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1
Ozsavci, Derya, A. Nazli, O. Bingol Ozakpinar, G. Yanikkaya Demirel, B. Vanizor Kural, and A. Sener. "Native High-Density Lipoprotein and Melatonin Improve Platelet Response Induced by Glycated Lipoproteins." Folia Biologica 64, no. 4 (2018): 144–52. http://dx.doi.org/10.14712/fb2018064040144.
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Activated platelets and glycated lipoproteins are responsible for atherothrombosis in diabetics. Melatonin and native high-density lipoproteins are crucial in the preservation of pro/oxidant-antioxidant balance. The aim of the present study was to investigate the in vitro effects of native high-density lipoproteins and melatonin on altering the platelet response induced by glycated lipoproteins. Low-density lipoproteins and high-density lipoproteins were purified from plasma by ultracentrifugation and were glycated with glucose for three weeks. After incubation with or without melatonin/or native highdensity lipoproteins, low-density lipoproteins, glycated low-density lipoproteins/glycated high-density lipoproteins were added to ADP-induced platelets. Oxidative parameters, caspase-3/9 and nitric oxide levels were measured spectrophotometrically; CD62-P/ annexin-V expression was determined by flow cytometry. In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, platelet malondialdehyde/ protein carbonyl, P-selectin, annexin-V, caspase-3/9 levels were increased (ranging from P < 0.001 to P < 0.01); glutathione and nitric oxide levels were reduced (ranging from P < 0.001 to P < 0.01). In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, melatonin treatment reduced malondialdehyde, protein carbonyl, CD62-P, annexin-V and caspase-3/9 (P < 0.001, P < 0.01) levels and elevated nitric oxide (only glycated low-density lipoproteins). In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, native high-density lipoprotein treatment reduced malondialdehyde, protein carbonyl, annexin-V, caspase-3/9 levels (P < 0.001, P < 0.01) and increased glutathione; nitric oxide levels (only with gly-HDL). Both melatonin and high-density lipoproteins should be regarded as novel promising mechanism-based potential therapeutic targets to prevent atherothrombosis in diabetics.
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Öörni, Katariina, Satu Lehti, Peter Sjövall, and Petri T. Kovanen. "Triglyceride-Rich Lipoproteins as a Source of Proinflammatory Lipids in the Arterial Wall." Current Medicinal Chemistry 26, no. 9 (May 21, 2019): 1701–10. http://dx.doi.org/10.2174/0929867325666180530094819.
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Apolipoprotein B –containing lipoproteins include triglyceride-rich lipoproteins (chylomicrons and their remnants, and very low-density lipoproteins and their remnants) and cholesterol-rich low-density lipoprotein particles. Of these, lipoproteins having sizes below 70-80 nm may enter the arterial wall, where they accumulate and induce the formation of atherosclerotic lesions. The processes that lead to accumulation of lipoprotein-derived lipids in the arterial wall have been largely studied with a focus on the low-density lipoprotein particles. However, recent observational and genetic studies have discovered that the triglyceriderich lipoproteins and their remnants are linked with cardiovascular disease risk. In this review, we describe the potential mechanisms by which the triglyceride-rich remnant lipoproteins can contribute to the development of atherosclerotic lesions, and highlight the differences in the atherogenicity between low-density lipoproteins and the remnant lipoproteins.
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Biggerstaff, Kyle D., and Joshua S. Wooten. "Understanding lipoproteins as transporters of cholesterol and other lipids." Advances in Physiology Education 28, no. 3 (September 2004): 105–6. http://dx.doi.org/10.1152/advan.00048.2003.
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A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is “bad” and high-density lipoprotein-cholesterol is “good.” This misconception leads to students thinking that lipoproteins are types of cholesterol rather than transporters of lipid. Describing lipoproteins as particles that are composed of lipid and protein and illustrating the variation in particle density that is determined by the constantly changing lipid and protein composition clarifies the metabolic pathway and physiological function of lipoproteins as lipid transporters. Such a description will also suggest the critical role played by apolipoproteins in lipid transport. The clarification of lipoproteins as particles that change density will help students understand the nomenclature used to classify lipoproteins as well.
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Yousef, Malaz, Nadia Bou Chacra, Neal M. Davies, and Raimar Löbenberg. "Lipoproteins within the lymphatic system: Insights into health, disease, and therapeutic implications." Applied Chemical Engineering 6, no. 2 (September 4, 2023): 2202. http://dx.doi.org/10.24294/ace.v6i2.2202.
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This analysis of contemporary findings aims to enhance our understanding of lipoprotein biology within the lymphatic system and its relevance to human health and disease. It delves into the complex interrelationship between lipoproteins and the lymphatic system, encompassing their diverse classes and pivotal roles in the absorption and transport of drugs, vitamins, and xenobiotics. Lipoproteins consist of a hydrophobic core comprising non-polar lipids and a hydrophilic membrane composed of phospholipids, free cholesterol, and apolipoproteins. The lymphatic system collaborates with lipoproteins in the absorption and transport of dietary lipids. Simultaneously, it plays a vital role in the regulation of body fluid levels and acts as a formidable defense mechanism against infections. Lipoprotein classes encompass chylomicrons, chylomicron remnants, very low-density lipoproteins, intermediate density lipoproteins, low-density lipoproteins, high-density lipoproteins, and lipoprotein (a). Understanding the intricate relationship between lipoproteins and the lymphatic system holds immense implications for comprehending the underlying pathological processes of various diseases such as atherosclerosis, diabetes and obesity among others. By shedding light on the interplay between lipoproteins and the lymphatic system, this report underscores the significance of conducting research that contributes to the advancement of our knowledge in this field. Ultimately, such research paves the way for potential therapeutic interventions and novel strategies to address numerous disorders.
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Giesecke, Yvonne, Samuel Soete, Katarzyna MacKinnon, Thanasis Tsiaras, Madeline Ward, Mohammed Althobaiti, Tamas Suveges, James E. Lucocq, Stephen J. McKenna, and John M. Lucocq. "Developing Electron Microscopy Tools for Profiling Plasma Lipoproteins Using Methyl Cellulose Embedment, Machine Learning and Immunodetection of Apolipoprotein B and Apolipoprotein(a)." International Journal of Molecular Sciences 21, no. 17 (September 2, 2020): 6373. http://dx.doi.org/10.3390/ijms21176373.
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Plasma lipoproteins are important carriers of cholesterol and have been linked strongly to cardiovascular disease (CVD). Our study aimed to achieve fine-grained measurements of lipoprotein subpopulations such as low-density lipoprotein (LDL), lipoprotein(a) (Lp(a), or remnant lipoproteins (RLP) using electron microscopy combined with machine learning tools from microliter samples of human plasma. In the reported method, lipoproteins were absorbed onto electron microscopy (EM) support films from diluted plasma and embedded in thin films of methyl cellulose (MC) containing mixed metal stains, providing intense edge contrast. The results show that LPs have a continuous frequency distribution of sizes, extending from LDL (> 15 nm) to intermediate density lipoprotein (IDL) and very low-density lipoproteins (VLDL). Furthermore, mixed metal staining produces striking “positive” contrast of specific antibodies attached to lipoproteins providing quantitative data on apolipoprotein(a)-positive Lp(a) or apolipoprotein B (ApoB)-positive particles. To enable automatic particle characterization, we also demonstrated efficient segmentation of lipoprotein particles using deep learning software characterized by a Mask Region-based Convolutional Neural Networks (R-CNN) architecture with transfer learning. In future, EM and machine learning could be combined with microarray deposition and automated imaging for higher throughput quantitation of lipoproteins associated with CVD risk.
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Faria, Eliana Cotta de, Adriana Celeste Gebrin, Wilson Nadruz Júnior, and Lucia Nassi Castilho. "Phospholipid transfer protein activity in two cholestatic patients." Sao Paulo Medical Journal 122, no. 4 (2004): 175–77. http://dx.doi.org/10.1590/s1516-31802004000400009.
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CONTEXT: Plasma phospholipid transfer protein mediates the transfer of phospholipids from triglyceride-rich lipoproteins, very low density lipoproteins and low density lipoproteins to high density lipoproteins, a process that is also efficient between high density lipoprotein particles. It promotes a net movement of phospholipids, thereby generating small lipid-poor apolipoprotein AI that contains particles and subfractions that are good acceptors for cell cholesterol efflux. CASE REPORT: We measured the activity of plasma phospholipid transfer protein in two cholestatic patients, assuming that changes in activity would occur in serum that was positive for lipoprotein X. Both patients presented severe hypercholesterolemia, high levels of low density lipoprotein cholesterol and, in one case, low levels of high density lipoprotein cholesterol and high levels of phospholipid serum. The phospholipid transfer activity was close to the lower limit of the reference interval. To our knowledge, this is the first time such results have been presented. We propose that phospholipid transfer protein activity becomes reduced under cholestasis conditions because of changes in the chemical composition of high density lipoproteins, such as an increase in phospholipids content. Also, lipoprotein X, which is rich in phospholipids, could compete with high density lipoproteins as a substrate for phospholipid transfer protein.
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Heeren, J., W. Weber, and U. Beisiegel. "Intracellular processing of endocytosed triglyceride-rich lipoproteins comprises both recycling and degradation." Journal of Cell Science 112, no. 3 (February 1, 1999): 349–59. http://dx.doi.org/10.1242/jcs.112.3.349.
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The current study was performed to investigate the intracellular fate of triglyceride-rich lipoproteins. Triglyceride-rich lipoproteins are responsible for the delivery of lipids to various tissues, however, their intracellular pathway has not yet been elucidated. Here radiolabeled triglyceride-rich lipoproteins, associated with lipoprotein lipase, were used for the quantitative evaluation of the intracellular metabolism. Pulse chase experiments showed that after 90 minutes approximately 60% of the labeled protein, mainly apoproteins E and C, was released intact into the medium, where it re-associates with lipoproteins. Apoprotein B, in contrast, was degraded, following the same pathway as the apoprotein B from low density lipoproteins. In kinetic experiments uptake and intracellular fate of triglyceride-rich lipoproteins was compared to that of transferrin and low density lipoproteins. These experiments revealed that apoproteins were retained inside the cell much longer than transferrin, and unlike low density lipoproteins were not degraded. Using immunofluorescence it was shown that apoprotein E and lipoprotein lipase follow a distinct route from the sorting compartment to the surface, which is clearly distinguishable from the perinuclear transferrin recycling compartment. In contrast, the fluorescence labeled lipids were delivered to lysosomal compartments. The data presented here show that surface proteins of triglyceride-rich lipoproteins, such as apoproteins E and C and lipoprotein lipase follow a recycling pathway, whereas lipids and high molecular mass core proteins are degraded.
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Karpe, F., A. S. Bickerton, L. Hodson, B. A. Fielding, G. D. Tan, and K. N. Frayn. "Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation." Biochemical Society Transactions 35, no. 3 (May 22, 2007): 472–76. http://dx.doi.org/10.1042/bst0350472.
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The triacylglycerol content of chylomicrons and VLDL (very-low-density lipoprotein) compete for the same lipolytic pathway in the capillary beds. Although chylomicron triacylglycerols appear to be the favoured substrate for lipoprotein lipase, VLDL particles compete in numbers. Methods to quantify the specific triacylglycerol removal from VLDL and chylomicrons may involve endogenous labelling of the triacylglycerol substrate with stable isotopes in combination with arteriovenous blood sampling in humans. Arteriovenous quantification of remnant lipoproteins suggests that adipose tissue with its high lipoprotein lipase activity is a principal site for generation of remnant lipoproteins. Under circumstances of reduced efficiency in the removal of triacylglycerols from lipoproteins, there is accumulation of remnant lipoproteins, which are potentially atherogenic.
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Levels, J. H. M., P. R. Abraham, A. van den Ende, and S. J. H. van Deventer. "Distribution and Kinetics of Lipoprotein-Bound Endotoxin." Infection and Immunity 69, no. 5 (May 1, 2001): 2821–28. http://dx.doi.org/10.1128/iai.69.5.2821-2828.2001.
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ABSTRACT Lipopolysaccharide (LPS), the major glycolipid component of gram-negative bacterial outer membranes, is a potent endotoxin responsible for pathophysiological symptoms characteristic of infection. The observation that the majority of LPS is found in association with plasma lipoproteins has prompted the suggestion that sequestering of LPS by lipid particles may form an integral part of a humoral detoxification mechanism. Previous studies on the biological properties of isolated lipoproteins used differential ultracentrifugation to separate the major subclasses. To preserve the integrity of the lipoproteins, we have analyzed the LPS distribution, specificity, binding capacity, and kinetics of binding to lipoproteins in human whole blood or plasma by using high-performance gel permeation chromatography and fluorescent LPS of three different chemotypes. The average distribution of O111:B4, J5, or Re595 LPS in whole blood from 10 human volunteers was 60% (±8%) high-density lipoprotein (HDL), 25% (±7%) low-density lipoprotein, and 12% (±5%) very low density lipoprotein. The saturation capacity of lipoproteins for all three LPS chemotypes was in excess of 200 μg/ml. Kinetic analysis however, revealed a strict chemotype dependence. The binding of Re595 or J5 LPS was essentially complete within 10 min, and subsequent redistribution among the lipoprotein subclasses occurred to attain similar distributions as O111:B4 LPS at 40 min. We conclude that under simulated physiological conditions, the binding of LPS to lipoproteins is highly specific, HDL has the highest binding capacity for LPS, the saturation capacity of lipoproteins for endotoxin far exceeds the LPS concentrations measured in clinical situations, and the kinetics of LPS association with lipoproteins display chemotype-dependent differences.
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Baumgärtner, Maja, Uwe Kärst, Birgit Gerstel, Martin Loessner, Jürgen Wehland, and Lothar Jänsch. "Inactivation of Lgt Allows Systematic Characterization of Lipoproteins from Listeria monocytogenes." Journal of Bacteriology 189, no. 2 (October 13, 2006): 313–24. http://dx.doi.org/10.1128/jb.00976-06.
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ABSTRACT Lipoprotein anchoring in bacteria is mediated by the prolipoprotein diacylglyceryl transferase (Lgt), which catalyzes the transfer of a diacylglyceryl moiety to the prospective N-terminal cysteine of the mature lipoprotein. Deletion of the lgt gene in the gram-positive pathogen Listeria monocytogenes (i) impairs intracellular growth of the bacterium in different eukaryotic cell lines and (ii) leads to increased release of lipoproteins into the culture supernatant. Comparative extracellular proteome analyses of the EGDe wild-type strain and the Δlgt mutant provided systematic insight into the relative expression of lipoproteins. Twenty-six of the 68 predicted lipoproteins were specifically released into the extracellular proteome of the Δlgt strain, and this proved that deletion of lgt is an excellent approach for experimental verification of listerial lipoproteins. Consequently, we generated Δlgt ΔprfA double mutants to detect lipoproteins belonging to the main virulence regulon that is controlled by PrfA. Overall, we identified three lipoproteins whose extracellular levels are regulated and one lipoprotein that is posttranslationally modified depending on PrfA. It is noteworthy that in contrast to previous studies of Escherichia coli, we unambiguously demonstrated that lipidation by Lgt is not a prerequisite for activity of the lipoprotein-specific signal peptidase II (Lsp) in Listeria.
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Trentalance, A., G. Bruscalupi, L. Conti Devirgiliis, S. Leoni, M. T. Mangiantini, L. Rossini, S. Spagnuolo, and S. K. Erickson. "Changes in lipoprotein binding and uptake by hepatocytes during rat liver regeneration." Bioscience Reports 9, no. 2 (April 1, 1989): 231–41. http://dx.doi.org/10.1007/bf01116000.
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The binding and uptake of cholesterol enriched lipoproteins by isolated hepatocytes was decreased at 16 hours after partial hepatectomy, with a tendency to return to control values as the regeneration proceeds. The number of lipoprotein binding sites of total cellular membranes remained similar to control at 16 and 24 hours. The plasma lipoprotein pattern, determined by electrophoretic analysis, showed a lower per cent of very low density lipoproteins (VLDL) and a higher per cent of low density lipoproteins (LDL) at 16 and 24 hours post-partial hepatectomy. At these times, plasma lecithin: cholesterol acyltransferase (LCAT) activity was decreased. It is intriguing to suggest that the regenerating liver could regulated the blood lipoprotein pattern and the uptake of lipoproteins by modulating the surface expression of the receptors.
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Basile-Borgia, Annette, and John H. Abel. "Lipoproteins in heart disease." Perfusion 11, no. 4 (July 1996): 338–45. http://dx.doi.org/10.1177/026765919601100407.
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Most lipids are carried in the circulation by lipoproteins. Liproproteins and their associated proteins, called apolipoproteins, are currently being studied in an effort to further our understanding of atherosclerotic cardiovascular disease. Lipoprotein assembly, secretion, transportation, modification and clearance are essential elements of healthy lipid metabolism. When one or more of these key steps becomes altered, various disease states are induced. Current data suggest that lipoprotein(a), a low density lipoprotein (LDL)-like particle, is an acute phase reactant that plays a critical role in the modulation of fibrinolysis. Several aspects of lipoproteins and lipoprotein metabolism will be examined. Emphasis will be placed on the proatherogenic and thrombogenic effects of oxidized LDL.
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Zheng, Chunyu, Allison B. Andraski, Christina Khoo, Jeremy D. Furtado, and Frank M. Sacks. "Food Intake Suppresses ApoB Secretion and Fractional Catabolic Rates in Humans." Arteriosclerosis, Thrombosis, and Vascular Biology 44, no. 2 (February 2024): 435–51. http://dx.doi.org/10.1161/atvbaha.123.319769.
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BACKGROUND: Humans spend much of the day in the postprandial state. However, most research and clinical guidelines on plasma lipids pertain to blood drawn after a 12-hour fast. We aimed to study the metabolic differences of apoB lipoproteins between the fasting and postprandial states. METHODS: We investigated plasma apoB metabolism using stable isotope tracers in 12 adult volunteers under fasting and continuous postprandial conditions in a randomized crossover study. We determined the metabolism of apoB in multiple lipoprotein subfractions, including light and dense VLDLs (very-low-density lipoproteins), IDLs (intermediate-density lipoproteins), and light and dense LDLs (low-density lipoproteins) that do or do not contain apoE or apoC3. RESULTS: A major feature of the postprandial state is 50% lower secretion rate of triglyceride-rich lipoproteins and concurrent slowdown of their catabolism in circulation, as shown by 34% to 55% lower rate constants for the metabolic pathways of conversion by lipolysis from larger to smaller lipoproteins and direct clearance of lipoproteins from the circulation. In addition, the secretion pattern of apoB lipoprotein phenotypes was shifted from particles containing apoE and apoC3 in the fasting state to those without either protein in the postprandial state. CONCLUSIONS: Overall, during the fasting state, hepatic apoB lipoprotein metabolism is activated, characterized by increased production, transport, and clearance. After food intake, endogenous apoB lipoprotein metabolism is globally reduced as appropriate to balance dietary input to maintain the supply of energy to peripheral tissues.
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Maran, Logeswaran, Auni Hamid, and Shahrul Bariyah Sahul Hamid. "Lipoproteins as Markers for Monitoring Cancer Progression." Journal of Lipids 2021 (September 13, 2021): 1–17. http://dx.doi.org/10.1155/2021/8180424.
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Lipoproteins are among the contributors of energy for the survival of cancer cells. Studies indicate there are complex functions and metabolism of lipoproteins in cancer. The current review is aimed at providing updates from studies related to the monitoring of lipoproteins in different types of cancer. This had led to numerous clinical and experimental studies. The review covers the major lipoproteins such as LDL cholesterol (LDL-C), oxidized low-density lipoprotein cholesterol (oxLDL-C), very low-density lipoprotein cholesterol (VLDL-C), and high-density lipoprotein cholesterol (HDL-C). This is mainly due to increasing evidence from clinical and experimental studies that relate association of lipoproteins with cancer. Generally, a significant association exists between LDL-C with carcinogenesis and high oxLDL with metastasis. This warrants further investigations to include Mendelian randomization design and to be conducted in a larger population to confirm the significance of LDL-C and its oxidized form as prognostic markers of cancer.
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Niu, You-Guo, and Rhys D. Evans. "Metabolism of very-low-density lipoprotein and chylomicrons by streptozotocin-induced diabetic rat heart: effects of diabetes and lipoprotein preference." American Journal of Physiology-Endocrinology and Metabolism 295, no. 5 (November 2008): E1106—E1116. http://dx.doi.org/10.1152/ajpendo.90260.2008.
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Very-low-density lipoprotein (VLDL) and chylomicrons (CM) are major sources of fatty acid supply to the heart, but little is known about their metabolism in diabetic myocardium. To investigate this, working hearts isolated from control rats and diabetic rats 2 wk following streptozotocin (STZ) injection were perfused with control and diabetic lipoproteins. Analysis of the diabetic lipoproteins showed that both VLDL and CM were altered compared with control lipoproteins; both were smaller and had different apolipoprotein composition. Heparin-releasable lipoprotein lipase (HR-LPL) activity was increased in STZ-induced diabetic hearts, but tissue residual LPL activity was decreased; moreover, diabetic lipoproteins stimulated HR-LPL activity in both diabetic and control hearts. Diabetic hearts oxidized lipoprotein-triacylglycerol (TAG) to a significantly greater extent than controls (>80% compared with deposition as tissue lipid), and the oxidation rate of exogenous lipoprotein-TAG was increased significantly in diabetic hearts regardless of TAG source. Significantly increased intracardiomyocyte TAG accumulation was found in diabetic hearts, although cardiac mechanical function was not inhibited, suggesting that lipotoxicity precedes impaired cardiac performance. Glucose oxidation was significantly decreased in diabetic hearts; additionally, however, diabetic lipoproteins decreased glucose oxidation in diabetic and control hearts. These results demonstrate increased TAG-rich lipoprotein metabolism concomitant with decreased glucose oxidation in type 1 diabetic hearts, and the alterations in cardiac lipoprotein metabolism may be due to the properties of diabetic TAG-rich lipoproteins as well as the diabetic state of the myocardium. These changes were not related to cardiomyopathy at this early stage of diabetes.
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Huang, Haibin, Mingqun Lin, Xueqi Wang, Takane Kikuchi, Heather Mottaz, Angela Norbeck, and Yasuko Rikihisa. "Proteomic Analysis of and Immune Responses to Ehrlichia chaffeensis Lipoproteins." Infection and Immunity 76, no. 8 (May 19, 2008): 3405–14. http://dx.doi.org/10.1128/iai.00056-08.
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ABSTRACT Ehrlichia chaffeensis is an obligately intracellular gram-negative bacterium and is the etiologic agent of human monocytic ehrlichiosis (HME). Although E. chaffeensis induces the generation of several cytokines and chemokines by leukocytes, E. chaffeensis lacks lipopolysaccharide and peptidoglycan. Bioinfomatic analysis of the E. chaffeensis genome, however, predicted genes encoding 15 lipoproteins and 3 posttranslational lipoprotein-processing enzymes. The present study showed that by use of multidimensional liquid chromatography followed by tandem mass spectrometry, all predicted lipoproteins as well as lipoprotein-processing enzymes were expressed by E. chaffeensis cultured in the human promyelocytic leukemia cell line HL-60. Consistent with this observation, a signal peptidase II inhibitor, globomycin, was found to inhibit E. chaffeensis infection and lipoprotein processing in HL-60 cell culture. To study in vivo E. chaffeensis lipoprotein expression and host immune responses to E. chaffeensis lipoproteins, 13 E. chaffeensis lipoprotein genes were cloned into a mammalian expression vector. When the DNA constructs were inoculated into naïve dogs, or when dogs were infected with E. chaffeensis, the animals developed delayed-type hypersensitivity reactions at cutaneous sites of the DNA construct deposition and serum antibodies to these lipoproteins. This is the first demonstration of lipoprotein expression and elicitation of immune responses by a member of the order Rickettsiales. Multiple lipoproteins expressed by E. chaffeensis in vitro and in vivo may play key roles in pathogenesis and immune responses in HME.
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Huemer, H. P., H. J. Menzel, D. Potratz, B. Brake, D. Falke, G. Utermann, and M. P. Dierich. "Herpes Simplex Virus Binds to Human Serum Lipoprotein." Intervirology 29, no. 2 (1988): 68–76. http://dx.doi.org/10.1159/000150031.
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Binding of herpes simplex virus (HSV) type 1 to the various subclasses of human serum lipoproteins was investigated. Studies were performed with human serum lipoproteins purified by differential ultracentrifugation and artificial proteoliposomes containing only one type of apolipoprotein (Al5 E) by using an enzyme-linked immunosorbent assay technique, column chromatography, and electron microscopy. All tested lipoprotein subclasses (very low, low-, high-density lipoproteins; VLDL, LDL, HDL, HDLi) showed significant binding of purified HSV type 1. Furthermore, HSV bound to all different synthetic proteoliposomes. Adsorption of envelope proteins isolated from purified HSV to Sepharose-bound lipoproteins revealed binding of HSV glycoprotein B. Based on these results we reached the conclusion that in HSV-lipoprotein complex formation the lipid component in the lipoproteins and the glycoprotein B in HSV are the preferential reaction partners.
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Ruiz-Albusac, J. M., E. Velázquez, and A. Montes. "Differential precipitation of isolated human plasma lipoproteins with heparin and manganese chloride." Clinical Chemistry 34, no. 2 (February 1, 1988): 240–43. http://dx.doi.org/10.1093/clinchem/34.2.235.
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Abstract We studied the precipitation of isolated lipoproteins with heparin and MnCl2. Lipoproteins were isolated from human plasma by preparative ultracentrifugation and their free cholesterol was labeled. Each lipoprotein fraction was then precipitated at various pHs, with or without bovine serum albumin (60 g/L) present. Under no set of conditions was one class of lipoproteins completely separated from the other two. Specifically, under standard conditions for precipitation of serum lipoproteins (pH 7.4 and protein 60 g/L), 12% of the very-low-density lipoprotein (VLDL) and 8% of the low-density lipoprotein (LDL) remained in the supernatant liquid, and 30% of the high-density lipoprotein (HDL) was precipitated. These results indicate that, under these conditions, so-called HDL cholesterol may be a mixture of VLDL, LDL, and HDL, although the sum of the amount of these three fractions remaining in the supernate is fortuitously very close to the value for HDL cholesterol isolated by ultracentrifugation.
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Rip, J. W., M. M. Blais, and L. W. Jiang. "Low-density lipoprotein as a transporter of dolichol intermediates in the mammalian circulation." Biochemical Journal 297, no. 2 (January 15, 1994): 321–25. http://dx.doi.org/10.1042/bj2970321.
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The cholesteryl esters which make up the bulk of the core of the human low-density lipoprotein particle were removed by extraction into heptane and replaced with the fluorescent anthroyl or N-(7-nitrobenzyl-2-oxa-1,3-diazol-4-yl)aminohexanoyl esters of dolichol. The reconstituted low-density lipoproteins were efficiently internalized by normocholesterolaemic human fibroblasts but not by fibroblasts from patients lacking the low-density-lipoprotein receptor, or lacking the ability to internalize the receptor-lipoprotein complex. In normal fibroblasts, the reconstituted low-density lipoproteins were delivered to lysosomes after internalization. The results suggest that (i) dolichol intermediates in the human circulation are normally carried on low-density lipoproteins and (ii) that low-density lipoproteins are involved in the accumulation of dolichol intermediates in lysosomes during normal human aging and in certain diseases involving the lysosome. In addition, by incorporating these very hydrophobic probes into low-density lipoprotein, they can be presented to cells in culture at high concentration in a water-soluble form.
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Fontanals-Ferrer, N., J. Serrat-Serrat, A. Sorribas-Vivas, C. Gonzalez-Garcia, F. Gonzalez-Sastre, and J. Gomez-Gerique. "Quick method of determining lipoproteins, including those of intermediate density, in serum." Clinical Chemistry 34, no. 9 (September 1, 1988): 1753–57. http://dx.doi.org/10.1093/clinchem/34.9.1749.
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Abstract We describe an ultracentrifugation method for isolating the different lipoprotein classes relatively quickly. In this method the very-low-density lipoproteins are first separated by non-density-adjusted ultracentrifugation. The resulting infranatant material is then stained with Coomassie Brilliant Blue R-250 and ultracentrifuged in a density gradient. The intermediate-density lipoproteins (IDL), low-density lipoproteins, and high-density lipoproteins fractions are separated by aspiration from the top of the tube. This method can be used to separate, analyze, and quantify lipoproteins, including anomalous lipoproteins such as the IDL. The CVs for the present method never exceeded 15%.
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Jameel, Ali H., Maeda M. T. Al-Sulaivany, Saad D. Oleiwi, and Mohammed J. Mohammed. "Physiological Effects of Nano-Magnesium Against Bisphenol A-induced Toxicity in Male Albino Rats." IOP Conference Series: Earth and Environmental Science 1262, no. 6 (December 1, 2023): 062004. http://dx.doi.org/10.1088/1755-1315/1262/6/062004.
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Abstract This study was conducted to determine the effect of oral administration with two concentrations of 30% and 40% of nano-magnesium on Bisphenol-A in liver enzyme parameters (ALT, AST, ALP), kidney function and lipid profile of male white rats Bisphenol-The concentrations of triglycerides (TG), cholesterol (TC), low-density lipoproteins (LDL), and very low-density lipoproteins (vLDL) were all increased by A, whereas the concentration of high-density lipoproteins (HDL) was decreased. while liver enzyme parameters decreased noticeably. Nano-magnesium treatment led to decreases in levels of uric acid, creatinine, triglycerides, cholesterol, low-density lipoprotein, very low-density lipoprotein, and an increase in high-density lipoprotein (HDL) values.
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Neufeld, Edward B., Masaki Sato, Scott M. Gordon, Vinay Durbhakula, Nicolas Francone, Angel Aponte, Gizem Yilmaz, et al. "ApoA-I-Mediated Lipoprotein Remodeling Monitored with a Fluorescent Phospholipid." Biology 8, no. 3 (July 12, 2019): 53. http://dx.doi.org/10.3390/biology8030053.
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We describe simple, sensitive and robust methods to monitor lipoprotein remodeling and cholesterol and apolipoprotein exchange, using fluorescent Lissamine Rhodamine B head-group tagged phosphatidylethanolamine (*PE) as a lipoprotein reference marker. Fluorescent Bodipy cholesterol (*Chol) and *PE directly incorporated into whole plasma lipoproteins in proportion to lipoprotein cholesterol and phospholipid mass, respectively. *Chol, but not *PE, passively exchanged between isolated plasma lipoproteins. Fluorescent apoA-I (*apoA-I) specifically bound to high-density lipoprotein (HDL) and remodeled *PE- and *Chol-labeled synthetic lipoprotein-X multilamellar vesicles (MLV) into a pre-β HDL-like particle containing *PE, *Chol, and *apoA-I. Fluorescent MLV-derived *PE specifically incorporated into plasma HDL, whereas MLV-derived *Chol incorporation into plasma lipoproteins was similar to direct *Chol incorporation, consistent with apoA-I-mediated remodeling of fluorescent MLV to HDL with concomitant exchange of *Chol between lipoproteins. Based on these findings, we developed a model system to study lipid transfer by depositing fluorescent *PE and *Chol-labeled on calcium silicate hydrate crystals, forming dense lipid-coated donor particles that are readily separated from acceptor lipoprotein particles by low-speed centrifugation. Transfer of *PE from donor particles to mouse plasma lipoproteins was shown to be HDL-specific and apoA-I-dependent. Transfer of donor particle *PE and *Chol to HDL in whole human plasma was highly correlated. Taken together, these studies suggest that cell-free *PE efflux monitors apoA-I functionality.
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Myers, D. E., W. N. Huang, and R. G. Larkins. "Lipoprotein-induced prostacyclin production in endothelial cells and effects of lipoprotein modification." American Journal of Physiology-Cell Physiology 271, no. 5 (November 1, 1996): C1504—C1511. http://dx.doi.org/10.1152/ajpcell.1996.271.5.c1504.
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Although lipoprotein modification has been implicated in atherogenesis, the effect of modified forms of lipoproteins on vascular cell function has not been fully resolved. We have investigated lipoprotein-induced prostaglandin production by macrovascular endothelial cells. This study delineates early responses of endothelial cells after exposure to native and modified forms of the lipoproteins. Modification of lipoproteins by oxidation or glycation significantly affected the capacity of lipoproteins to induce prostacyclin (PGI2) production by bovine aortic endothelial cells (BAEC). Modified low-density lipoprotein (LDL) increased PGI2 production in the short term (up to 24 h), but oxidized LDL caused an inhibition of PGI2-producing capacity in longer term incubations (48-72 h). Glycated (Glc) high-density lipoprotein 3 (HDL3) caused higher production of PGI2 in the short term (4-24 h) but reached similar levels as HDL3 over time. Glycation of high-density lipoprotein 2 had no effect on the PGI2-producing capacity of the lipoprotein. Thus modification of the lipoproteins affects their potential to induce PGI2 production in endothelial cells, and this may have an influence on vascular function in disease states such as diabetes and atherosclerosis. Although the changes appear to contradict data from long-term in vivo studies, these results from in vitro studies may reflect the situation in very early lesion development. GlcLDL, while causing an increase in endothelial cell PGI2 production, may be involved in compromised endothelial function, since GlcLDL is prone to oxidation.
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Konovalova, Anna, and Thomas J. Silhavy. "Outer membrane lipoprotein biogenesis: Lol is not the end." Philosophical Transactions of the Royal Society B: Biological Sciences 370, no. 1679 (October 5, 2015): 20150030. http://dx.doi.org/10.1098/rstb.2015.0030.
Full textAbstract:
Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology.
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Zilversmit, D. B. "Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich remnant lipoproteins." Clinical Chemistry 41, no. 1 (January 1, 1995): 153–58. http://dx.doi.org/10.1093/clinchem/41.1.153.
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Abstract In addition to low-density lipoproteins, plasma chylomicrons and very-low-density lipoproteins (VLDL) contribute to atherogenesis. When triglyceride-rich particles bind to arterial endothelium and to deendothelialized areas, locally present lipoprotein lipase initiates triglyceride hydrolysis and decreases the size of the adhering particles. Additional changes in composition are brought about by the exchange of lipids between chylomicron/VLDL remnants and the cholesteryl ester-rich low- and high-density lipoproteins. These exchanges are mediated by lipid transfer proteins in plasma. Animal studies with doubly labeled lipoproteins show that the size of lipoprotein particles determines their rate of entering the artery and contributes to the formation of lesions. This model supports epidemiologic studies that have identified plasma triglycerides as a risk factor for atherogenesis. The model for a causal role of pre- and postprandial triglyceride-rich lipoproteins in atherogenesis suggests that measuring them may improve the assessment of cardiovascular risk factors.
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Grabowicz, Marcin, and Thomas J. Silhavy. "Redefining the essential trafficking pathway for outer membrane lipoproteins." Proceedings of the National Academy of Sciences 114, no. 18 (April 17, 2017): 4769–74. http://dx.doi.org/10.1073/pnas.1702248114.
Full textAbstract:
The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins’ key function is to prevent lethal accumulation of mislocalized lipoproteins.
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Ilves, Liis, Aigar Ottas, Liisi Raam, Mihkel Zilmer, Tanel Traks, Viljar Jaks, and Külli Kingo. "Changes in Lipoprotein Particles in the Blood Serum of Patients with Lichen Planus." Metabolites 13, no. 1 (January 6, 2023): 91. http://dx.doi.org/10.3390/metabo13010091.
Full textAbstract:
Lichen planus is a chronic inflammatory mucocutaneous disease that belongs to the group of papulosquamous skin diseases among diseases like psoriasis, a widely studied disease in dermatology. The aim of the study was to identify the changes between the blood sera of lichen planus patients and healthy controls to widen the knowledge about the metabolomic aspect of lichen planus and gain a better understanding about the pathophysiology of the disease. We used high-throughput nuclear magnetic resonance (NMR) spectroscopy to measure the levels of blood serum metabolites, lipoproteins and lipoprotein particles. Dyslipidemia has relatively recently been shown to be one of the comorbidities of lichen planus, but the changes in the components of lipoproteins have not been described yet. We found statistically significant changes in the concentrations of 16 markers regarding lipoproteins, which included the components of intermediate-density lipoproteins, low-density lipoproteins and large low-density lipoproteins. We propose that the detected changes may increase the risk for specific comorbidities (e.g., dyslipidemia) and resulting cardiovascular diseases, as the turnover and hepatic uptake of the altered/modified lipoprotein particles are disturbed.
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Imamura, Hiroyuki, Keiko Mizuuchi, and Reika Oshikata. "Physical Activity and Blood Lipids and Lipoproteins in Dialysis Patients." International Journal of Nephrology 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/106914.
Full textAbstract:
The relationship between physical activity and blood lipids and lipoproteins in dialysis patients is reviewed in the context of the potentially confounding factors such as nutritional intake, cigarette smoking, obesity, alcohol intake, and physical activity levels in the general population and additional confounding factors such as mode of dialysis and diabetes in dialysis patients. The known associations in the general population of physical activity with high-density-lipoprotein cholesterol subfractions and apolipoprotein A-I are more pronounced in hemodialysis patients than in peritoneal dialysis patients even after adjusting for these confounding factors. Examining studies on the effects of physical activity on blood lipids and lipoproteins, the most consistent observation is the noted decrease in triglycerides and increase in high-density-lipoprotein cholesterol and insulin sensitivity in hemodialysis patients. The changes in lipids and lipoproteins in hemodialysis patients could be caused by changes in activity levels of lipoprotein lipase, insulin sensitivity, and/or glucose metabolism. Future research investigating the relationship between physical activity and blood lipids and lipoproteins in dialysis patients should direct research towards the underlying mechanisms for changes in blood lipids and lipoproteins.
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Radolf, J. D., M. V. Norgard, M. E. Brandt, R. D. Isaacs, P. A. Thompson, and B. Beutler. "Lipoproteins of Borrelia burgdorferi and Treponema pallidum activate cachectin/tumor necrosis factor synthesis. Analysis using a CAT reporter construct." Journal of Immunology 147, no. 6 (September 15, 1991): 1968–74. http://dx.doi.org/10.4049/jimmunol.147.6.1968.
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Abstract Lipoproteins from two pathogenic spirochetes (Borrelia burgdorferi and Treponema pallidum) induced the biosynthesis of TNF in murine macrophages and in permanently transformed macrophages of the cell line RAW 264.7. Induction was studied by measuring the secretion of biologically active TNF and by measuring the activity of the reporter enzyme chloramphenicol acetyltransferase (CAT) produced within macrophages transfected with an endotoxin-responsive CAT construct. Several lines of evidence indicated that the induction of TNF and CAT was attributable to the spirochete lipoproteins rather than to contaminating or endogenous LPS: 1) the dose response curves observed for the lipoproteins were markedly different from those obtained with LPS; 2) lipoprotein-mediated activation was unaffected by amounts of polymyxin B that completely neutralized the induction of TNF and CAT by LPS, 3) low concentrations of the lipoproteins induced TNF in macrophages from endotoxin-unresponsive C3H/HeJ mice as effectively as in macrophages from normal C3H/HeN mice, and 4) isolated spirochete lipoproteins, but not a non-lipoprotein immunogen, were potent inducers of CAT in the transformed macrophages. Moreover, LPS was not detected in the B. burgdorferi lipoprotein mixtures by Limulus amebocyte lysate assay. Proteolytic digestion of the intact bacterial protein preparations only modestly diminished their ability to activate the cells, suggesting that small lipopeptides comprise the biologically active portions of the molecules, as is the case with the murein lipoprotein of Escherichia coli. Through their ability to induce TNF production by macrophages, spirochete lipoproteins may play important roles in the development of the local inflammatory changes and the systemic manifestations that characterize syphilis and Lyme disease.
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Takashima, Yoshiki, Tatsuhiko Kodama, Hisaya lida, Masahiko Kawamura, Hiroyuki Aburatani, Hiroshige Itakura, Yasua Akanuma, Fumimaro Takaku, and Masaka Kawade. "Normotriglyceridemic Abetalipoproteinemia in Infancy: An Isolated Apolipoprotein B-100 Deficiency." Pediatrics 75, no. 3 (March 1, 1985): 541–46. http://dx.doi.org/10.1542/peds.75.3.541.
Full textAbstract:
The plasma lipoproteins of a 1-year-old Japanese infant were studied because of malnutrition, severe decrease in plasma lipid level, and acanthocytosis. Plasma lipoprotein analysis revealed that low-density lipoproteins were deficient; however, low levels of triglyceride-rich lipoproteins were found in the plasma. On sodium dodecylsulfate (SDS) polyacrylamide gel electro-phoresis, apoprotein B-48 and a faint band corresponding to apoprotein B-100 were detected in the lipoprotein fraction of density < 1.006 g/mL when the infant was 6 months old. Apoprotein B-48 was more clearly detected after 1 year, but the band corresponding to apoprotein B-100 on the sodium dodecylsulfate gel electrophoresis had disappeared. The apoprotein B-48 content of the fraction with density < 1.006 g/mL was about 0.05 to 0.3 mg/dL. The patient's lipoproteins consisted mainly of high-density lipoproteins. These results suggest that the disorder in this patient is caused by apoprotein B-100 deficiency.
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Virella, Gabriel, M. Brooks Derrick, Virginia Pate, Charlyne Chassereau, Suzanne R. Thorpe, and Maria F. Lopes-Virella. "Development of Capture Assays for Different Modifications of Human Low-Density Lipoprotein." Clinical Diagnostic Laboratory Immunology 12, no. 1 (January 2005): 68–75. http://dx.doi.org/10.1128/cdli.12.1.68-75.2005.
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ABSTRACT Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), N ε(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and also with oxLDL. CML-LDL antibodies reacted strongly with CML-LDL and also AGE-LDL. oxLDL antibodies reacted with oxLDL but not with MDA-LDL, and AGE-LDL antibodies reacted with AGE-LDL but not with CML-LDL. Capture assays were set with each antiserum, and we tested their ability to capture ApoB-containing lipoproteins isolated from precipitated immune complexes (IC) and from the supernatants remaining after IC precipitation (free lipoproteins). All antibodies captured lipoproteins contained in IC more effectively than free lipoproteins. Analysis of lipoproteins in IC by gas chromatography-mass spectrometry showed that they contained MDA-LDL and CML-LDL in significantly higher concentrations than free lipoproteins. A significant correlation (r = 0.706, P < 0.019) was obtained between the MDA concentrations determined by chemical analysis and by the capture assay of lipoproteins present in IC. In conclusion, we have developed capture assays for different LDL modifications in human ApoB/E lipoprotein-rich fractions isolated from precipitated IC. This approach obviates the interference of IC in previously reported modified LDL assays and allows determination of the degree of modification of LDL with greater accuracy.
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Bei, Weiwei, Qingshan Luo, Huigang Shi, Haizhen Zhou, Min Zhou, Xinzheng Zhang, and Yihua Huang. "Cryo-EM structures of LolCDE reveal the molecular mechanism of bacterial lipoprotein sorting in Escherichia coli." PLOS Biology 20, no. 10 (October 13, 2022): e3001823. http://dx.doi.org/10.1371/journal.pbio.3001823.
Full textAbstract:
Bacterial lipoproteins perform a diverse array of functions including bacterial envelope biogenesis and microbe–host interactions. Lipoproteins in gram-negative bacteria are sorted to the outer membrane (OM) via the localization of lipoproteins (Lol) export pathway. The ATP-binding cassette (ABC) transporter LolCDE initiates the Lol pathway by selectively extracting and transporting lipoproteins for trafficking. Here, we report cryo-EM structures of LolCDE in apo, lipoprotein-bound, and AMPPNP-bound states at a resolution of 3.5 to 4.2 Å. Structure-based disulfide crosslinking, photo-crosslinking, and functional complementation assay verify the apo-state structure and reveal the molecular details regarding substrate selectivity and substrate entry route. Our studies snapshot 3 functional states of LolCDE in a transport cycle, providing deep insights into the mechanisms that underlie LolCDE-mediated lipoprotein sorting in E. coli.
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Sparks, D. L., J. Frohlich, P. Cullis, and P. H. Pritchard. "Cholesteryl ester transfer activity in plasma measured by using solid-phase-bound high-density lipoprotein." Clinical Chemistry 33, no. 3 (March 1, 1987): 390–93. http://dx.doi.org/10.1093/clinchem/33.3.390.
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Abstract We studied the ability of lipid-transfer factors in plasma to promote transfer, to endogenous lipoproteins, of [3H]cholesteryl ester from high-density lipoprotein (HDL) covalently bound to Sepharose 4B beads. After incubation for 2 h at 37 degrees C, 12 to 14% of the [3H]cholesteryl ester had been transferred to the lipoproteins of the plasma, in the proportions 57% to HDL and 43% to low- and very-low-density lipoproteins. This process was a function of the amount of plasma present and was stimulated by addition of partly purified lipid-transfer protein. Transfer also depended on the concentration of donor HDL but was independent of the amount of acceptor lipoprotein. This simple evaluation of cholesteryl ester transfer does not require removal of lipoproteins from the plasma before incubation.
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Mahmoodi, Bakhtawar, Ron Gansevoort, Friso Muntinghe, Robin Dullaart, Hanneke Kluin-Nelemans, Nic Veeger, Inge van Schouwenburg, and Karina Meijer. "Lipid levels do not influence the risk of venous thromboembolism." Thrombosis and Haemostasis 108, no. 11 (2012): 923–29. http://dx.doi.org/10.1160/th12-06-0426.
Full textAbstract:
SummaryStudies on the association between lipid profile and venous thromboembolism (VTE) are inconsistent. This could be caused by classical lipoproteins being inferior to apolipoproteins as markers for VTE risk. Therefore, we examined whether apolipoproteins are more strongly related to VTE than lipoproteins. For this analysis we used the PREVEND prospective community based observational cohort study. Levels of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (TC), high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL), triglycerides (TG), lipoprotein(a), ApoB/ApoA1 and TC/HDL ratio were assessed. Subjects with VTE were identified using databases of the national registries of hospital discharge diagnoses, death certificates, and the regional anticoagulation clinic. Out of 7,627 subjects, 110 developed VTE during a median follow-up of 10.5 years. In both univariate and multivariable analyses no significant associations between apolipoproteins and overall VTE were observed. Of the classical lipoproteins, TC, non-HDL, LDL, TG, and TC/HDL ratio were significantly associated with overall VTE in univariate analysis. Significant associations were no longer present in multivariable analysis. TGL and LDL were significantly associated with unprovoked VTE in univariate analysis. After adjustment for age and sex this significance was lost. No significant associations between (apo-) lipoproteins and provoked VTE were found. We conclude that apolipoproteins are not better in predicting VTE risk than the classical lipoproteins. Our population-based cohort study does not show an association between both apolipoproteins and the classical lipoproteins and VTE risk.
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Polyakov, L. M., D. V. Sumenkova, R. A. Knyazev, and L. E. Panin. "The analysis of interaction between lipoproteins and steroid hormones." Biomeditsinskaya Khimiya 57, no. 3 (2011): 308–13. http://dx.doi.org/10.18097/pbmc20115703308.
Full textAbstract:
Using the methods of ultracentrifugation, gel-filtration and fluorescence quenching, we demonstrated, that plasma lipoproteins bind steroid hormones and can therefore play a role of their active transport form in an organism. High density lipoproteins have revealed the highest affinity to steroids for. It has been found, that protein component of lipoproteins takes part in the formation of lipoprotein-steroid complex. The apolipoprotein A-I, the main protein component of high density lipoproteins, is responsible for binding of steroid hormones. The calculated constants formation of the complexes of lipoproteins with steroid hormones testifies to specificity of linkage. The results obtained allow to considering real opportunity of transfer of steroid hormones into cell by a receptor-mediated endocytosis in structure of lipoproteins complexes.
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Hornick, C. A., R. L. Hamilton, E. Spaziani, G. H. Enders, and R. J. Havel. "Isolation and characterization of multivesicular bodies from rat hepatocytes: an organelle distinct from secretory vesicles of the Golgi apparatus." Journal of Cell Biology 100, no. 5 (May 1, 1985): 1558–69. http://dx.doi.org/10.1083/jcb.100.5.1558.
Full textAbstract:
Hepatocytes of estradiol-treated rats, which express many low density lipoprotein receptors, rapidly accumulate intravenously injected low density lipoprotein in multivesicular bodies (MVBs). We have isolated MVBs and Golgi apparatus fractions from livers of estradiol-treated rats. MVB fractions were composed mainly of large vesicles, approximately 0.55 micron diam, filled with remnantlike very low density lipoproteins, known to be taken up into hepatocytes by receptor-mediated endocytosis. MVBs also contained numerous small vesicles, 0.05-0.07 micron in diameter, and had two types of appendages: one fingerlike and electron dense and the other saclike and electron lucent. MVBs contained little galactosyltransferase or arylsulfatase activity, and content lipoproteins were largely intact. Very low density lipoproteins from Golgi fractions, which are derived to a large extent from secretory vesicles, were larger than those of MVB fractions and contained newly synthesized triglycerides. Membranes of MVBs contained much more cholesterol and less protein than did Golgi membranes. We conclude that two distinct lipoprotein-filled organelles are located in the bile canalicular pole of hepatocytes. MVBs, a major prelysosomal organelle of low density in the endocytic pathway, contain remnants of triglyceride-rich lipoproteins, whereas secretory vesicles of the Golgi apparatus contain nascent very low density lipoproteins.
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Rota, Simin, Nicola A. McWilliam, Trevor P. Baglin, and Christopher D. Byrne. "Atherogenic Lipoproteins Support Assembly of the Prothrombinase Complex and Thrombin Generation: Modulation by Oxidation and Vitamin E." Blood 91, no. 2 (January 15, 1998): 508–15. http://dx.doi.org/10.1182/blood.v91.2.508.
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AbstractThe importance of lipoproteins in the etiology of atherosclerosis is well established. Evidence is now accumulating to implicate thrombin in the pathogenesis of atherosclerosis. We have investigated whether atherogenic lipoproteins can support thrombin generation. In the absence of platelets or endothelial cells, both very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (LDL) support assembly of the prothrombinase complex and generation of thrombin. Thrombin generation (per μg of apolipoprotein) supported by VLDL was 19.4-fold greater than that supported by high-density lipoprotein (HDL), P < .00001, and 11.7-fold greater than that supported by LDL, P < .00001. Oxidation of LDL increased lipoprotein-supported thrombin generation 12-fold compared to unmodified LDL, P < .0001. We have shown that the phenomenon of lipoprotein-supported thrombin generation is mediated predominantly by specific phospholipids and is enhanced by oxidation of these phospholipids. The addition of vitamin E (α-tocopherol) markedly reduced the increase in thrombin generation observed after oxidation of LDL (822 ± 57 v 138 ± 47 nmol/L;P < .0001). These effects suggest that lipoproteins are important in the production of thrombin and that vitamin E may confer protection from the detrimental effects of lipoprotein oxidation by limiting thrombin formation. These results suggest that atherogenic lipoproteins are linked to the development of atherosclerosis in part by their capacity to support thrombin generation.
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Rota, Simin, Nicola A. McWilliam, Trevor P. Baglin, and Christopher D. Byrne. "Atherogenic Lipoproteins Support Assembly of the Prothrombinase Complex and Thrombin Generation: Modulation by Oxidation and Vitamin E." Blood 91, no. 2 (January 15, 1998): 508–15. http://dx.doi.org/10.1182/blood.v91.2.508.508_508_515.
Full textAbstract:
The importance of lipoproteins in the etiology of atherosclerosis is well established. Evidence is now accumulating to implicate thrombin in the pathogenesis of atherosclerosis. We have investigated whether atherogenic lipoproteins can support thrombin generation. In the absence of platelets or endothelial cells, both very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (LDL) support assembly of the prothrombinase complex and generation of thrombin. Thrombin generation (per μg of apolipoprotein) supported by VLDL was 19.4-fold greater than that supported by high-density lipoprotein (HDL), P < .00001, and 11.7-fold greater than that supported by LDL, P < .00001. Oxidation of LDL increased lipoprotein-supported thrombin generation 12-fold compared to unmodified LDL, P < .0001. We have shown that the phenomenon of lipoprotein-supported thrombin generation is mediated predominantly by specific phospholipids and is enhanced by oxidation of these phospholipids. The addition of vitamin E (α-tocopherol) markedly reduced the increase in thrombin generation observed after oxidation of LDL (822 ± 57 v 138 ± 47 nmol/L;P < .0001). These effects suggest that lipoproteins are important in the production of thrombin and that vitamin E may confer protection from the detrimental effects of lipoprotein oxidation by limiting thrombin formation. These results suggest that atherogenic lipoproteins are linked to the development of atherosclerosis in part by their capacity to support thrombin generation.
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Narita, Shin-ichiro, Kimie Tanaka, Shin-ichi Matsuyama, and Hajime Tokuda. "Disruption of lolCDE, Encoding an ATP-Binding Cassette Transporter, Is Lethal for Escherichia coli and Prevents Release of Lipoproteins from the Inner Membrane." Journal of Bacteriology 184, no. 5 (March 1, 2002): 1417–22. http://dx.doi.org/10.1128/jb.184.5.1417-1422.2002.
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ABSTRACT ATP-binding cassette transporter LolCDE was previously identified, by using reconstituted proteoliposomes, as an apparatus catalyzing the release of outer membrane-specific lipoproteins from the inner membrane of Escherichia coli. Mutations resulting in defective LolD were previously shown to be lethal for E. coli. The amino acid sequences of LolC and LolE are similar to each other, but the necessity of both proteins for lipoprotein release has not been proved. Moreover, previous reconstitution experiments did not clarify whether or not LolCDE is the sole apparatus for lipoprotein release. To address these issues, a chromosomal lolC-lolD-lolE null mutant harboring a helper plasmid that carries the lolCDE genes and a temperature-sensitive replicon was constructed. The mutant failed to grow at a nonpermissive temperature because of the depletion of LolCDE. In addition to functional LolD, both LolC and LolE were required for growth. At a nonpermissive temperature, the outer membrane lipoproteins were mislocalized in the inner membrane since LolCDE depletion inhibited the release of lipoproteins from the inner membrane. Furthermore, both LolC and LolE were essential for the release of lipoproteins. On the other hand, LolCDE depletion did not affect the translocation of a lipoprotein precursor across the inner membrane and subsequent processing to the mature lipoprotein. From these results, we conclude that the LolCDE complex is an essential ABC transporter for E. coli and the sole apparatus mediating the release of outer membrane lipoproteins from the inner membrane.
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Otvos, J. D., E. J. Jeyarajah, L. W. Hayes, D. S. Freedman, N. A. Janjan, and T. Anderson. "Relationships between the proton nuclear magnetic resonance properties of plasma lipoproteins and cancer." Clinical Chemistry 37, no. 3 (March 1, 1991): 369–76. http://dx.doi.org/10.1093/clinchem/37.3.369.
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Abstract We conducted a comprehensive investigation of the origin of nuclear magnetic resonance (NMR) lineshape variability of plasma lipids among healthy individuals and those with cancer. The methyl and methylene resonances of lipid in human plasma, whose linewidths have been reported to correlate with the presence of malignancy, are composed of the overlapping resonances of "mobile" protons from the major lipoproteins (very-low-, low-, and high-density lipoproteins). We tested two hypotheses for the origin of the narrower plasma linewidths observed for cancer patients: (a) malignancy-associated differences in the spectral properties (chemical shift, lineshape) of one or more of the lipoproteins, and (b) differences in the fraction of lipoprotein lipid giving rise to detectable NMR signal. Analysis of the concentrations of lipoprotein lipid and of 500 MHz NMR spectra of the lipoprotein constituents in greater than 100 plasma samples failed to provide support for either hypothesis. Although linewidths were found to be significantly narrower for the cancer group, the difference is entirely attributable to differences in the concentrations of the lipoproteins.
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Labreche, Dustan G., George T. Kondos, David W. Bartels, and Jerry L. Bauman. "Variability in Plasma Lipoprotein Profiles When Comparing Diltiazem and Propranolol." Annals of Pharmacotherapy 27, no. 9 (September 1993): 1048–52. http://dx.doi.org/10.1177/106002809302700906.
Full textAbstract:
OBJECTIVE: To examine the effects of diltiazem and propranolol on plasma lipoproteins in a double-blind, comparative trial. PATIENTS: Twenty-one mild-to-moderate hypertensive patients. METHODS: Following discontinuation of previous antihypertensive treatments, and a 4-week, single-blind, placebo run-in, subjects were randomized to receive sustained-release diltiazem or propranolol. Total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) were measured during placebo administration and after 12–16 weeks of treatment. RESULTS: No significant changes in plasma lipoprotein concentrations were noted in either the diltiazem or propranolol group compared with baseline values or each other. Marked variation in HDL, LDL, and VLDL were noted following drug treatment and in eight subjects whose lipoprotein concentrations were remeasured prior to drug treatment during the placebo period. The alterations were bidirectional, and similar in magnitude to those found following drug treatment. CONCLUSIONS: In many cases, changes in plasma lipoproteins reported to be a consequence of antihypertensive treatment may merely reflect normal intrapatient variability.
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Fernández, José, Hiroshi Deguchi, and John Griffin. "Plasma Lipoproteins, Hemostasis and Thrombosis." Thrombosis and Haemostasis 86, no. 07 (2001): 386–94. http://dx.doi.org/10.1055/s-0037-1616236.
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SummaryRegulation of hemostasis and thrombosis involves numerous plasma factors that contribute to procoagulant and anticoagulant pathways. Lipid-containing surfaces provide sites where both procoagulant and anticoagulant enzymes, cofactors and substrates are assembled to express their activities. Plasma and lipoproteins can contribute to either procoagulant or anticoagulant reactions. Procoagulant lipids/lipoproteins include triglyceride-rich particles in plasma and oxidized low density lipoprotein (LDL) which can accelerate activation of prothrombin, factor X and factor VII. Potentially anticoagulant lipids and lipoproteins, each of which enhances inactivation of factor Va by activated protein C, include phosphatidylethanolamine, cardiolipin, the neutral glycosphingolipids glucosylceramide and Gb3 ceramide (CD77), and high density lipoprotein (HDL). Remarkably, treatment of hyperlipidemia with statins not only lowers lipids but also provides antithrombotic effects whose mechanisms remain to be clarified. We hypothesize that procoagulant and anticoagulant lipids and lipoproteins in plasma may contribute to a Yin-Yang balance that helps influence the up-regulation and down-regulation of thrombin generation.
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Renee Ruhaak, L., Arnoud van der Laarse, and Christa M. Cobbaert. "Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 56, no. 3 (March 19, 2019): 338–56. http://dx.doi.org/10.1177/0004563219827620.
Full textAbstract:
An elevated low-density lipoprotein cholesterol concentration is a classical risk factor for cardiovascular disease. This has led to pharmacotherapy in patients with atherosclerotic heart disease or high heart disease risk with statins to reduce serum low-density lipoprotein cholesterol. Even in patients in whom the target levels of low-density lipoprotein cholesterol are reached, there remains a significant residual cardiovascular risk; this is due, in part, to a focus on low-density lipoprotein cholesterol alone and neglect of other important aspects of lipoprotein metabolism. A more refined lipoprotein analysis will provide additional information on the accumulation of very low-density lipoproteins, intermediate density lipoproteins, chylomicrons, chylomicron-remnants and Lp(a) concentrations. Instead of measuring the cholesterol and triglyceride content of the lipoproteins, measurement of their apolipoproteins (apos) is more informative. Apos are either specific for a particular lipoprotein or for a group of lipoproteins. In particular measurement of apos in atherogenic particles is more biologically meaningful than the measurement of the cholesterol concentration contained in these particles. Applying apo profiling will not only improve characterization of the lipoprotein abnormality, but will also improve definition of therapeutic targets. Apo profiling aligns with the concept of precision medicine by which an individual patient is not treated as ‘average’ patient by the average (dose of) therapy. This concept of precision medicine fits the unmet clinical need for stratified cardiovascular medicine. The requirements for clinical application of proteomics, including apo profiling, can now be met using robust mass spectrometry technology which offers desirable analytical performance and standardization.
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Rose, Jeffrey R., Maureen A. Mullarkey, William J. Christ, Lynn D. Hawkins, Melvyn Lynn, Yoshito Kishi, Kishor M. Wasan, Kathy Peteherych, and Daniel P. Rossignol. "Consequences of Interaction of a Lipophilic Endotoxin Antagonist with Plasma Lipoproteins." Antimicrobial Agents and Chemotherapy 44, no. 3 (March 1, 2000): 504–10. http://dx.doi.org/10.1128/aac.44.3.504-510.2000.
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ABSTRACT E5531, a novel synthetic lipid A analogue, antagonizes the toxic effects of lipopolysaccharide, making it a potential intravenously administered therapeutic agent for the treatment of sepsis. This report describes the distribution of E5531 in human blood and its activity when it is associated with different lipoprotein subclasses. After in vitro incubation of [14C]E5531 with blood, the great majority (>92%) of material was found in the plasma fraction. Analysis by size-exclusion and affinity chromatographies and density gradient centrifugation indicates that [14C]E5531 binds to lipoproteins, primarily high-density lipoproteins (HDLs), with distribution into low-density lipoproteins (LDLs) and very low density lipoproteins (VLDLs) being dependent on the plasma LDL or VLDL cholesterol concentration. Similar results were also seen in a limited study of [14C]E5531 administration to human volunteers. The potency of E5531 in freshly drawn human blood directly correlates to increasing LDL cholesterol levels. Finally, preincubation of E5531 with plasma or purified lipoproteins indicated that binding to HDL resulted in a time-dependent loss of drug activity. This loss in activity was not observed with drug binding to LDLs or to VLDLs or chylomicrons. Taken together, these results indicate that E5531 binds to plasma lipoproteins, making its long-term antagonistic potency dependent on the plasma lipoprotein composition.
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Neels, Jaap G., Georges Leftheriotis, and Giulia Chinetti. "Atherosclerosis Calcification: Focus on Lipoproteins." Metabolites 13, no. 3 (March 21, 2023): 457. http://dx.doi.org/10.3390/metabo13030457.
Full textAbstract:
Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids in the vessel wall, leading to the formation of an atheroma and eventually to the development of vascular calcification (VC). Lipoproteins play a central role in the development of atherosclerosis and VC. Both low- and very low-density lipoproteins (LDL and VLDL) and lipoprotein (a) (Lp(a)) stimulate, while high-density lipoproteins (HDL) reduce VC. Apolipoproteins, the protein component of lipoproteins, influence the development of VC in multiple ways. Apolipoprotein AI (apoAI), the main protein component of HDL, has anti-calcific properties, while apoB and apoCIII, the main protein components of LDL and VLDL, respectively, promote VC. The role of lipoproteins in VC is also related to their metabolism and modifications. Oxidized LDL (OxLDL) are more pro-calcific than native LDL. Oxidation also converts HDL from anti- to pro-calcific. Additionally, enzymes such as autotaxin (ATX) and proprotein convertase subtilisin/kexin type 9 (PCSK9), involved in lipoprotein metabolism, have a stimulatory role in VC. In summary, a better understanding of the mechanisms by which lipoproteins and apolipoproteins contribute to VC will be crucial in the development of effective preventive and therapeutic strategies for VC and its associated cardiovascular disease.
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Remans, Kim, Ken Vercammen, Josselin Bodilis, and Pierre Cornelis. "Genome-wide analysis and literature-based survey of lipoproteins in Pseudomonas aeruginosa." Microbiology 156, no. 9 (September 1, 2010): 2597–607. http://dx.doi.org/10.1099/mic.0.040659-0.
Full textAbstract:
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen able to cause acute or chronic infections. Like all other Pseudomonas species, P. aeruginosa has a large genome, >6 Mb, encoding more than 5000 proteins. Many proteins are localized in membranes, among them lipoproteins, which can be found tethered to the inner or the outer membrane. Lipoproteins are translocated from the cytoplasm and their N-terminal signal peptide is cleaved by the signal peptidase II, which recognizes a specific sequence called the lipobox just before the first cysteine of the mature lipoprotein. A majority of lipoproteins are transported to the outer membrane via the LolCDEAB system, while those having an avoidance signal remain in the inner membrane. In Escherichia coli, the presence of an aspartate residue after the cysteine is sufficient to cause the lipoprotein to remain in the inner membrane, while in P. aeruginosa the situation is more complex and involves amino acids at position +3 and +4 after the cysteine. Previous studies indicated that there are 185 lipoproteins in P. aeruginosa, with a minority in the inner membrane. A reanalysis led to a reduction of this number to 175, while new retention signals could be predicted, increasing the percentage of inner-membrane lipoproteins to 20 %. About one-third (62 out of 175) of the lipoprotein genes are present in the 17 Pseudomonas genomes sequenced, meaning that these genes are part of the core genome of the genus. Lipoproteins can be classified into families, including those outer-membrane proteins having a structural role or involved in efflux of antibiotics. Comparison of various microarray data indicates that exposure to epithelial cells or some antibiotics, or conversion to mucoidy, has a major influence on the expression of lipoprotein genes in P. aeruginosa.
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Kurano, Makoto, Kuniyuki Kano, Masumi Hara, Kazuhisa Tsukamoto, Junken Aoki, and Yutaka Yatomi. "Regulation of plasma glycero-lysophospholipid levels by lipoprotein metabolism." Biochemical Journal 476, no. 23 (December 3, 2019): 3565–81. http://dx.doi.org/10.1042/bcj20190498.
Full textAbstract:
Glycero-lysophospholipids, such as lysophosphatidic acids and lysophosphatidylserine, are gathering attention, since specific receptors have been identified. Most of these compounds have been proposed to be bound to albumin, while their associations with lipoproteins have not been fully elucidated. Therefore, in this study, we aimed to investigate the contents of glycero-lysophospholipids (lysophosphatidic acids, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, and lysophosphatidylserine) on lipoproteins and the modulation of their metabolism by lipoprotein metabolism. We observed that moderate amounts of glycero-lysophospholipids, with the exception of lysophosphatidylserine, were distributed on the LDL and HDL fractions, and glycero-lysophospholipids that had bound to albumin were observed in lipoprotein fractions when they were co-incubated. The overexpression of cholesteryl ester transfer protein decreased the plasma levels of lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, and lysophosphatidylinositol and it increased their contents in apoB-containing lipoproteins, while it decreased their contents in HDL and lipoprotein-depleted fractions in mice. The overexpression of the LDL receptor (LDLr) decreased the plasma levels of lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, and lysophosphatidylinositol and decreased the contents of these compounds in the LDL, HDL, and lipoprotein-depleted fractions, while the knockdown of the LDLr increased them. These results suggest the potential importance of glycero-lysophospholipids in the pleiotropic effects of lipoproteins as well as the importance of lipoprotein metabolism in the regulation of glycero-lysophospholipids.
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De Vriese, Carine, Mirjam Hacquebard, Françoise Gregoire, Yvon Carpentier, and Christine Delporte. "Ghrelin Interacts with Human Plasma Lipoproteins." Endocrinology 148, no. 5 (May 1, 2007): 2355–62. http://dx.doi.org/10.1210/en.2006-1281.
Full textAbstract:
Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and GH secretion. The Ser3 residue of ghrelin is mainly modified by a n-octanoic acid. In the human bloodstream, ghrelin circulates in two forms: octanoylated and desacylated. We previously demonstrated that ghrelin is desoctanoylated in human serum by butyrylcholinesterase (EC 3.1.1.8) and other esterase(s), whereas in rat serum, only carboxylesterase (EC 3.1.1.1) is involved. The aims of this study were to determine the role of lipoprotein-associated enzymes in ghrelin desoctanoylation and the role of lipoproteins in the transport of circulating ghrelin. Our results show that ghrelin desoctanoylation mostly occurred in contact with low-density lipoproteins (LDLs) and lipoprotein-poor plasma subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the lipoprotein-poor plasma and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRLs), high-density lipoproteins (HDLs), very high-density lipoproteins (VHDLs), and to some extent LDLs. In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs. Ghrelin interacts via its N- and C-terminal parts with HDLs and VHDLs. This suggests that, whereas TRLs mostly transport acylated ghrelin, HDLs and VHDLs transport both ghrelin and des-acyl ghrelin.
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Dolphin, Peter J. "Lipoprotein metabolism and the role of apolipoproteins as metabolic programmers." Canadian Journal of Biochemistry and Cell Biology 63, no. 8 (August 1, 1985): 850–69. http://dx.doi.org/10.1139/o85-107.
Full textAbstract:
The plasma lipoproteins are large spherical macromolecular structures containing hydrophobic core lipids with phospholipids, cholesterol, and specific proteins (apoproteins) providing an amphipathic interface with the hydrophilic environment of the plasma. The major function of these particles, which are biosynthesized by the intestine and liver, is the transport of dietary or endogenously synthesized lipids to those tissues which utilize exogenous lipids for oxidative metabolism, storage, steroid hormone biosynthesis, or maintenance of their membrane integrity. The triacylglycerol-rich lipoproteins are biosynthesized as metabolically inert particles which are catabolically programmed by postsecretory addition of apoproteins which activate the major lipolytic enzymes, inhibit premature removal, and ensure the later interaction of the degraded particles with specific cellular receptors. During the course of lipolysis, those apoproteins which activate catabolic enzymes are lost from the lipoprotein particles and are transferred to the high-density lipoproteins from which they were initially acquired. High-density lipoprotein also mediates the removal of cholesterol deposited in peripheral tissues as a result of uptake of degraded triacylglycerol-rich lipoproteins. Acquisition of cellular cholesterol by high-density lipoproteins results in its apoprotein-stimulated esterification and the later addition of an apoprotein which mediates receptor recognition and removal of the particle from the plasma. The presence or absence of specific apoproteins on the surface of a lipoprotein particle is modulated by the lipid-binding properties of the apoprotein, the surface lipid composition, and the size of the particle. The nature and mass ratios of these surface lipids are themselves dependent upon the activity of apoprotein-stimulated catabolic enzymes and other proteins which mediate the exchange of surface lipids between lipoprotein particles. Thus the apoproteins are effective programmers of lipoprotein metabolism and fulfil their role as such by cycling, in a directed fashion, between nascent and existing plasma lipoproteins. Genetic defects resulting in a perturbation of this intricate mechanism can lead to premature and pronounced atherosclerosis.
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Whayne, Thomas F. "High-density Lipoprotein Cholesterol: Current Perspective for Clinicians." Angiology 60, no. 5 (February 23, 2009): 644–49. http://dx.doi.org/10.1177/0003319709331392.
Full textAbstract:
High-density lipoproteins are regarded as “good guys” but not always. Situations involving high-density lipoproteins are discussed and medication results are considered. Clinicians usually consider high-density lipoprotein cholesterol. Nicotinic acid is the best available medication to elevate high-density lipoprotein cholesterol and this appears beneficial for cardiovascular risk. The major problem with nicotinic acid is that many patients do not tolerate the associated flushing. Laropiprant decreases this flushing and has an approval in Europe but not in the United States. The most potent medications for increasing high-density lipoprotein cholesterol are cholesteryl ester transfer protein inhibitors. The initial drug in this class, torcetrapib, was eliminated by excess cardiovascular problems. Two newer cholesteryl ester transfer protein inhibitors, R1658 and anacetrapib, initially appear promising. High-density lipoprotein cholesterol may play an important role in improving cardiovascular risk in the 60% of patients who do not receive cardiovascular mortality/morbidity benefit from low-density lipoproteins reduction by statins.