Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood.

ABSTRACT: Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1 ^+/+ and Abca1 ^-/- mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.

SUBMITTER: Ohkawa R

PROVIDER: S-EPMC7707172 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Metformin Transport Rates Between Plasma and Red Blood Cells in Humans.

Project description:BackgroundMetformin has been used for the treatment of type 2 diabetes for over 60 years; however, its mechanism of pharmacological action is not fully clear. Different hypotheses exist regarding metformin distribution and redistribution mechanisms between plasma and erythrocytes/red blood cells (RBCs).ObjectiveWe aimed to test the hypothesis that the metformin distribution between plasma and RBC occurs via concentration difference-driven passive transport and estimated transport rate coefficient values based on metformin concentration time series in plasma and RBCs from in vivo studies.MethodsAn ordinary differential equation (ODE) system with two compartments was used to describe diffusion-based passive transport between plasma and RBCs. Metformin concentration time series in plasma and RBCs of 35 individuals were used for metformin transport parametrization. Plasma concentration has been approximated by biexponential decline.ResultsA single passive transport coefficient, k = 0.044 ± 0.014 (h-1), can be applied, describing the uptake and release transport rate versus the linear equation v = k × (Mpl - MRBC), where Mpl is the metformin concentration in plasma and MRBC is the metformin concentration in RBCs.ConclusionsOur research suggests that passive transport can explain metformin distribution dynamics between plasma and RBCs because transport speed is proportional to the metformin concentration difference and independent of the transport direction. Concentration difference-driven passive transport can explain the mechanism of faster metformin distribution to RBCs the first few hours after administration, and faster release and domination of the redistribution transport rate after metformin concentration in plasma becomes smaller than in RBCs.

| S-EPMC8761711 | biostudies-literature

Exogenous cholesterol transport in rabbit plasma lipoproteins.

Project description:1. The appearance of exogenous cholesterol in free cholesterol and ester cholesterol of plasma chylomicra, very-low-density (VLD), low-density (LD) and high-density (HD) lipoproteins was studied in unanaesthetized rabbits after ingestion of a meal containing 5% fat and 0.08% [(3)H]cholesterol. 2. The specific radioactivity of ester cholesterol of VLD lipoproteins reached the highest value of any lipoprotein fraction and for each lipoprotein it increased at a faster rate and reached a higher maximum than that of free cholesterol; the maximum in VLD lipoproteins occurred later than in chylomicra. 3. The pattern of appearance of exogenous cholesterol in chylomicra and VLD lipoproteins of plasma was similar to the pattern previously observed in lymph. The specific radioactivity of ester cholesterol in plasma VLD lipoproteins was higher than that in chylomicra in spite of a larger pool size and dilution of cholesteryl esters from VLD lipoproteins produced by the liver. These results support the concept that during absorption the major portion of exogenous cholesterol is transported in VLD lipoproteins as ester cholesterol. 4. The specific radioactivity of ester cholesterol of chylomicra and VLD lipoproteins increased at a faster rate than that of LD and HD lipoproteins. However, the rate of increase and the absolute values of the specific radioactivity in LD and HD lipoproteins were identical. Since cholesteryl esters are thought not to exchange between lipoproteins, this observation supports the hypothesis that a result of VLD lipoprotein and chylomicron metabolism is the formation of LD and HD lipoproteins. 5. Results in vivo showed that the free cholesterol of individual plasma lipoproteins does not equilibrate within a period of 24h.

| S-EPMC1177840 | biostudies-other

Cholesterol Deficiency Causes Impaired Osmotic Stability of Cultured Red Blood Cells.

Project description:Ex vivo generation of red blood cells (cRBCs) is an attractive tool in basic research and for replacing blood components donated by volunteers. As a prerequisite for the survival of cRBCs during storage as well as in the circulation, the quality of the membrane is of utmost importance. Besides the cytoskeleton and embedded proteins, the lipid bilayer is critical for membrane integrity. Although cRBCs suffer from increased fragility, studies investigating the lipid content of their membrane are still lacking. We investigated the membrane lipid profile of cRBCs from CD34+ human stem and progenitor cells compared to native red blood cells (nRBCs) and native reticulocytes (nRETs). Ex vivo erythropoiesis was performed in a well-established liquid assay. cRBCs showed a maturation grade between nRETs and nRBCs. High-resolution mass spectrometry analysis for cholesterol and the major phospholipid classes, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, sphingomyelin and lysophosphatidylcholin, demonstrated severe cholesterol deficiency in cRBCs. Although cRBCs showed normal deformability capacity, they suffered from increased hemolysis due to minimal changes in the osmotic conditions. After additional lipid supplementation, especially cholesterol during culturing, the cholesterol content of cRBCs increased to a subnormal amount. Concurrently, the osmotic resistance recovered completely and became comparable to that of nRETs. Minor differences in the amount of phospholipids in cRBCs compared to native cells could mainly be attributed to the ongoing membrane remodeling process from the reticulocyte to the erythrocyte stage. Obtained results demonstrate severe cholesterol deficiency as a reason for enhanced fragility of cRBCs. Therefore, the supplementation of lipids, especially cholesterol during ex vivo erythropoiesis may overcome this limitation and strengthens the survival of cRBCs ex vivo and in vivo.

| S-EPMC6933518 | biostudies-literature

Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin.

Project description:Cholesterol partitions into accessible and sequestered pools in cell membranes. Here, we describe a new assay using fluorescently-tagged anthrolysin O, a cholesterol-binding bacterial toxin, to measure accessible cholesterol in human red blood cells (RBCs). Accessible cholesterol levels were stable within individuals, but varied >10 fold among individuals. Significant variation was observed among ethnic groups (Blacks>Hispanics>Whites). Variation in accessibility of RBC cholesterol was unrelated to the cholesterol content of RBCs or plasma, but was associated with the phospholipid composition of the RBC membranes and with plasma triglyceride levels. Pronase treatment of RBCs only modestly altered cholesterol accessibility. Individuals on hemodialysis, who have an unexplained increase in atherosclerotic risk, had significantly higher RBC cholesterol accessibility. Our data indicate that RBC accessible cholesterol is a stable phenotype with significant inter-individual variability. Factors both intrinsic and extrinsic to the RBC contribute to variation in its accessibility. This assay provides a new tool to assess cholesterol homeostasis among tissues in humans.

| S-EPMC5323040 | biostudies-literature

GPU-accelerated Red Blood Cells Simulations with Transport Dissipative Particle Dynamics.

Project description:Mesoscopic numerical simulations provide a unique approach for the quantification of the chemical influences on red blood cell functionalities. The transport Dissipative Particles Dynamics (tDPD) method can lead to such effective multiscale simulations due to its ability to simultaneously capture mesoscopic advection, diffusion, and reaction. In this paper, we present a GPU-accelerated red blood cell simulation package based on a tDPD adaptation of our red blood cell model, which can correctly recover the cell membrane viscosity, elasticity, bending stiffness, and cross-membrane chemical transport. The package essentially processes all computational workloads in parallel by GPU, and it incorporates multi-stream scheduling and non-blocking MPI communications to improve inter-node scalability. Our code is validated for accuracy and compared against the CPU counterpart for speed. Strong scaling and weak scaling are also presented to characterizes scalability. We observe a speedup of 10.1 on one GPU over all 16 cores within a single node, and a weak scaling efficiency of 91% across 256 nodes. The program enables quick-turnaround and high-throughput numerical simulations for investigating chemical-driven red blood cell phenomena and disorders.

| S-EPMC5667691 | biostudies-literature

Rhythmic potassium transport regulates the circadian clock in human red blood cells.

Project description:Circadian rhythms organize many aspects of cell biology and physiology to a daily temporal program that depends on clock gene expression cycles in most mammalian cell types. However, circadian rhythms are also observed in isolated mammalian red blood cells (RBCs), which lack nuclei, suggesting the existence of post-translational cellular clock mechanisms in these cells. Here we show using electrophysiological and pharmacological approaches that human RBCs display circadian regulation of membrane conductance and cytoplasmic conductivity that depends on the cycling of cytoplasmic K+ levels. Using pharmacological intervention and ion replacement, we show that inhibition of K+ transport abolishes RBC electrophysiological rhythms. Our results suggest that in the absence of conventional transcription cycles, RBCs maintain a circadian rhythm in membrane electrophysiology through dynamic regulation of K+ transport.

| S-EPMC5719349 | biostudies-literature

Uptake and metabolism of dipeptides by human red blood cells.

Project description:A function of the abundant cytoplasmic peptidases in red blood cells could be hydrolysis of oligopeptides circulating in plasma. To investigate whether human red blood cells actively transport dipeptides for this purpose, these cells were incubated with 14C-labelled glycylproline, glycylsarcosine, glycine, proline and alanine. There was uptake of each dipeptide, as indicated by their recovery as dipeptides in the cell cytoplasm. However, after a brief time (1-2 min) uptake of dipeptides abruptly ceased, while that of amino acids continued. As a result, after 30 min red blood cell uptake of amino acids was 5-13-fold greater than that of any dipeptide. Investigation of intracellular contents after 1 min of incubation revealed different metabolism for different dipeptides. The composition of intracellular radioactivity was 19-71% as intact dipeptides, 0-20% as free amino acids and 8-77% as neither dipeptides nor constituent amino acids. Investigation of the mechanism of dipeptide uptake by red blood cells showed: (1) a lack of hydrolysis by the plasma membrane, (2) no non-specific binding to the plasma membrane, and (3) a lack of saturation over a wide range of concentrations (0.05-50 mM). The data suggest that the mechanism of uptake of trace amounts of dipeptides by human red blood cells is either by simple diffusion or by a carrier system which has a very weak affinity for dipeptides. Upon entry, depending on the molecular structure, dipeptides are either hydrolysed or transformed into new compounds. The red blood cell uptake, however, does not appear to play any appreciable role in clearance of dipeptides from the plasma in the human.

| S-EPMC1149523 | biostudies-other

High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol.

Project description:A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge. HDL heterogeneity is the result of the activity of several factors that assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1 (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP), endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). The RCT pathway consists of the following steps: 1. Cholesterol efflux from peripheral tissues to plasma, 2. LCAT-mediated esterification of cholesterol and remodeling of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and 4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated transfer There are several established strategies for raising HDL cholesterol in humans, such as lifestyle changes; use of drugs including fibrates, statins, and niacin; and new therapeutic approaches. The therapeutic approaches include CETP inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic farnesoid X receptor agonists, and gene therapy. Results of clinical trials should be awaited before further clinical management of atherosclerotic cardiovascular disease.

| S-EPMC5731265 | biostudies-literature

Hypoxic storage of red blood cells improves metabolism and post-transfusion recovery.

Project description:BackgroundBlood transfusion is a lifesaving intervention for millions of recipients worldwide every year. Storing blood makes this possible but also promotes a series of alterations to the metabolism of the stored erythrocyte. It is unclear whether the metabolic storage lesion is correlated with clinically relevant outcomes and whether strategies aimed at improving the metabolic quality of stored units, such as hypoxic storage, ultimately improve performance in the transfused recipient.Study design and methodsTwelve healthy donor volunteers were recruited in a two-arm cross-sectional study, in which each subject donated 2 units to be stored under standard (normoxic) or hypoxic conditions (Hemanext technology). End-of-storage measurements of hemolysis and autologous posttransfusion recovery (PTR) were correlated to metabolomics measurements at Days 0, 21, and 42.ResultsHypoxic red blood cells (RBCs) showed superior PTR and comparable hemolysis to donor-paired standard units. Hypoxic storage improved energy and redox metabolism (glycolysis and 2,3-diphosphoglycerate), improved glutathione and methionine homeostasis, decreased purine oxidation and membrane lipid remodeling (free fatty acid levels, unsaturation and hydroxylation, acyl-carnitines). Intra- and extracellular metabolites in these pathways (including some dietary purines) showed significant correlations with PTR and hemolysis, though the degree of correlation was influenced by sulfur dioxide (SO2 ) levels.ConclusionHypoxic storage improves energy and redox metabolism of stored RBCs, which results in improved posttransfusion recoveries in healthy autologous recipients-a Food and Drug Administration gold standard of stored blood quality. In addition, we identified candidate metabolic predictors of PTR for RBCs stored under standard and hypoxic conditions.

| S-EPMC7899235 | biostudies-literature

Accelerating metabolism and transmembrane cation flux by distorting red blood cells.

Project description:Under static conditions, mammalian red blood cells (RBCs) require a continuous supply of energy, typically via glucose, to maintain their biconcave disc shape. Mechanical distortion, in a complementary way, should lead to increased energy demand that is manifest in accelerated glycolysis. The experimental challenge in observing this phenomenon was met by reversibly and reproducibly distorting the cells and noninvasively measuring glycolytic flux. This was done with a gel-distorting device that was coupled with 13C nuclear magnetic resonance (NMR) spectroscopy. We measured [3-13C]l-lactate production from [1,6-13C]d-glucose in the RBCs suspended in gelatin gels, and up to 90% rate enhancements were recorded. Thus, for the first time, we present experiments that demonstrate the linkage of mechanical distortion to metabolic changes in whole mammalian cells. In seeking a mechanism for the linkage between shape and energy supply, we measured transmembrane cation flux with Cs+ (as a K+ congener) using 133Cs NMR spectroscopy, and the cation flux was increased up to fivefold. The postulated mechanism for these notable (in terms of whole-body energy consumption) responses is stimulation of Ca-adenosine triphosphatase by increased transmembrane flux of Ca2+ via the channel protein Piezo1 and increased glycolysis because its flux is adenosine triphosphate demand-regulated.

| S-EPMC5647125 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data