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At least 235 records · Page 13Linked to original sources
PubMed1994

Enhanced cytochrome oxidase activity and modification of lipids in heart mitochondria from hyperthyroid rats.

In order to further investigate the mechanism regulating the control of mitochondrial respiration by thyroid hormones, the effect of the hyperthyroidism on the kinetic characteristics of cytochrome c oxidase in rat heart mitochondria was studied. Mitochondrial preparations from both control and hyperthyroid rats had equivalent Km values for cytochrome c, while the maximal activity of cytochrome oxidase was significantly increased (by around 30%) in mitochondrial preparation from hyperthyroid rats. This enhanced activity of cytochrome oxidase was associated to a parallel increase in mitochondrial State 3 respiration. The hormone treatment resulted in a decrease in the flux control coefficient of the oxidase. The enhanced activity of cytochrome oxidase in hyperthyroid rats does not appear to be dependent on an increase in the mass of this enzyme complex in that the heme aa3 content was equivalent in both hyperthyroid and control preparations. The Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria from hyperthyroid rats as compared with control rats in that the breakpoint of the biphasic plot is shifted to a lower temperature. Cardiolipin content was significantly increased in mitochondrial preparations from hyperthyroid rats, while there were no significant alterations in the fatty acid composition of cardiolipin of control and hyperthyroid preparations. The results support the conclusion that the enhanced cytochrome oxidase activity in heart mitochondrial preparations from hyperthyroid rats is due to a specific increase in the content of cardiolipin.

Animals↗
PubMed1989

Structural modifications of lipid vesicles by 8-methoxypsoralen.

On prolonged UV-A illumination the ESR spectrum of 16-doxylstearic acid in dimyristoyl phosphatidylcholine vesicles loaded with 8-methoxypsoralen changed dramatically as a second broad component gradually appeared. The composite nature of the spectrum was proven by digital subtraction and the two components were simulated using the modified Bloch equations. From the spectral anisotropy of the motionally averaged three-line component, the molecular order was found to decrease during UV-A illumination, and isotropic rotation of the spin probe was observed well below the phase transition temperature. In parallel an exchange averaged component dominated the central part of the spectrum, indicating the segregation of spin probes into separate domains. The build-up of the composite lineshape was followed by fitting weighted sums of the above two components to spectra recorded after various time intervals. It is concluded that PUVA therapy, which is routinely used against psoriasis, might also induce overlooked damage to the saturated lipid species of biological membranes.

Electron Spin Resonance Spectroscopy↗
PubMed1998

An intracellular role for pancreatic bile salt-dependent lipase: evidence for modification of lipid turnover in transfected CHO cells.

Pancreatic bile salt-dependent lipase (BSDL) hydrolyzes cholesteryl esters, triglycerides and phospholipids. BSDL is also capable of transferring free fatty acid to cholesterol. BSDL has been detected in many cells including fetal and tumor cells, hepatocytes, macrophages and eosinophils and in tissues such as adrenal glands and testes. The enzyme may be secreted or located within subcellular compartments such as the endoplasmic reticulum or the cytosol. Although the role of the secreted enzyme is well documented, that of the intracellular form(s) is still hypothetical. In the present study, we addressed the effects of BSDL on cell lipid metabolism. For that purpose, the cDNA of rat BSDL was transfected into CHO K1 cells (CHO K1-BSDL clone) which were then loaded with [3H]oleic acid. The results demonstrate that the transfected BSDL is secreted; in spite of that, a large fraction of catalytically active BSDL is found in cell lysate. The lipid metabolism of transfected cells is affected and BSDL induces an enhanced incorporation of [3H]oleic acid in cholesteryl esters whereas fatty acid incorporation in phosphatidylcholine is decreased. These effects were particularly important in the cytosol of transfected cells where transfected BSDL preferentially locates. These data suggested that BSDL could be implicated in the cycle of the cellular homeostasis of cholesterol which is particularly affected in tumoral cells leading to cholesteryl ester storage within cytosolic lipid droplets.

Animals↗
PubMed2002

Cholesterol-induced modifications in lipid bilayers: a simulation study.

We present analysis of new configurational bias Monte Carlo and molecular dynamics simulation data for bilayers of dipalmitoyl phosphatidyl choline and cholesterol for dipalmitoyl phosphatidyl choline:cholesterol ratios of 24:1, 47:3, 11.5:1, 8:1, 7:1, 4:1, 3:1, 2:1, and 1:1, using long molecular dynamics runs and interspersed configurational bias Monte Carlo to ensure equilibration and enhance sampling. In all cases with cholesterol concentrations above 12.5% the area per molecule of the heterogeneous membrane varied linearly with cholesterol fraction. By extrapolation to pure cholesterol, we find the cross-sectional area of cholesterol in these mixtures is approximately 22.3 A(2). From the slope of the area/molecule relationship, we also find that the phospholipid in these mixtures is in a liquid ordered state with an average cross-sectional area per lipid of 50.7 A(2), slightly above the molecular area of a pure phospholipid gel. For lower concentrations of cholesterol, the molecular area rises above the straight line, indicating the "melting" of at least some of the phospholipid into a fluid state. Analysis of the lateral distribution of cholesterol molecules in the leaflets reveals peaks in radial distributions of cholesterols at multiples of approximately 5 A. These peaks grow in size as the simulation progresses, suggesting a tendency for small subunits of one lipid plus one cholesterol, hydrogen bonded together, to act as one composite particle, and perhaps to aggregate with other composites. Our results are consistent with experimentally observed effects of cholesterol, including the condensation effect of cholesterol in phospholipid monolayers and the tendency of cholesterol-rich domains to form in cholesterol-lipid bilayers. We are continuing to analyze this tendency on longer timescales and for larger bilayer patches.

Biophysical Phenomena↗
PubMed1983

Chain length dependent modification of lipid organization by low levels of 25-hydroxycholesterol and 25-hydroxycholecalciferol. A laser Raman study.

We have used Raman spectroscopy to investigate the thermal transitions of multibilayered liposomes composed of lecithins, i.e., dilauroyllecithin, dimyristoyllecithin, dipalmitoyllecithin, distearoyllecithin, or egg lecithin, plus 5-cholesten-3,25-diol (25-hydroxycholesterol), 25-hydroxycholecalciferol, and vitamin D3. We recorded the CH-stretching (2800-3000-cm-1) regions of the Raman spectra at various temperatures and employed plots of temperature vs. the intensity of the 2880- or 2930-cm-1 bands relative to that of the 2850-cm-1 feature, i.e., the ratios I2880/I2850 and I2930/I2850, to estimate thermal transitions. These plots show multiple discontinuities, each of which may be ascribed to a state change of a separate phase with distinctive proportions of lecithins and cholesterol derivatives. Low concentrations of 25-hydroxycholesterol and 25-OH-D3 (greater than or equal to 0.2 mol%) abolish the pretransition and split the main transitions of dilauroyllecithin (4 degrees C) and dimyristoyllecithin (23 degrees C) into two. The midpoint of the new small transition centers at about 3-4 degrees C lower than those of the respective main transitions of dilauroyllecithin and dimyristoyllecithin. A further increase in the molar ratio of 25-hydroxycholesterol and 25-hydroxycholecalciferol decreases the amplitudes of the new and the main transitions (dilauroyl- and dimyristoyllecithin). The transitions of dipalmitoyllecithin and distearoyllecithin at 2 mol % concentrations of either sterol remain unaffected. There was no splitting in the main transition of either dipalmitoyllecithin or distearoyllecithin in the presence of these sterols. The perturbing effect of the 25-hydroxysterols follows the order dilauroyllecithin greater than dimyristoyllecithin greater than dipalmitoyllecithin greater than distearoyllecithin.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcifediol↗
PubMed1981

Determination of cholesterol asymmetry by rapid kinetics of filipin-cholesterol association: effect of modification in lipids and proteins.

The rapid kinetic behavior of filipin association with cholesterol was unaffected by binding of water-soluble proteins to vesicle and mycoplasma membranes and by proteolytic digestion of mycoplasma membrane proteins. The kinetic properties were, however, dependent on the membrane phospholipids, in that the initial rate of filipin association with cholesterol was enhanced by phospholipase A2 treatment by the incorporation of lysophosphatidylcholine, and by increasing the degree of unsaturation in phospholipid vesicles and mycoplasma membranes. The second-order rate constant was also dependent on th mol % of cholesterol in small unilamellar vesicles but not in large unilamellar vesicles. The ratio of rate constants in intact mycoplasma cells relative to isolated membranes provides an estimate of cholesterol distribution in membranes [Bittman, R., & Rottem, S. (1076) Biochem. Biophys. Res. Commun. 71, 318; Clejan, S., Bittman, R., & Rottem, S. (1978) Biochemistry 17, 4579]. This ratio was unaffected by proteolytic digestion of intact cells and by the incorporation of exogenous phospholipids into the Mycoplasma capricolum cell membrane. However, on cross-linking of surface proteins of M. capricolum by dimethylsuberimidate, cholesterol was localized predominantly in the outer half of the bilayer. On aging of mycoplasma cultures, the cholesterol distribution remained constant in membranes of M. capricolum cells but was enriched in the outer leaflet of the Mycoplasma gallisepticum cell membrane. The results of these experiments are discussed in relation to the use of the rapid kinetics of filipin binding as a probe of cholesterol distribution.

Cell Membrane↗
PubMed2003

Effects of lifestyle modification and lipid intake variations on patients with peripheral vascular disease.

The aim of the present study was to evaluate the effects of diets enriched in monounsaturated fatty acids (MUFA) (olive oil) or MUFA plus n-3 polyunsaturated fatty acids (PUFA) (olive oil plus fish oil), associated with an intervention program that focused on lifestyle habits, physical performance, plasma lipids, and lipoprotein composition in patients with peripheral vascular disease (PVD). A 15-month longitudinal nutritional and lifestyle intervention study was carried out with 24 free-living male patients aged 58.0 +/- 2.2 years diagnosed with PVD (Fontaine grade II). The patients were clinically evaluated and counseled to change their dietary and lifestyle habits for six months, after this period they consumed an olive oil-based diet for three months: after a three-month wash-out period, their diet was supplemented with a combination of fish oil and olive oil for the final three months. Lifestyle interventions resulted in a significant decrease in cigarette smoking and an increase in physical activity. Claudicometry was lower at the end of the study than at the beginning. Intake of the fish oil supplement led to significant changes in lipid lipoprotein composition, decreasing low-density lipoprotein (LDL) cholesterol. The lifestyle intervention program, together with a high intake of olive plus fish oil, seems to produce important beneficial effects in nutritional management, physical performance, and clinical parameters of PVD patients.

Biomarkers↗
PubMed2001

Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fisher-344 rats.

Oxidative stress has been shown to play a role in aging and in neurodegenerative disorders. Some of the consequences of oxidative stress are DNA base modifications, lipid peroxidation, and protein modifications such as formation of carbonyls and nitrotyrosine. These events may play a role in apoptosis, another factor in aging and neurodegeneration, in response to uncompensated oxidative stress. Bcl-2 is a mitochondrial protein that protects neurons from apoptotic stimuli including oxidative stress. Using immunohistochemistry and western blot analysis, here we show that Bcl-2 is up-regulated in the hippocampus and cerebellum of aged (24 months) Fisher 344 rats. Treatment with the free radical spin trap N-tert-butyl-alpha-phenylnitrone (PBN) effectively reverses this age-dependent Bcl-2 up-regulation indicating that this response is redox sensitive. This conclusion was further supported by inducing the same regional Bcl-2 up-regulation in young (3 months) Fisher 344 rats exposed to 100% normobaric O(2) for 48 h. Our results indicate that Bcl-2 expression is increased in the aged brain, possibly as a consequence of oxidative stress challenges. These results also illustrate the effectiveness of antioxidants in reversing age-related changes in the CNS and support further research to investigate their use in aging and in age-related neurodegenerative disorders.

Aging↗
PubMed1987

[Modification of lipid metabolism by hPL in late pregnancy].

In the clinical study reported here, the relationship between the behavior of the serum lipids and the concentration of placental lactogen (HPL) was investigated in 107 gravidae in the last trimester. Among the patients examined there were 99 single pregnancies and eight multiple pregnancies--2x twins, 3x triplets, and 3x quadruplets. In these examinations, a significant positive correlation (p less than 0.01) was found between the HPL concentrations and the triglyceride values. Increases in HPL concentrations were associated with increasing total cholesterol and LDL cholesterol values. There was no relation to HPL values in the HDL and VLDL fraction of the cholesterol. Nor was there any relation between estrogen secretion in urine, which was measured in 42 patients, and plasma lipid concentrations. Extreme HPL values in multiple pregnancies, of more than 9 micrograms/ml, were associated with triglyceride concentrations of 383 +/- 37 mg/dl. Total cholesterol in these patients reached values of 294 +/- 19 mg/dl. These values returned to normal on the third day post partum. The mean HDL: total cholesterol ratio was 0.245 +/- 0.065 and was thus clearly above the pathognomonic limit of 0.150. The findings obtained in this study are indicative of the pronounced lipolytic potency of HPL.

Cholesterol↗
PubMed2003

Transferrin modifications and lipid peroxidation: implications in diabetes mellitus.

Free iron is capable of stimulating the production of free radicals which cause oxidative damage such as lipid peroxidation. One of the most important mechanisms of antioxidant defense is thus the sequestration of iron in a redox-inactive form by transferrin. In diabetes mellitus, increased oxidative stress and lipid peroxidation contribute to chronic complications but it is not known if this is related to abnormalities in transferrin function. In this study we investigated the role of transferrin concentration and glycation. The antioxidant capacity of apotransferrin to inhibit lipid peroxidation by iron-binding decreased in a concentration-dependent manner from 89% at > or = 2 mg/ml to 42% at 0.5 mg/ml. Pre-incubation of apotransferrin with glucose for 14 days resulted in a concentration-dependent increase of glycation: 1, 5 and 13 micromol fructosamine/g transferrin at 0, 5.6 and 33.3 mmol/l glucose respectively, p < 0.001. This was accompanied by a decrease in the iron-binding antioxidant capacity of apotransferrin. In contrast, transferrin glycation by up to 33.3 mmol/l glucose did not affect chemiluminescence-quenching antioxidant capacity, which is iron-independent. Colorimetric evaluation of total iron binding capacity in the presence of an excess of iron (iron/transferrin molar ratio = 2.4) also decreased from 0.726 to 0.696 and 0.585mg/g transferrin after 0, 5.6 and 33.3 mmol/l glucose, respectively, p < 0.01. In conclusion, these results suggest that lower transferrin concentration and its glycation can, by enhancing the pro-oxidant effects of iron, contribute to the increased lipid peroxidation observed in diabetes.

Animals↗
PubMed2005

Lipopolysaccharide heterogeneity: innate host responses to bacterial modification of lipid a structure.

The innate host response system is composed of various mechanisms designed to detect and facilitate host responses to microbial components, such as lipopolysaccharides (LPS). To enable this to occur, innate systems contain multiple pattern recognition receptors (i.e., LBP, CD14, and TLRs), which identify certain features within bacterial LPS that are foreign to the host, as well as essential and uniquely specific for bacteria. Innate host identification of unique bacterial components or patterns, therefore, relies on the inability of bacteria to alter these essential or critical components dramatically. Historically, LPS have been viewed as essential outer-membrane molecules containing both a highly variable outer region (O-segment) as well as a relatively conserved inner region (lipid A). However, over the last decade, new evidence has emerged, revealing that increased natural diversity or heterogeneity within specific components of LPS, such as lipid A-resulting in minor to moderate changes in lipid A structure-can produce dramatic host responses. Therefore, examples of natural lipid A heterogeneity, and the mechanisms that control it, represent a novel approach in which bacteria modulate host responses and may thereby confer specific advantages to certain bacterial species under changing environmental host conditions.

Animals↗
PubMed2005

Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation.

Protein farnesylation is a form of posttranslational modification that occurs in most, if not all, eukaryotic cells. Inhibitors of protein farnesyltransferase (PFTIs) have been developed as anticancer chemotherapeutic agents. Using the knowledge gained from the development of PFTIs for the treatment of cancer, researchers are currently investigating the use of PFTIs for the treatment of eukaryotic pathogens. This "piggy-back" approach not only accelerates the development of a chemotherapeutic agent for protozoan pathogens but is also a means of mitigating the costs associated with de novo drug design. PFTIs have already been shown to be efficacious in the treatment of eukaryotic pathogens in animal models, including both Trypanosoma brucei, the causative agent of African sleeping sickness, and Plasmodium falciparum, one of the causative agents of malaria. Here, current evidence and progress are summarized that support the targeting of protein farnesyltransferase for the treatment of parasitic diseases.

Animals↗
PubMed2006

Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras.

Proteins that terminate with a consensus sequence known as CAAX undergo a series of posttranslational modifications that include polyisoprenylation, endoproteolysis, and carboxyl methylation. These modifications render otherwise hydrophilic proteins hydrophobic at their C termini such that they associate with membranes. Whereas prenylation occurs in the cytosol, postprenylation processing is accomplished on the cytoplasmic surface of the endoplasmic reticulum and Golgi apparatus. Among the numerous CAAX proteins encoded in mammalian genomes are many signaling molecules such as monomeric GTPases, including the Ras proteins that play an important role in cancer. In the course of their processing, nascent Ras proteins traffic from their site of synthesis in the cytosol to the endomembrane and then out to the plasma membrane (PM) by at least two pathways. Recently, retrograde pathways have been discovered that deliver mature Ras from the PM back to the Golgi. The Golgi has been identified as a platform upon which Ras can signal. Thus, the subcellular trafficking of Ras proteins has the potential to increase the complexity of Ras signaling by adding a spatial dimension. The complexity of Ras trafficking also affords a wider array of potential targets for the discovery of drugs that might inhibit tumors by interfering with Ras trafficking.

Alkyl and Aryl Transferases↗