Lipid and fatty acid modifications in plasma lipoproteins of baboons under atherogenic diet.
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Animals↗
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Modifications and oxidation of lipids and proteins in human serum detected by thermochemiluminescence.
Detection of electronically excited species (EES) in body fluids may constitute an important diagnostic tool in various pathologies. Examples of such products are triplet excited carbonyls (TEC), which can be a source for photon emission in the 400-550 nm range. The aim of the present study was to determine the actual contribution of lipid and protein components (protein carbonyls) to photon emission generated by thermochemiluminescence (TCL) during the heating of biological fluids. In this study, a new TCL Photometer device, designed by Lumitest Ltd, Israel, was used. Samples were heated to a constant temperature of 80 +/- 0.5 degrees C for 280 s and photon emission was measured at several time points. In order to compare the results of TCL measurements to conventional methods of detecting lipid and protein oxidation, each examined sample was also heated in a waterbath at 80 degrees C for 10-280 s. Lipid and protein oxidation were subsequently measured using conventional methods. The TCL of four polyunsaturated fatty acids (PUFA) with three to six double bonds was measured. The elevation of the PUFA TCL amplitude correlated with the increase in the number of double bonds of PUFA. A correlation between the increase in TCL intensity and protein carbonyl generation in bovine serum albumin (BSA) was also observed. In the venous blood serum, our study showed that an increase of TCL intensity during heating reflected the cleavage of TEC of lipid origin. Our study suggests that biological molecules such as proteins, lipids and other molecules, which may become unstable during heating, are capable of generating EES. We demonstrated that a TCL curve can be used as a kinetic model for measuring oxidative processes, which reflects modifications of different molecules involved in the oxidative stress phenomena.
Arachidonic Acids↗
Effects of octreotide on lipid metabolism in acromegaly.
Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.
Acromegaly↗
The importance of indirect costs in primary cardiovascular disease prevention: can we save lives and money with statins?
BACKGROUND: The losses in productivity due to cardiovascular disease (CVD) are substantial but rarely considered in health economic analyses. We compared the cost-effectiveness of lipid level modification in the primary prevention of CVD with and without these indirect costs. METHODS: We used the Cardiovascular Life Expectancy Model to estimate the long-term benefits and cost-effectiveness of lipid level modification with atorvastatin calcium, including 28% and 38% reductions in total cholesterol and low-density lipoprotein cholesterol levels, respectively, and a 5.5% increase in high-density lipoprotein cholesterol level. The direct costs included all medical care costs associated with CVD. The indirect costs represented the loss of employment income and the decreased value of housekeeping services after different manifestations of CVD. All costs were expressed in 2000 Canadian dollars. RESULTS: When only direct medical care costs were considered, the incremental cost-effectiveness ratios for lifelong therapy with atorvastatin calcium, 10 mg/d, were generally positive, ranging from a few thousand to nearly $20 000 per year of life saved. When the societal point of view was adopted and indirect costs were included, the total costs were generally negative, representing substantial cost savings (up to $50 000) and increased life expectancy for most groups of individuals. CONCLUSIONS: Lipid therapy with statins can reduce CVD morbidity and mortality as demonstrated in a number of clinical trials. Adding the indirect CVD costs associated with productivity losses at work and home can result in forecasted cost savings to society as a whole such that lipid therapy could potentially save lives and money.
Adult↗
Modification of plasma membrane lipid order and H+-ATPase activity as part of the response of Saccharomyces cerevisiae to cultivation under mild and high copper stress.
Plasma membrane lipid disorganization takes place in cells of Saccharomyces cerevisiae grown under copper stress, as shown by fluorescence anisotropy measurements with the lipid reporter probe 1,6-diphenyl-1,3,5-hexatriene. The extent of plasma membrane disorganization, presumably due to copper-induced lipid peroxidation, was discontinuous when measured in cells grown in media supplemented with different concentrations of CuSO4. Results suggested the existence of adaptive mechanisms that cells employ to protect themselves against the deleterious effects of copper. The adaptive mechanisms examined in this study included the coordinate increase in the activities of Cu,Zn-superoxide dismutase (up to five-fold), glutathione reductase (up to 1.7-fold), and plasma membrane H+-ATPase (up to three-fold). These enzyme activities showed maximal levels in cells grown with copper supplied at intermediate concentrations, within the range that allowed growth. Significantly, at these concentrations, plasma membrane disorganization did not increase when increasing amounts of CuSO4 were supplied. However, at copper concentrations close to the maximal that allowed growth, the capacity of the yeast cell response to cope with the deleterious effects of copper was exceeded; plasma membrane lipid organization and plasma-membrane-bound H+-ATPase activity drastically declined in response to the increased levels of copper stress and the consequences on growth kinetics were even more severe. Our results clearly suggest that modification of plasma membrane H+-ATPase activity is either part of or the result of the global response of yeast to mild or high copper stress.
Cell Membrane↗
Detection of redox-based modification in two-dimensional electrophoresis proteomic separations.
Oxidative stress arises when cellular defenses against molecular oxygen and its by-products (reactive oxygen species; ROS) are overcome leading to covalent modification of lipids, DNA, and protein. Redox-based modification of proteins can be conveniently studied by proteomic analysis using two-dimensional electrophoresis (2D SDS-PAGE). Despite some technical shortcomings, this technique allows rapid and quantitative analysis of paired samples, the visualization of discrete protein spots, and provides a robust platform for subsequent analysis and identification of specific proteins. Exposure to oxidative stress introduces a wide range of reversible or irreversible alterations to amino acid side chains. These include carbonylation, glutathionylation, formation of mixed disulphides, effects on disulphide bridge patterns, ubiquitinylation, and racemization. Identification of proteins targeted for specific modification adds a deeper dimension to the dissection of effects of oxidative stress on the proteome with potentially far-reaching implications. This article describes key methodologies now available for identification of redox-based modifications in proteins separated by 2D SDS-PAGE.
Animals↗
Inhibitory effects of aromatic herbs on lipid peroxidation and protein oxidative modification by copper.
Aromatic herbs have been used as carminatives. Oxygen free radicals are generated in ischaemia/reperfusion injury in the stomach, and induce lipid peroxidation or protein oxidative modification. Several aromatic herbs were shown to have inhibitory effects on the generation of oxygen free radicals. It was shown that several aromatic herbs, Caryophylli Flos, Cinnamomi Cortex, Foeniculi Fructus and Zedoariae Rhizoma, have inhibitory effects on lipid peroxidation or protein oxidative modification by copper.
Cinnamomum↗
Apolipoprotein A-I lysine modification: effects on helical content, lipid binding and cholesterol acceptor activity.
We examined the role of the positively charged lysine residues in apoAI by chemical modification. Lysine modification by reductive methylation did not alter apoAI's net charge, secondary or tertiary structure as observed by circular dichroism and trytophan fluorescence, respectively, or have much impact on lipid binding or ABCA1-dependent cholesterol acceptor activity. Acetylation of lysine residues lowered the isoelectric point of apoAI, altered its secondary and tertiary structure, and led to a 40% decrease in cholesterol acceptor activity, while maintaining 93% of its lipid binding activity. Exhaustive lysine acetoacetylation lowered apoAI's isoelectric point, profoundly disrupted its secondary and tertiary structure, and led to 90% and 82% reductions in cholesterol acceptor and lipid binding activities, respectively. The dose-dependent acetoacetylation of an increasing proportion of apoAI lysine residues demonstrated that cholesterol acceptor activity was more sensitive to this modification than lipid binding activity, suggesting that apoAI lysine positive charges play an important role in ABCA1 mediated lipid efflux beyond the role needed to maintain alpha-helical content and lipid binding activity.
Acetylation↗
[Lipids, hemostasis and diabetes].
Modifications of hemostasis and plasma lipids are an integral part of diabetes mellitus, and probably play a key role in the evolution of vascular complications. This review points to the important relationships between hemostasis and lipids and their modifications in diabetes, with a special attempt to link the abnormalities described with the pathogenic mechanisms of diabetes.
Animals↗
Evaluation of 1-naphthol as a convenient fluorescent probe for monitoring ethanol-induced interdigitation in lipid bilayer membrane.
In this work we have tried to evaluate the usefulness of 1-naphthol as an excited state proton transfer fluorescent probe for studying the ethanol-induced interdigitation in lipid bilayer membranes. When ethanol concentration in lipisome is progressively increased, the neutral form fluorescence of 1-naphthol is found to decrease with corresponding increase in the anionic form intensity. This behavior is in contrast to that observed in the absence of lipid where a reverse effect is noticed. Modification of lipid bilayer is known to occur in the presence of ethanol, which increases the packing density of the membrane. Due to this induction of interdigitated gel phase, redistribution of naphthol between the inner core and interfacial region of the lipid bilayer takes places, accounting for the reduction in neutral form fluorescence intensity. The partition coefficient values and the quenching studies also support the redistribution of 1-naphthol in the liposome membrane. The neutral form fluorescence of 1-naphthol successfully monitors the shift in phase transition temperature due to ethanol-induced interdigitation. It also explains the prevention of interdigitation in lipid bilayer at high cholesterol concentration.
Journal Article↗
Structural studies of Salmonella typhimurium ArnB (PmrH) aminotransferase: a 4-amino-4-deoxy-L-arabinose lipopolysaccharide-modifying enzyme.
Lipid A modification with 4-amino-4-deoxy-L-arabinose confers on certain pathogenic bacteria, such as Salmonella, resistance to cationic antimicrobial peptides, including those derived from the innate immune system. ArnB catalysis of amino group transfer from glutamic acid to the 4"-position of a UDP-linked ketopyranose molecule to form UDP-4-amino-4-deoxy-L-arabinose represents a key step in the lipid A modification pathway. Structural and functional studies of the ArnB aminotransferase were undertaken by combining X-ray crystallography with biochemical analyses. High-resolution crystal structures were solved for two native forms and one covalently inhibited form of S. typhimurium ArnB. These structures permitted identification of key residues involved in substrate binding and catalysis, including a rarely observed nonprolyl cis peptide bond in the active site.
Amino Acid Sequence↗
Quantification of oligonucleotide modifications of small unilamellar lipid vesicles.
We present a new method for quantification of the coupling efficiency between amphiphilic oligonucleotides and suspended small unilamellar lipid vesicles (SUVs). The method employs a supported (phospho)lipid bilayer (SLB)-modified sensor template, which upon exposure to a mixture of SUVs and amphiphilic DNA reacts neither with free SUVs nor with DNA-modified SUVs, but with free DNA only. Using calibration curves obtained by recording the concentration dependence of the initial binding rate of free amphiphilic DNA (in the absence of SUVs), it is demonstrated how concentration determinations of both free and bound DNA in the two-component mixture (amphiphilic DNA and lipid vesicles) can be obtained. The calibration curves and the binding analysis were obtained using a quartz crystal microbalance with dissipation (QCM-D) monitoring. The binding efficiency of DNA coupled to SUVs (Ø approximately 50 nm) with two cholesterol moieties revealed that the bivalent coupling is essentially 100% in the range of approximately 1 to approximately 35 oligonucleotides per vesicle, whereas reversible coupling was confirmed in the case of monovalent coupling. Coupling of DNA via two cholesterol moieties was obtained by prehybridization of two single-stranded DNA strands modified with single cholesterol moieties in their 3' and 5' ends, respectively, and the monovalent coupling was obtained using single-stranded DNA. In the latter case, the analysis of the amount of free DNA at different DNA-SUV ratios also allowed for a determination of the maximum number of available binding sites on the SUVs, shown to be in good agreement with data obtained for DNA coupling on planar surfaces. With the only requirement that the SLB-modified sensor template react with one of the components in the two-component mixture only, as verified through fingerprint analysis of frequency, f, and energy dissipation, D, QCM-D measurements, it is emphasized that the method is generic and offers a fast and reliable method for evaluations of biomolecular modifications of any type of colloidal nanoparticles.
Base Sequence↗
The lipidated membrane anchor of full length N-Ras protein shows an extensive dynamics as revealed by solid-state NMR spectroscopy.
Many proteins involved in signal transduction are equipped with covalently attached lipid chains providing a hydrophobic anchor targeting these molecules to membranes. Despite the considerable biological significance of this membrane binding mechanism for 5-10% of all cellular proteins, to date very little is known about structural and dynamical features of lipidated membrane binding domains. Here we report the first comprehensive study of the molecular dynamics of the C-terminus of membrane-associated full-length lipidated Ras protein determined by solid-state NMR. Fully functional lipid-modified N-Ras protein was obtained by chemical-biological synthesis ligating the expressed water soluble N-terminus with a chemically synthesized (2)H or (13)C labeled lipidated heptapeptide. Dynamical parameters for the lipid chain modification at Cys 181 were determined from static (2)H NMR order parameter and relaxation measurements. Order parameters describing the amplitude of motion in the protein backbone and the side chain were determined from site-specific measurements of (1)H-(13)C dipolar couplings for all seven amino acids in the membrane anchor of Ras. Finally, the correlation times of motion were determined from temperature dependent relaxation time measurements and analyzed using a modified Lipari Szabo approach. Overall, the C-terminus of Ras shows a versatile dynamics with segmental fluctuations and axially symmetric overall motions on the membrane surface. In particular, the lipid chain modifications are highly flexible in the membrane.
Amino Acid Sequence↗
Modifications induced by dietary lipid source in adipose tissue phospholipid fatty acids and their consequences in lipid mobilization.
The aim of the present work was to assess the influence of dietary lipid source on fatty acid phospholipid profiles and on lipid mobilization. Forty male Wistar rats were divided into four groups and fed on high-fat diets which provided olive oil, sunflower oil, palm oil or beef tallow. All rats received the same amount of energy to avoid hyperphagia and differences in energy intake among groups. Phospholipid fatty acids were determined by GC. Lipolysis was stimulated in subcutaneous and perirenal isolated adipocytes by several lipolytic agents, and assessed by the determination of released glycerol. After 4 weeks of feeding, differences in body and adipose tissue weights were not observed. Dietary regimens caused great changes in adipose tissue phospholipid composition: rats fed on palm oil and beef tallow had higher concentrations of saturated fatty acids and animals fed on olive oil or sunflower oil had greater amounts of oleic and linoleic acids, respectively. These modifications did not lead to important changes in adipocyte lipolysis. Significant differences were only observed between palm-oil- and beef-tallow-fed groups when lipolysis was stimulated by isoproterenol in subcutaneous adipocytes. The fact that our feeding protocol did not induce differences in fat accumulation among groups avoids misinterpretations due to adiposity changes. The differences observed between both saturated-fat-fed groups, therefore, should only be attributable to dietary lipids. Despite this effect, the data from this work indicate that some diet-induced changes in adipose tissue fatty acid composition may have little effect on overall function.
Adipocytes↗
Effect of apolipoprotein E polymorphism on serum lipid response to the separate modification of dietary fat and dietary cholesterol.
BACKGROUND: The magnitude of the influence of the apolipoprotein (apo) E genotype on the lipid response to different cholesterol-lowering diet modifications has been controversial. OBJECTIVE: The aim of the study was to investigate the effect of apo E genotype on serum lipid response to the separate modification of dietary fat and cholesterol. DESIGN: A prospective study design with the 3 main apo E genotype groups (3/3, 3/4, and 4/4; n = 15 in each group) was used. Groups were matched for sex, age, body mass index, menopausal status, and baseline serum cholesterol concentration. Subjects followed 3 different diets in fixed order: 1) a standardized baseline diet (38% fat, 300 mg cholesterol/d), 2) a modified National Cholesterol Education Program (NCEP) diet (34% fat, 265 mg cholesterol/d), and 3) the modified NCEP diet + cholesterol (566 mg cholesterol/d). Subjects were middle-aged (50.9 +/- 8.0 y) and mildly hypercholesterolemic (6.55 +/- 1.05 mmol/L). RESULTS: The genotype groups differed in their total cholesterol response to the NCEP diet; the mean (95% CI) decrease being greatest, -14.1% (-19.8%, -8.6% ), in subjects with apo E genotype 4/4 (P = 0.03, analysis of variance). The increase in total cholesterol after addition of 300 mg cholesterol was also greatest in subjects with apo E 4/4 [10.4% (5.8%, 15.1%)] (P = 0.03, analysis of variance). CONCLUSIONS: Apo E genotype modified the lipid response to changes in both dietary fat and cholesterol in mildly hypercholesterolemic subjects; the response was greatest in subjects with apo E genotype 4/4 and even a moderate increase in dietary cholesterol resulted in a 10% elevation in serum total cholesterol in them.
Adult↗
Modulation of chloroplast membrane lipids by homogeneous catalytic hydrogenation.
A method is reported for the modification of lipids in situ in chloroplast membrane by which a homogeneous, water-soluble catalyst Pd(QS)2 (QS, sulphonated alizarine; C14H6O7NaS) is incorporated into the thylakoids of isolated chloroplast. The catalyst itself did not affect the photosynthetic activity but caused an extensive loss of unsaturated fatty acids in the presence of hydrogen gas. The polyunsaturated fatty acids were hydrogenated at a faster rate than the monoenoic acids. During hydrogenation the orientational ordering of membrane lipids, as measured with the C-12 positional isomer of spin-labelled stearic acid, displayed a slight increase in agreement with the alterations in membrane composition. Progressive saturation of double bonds of lipids primarily inhibits electron transport between the photosystems followed by the inhibition of electron flow around photosystem II. Photosystem I electron transport was not inhibited even by 50% fatty acid hydrogenation. We suggest that using Pd(QS)2 catalyst for thylakoid hydrogenation offers an excellent technique to study the role of various unsaturated fatty acids in the regulation of membrane fluidity and photosynthetic processes.
Catalysis↗
Modified forms of low density lipoprotein and atherosclerosis.
Modified forms of low density lipoprotein (LDL) are associated with increased atherogenicity. Modified LDL, in comparison with native LDL, demonstrates enhanced cellular uptake by macrophages, foam cell formation and also causes the secretion of cytokines and growth factors from arterial wall cells. Non-enzymatic modifications of LDL (proteoglycans, glycosylation, immune complexes) and enzymatic modifications (lipases, oxygenases) were shown to affect the physicochemical (size, charge) as well as the biological (cellular uptake, secretion) properties of the lipoprotein. Of special interest is the oxidative modification of LDL which was demonstrated to occur in vivo. The mechanism of this process involves cellular lipid peroxidation and requires the binding of LDL to its receptor on macrophages. Some of the modifications can render the LDL more susceptible to other types of modifications (lipid modifications, aggregation, oxidation). As atherosclerosis is a multifactorial disease and since lipases and oxygenases exist in cells of the arterial wall, several forms of modified LDL may exist in vivo. These modifications can occur either in parallel or along different stages of atherogenesis. Inhibition of such LDL modifications may arrest the development of the atherosclerotic lesion.
Arteriosclerosis↗
Effect of dietary modification on changes in serum lipids among rural Thai persons with hypercholesterolemia.
This article reports on the effect of dietary modification on changes in eating patterns and serum lipids among hypercholesterolemic persons aged 40-59 years with no evidence of coronary heart disease in Mae Sot District, Tak Province, between 1995 and 1996. A total of 381 persons with total cholesterol levels > or = 240 mg/dl and triglyceride levels < 400 mg/dl were educated, counseled, and followed-up by the mobile health team at the health centres in the communities. The team comprised both hospital personnel (a physician, a health educator, and public health nurses) and the health centre workers. Of the 381 study persons, 331 (86.9%) completed the one-year follow-up. The participants at one-year follow-up were more likely than at baseline to reduce intakes of dietary fat and cholesterol, whereas, there was an increased intake of vegetables and fruits. The mean total cholesterol level significantly decreased from 258.9 mg/dl at baseline to 236.1 mg/dl at one-year follow-up (p < 0.01), giving an 8.8 per cent reduction. The mean change in low-density lipoprotein cholesterol levels was a 26.0 mg/dl decrease (p < 0.01), yielding a 15.1 per cent fall. The mean high-density lipoprotein cholesterol level increased from 44.6 mg/dl at baseline to 46.8 mg/dl at one-year follow-up (p < 0.01). The proportion of those who had a body mass index of < 25 slightly increased from 70.7 per cent at baseline to 72.5 per cent at one-year follow-up. The dietary intervention program by the mobile team may be useful for lowering serum cholesterol among the rural population with hypercholesterolemia.
Adult↗