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At least 1,135 records · Page 63Linked to original sources
PubMed1979

Lecithin:cholesterol acyltransferase activity, plasma and lipoprotein lipids and obesity in men and women.

Lecithin:cholesterol acyltransferase (LCAT) activity, lipid concentration, lipoprotein lipid concentrations and cholesteryl ester linoleic acid proportion were determined in the plasma of 85 subjects randomly selected from a population during a health screen survey. Mean fractional LCAT rate was significantly higher in men than in women. Molar LCAT rate correlated with low density lipoprotein (LDL) cholesterol concentration in men and with nearly all lipoprotein lipid concentrations in women. Most of these relationships were dependent on plasma unesterified cholesterol (UC) concentration. Fractional LCAT rate was correlated only with HDL cholesterol concentration in women and this relation was dependent on the influence of obesity. An inverse relationship between plasma cholesteryl ester (PCE) linoleic acid proportion and molar LCAT rate in women was also explained by influences of obesity on the data. Both fractional and molar LCAT rates were positively correlated with obesity (Quetelet's Index and subscapular skinfold thickness) in women but not in men. This study showed the influence of sex on nearly all correlations involving LCAT activity in combined groups of men and women.

Adolescent↗
PubMed1998

Evidence against alterations in Lecithin:cholesterol acyltransferase (LCAT) activity in familial combined hyperlipidemia.

Elevated concentrations of plasma cholesterol and triglycerides are characteristic of familial combined hyperlipidemia (FCHL) which may also present with reduced high density lipoprotein (HDL) cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by converting unesterified cholesterol to cholesterol ester in the process of maturation of HDL in the presence of its activator, apolipoprotein (apo) A-I. We hypothesised that alterations in LCAT activity or plasma concentrations or gene sequence of apo A-I could influence HDL metabolism in these patients. We studied cholesterol concentrations of high density lipoprotein subfractions and LCAT activity in 25 FCHL subjects and 48 controls. Total HDL (p=0.018) and HDL2 (p=0.008) were significantly decreased in the FCHL group compared with controls. After analyses with adjusted data only HDL2 remained significantly decreased in the FCHL group (p=0.050). The LDLc/HDLc and A-I/HDLc ratios were significantly elevated in the FCHL group (p <0.0001), the latter suggesting the existence of compositional differences in the HDL particles of the FCHL individuals. LCAT activity assessed in the FCHL (19.94+/-3.95 nmol/ml per h) and control (20.13+/-6.86 nmol/ml per h) groups showed no statistically significant differences. A significant positive correlation of LCAT activity with total HDL (r=0.42), HDL3 cholesterol (r=0.46) and apolipoprotein A-I (r=0.47) was observed in affected subjects but not in controls. An association between a Ga(-75)-A variation in the promoter region of the apo A-I gene and elevated concentrations of apo A-I (p=0.009) and apo C-III (p=0.041) was observed. This association was strongly influenced by the status of the subject providing further evidence for a regulatory role of this genetic region in the expression of FCHL. Our data suggests that LCAT activity is normal in FCHL and, therefore, does not account for the abnormalities observed in these patients essentially with regard to the HDL2 subfraction.

Adult↗
PubMed1998

In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipase.

As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced than that in mildly HTG plasma, but they became highly pronounced upon increase of its TG-rich lipoprotein level by the addition of preisolated VLDL or by the induction of postprandial lipemia. Although the effect of LCAT, CETP and LpL reactions in non-circulating plasma in vitro may be different from that in vivo, the above data suggests that the plasma TG-rich lipoprotein level and the extent of intraplasma LCAT, CETP, LpL and likely hepatic lipase (HL) reactions in vivo may play a role in determining the LDL phenotype.

Carrier Proteins↗
PubMed1999

Fractional efflux and net change in cellular cholesterol content mediated by sera from mice expressing both human apolipoprotein AI and human lecithin:cholesterol acyltransferase genes.

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport. We have used transgenic mice (Tgm) expressing either both human apolipoprotein AI (apo AI) and human LCAT genes or only the human apo AI gene (HuAILCAT or HuAI Tgm, respectively) to assess the consequences of LCAT overexpression on serum lipid and lipoprotein profiles and on the ability of each serum to promote bidirectional flux of cholesterol between serum and Fu5AH hepatoma cells. Mean serum LCAT activity of HuAILCAT Tgm was 2-fold increased compared to the HuAI group (48+/-9 vs. 24+/-5 nmol/ml per h, P<0.01 for HuAILCAT and HuAI Tgm, respectively) and the cholesterol esterification rates were not significantly different between the two groups of animals (66+/-11 vs. 74+/-18 nmol/ml per h for HuAILCAT and HuAI Tgm, respectively). HuAILCAT Tgm exhibited higher total cholesterol serum values (2.3-fold) due to an increase in both HDL-cholesterol (1. 9-fold) and non-HDL-cholesterol (3-fold). The HDL particles from HuAILCAT Tgm were relatively phospholipid depleted and cholesterol enriched compared to HuAI mice. When cells were incubated for six hours with the mouse serum, the fractional efflux of radiolabeled cholesterol was slightly increased with the HuAILCAT Tgm (1.2-fold) but the increase in intracellular cholesterol content was also 2-fold higher than with the HuAI Tgm. Fu5AH can be viewed as a model for the evaluation of bidirectional flux of cholesterol in SR-BI-rich cells. In this model LCAT overexpression in mice, by increasing both HDL and non-HDL-cholesterol, mostly enhances the uptake of cholesterol by the cells, which would be of benefit for the last step of reverse cholesterol transport in hepatocytes.

Animals↗
PubMed1999

Construction and characterization of polycistronic retrovirus vectors for sustained and high-level co-expression of apolipoprotein A-I and lecithin-cholesterol acyltransferase.

Apolipoprotein A-I (apo A-I) and lecithin-cholesterol acyltransferase (LCAT) are constituents of circulating high-density lipoprotein (HDL) particles and play an important role in 'reverse cholesterol transport', the process by which cholesterol in peripheral tissues is transferred to the liver for excretion. Enhancing levels of apo A-I, as well as LCAT, in plasma may promote the removal of excess cholesterol from the arterial wall and thus reduce the formation of atherosclerotic lesions. Indeed, both apo A-I and LCAT genes have been identified as therapeutic targets to prevent or limit atherogenesis. Here, we have constructed two retroviral vectors, one containing LCAT cDNA and the neomycin phosphotransferase (NEO) gene (pLLEN), the other apo A-I cDNA, LCAT cDNA and the NEO gene (pLAPLEN) linked by internal ribosome entry sites (IRES). Both bi- and tricistronic retroviral vectors efficiently co-expressed their two or three genes when transfected into cultured mouse C2C12 muscle cells or human 293 cells. After 30 days, the retroviral vector sequences were retained by the host cells, whereas those of a conventional plasmid vector were lost. Moreover, transduced C2C12 mouse myoblasts maintained the ability for heterologous expression of human LCAT and apo A-I even after differentiation into myotubes. Stably-transduced clones of C2C12 cells were selected by neomycin (G418) resistance and continued to efficiently express human LCAT for 60 days. These findings indicate that the use of polycistronic retrovirus vectors to genetically modify myoblasts, which can be transplanted back into skeletal muscle, might be a safe and feasible strategy to express human apo A-I and LCAT and hence have therapeutic potential to regress atherosclerotic lesions.

Animals↗
PubMed1998

Increased activity of lecithin:cholesterol acyltransferase during short-term oral estrogen progestin replacement therapy in a group of postmenopausal women.

The aim of the study was to assess the short-term effect of estrogen-progestin therapy on the plasma level of lecithin: cholesterol acyltransferase ([LCAT] EC 2.3.1.43), a key enzyme in the cholesterol reverse-transport process. The trial included 21 women with at least 6 months of menopause, which was confirmed by anamnesis, physical evaluation, and follicle-stimulating hormone (FSH) determination. Women receiving pharmacological treatment or who had any kind of endocrine disorder were excluded. In addition, we evaluated and confirmed normal Papanicolaou and mammography tests in all 21 women included in the trial. They received conjugated equine estrogen 0.625 mg daily, plus cyclic medroxyprogesterone acetate (5 mg daily) for 12 days each month. Plasma levels of LCAT, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apoB, and apoAI were evaluated before and after 1 and 3 months of therapy. Pretherapy and posttherapy results were analyzed statistically by Wilcoxon's rank-sum test for paired samples. No significant changes were observed either for body mass index or for blood pressure. A significant increase in plasma LCAT activity was found at the first and third month posttherapy (P < .005). In addition, after 3 months of therapy, HDL-C significantly increased (P < .005), in contrast to the significant decrease detected in total cholesterol (P < .025), LDL-C (P < .005), cholesterol to HDL-C and LDL-C/HDL-C ratios (P < .005). Triglyceride levels did not show significant modification. In conclusion, our results indicate that short-term estrogen-progestin therapy produces a significant increase in plasma LCAT activity, as well as beneficial changes in the lipid profile, in postmenopausal women.

Adult↗
PubMed2003

Effects of lecithinized superoxide dismutase on neuronal cell loss in CA3 hippocampus after traumatic brain injury in rats.

BACKGROUND: The protective effect of excitatory amino acid antagonists for CA3 hippocampal neuronal loss has been well documentated. From a clinical point of view, however, alternative therapies should also be explored because excitatory amino acid antagonists have relatively deleterious side effects. Administration of lecithinized superoxide dismutase (PC-SOD) has recently been demonstrated to reduce brain edema after traumatic brain injury (TBI) in the cerebral cortex. In this study, we investigated the effectiveness of PC-SOD on CA3 hippocampal cell loss by examining hematoxylin and eosin-stained sections. METHODS: Rats were divided at random into three groups. The first group received 1 mL of saline (contusion + saline group, n = 5). Rats of the second group were treated with 3000 IU/kg of PC-SOD (contusion + SOD 1 group, n = 5), while the third group received 5000 IU/kg of PC-SOD (contusion + SOD 2 group, n = 5). All agents were administered intraperitoneally 1 minute after traumatic insult and every 24 hours until 2 or 3 days post-TBI. Animals were sacrificed 3 or 7 days after contusion injury. RESULTS: PC-SOD prevented CA3 neuronal loss 3 days after TBI, and increased the number of surviving CA3 neurons 7 days after TBI. CONCLUSION: Our findings suggest that PC-SOD may serve as a pharmacological agent in the treatment of neuronal loss after TBI.

Animals↗
PubMed1998

Comparison of bacteriological qualities of various egg yolk sources and the in vitro and in vivo fertilizing potential of bovine semen frozen in egg yolk or lecithin based diluents.

The addition of components of animal origin (egg yolk, milk) to most commercial diluents used to freeze bull semen represents a potential risk of contamination of the doses with bacteria or mycoplasma. A series of quantitative and qualitative analyses were performed to detect microbiological contamination observed in Biociphos plus (a new lecithin-glycerol based freezing salt buffer), in an egg yolk diluent (Triladyl) or in an egg yolk + milk-based (Laiciphos) diluent of bull semen. The 2 diluents containing animal products showed moderate (10 to 60 CFU/mL) contamination (17/17 samples) with bacteria or mycoplasma, or both, while no contamination was observed in the 6 examined batches of Biociphos plus. Biociphos plus was also compared with another commercial diluent (Laiciphos) for use in freezing bull semen intended for in vitro and/or in vivo fertilization. No difference (P > 0.05) could be detected between the 2 diluents for in vitro fertility rates (percentage of cleaved zygotes: 85.7% and 88.0%, respectively, for Laiciphos and Biociphos plus). Similarly, 2 series of comparisons conducted in dairy cows artificially inseminated with semen frozen in either Biociphos plus or Laiciphos showed no difference in fertilizing capacity (tested at 60 to 90 d; P > 0.05) irrespective of the age of the bulls (Trial 1, bulls aged 14 to 15 m.o.; Trial 2, bulls aged 2 to 5 yr, field trials). It is concluded that, in addition to maintaining the fertilizing capacity of bull semen at levels comparable to those observed with standard freezing diluent, Biociphos plus also prevents microbiological contamination by bacteria or mycoplasma, both of which are generally present in the various commercially available sources of egg yolk.

Animals↗
PubMed1975

Gallstone dissolution in man using cholic acid and lecithin.

Seven patients with radiolucent stones in the gallbladder and two patients with radiolucent stones in the biliary tree were treated with oral cholic acid and purified soya-bean lecithin for 6 months. In two patients the stones disappeared and in one patient the stones were reduced in size. In five patients fasting bile samples were obtained before and during treatment and assayed for cholesterol, bile acid, and phospholipid. In all five patients the lithogenic index of bile was reduced during treatment. The biliary deoxycholic acid concentration was increased and chenodeoxycholic acid concentration decreased during treatment.

Administration, Oral↗
PubMed2002

Selective extraction of lecithin:cholesterol acyltransferase (EC 2.3.1.43) from human plasma.

A method for the rapid extraction of lecithin:cholesterol acyltransferase (LCAT) from human plasma or serum has been developed. The method is based on direct treatment of acidified plasma of fully conserved enzyme activity, with the strong ion exchanger Q-Sepharose, which under the experimental conditions bound all LCAT but only about 10% of the total protein content of the plasma, no albumin and essentially no lipoproteins. This corresponds to a 10-fold purification. Only traces of apolipoprotein A-I remained in the quantitatively desorbed LCAT preparation which, however, contained a residual fraction of apolipoprotein D and acidic plasma proteins. The present one-step procedure for extraction of LCAT in high yields from human plasma represents a simple and efficient alternative to the first step in previously described methods for preparation of the enzyme to homogeneity.

Anions↗
PubMed2000

Spontaneous electrical potential oscillation on a filter impregnated with soybean lecithin placed between identical solutions of alanine.

Filters impregnated with soybean lecithin, placed between two identical aqueous alanine solutions, display spontaneous electric potential oscillations. Alanine solutions used in a large concentration range from 1 mM to 1 M produce damped oscillatory behaviour with an exponential decay in time. The dependence of decay time on concentration shows saturation behaviour which is well fitted with a sigmoidal curve. Power spectra obtained by Fourier transform show peaks specific for each concentration. When fitted with a Lorentzian curve in the peak domain, the centre of the peak height and width at half height could be extracted. All these parameters depend on alanine concentration in a saturating pattern.

Alanine↗
PubMed1996

Diffusion of mixed micelles of bile salt-lecithin in amylopectin gels: a Fourier transform infrared microspectroscopy approach.

Using fourier transform infrared (FTIR) microspectroscopy the average translational diffusion coefficients of bile salt-lecithin mixed micelles diffusing in amylopectin gels of varying concentration were measured, on the assumption that the diffusion coefficient was constant during diffusion. This assumption was examined based on quasielastic light scattering (QLS) measurements of the change in the mixed micellar size on dilution. The size increased significantly on dilution with a buffer without the bile salt, whereas the size was almost constant on dilution with a solution of the bile salt in the same buffer. Because bile salt molecules in intermicellar solution (being much smaller) diffuse much faster than the mixed micelles, the mixed micelles in the diffusing front can be treated as if diluted with the bile salt solution. Therefore their size will be constant during diffusion, validating the assumption of a constant diffusion coefficient. Based on this it is possible to show that the micelles diffuse with a diffusion coefficient of approximately 10(-11) m2 s-1, independent (within experimental error) of the amylopectin gel concentration over the range 5%-10% w/w.

Amylopectin↗
PubMed1997

Alternative splicing in lecithin:cholesterol acyltransferase mRNA: an evolutionary paradigm in humans and great apes.

Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affecting reverse cholesterol transport, is expressed in liver and cultured fibroblasts. Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRNA products. In addition to the normal transcript, we identified an alternate message with a splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and 6. In humans, the alternate transcript represents 5-20% of the complete LCAT message in cultured fibroblasts and liver. It is present in humans and the great apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g., old or new world monkeys). Sequencing of intron 5 of the LCAT locus in several primates revealed a G-->A transition at the splice donor recognition site in the Alu repeat of the gibbon and a G-->A substitution in the last position of the 95 bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions have been associated with exon skipping in other genes. These results demonstrate that alternative splicing of LCAT mRNA is variant among primates and suggest a potential role of Alu elements in the evolutionary diversity of proteins.

Alternative Splicing↗
PubMed1998

Fatty acid composition of plasma and erythrocytes in term infants fed human milk and formulae with and without docosahexaenoic and arachidonic acids from egg yolk lecithin.

Human milk contains small but nutritionally significant amounts of long-chain polyunsaturated fatty acids (LCP), such as arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids, which are not present in most infant formulae. In the present study, the fatty acid composition of plasma and erythrocytes was determined at birth and again at 7 days, 1 and 3 months in 49 healthy full-term infants (37-42 week's gestation). One group of infants was fed exclusively with human milk (n=16) and the others were randomly assigned to a standard term formula (F) (n=15) or the same formula with egg yolk lecithin providing DHA (0.15%) and AA (0.30%) (LCP-F) (n=18). Plasma and erythrocyte LCP values of the three dietary groups did not differ at 7 days of age, but the contents of DHA and AA in plasma and erythrocytes at 1 and 3 months were significantly lower (P<0.05) in infants fed non supplemented formula than in infants fed breast milk and supplemented formula. There were no differences in plasma or erythrocyte AA or DHA concentrations between the group fed breast milk and the group fed supplemented formula during the period studied.

Aging↗
PubMed1980

Miniature two-dimensional thin-layer chromatographic separation of lecithin and sphingomyelin.

A miniature two-dimensional thin-layer chromatographic procedure employing silica gel impregnated glass-microfiber chromatography sheets (commercial product, ITLC-type SG sheets) has been developed for the separation of lecithin (L) and sphingomyelin (S) from a standard lipid mixture containing L, S, lysolecithin, phosphatidyl inositol (PI), phosphatidyl serine (PS), phosphatidyl ethanolamine, phosphatidyl glycerol, and diphosphatidyl glycerol. The newly developed procedure eliminates possible interference from PI and PS. Complete separation of L and S was easily achieved with chromatographic solvent migration times of approximately 3 and 2 min for the first and second dimensions, respectively. The lipids were visualized by charring and fluorescent staining techniques. The procedure has been adapted for the separation of L and S from amniotic fluid samples.

Amniotic Fluid↗
PubMed2003

The absorption behavior of cyclosporin A lecithin vesicles in rat intestinal tissue.

The purpose of the study was to investigate the absorption behavior of lecithin vesicles of cyclosporin A (CsA-VES), prepared by the rotary evaporation method and treated further with sonication. The everted gut sac technique and in situ circulation method were used to examine: (1) relationship between the CsA-VES absorption velocity and the CsA-VES content; (2) the influence of the intestinal mucus, blank vesicles, concentration of Na(+), energy inhibitor and P-gp inhibitor on the absorption of CsA-VES; and (3) the respective accumulated content of CsA in the incubating medium and the sacs after incubation with Sandimmum Neoral((R))(CsA-NEO) and CsA-VES. Our results showed there was a saturated absorption of CsA. Most CsA-VES accumulated in the mucus before it reached the intestinal tissue. There was no significant difference in the accumulated absorption content in the incubating medium and the sacs of CsA-NEO and CsA-VES. The addition of blank vesicles and concentration of Na(+) had no significant influence on the accumulated absorption of CsA (P>0.05). The energy inhibitor and P-gp inhibitor influenced the accumulated absorption of CsA significantly (P<0.05). CsA-VES may be transported by phagocytosis. Mucus was a barrier blocking the diffusion of CsA-VES. CsA-NEO and CsA-VES showed equal absorption levels in the intestine.

Animals↗
PubMed1999

Surfactant-induced leakage from liposomes: a comparison among different lecithin vesicles.

The interactions, at sublytic concentration, of Triton X-100 and sodium cholate with sonicated and extruded liposomes of egg and soya lecithins were considered to analyze the integrity and/or the barrier efficiency of liposomal membranes. Results are discussed in terms of surfactant partition between the aqueous and the lipid phases and of the release of a fluorescent hydrophilic probe. Phospholipid nature and liposome size influence detergent partition, whereas the content release is mainly affected by the surfactant mole fraction in the bilayer, and by the liposome size.

Detergents↗
PubMed1998

Analysis of lecithin in pharmaceutical products and diet integrators using a new biosensor operating directly in non aqueous solvent.

One of the first examples of a bienzymatic organic phase enzyme electrode (OPEE) is described. It was obtained using two enzymes (phospholipase D and choline oxidase), both immobilised in kappa-Carrageenan gel and, as electrochemical transducer, an amperometric gas diffusion electrode for oxygen. The response of the biosensor was recorded and its sensitivity, linearity range, response time evaluated. Lastly drugs and diet products containing lecithin were analysed using the new biosensor device working in an organic mixture.

Alcohol Oxidoreductases↗