidence-based recommendations on the classification, diagnosis, and treatment of lipid disorders. New features of the guidelines include a scoring system for calculating CHD risk, as well as the identification of CHD risk equivalents, lower treatment target goals, and an emphasis on conditions conferring a higher risk for CHD, such as the metabolic syndrome. The ATP III emphasis on risk assessment substantially increases the number of patients considered at risk for CHD and will expand the number eligible for lifestyle and drug interventions. This article highlights the new recommendations and reviews the impact of ATP III on osteopathic physicians.

Adult↗
PubMed1992

The role of lipid anchors for small G proteins in membrane trafficking.

Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. In order to perform these functions, the proteins must associate with specific donor vesicles and be recycled after fusion of these vesicles with their acceptor membrane target. Recent results have identified a number of lipid modifications of these proteins, occurring at the N- or C-termini, that contribute to their membrane binding. Recycling appears, in some cases, to be mediated by soluble proteins that bind the lipid-modified tails, removing them from the membrane and allowing their reutilization via the cytosol.

Journal Article↗
PubMed1999

A non-farnesylated Ha-Ras protein can be palmitoylated and trigger potent differentiation and transformation.

Ha-Ras undergoes post-translational modifications (including attachment of farnesyl and palmitate) that culminate in localization of the protein to the plasma membrane. Because palmitate is not attached without prior farnesyl addition, the distinct contributions of the two lipid modifications to membrane attachment or biological activity have been difficult to examine. To test if palmitate is able to support these crucial functions on its own, novel C-terminal mutants of Ha-Ras were constructed, retaining the natural sites for palmitoylation, but replacing the C-terminal residue of the CAAX signal for prenylation with six lysines. Both the Ext61L and ExtWT proteins were modified in a dynamic fashion by palmitate, without being farnesylated; bound to membranes modestly (40% as well as native Ha-Ras); and retained appropriate GTP binding properties. Ext61L caused potent transformation of NIH 3T3 cells and, unexpectedly, an exaggerated differentiation of PC12 cells. Ext61L with the six lysines but lacking palmitates was inactive. Thus, farnesyl is not needed as a signal for palmitate attachment or removal, and a combination of transient palmitate modification and basic residues can support Ha-Ras membrane binding and two quite different biological functions. The roles of palmitate can therefore be independent of and distinct from those of farnesyl. Reciprocally, if membrane association can be sustained largely through palmitates, farnesyl is freed to interact with other proteins.

3T3 Cells↗
PubMedDate not supplied

Overview of pharmacologic therapy for the treatment of dyslipidemia.

Although the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines stress the importance of nonpharmacologic lipid modification interventions such as diet and exercise, the guidelines also recognize that many patients will require drug therapy to achieve low-density lipoprotein cholesterol (LDL-C) target goals. Currently available lipid-modifying drugs include bile acid sequestrants (or resins), fibrates, nicotinic acid, and statins, with each class exerting different effects on the lipid profile. In addition, nonprescription agents such as plant stanols and sterols have been shown to be effective in modifying plasma lipids. Of these agents, the statins are the most effective, most widely prescribed, and best-tolerated form of lipid-lowering drug therapy. New formulations of other drugs, such as niacin and bile acid sequestrants, can also improve treatment regimes and reduce side effects, thereby improving patient compliance with these therapies. In patients who have high levels of LDL-C and triglycerides together with low concentrations of high-density lipoprotein cholesterol (HDL-C), combination therapy may be required. Ezetimibe, a selective cholesterol absorption inhibitor, is the first of a new class of lipid-lowering agents and provides a new agent for the management of patients with dyslipidemia. Data from the ezetimibe clinical development program suggests that this agent can be used alone or in combination with statins to reduce LDL-C, improve compliance, and bring more patients to ATP III target goal.

Allylamine↗
PubMed2003

Mevastatin suppresses lipopolysaccharide-induced Rac activation in the human monocyte cell line THP-1.

BACKGROUND: Rac is a member of the Rho family of small guanosine triphosphatases that regulate the actin cytoskeleton. Activation of Rac requires lipid modification that can be blocked by statins. Lipopolysaccharide-induced rearrangements in the actin cytoskeleton lead to changes in cell adhesion and motility that play a role in the cellular response to infection. The lipid products of phosphatidylinositol-3 kinase (PI3K) modulate Rac effector pathways and have been linked to the activation of the Rac-guanosine triphosphatase. We hypothesize that lipopolysaccharide stimulation leads to Rac activation and that this may be inhibited by statin pretreatment. Furthermore, signaling downstream of Rac is linked to PI3K; therefore, we hypothesize that a signaling complex between PI3K and Rac may be involved. METHODS: THP-1 cells were maintained in 1% fetal calf serum with or without 20 micromol/L mevastatin for 24 hours, followed by lipopolysaccharide stimulation. Active Rac was precipitated from THP-1 total cell lysate and then detected by immunoblotting. The PI3K-Rac complex was immunoprecipitated from total cell lysate, and the p85 regulatory subunit of PI3K was detected by immunoblotting. RESULTS: Lipopolysaccharide stimulation activated Rac. Rac activation was suppressed by pretreatment with mevastatin. The p85 subunit of PI3K was associated with Rac. CONCLUSIONS: Lipopolysaccharide stimulation leads to Rac activation in THP-1 cells, which may be suppressed with mevastatin pretreatment. There is an association between Rac and PI3K that demonstrates a role for PI3K in the activation of downstream Rac effector pathways.

Cell Line↗
PubMed1998

In vivo analysis of sequence requirements for processing and degradation of the colicin A lysis protein signal peptide.

The lipid modification and processing of a number of colicin lysis proteins take place exceedingly slowly and result in the release of a stable signal peptide. It is possible that this peptide or the presence of lipid-modified precursors which result from the slow processing plays a role in the release of colicins and in the quasilysis that occurs in induced colicinogenic cultures. We used in vitro mutagenesis and pulse-chase radiolabeling and immunoprecipitation to examine the reasons for the slow processing and signal peptide degradation reactions for the colicin A lysis protein (Cal). In one mutant, isoleucine 13 was replaced with serine, and in another, alanine 18, the last residue of the signal peptide, was replaced with glycine. In each case, the mutation caused a striking increase in the rate of maturation of the precursor, and in the case of the serine 13 derivative, the mutation also destabilized the signal peptide. A precursor containing both of these mutations was completely matured and its signal sequence degraded within seconds of its synthesis. The release of colicin A and the quasilysis of producing cultures were unchanged for each of these mutants, indicating that neither the stable signal peptide nor lipid-modified processing intermediates of Cal are required for either of these events in wild-type cells.

Bacterial Proteins↗
PubMed1980

Effect of fatty acid modifications of cultured hepatoma cells on susceptibility to complement-mediated cytolysis.

The fatty acid composition of Morris Hepatoma 7777 cells was modified by exposure to culture media that were supplemented with 0.1 to 0.36 mM oleic or linoleic acid for 5 days. Changes occurred in the fatty acid composition of both the cellular phospholipid and the neutral lipid fractions. Exposure to linoleic acid caused a large increase in the polyunsaturated fatty acid content of the cell lipids, whereas enrichment in monoenoic fatty acids occurred when the cells were exposed to high levels of oleic acid. Cellular phospholipid content decreased, cholesterol content did not change, and triglyceride content increased as a result of fatty acid supplementation. The fatty acid-modified cells showed increased susceptibility to complement-mediated cytolysis as compared with control cells grown in unsupplemented culture media. The extent of the increase in susceptibility to cytolysis depended on the degree of lipid modification and also on the cell number and antibody titer used in the assay. Cells enriched with linoleic acid were the most susceptible, but oleic acid enrichment also produced increased susceptibility to immune cytolysis. The kinetic study showed that the initial rate of cytolysis was higher in fatty acid-modified cells than in the control cells. There was no difference in the osmotic fragility of the control and fatty acid-modified cells. These results indicate that changes in the lipid composition of a target cell can influence its susceptibility to complement-dependent cytolysis.

Animals↗
PubMed1996

[Modification of the lipid profile in coronary patients undergoing cardiac rehabilitation].

To assess the effect of continuous and controlled exercise training on the lipid profile of coronary pts. in a cardiac rehabilitation program, we evaluated forty-nine males aged 56.8 +/- 9.6 years, thirty-two with previous surgical myocardial revascularization, two submitted to percutaneous transluminal coronary angioplasty and fifteen on exclusive pharmacological therapy. Patients with changes in drugs that could potentially induce modifications in serum lipid values, were excluded. The values of total cholesterol, triglycerides, HDL-cholesterol, the HDL-cholesterol/total cholesterol ratio, weight and the body mass index at admission of training phase, end of training phase (III)-21 patients (Group I) and maintenance (IV)-28 patients (Group II), were assessed. The training phase (III) had a duration of 3-4 months and maintenance (IV) nine months. In Group I, evaluated at the end of the training period (phase III), there was no significant modification in lipid profile reduction; only 1% and 20% reduction (p = NS) in values of total cholesterol and triglycerides, was detected. The HDL-cholesterol rose 12.5% (p = NS), and the HDL cholesterol/total cholesterol ratio 10.5% (p = NS). In Group II (at the end of the maintenance phase-IV-) there was no important change in total cholesterol levels. The HDL-cholesterol rose 19.5% (p = 0.003) and the HDL-cholesterol/total cholesterol ratio, also increased 33.3% (p < 0.0001). The benefit in relation to triglycerides was restricted to patients with higher values (> 200 mg/dl), where a reduction of 36% (p = 0.004) was found. There was no change in the weight or in body mass index, induced by the program. We concluded that the participation in a cardiac rehabilitation program induces a favourable modification of lipid profile in our population, with potential interest for secondary prevention of coronary heart disease. This change was particularly in serum values of triglycerides, HDL-cholesterol and the ratio HDL-cholesterol/total cholesterol. In what concerns triglycerides, the benefits were seen only in the group of patients with the highest serum values.

Adult↗
PubMed1997

Cost-effective strategies for the management of vascular disease.

Cardiovascular disease accounts for over 950,000 deaths and an estimated $151 billion in direct and indirect costs. Because of this escalating clinical and financial burden, economic analysis has become essential for the evaluation of preventative therapies for vascular disease. Economic analysis compares competing interventions or management strategies for costs and benefits; more specifically, cost-effectiveness analysis compares cost in financial terms like dollars to measures of effectiveness like years of life saved. Important concepts in the creation of a valid cost-effectiveness analysis include perspective, time horizon, measurement of costs and effectiveness and sensitivity analysis. In patients with peripheral arterial occlusive disease, most morbidity and mortality arises from complications of coronary artery disease. Because coronary artery disease and peripheral arterial occlusive disease commonly occur together and share risk factors, pathophysiology and response to preventative therapy, economic evaluations of preventative therapies for coronary artery disease have relevance for patients with vascular disease. Cost-effectiveness analysis reveals that modification of vascular risk factors like tobacco use, hypertension and hypercholesterolemia improve clinical outcomes at acceptable cost-effectiveness ratios, usually less than $20,000 per year of life saved. More importantly, interventions like smoking cessation or lipid modification in high-risk groups may be cost saving, with treatment costs outweighed by financial benefits. From the patient, clinician and societal perspective, cost-effectiveness analysis supports the aggressive modification of cardiovascular risk factors in patients with peripheral arterial occlusive disease.

Cost-Benefit Analysis↗
PubMed1988

Serum lipids in spontaneously hypertensive rats and Sprague-Dawley rats fed menhaden oil.

Dietary n-3 fatty acids, abundant in fish oil, exert a variety of effects that attenuate cardiovascular disease. In this study, we assessed the effect of fish oil (menhaden oil) on the serum lipid profile in hypertensive and normotensive rats. Spontaneously hypertensive rats (SHR) or Sprague-Dawley rats (SD) were fed either standard powdered diet (L-485), or L-485 + 5% menhaden oil (MO) or L-485 + 5% corn oil (CO) from weaning through eight months of age. Systolic blood pressure (BP) was periodically determined on SHR. Serum lipid profiles were performed at eight months on samples taken from the exposed hearts of anesthetized, fasted rats. SHR, compared with SD (diets combined) had significantly lower triacylglycerols (TG), higher cholesterol (CHOL), higher high density lipoprotein cholesterol (HDL CHOL), higher low density lipoprotein cholesterol (LDL CHOL), and a higher LDL:HDL ratio. Comparisons among diets (strains combined) revealed that rats fed MO had the lowest values for TG, CHOL, LDL and LDL:HDL; HDL did not vary with diet. SHR were less responsive to diet-induced changes than were SD; no decrease in TG, LDL or LDL:HDL was observed in SHR, nor was degree of hypertension altered in SHR by the MO or CO diet. In summary, MO is more effective than CO in shifting the lipid profile of rats toward one that is less atherogenic. However, the SD rat is more susceptible to diet-induced lipid modification than is the SHR.

Animals↗