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Blood Dec 2017The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the... (Review)
Review
The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the erythrocyte to maintain a narrow range of cell hemoglobin concentration, a process critical for normal red blood cell function and survival. Primary disorders that perturb volume homeostasis jeopardize the erythrocyte and may lead to its premature destruction. These disorders are marked by clinical, laboratory, and physiologic heterogeneity. Recent studies have revealed that these disorders are also marked by genetic heterogeneity. They have implicated roles for several proteins, PIEZO1, a mammalian mechanosensory protein; GLUT1, the glucose transporter; SLC4A1, the anion transporter; RhAG, the Rh-associated glycoprotein; KCNN4, the Gardos channel; and ABCB6, an adenosine triphosphate-binding cassette family member, in the maintenance of erythrocyte volume homeostasis. Secondary disorders of erythrocyte hydration include sickle cell disease, thalassemia, hemoglobin CC, and hereditary spherocytosis, where cellular dehydration may be a significant contributor to disease pathology and clinical complications. Understanding the pathways regulating erythrocyte water and solute content may reveal innovative strategies to maintain normal volume in disorders associated with primary or secondary cellular dehydration. These mechanisms will serve as a paradigm for other cells and may reveal new therapeutic targets for disease prevention and treatment beyond the erythrocyte.
Topics: Animals; Dehydration; Erythrocyte Volume; Erythrocytes; Homeostasis; Humans
PubMed: 29051181
DOI: 10.1182/blood-2017-04-590810 -
Biological Chemistry Jun 2015Anemia and hemorrhagic shock are leading causes of morbidity and mortality worldwide, and transfusion of human blood products is the ideal treatment for these... (Review)
Review
Anemia and hemorrhagic shock are leading causes of morbidity and mortality worldwide, and transfusion of human blood products is the ideal treatment for these conditions. As human erythrocytes age during storage in blood banks they undergo many biochemical and structural changes, termed the red blood cell 'storage lesion'. Specifically, ATP and pH levels decrease as metabolic end products, oxidative stress, cytokines, and cell-free hemoglobin increase. Also, membrane proteins and lipids undergo conformational and organizational changes that result in membrane loss, viscoelastic changes and microparticle formation. As a result, transfusion of aged blood is associated with a host of adverse consequences such as decreased tissue perfusion, increased risk of infection, and increased mortality. This review summarizes current research detailing the known parts of the erythrocyte storage lesion and their physiologic consequences.
Topics: Blood Banks; Cytokines; Erythrocyte Aging; Erythrocytes; Hemoglobins; Humans; Oxidative Stress
PubMed: 25803075
DOI: 10.1515/hsz-2014-0292 -
Biomolecules May 2021There has been a recent increase in the development of delivery systems based on red blood cells (RBCs) for light-mediated imaging and therapeutic applications. These... (Review)
Review
There has been a recent increase in the development of delivery systems based on red blood cells (RBCs) for light-mediated imaging and therapeutic applications. These constructs are able to take advantage of the immune evasion properties of the RBC, while the addition of an optical cargo allows the particles to be activated by light for a number of promising applications. Here, we review some of the common fabrication methods to engineer these constructs. We also present some of the current light-based applications with potential for clinical translation, and offer some insight into future directions in this exciting field.
Topics: Animals; Drug Delivery Systems; Erythrocyte Membrane; Erythrocytes; Humans; Nanoparticles; Optical Imaging; Photochemotherapy; Photosensitizing Agents
PubMed: 34068081
DOI: 10.3390/biom11050729 -
International Journal of Molecular... May 2023The chicken genome is one-third the size of the human genome and has a similarity of sixty percent when it comes to gene content. Harboring similar genome sequences,... (Review)
Review
The chicken genome is one-third the size of the human genome and has a similarity of sixty percent when it comes to gene content. Harboring similar genome sequences, chickens' gene arrangement is closer to the human genomic organization than it is to rodents. Chickens have been used as model organisms to study evolution, epigenome, and diseases. The chicken nucleated erythrocyte's physiological function is to carry oxygen to the tissues and remove carbon dioxide. The erythrocyte also supports the innate immune response in protecting the chicken from pathogens. Among the highly studied aspects in the field of epigenetics are modifications of DNA, histones, and their variants. In understanding the organization of transcriptionally active chromatin, studies on the chicken nucleated erythrocyte have been important. Through the application of a variety of epigenomic approaches, we and others have determined the chromatin structure of expressed/poised genes involved in the physiological functions of the erythrocyte. As the chicken erythrocyte has a nucleus and is readily isolated from the animal, the chicken erythrocyte epigenome has been studied as a biomarker of an animal's long-term exposure to stress. In this review, epigenomic features that allow erythroid gene expression in a highly repressive chromatin background are presented.
Topics: Humans; Animals; Chickens; Epigenomics; Chromatin; Histones; Erythrocytes
PubMed: 37175991
DOI: 10.3390/ijms24098287 -
Microbiology and Molecular Biology... Nov 2019The asexual intraerythrocytic development of , causing the most severe form of human malaria, is marked by extensive host cell remodeling. Throughout the processes of... (Review)
Review
The asexual intraerythrocytic development of , causing the most severe form of human malaria, is marked by extensive host cell remodeling. Throughout the processes of invasion, intracellular development, and egress, the erythrocyte membrane skeleton is remodeled by the parasite as required for each specific developmental stage. The remodeling is facilitated by a plethora of exported parasite proteins, and the erythrocyte membrane skeleton is the interface of most of the observed interactions between the parasite and host cell proteins. Host cell remodeling has been extensively described and there is a vast body of information on protein export or the description of parasite-induced structures such as Maurer's clefts or knobs on the host cell surface. Here we specifically review the molecular level of each host cell-remodeling step at each stage of the intraerythrocytic development of We describe key events, such as invasion, knob formation, and egress, and identify the interactions between exported parasite proteins and the host cell cytoskeleton. We discuss each remodeling step with respect to time and specific requirement of the developing parasite to explain host cell remodeling in a stage-specific manner. Thus, we highlight the interaction with the host membrane skeleton as a key event in parasite survival.
Topics: Cytoskeleton; Erythrocyte Membrane; Erythrocytes; Host-Parasite Interactions; Humans; Life Cycle Stages; Malaria, Falciparum; Plasmodium falciparum; Protein Transport
PubMed: 31484690
DOI: 10.1128/MMBR.00013-19 -
BioMed Research International 2015Suicidal erythrocyte death or eryptosis is characterized by erythrocyte shrinkage, cell membrane blebbing, and cell membrane scrambling with phosphatidylserine... (Review)
Review
Suicidal erythrocyte death or eryptosis is characterized by erythrocyte shrinkage, cell membrane blebbing, and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca(2+) entry, ceramide formation, stimulation of caspases, calpain activation, energy depletion, oxidative stress, and dysregulation of several kinases. Eryptosis is triggered by a wide variety of xenobiotics. It is inhibited by several xenobiotics and endogenous molecules including NO and erythropoietin. The susceptibility of erythrocytes to eryptosis increases with erythrocyte age. Phosphatidylserine exposing erythrocytes adhere to the vascular wall by binding to endothelial CXC-Motiv-Chemokin-16/Scavenger-receptor for phosphatidylserine and oxidized low density lipoprotein (CXCL16). Phosphatidylserine exposing erythrocytes are further engulfed by phagocytosing cells and are thus rapidly cleared from circulating blood. Eryptosis eliminates infected or defective erythrocytes thus counteracting parasitemia in malaria and preventing detrimental hemolysis of defective cells. Excessive eryptosis, however, may lead to anemia and may interfere with microcirculation. Enhanced eryptosis contributes to the pathophysiology of several clinical disorders including metabolic syndrome and diabetes, malignancy, cardiac and renal insufficiency, hemolytic uremic syndrome, sepsis, mycoplasma infection, malaria, iron deficiency, sickle cell anemia, thalassemia, glucose 6-phosphate dehydrogenase deficiency, and Wilson's disease. Facilitating or inhibiting eryptosis may be a therapeutic option in those disorders.
Topics: Animals; Apoptosis; Cytokines; Erythrocyte Aging; Erythrocytes; Hemolysis; Humans; Models, Cardiovascular
PubMed: 25821808
DOI: 10.1155/2015/513518 -
BioMed Research International 2018Erythrocytes play an important role in oxygen and carbon dioxide transport. Although erythrocytes possess no nucleus or mitochondria, they fulfil several metabolic... (Review)
Review
Erythrocytes play an important role in oxygen and carbon dioxide transport. Although erythrocytes possess no nucleus or mitochondria, they fulfil several metabolic activities namely, the Embden-Meyerhof pathway, as well as the hexose monophosphate shunt. Metabolic processes within the erythrocyte contribute to the morphology/shape of the cell and important constituents are being kept in an active, reduced form. Erythrocytes undergo a form of suicidal cell death called eryptosis. Eryptosis results from a wide variety of contributors including hyperosmolarity, oxidative stress, and exposure to xenobiotics. Eryptosis occurs before the erythrocyte has had a chance to be naturally removed from the circulation after its 120-day lifespan and is characterised by the presence of membrane blebbing, cell shrinkage, and phosphatidylserine exposure that correspond to nucleated cell apoptotic characteristics. After eryptosis is triggered there is an increase in cytosolic calcium (Ca) ion levels. This increase causes activation of Ca-sensitive potassium (K) channels which leads to a decrease in intracellular potassium chloride (KCl) and shrinkage of the erythrocyte. Ceramide, produced by sphingomyelinase from the cell membrane's sphingomyelin, contributes to the occurrence of eryptosis. Eryptosis ensures healthy erythrocyte quantity in circulation whereas excessive eryptosis may set an environment for the clinical presence of pathophysiological conditions including anaemia.
Topics: Anemia; Apoptosis; Calcium; Cell Death; Eryptosis; Erythrocytes; Humans; Oxidative Stress; Potassium Channels
PubMed: 29516014
DOI: 10.1155/2018/9405617 -
Bulletin of the World Health... 1977Merozoite endocytosis initiates Plasmodium development in a vacuole bounded by an erythrocyte-derived membrane, whose asymmetrical distribution of lipids and proteins is... (Review)
Review
Merozoite endocytosis initiates Plasmodium development in a vacuole bounded by an erythrocyte-derived membrane, whose asymmetrical distribution of lipids and proteins is reversed in its orientation with respect to the parasite plasma membrane. Reorientation may accompany the proliferation of the membrane associated with the parasite's growth and phagocytic and pinocytic feeding. Increases in the membrane surface area of the parasite, and in some cases of the erythrocyte, parallel parasite growth and segmentation. Augmentation of all the membrane systems of the infected erythrocyte causes the lipid content to rise rapidly, but the parasite lipid composition differs from that of the erythrocyte in many respects: it is higher in diacyl phosphatidylethanolamine, phosphatidylinositol, polyglycerol phosphatides, diacylglycerols, unesterified fatty acids, triacylglycerols, and hexadecanoic and octadecenoic fatty acids and lower in sphingomyelin, phosphatidylserine, alkoxy phosphatidylethanolamine, cholesterol, and polyunsaturated fatty acids. Active lipid metabolism accompanies the membrane proliferation associated with feeding, growth, and reproduction. Plasmodium is incapable of de novo biosynthesis of fatty acids and cholesterol; however, it can fabricate its glycerides and phosphoglycerides with host-supplied fatty acids, nitrogenous bases, alcohols, ATP, and coenzyme A, and can generate the glyceryl moiety during glycolysis. Cholesterol is obtained from the host but nothing is known of sphingolipid origins. Lipid metabolism of the parasite may be associated with alterations in the amounts of octadecenoic fatty acids and cholesterol in the erythrocyte plasma membrane, which in turn are responsible for changes in permeability and fragility.
Topics: Animals; Birds; Cell Membrane; Cholesterol; Erythrocytes; Fatty Acids; Haplorhini; Lipid Metabolism; Lipids; Plasmodium; Rats
PubMed: 412602
DOI: No ID Found -
Haematologica Apr 2017Hematopoietic-specific microRNA-142 is a critical regulator of various blood cell lineages, but its role in erythrocytes is unexplored. Herein, we characterize the...
Hematopoietic-specific microRNA-142 is a critical regulator of various blood cell lineages, but its role in erythrocytes is unexplored. Herein, we characterize the impact of microRNA-142 on erythrocyte physiology and molecular cell biology, using a mouse loss-of-function allele. We report that microRNA-142 is required for maintaining the typical erythrocyte biconcave shape and structural resilience, for the normal metabolism of reactive oxygen species, and for overall lifespan. microRNA-142 further controls ACTIN filament homeostasis and membrane skeleton organization. The analyses presented reveal previously unappreciated functions of microRNA-142 and contribute to an emerging view of small RNAs as key players in erythropoiesis. Finally, the work herein demonstrates how a housekeeping network of cytoskeletal regulators can be reshaped by a single micro-RNA denominator in a cell type specific manner.
Topics: Animals; Cell Line; Cell Survival; Erythrocyte Aging; Erythrocytes; Erythropoiesis; Humans; Mice; Mice, Knockout; MicroRNAs; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 27909218
DOI: 10.3324/haematol.2016.156109 -
Blood Transfusion = Trasfusione Del... May 2017Haemolysis occurs in many haematologic and non-haematologic diseases. Transfusion of packed red blood cells (pRBCs) can result in intravascular haemolysis, in which the... (Review)
Review
Haemolysis occurs in many haematologic and non-haematologic diseases. Transfusion of packed red blood cells (pRBCs) can result in intravascular haemolysis, in which the RBCs are destroyed within the circulation, and extravascular haemolysis, in which RBCs are phagocytosed in the monocyte-macrophage system. This happens especially after RBCs have been stored under refrigerated conditions for long periods. The clinical implications and the relative contribution of intra- vs extra-vascular haemolysis are still a subject of debate. They have been associated with adverse effects in animal models, but it remains to be determined whether these may be involved in mediating adverse effects in humans.
Topics: Animals; Blood Preservation; Erythrocyte Transfusion; Erythrocytes; Hemolysis; Humans
PubMed: 28518048
DOI: 10.2450/2017.0311-16