Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.Receptors, Erythropoietin: Cell surface proteins that bind erythropoietin with high affinity and trigger intracellular changes influencing the behavior of cells.Erythropoiesis: The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.Anemia: A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.Polycythemia: An increase in the total red cell mass of the blood. (Dorland, 27th ed)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Erythroid Precursor Cells: The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.Hematocrit: The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value.Hemoglobins: The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.Erythroblasts: Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts.Reticulocyte Count: The number of RETICULOCYTES per unit volume of BLOOD. The values are expressed as a percentage of the ERYTHROCYTE COUNT or in the form of an index ("corrected reticulocyte index"), which attempts to account for the number of circulating erythrocytes.Hematinics: Agents which improve the quality of the blood, increasing the hemoglobin level and the number of erythrocytes. They are used in the treatment of anemias.Erythrocyte Count: The number of RED BLOOD CELLS per unit volume in a sample of venous BLOOD.Leukemia, Erythroblastic, Acute: A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Spleen Focus-Forming Viruses: Strains of MURINE LEUKEMIA VIRUS that are replication-defective and rapidly transforming. The envelope gene plays an essential role in initiating erythroleukemia (LEUKEMIA, ERYTHROBLASTIC, ACUTE), manifested by splenic foci, SPLENOMEGALY, and POLYCYTHEMIA. Spleen focus-forming viruses are generated by recombination with endogenous retroviral sequences.Kidney Failure, Chronic: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.Anemia, Neonatal: The mildest form of erythroblastosis fetalis in which anemia is the chief manifestation.Interleukin-3: A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.Renal Dialysis: Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Colony-Forming Units Assay: A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.STAT5 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.Anoxia: Relatively complete absence of oxygen in one or more tissues.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Polycythemia Vera: A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs.Blood Transfusion: The introduction of whole blood or blood component directly into the blood stream. (Dorland, 27th ed)Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Doping in Sports: Illegitimate use of substances for a desired effect in competitive sports. It includes humans and animals.Milk Proteins: The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)Hypoxia-Inducible Factor 1: A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Phenylhydrazines: Diazo derivatives of aniline, used as a reagent for sugars, ketones, and aldehydes. (Dorland, 28th ed)Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Friend murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.Reticulocytes: Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.Stem Cell Factor: A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Hematopoiesis: The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).Phlebotomy: The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda.Erythrocyte Volume: Volume of circulating ERYTHROCYTES . It is usually measured by RADIOISOTOPE DILUTION TECHNIQUE.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Anemia, Hypochromic: Anemia characterized by a decrease in the ratio of the weight of hemoglobin to the volume of the erythrocyte, i.e., the mean corpuscular hemoglobin concentration is less than normal. The individual cells contain less hemoglobin than they could have under optimal conditions. Hypochromic anemia may be caused by iron deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by infections or other diseases, therapeutic drugs, lead poisoning, and other conditions. (Stedman, 25th ed; from Miale, Laboratory Medicine: Hematology, 6th ed, p393)RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Erythroid Cells: The series of cells in the red blood cell lineage at various stages of differentiation.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Ferritins: Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store IRON in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (APOFERRITINS) made of 24 subunits of various sequences depending on the species and tissue types.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Bloodletting: Puncture of a vein to draw blood for therapeutic purposes. Bloodletting therapy has been used in Talmudic and Indian medicine since the medieval time, and was still practiced widely in the 18th and 19th centuries. Its modern counterpart is PHLEBOTOMY.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.GATA1 Transcription Factor: A GATA transcription factor that is specifically expressed in hematopoietic lineages and plays an important role in the CELL DIFFERENTIATION of ERYTHROID CELLS and MEGAKARYOCYTES.Erythrocyte Transfusion: The transfer of erythrocytes from a donor to a recipient or reinfusion to the donor.Hypoxia-Inducible Factor-Proline Dioxygenases: Dioxygenase enzymes that specifically hydroxylate a PROLINE residue on the HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA.Iron Radioisotopes: Unstable isotopes of iron that decay or disintegrate emitting radiation. Fe atoms with atomic weights 52, 53, 55, and 59-61 are radioactive iron isotopes.Hematopoietic Cell Growth Factors: These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Receptors, Transferrin: Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.

Human, rat, and mouse kidney cells express functional erythropoietin receptors. (1/3892)

BACKGROUND: Erythropoietin (EPO), secreted by fibroblast-like cells in the renal interstitium, controls erythropoiesis by regulating the survival, proliferation, and differentiation of erythroid progenitor cells. We examined whether renal cells that are exposed to EPO express EPO receptors (EPO-R) through which analogous cytokine responses might be elicited. METHODS: Normal human and rat kidney tissue and defined cell lines of human, rat, and mouse kidney were screened, using reverse transcription-polymerase chain reaction, nucleotide sequencing, ligand binding, and Western blotting, for the expression of EPO-R. EPO's effects on DNA synthesis and cell proliferation were also examined. RESULTS: EPO-R transcripts were readily detected in cortex, medulla, and papilla of human and rat kidney, in mesangial (human, rat), proximal tubular (human, mouse), and medullary collecting duct cells (human). Nucleotide sequences of EPO-R cDNAs from renal cells were identical to those of erythroid precursor cells. Specific 125I-EPO binding revealed a single class of high- to intermediate-affinity EPO-Rs in each tested cell line (kD 96 pm to 1. 4 nm; Bmax 0.3 to 7.0 fmol/mg protein). Western blots of murine proximal tubular cell membranes revealed an EPO-R protein of approximately 68 kDa. EPO stimulated DNA synthesis and cell proliferation dose dependently. CONCLUSION: This is the first direct demonstration, to our knowledge, that renal cells possess EPO-Rs through which EPO stimulates mitogenesis. This suggests currently unrecognized cytokine functions for EPO in the kidney, which may prove beneficial in the repair of an injured kidney while being potentially detrimental in renal malignancies.  (+info)

Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells: functional analysis of signaling molecules by retrovirus-mediated expression. (2/3892)

Erythropoietin (EPO) and its cell surface receptor (EPOR) play a central role in proliferation, differentiation, and survival of erythroid progenitors. Signals induced by EPO have been studied extensively by using erythroid as well as nonerythroid cell lines, and various controversial results have been reported as to the role of signaling molecules in erythroid differentiation. Here we describe a novel approach to analyze the EPO signaling by using primary mouse fetal liver hematopoietic cells to avoid possible artifacts due to established cell lines. Our strategy is based on high-titer retrovirus vectors with a bicistronic expression system consisting of an internal ribosome entry site (IRES) and green fluorescent protein (GFP). By placing the cDNA for a signaling molecule in front of IRES-GFP, virus-infected cells can be viably sorted by fluorescence-activated cell sorter, and the effect of expression of the signaling molecule can be assessed. By using this system, expression of cell-survival genes such as Bcl-2 and Bcl-XL was found to enhance erythroid colony formation from colony-forming unit-erythroid (CFU-E) in response to EPO. However, their expression was not sufficient for erythroid colony formation from CFU-E alone, indicating that EPO induces signals for erythroid differentiation. To examine the role of EPOR tyrosine residues in erythroid differentiation, we introduced a chimeric EGFR-EPOR receptor, which has the extracellular domain of the EGF receptor and the intracellular domain of the EPOR, as well as a mutant EGFR-EPOR in which all the cytoplasmic tyrosine residues are replaced with phenylalanine, and found that tyrosine residues of EPOR are essential for erythroid colony formation from CFU-E. We further analyzed the function of the downstream signaling molecules by expressing modified signaling molecules and found that both JAK2/STAT5 and Ras, two major signaling pathways activated by EPOR, are involved in full erythroid differentiation.  (+info)

Iron depletion by phlebotomy with recombinant erythropoietin prior to allogeneic transplantation to prevent liver toxicity. (3/3892)

Iron overload may induce liver toxicity after hematopoietic stem cell transplantation (HSCT), but it is not known if iron depletion prior to HSCT can reduce the risk of severe toxicity in this setting. We used subcutaneous recombinant erythropoietin (EPO) (25 UI/kg) three times a week and phlebotomy once a week, to prevent liver toxicity in a patient with advanced acute leukemia and liver disease due to severe iron overload, previous drug toxicity and hepatitis C viral infection. Over the 9 months prior to allogeneic HSCT, 34 phlebotomies were carried out. Serum ferritin dropped from 2964 to 239 microg/l and the ALT dropped to near normal values. At allogeneic HSCT no liver toxicity was observed, suggesting that iron depletion in the pretransplant period may contribute to reducing transplant-related toxicity in selected cases.  (+info)

Association of plasma fibrinogen concentration with vascular access failure in hemodialysis patients. (4/3892)

BACKGROUND: Elevated plasma fibrinogen is an important risk factor for coronary artery disease in the general population and patients with chronic renal failure. High plasma fibrinogen may trigger thrombus formation in arteriovenous fistulas. We performed a prospective, cohort study to evaluate the association of plasma fibrinogen concentration with vascular access failure in patients undergoing long-term haemodialysis. METHODS: Between September 1989 and October 1995, 144 patients underwent a vascular access operation. In March 1997, 102 patients (56 M, 46 F) who had been followed up for more than 18 months (median; 37 months, range; 18-102 months) were included in the study. The median age of the patients was 52 years (range; 19-78 years). In 35 patients, renal disease was secondary to diabetes mellitus. The type of vascular access was a polytetrafluoroethylene (PTFE) graft in 17 patients. Seventy-seven patients received recombinant human erythropoietin (r-HuEPO) therapy during the follow-up period. Plasma fibrinogen, albumin, total cholesterol, hematocrit, platelets and creatinine were measured at the time of operation. Vascular access failure was defined as the occurrence of complications requiring transluminal angioplasty, thrombolytic therapy or surgical repair. RESULTS: Thirty-eight patients had at least one vascular access failure and the incidence was 0.3 (range; 0-2.4) episodes per patient-year. The survival rate of vascular access was 78% (native fistula; 80%, PTFE graft; 71%) after 12 months and 70% (native fistula; 73%, PTFE graft; 51%) after 24 months. Older age, a PTFE graft, r-HuEPO therapy, higher hematocrit, lower albumin and higher fibrinogen levels were significantly associated with vascular access failure, whereas gender, diabetes mellitus, total cholesterol and platelet count were not. Plasma fibrinogen was inversely correlated with albumin (r=-0.38, P=0.001). The cumulative vascular access survival was significantly lower in patients with high plasma fibrinogen levels (> or = 460 mg/dl) compared with patients with low levels (< 460 mg/dl) (P=0.007). Independent risk factors for vascular access failure analysed by Cox's proportional hazards model were older age (RR; 1.36 by 10-year increment), higher fibrinogen level (RR; 1.20 by 100 mg/dl increment), PTFE graft (RR; 2.28) and r-HuEPO therapy (RR; 3.79). CONCLUSION: High plasma fibrinogen level is an independent risk factor for vascular access failure in haemodialysis patients.  (+info)

Advances in the biological therapy and gene therapy of malignant disease. (5/3892)

Biological and gene therapy of cancer have become important components of clinical cancer research. Advances in this area are based on evidence for the presence of tumor antigens, antitumor immune responses, evasion of host control by tumors, and the recognition of host defense failure in cancer patients. These mechanisms are being corrected or exploited in the development of biological and gene therapy. Over the last decade, 9 biological therapies have received Food and Drug Administration approval, and another 12 appear promising and will likely be approved in the next few years. Our approach to gene therapy has been to allogenize tumors by the direct intratumoral injection of HLA-B7/beta2-microglobulin genes as plasmid DNA in a cationic lipid into patients with malignant melanoma. In four Phase I studies, we found a 36% response by the local injected tumor and a 19% systemic antitumor response. In other cancers, gene transfer, expression, and an intratumoral T-cell response were seen, but no clinical response was seen. A variety of follow-up studies with HLA-B7 and other genes are planned. Evasion of host control is now a major target of gene therapy. Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes. With these approaches, it seems likely that gene therapy may become the fifth major modality of cancer treatment in the next decade.  (+info)

Identification of the poly(C) binding protein in the complex associated with the 3' untranslated region of erythropoietin messenger RNA. (6/3892)

Hypoxia regulates expression of erythropoietin (EPO), a glycoprotein that stimulates erythrocytosis, at the level of transcription and also possibly at the level of messenger RNA (mRNA) stability. A pyrimidine-rich region within the EPO mRNA 3' untranslated region was implicated in regulation of EPO mRNA stability element and shown to bind protein factors. In the present study we wished to identify the protein factor binding to the pyrimidine-rich sequence in the EPO mRNA stability element. Using mobility shift assays, ultraviolet light cross-linking, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and electroelution of protein factors from the gel slices corresponding to the ribonucleoprotein complexes, we found that two isoforms of a 40 kD poly(C) binding protein (PCBP, also known as alphaCP or hnRNPE), PCBP1, and PCBP2 are present in that complex. In Hep3B or HepG2 cells hypoxia induces neither expression of PCBP nor formation of the ribonucleoprotein complex associated with EPO mRNA that involves PCBP.  (+info)

Erythropoietin depresses nitric oxide synthase expression by human endothelial cells. (7/3892)

We have recently shown that erythropoietin (EPO)-induced hypertension is unrelated to the rise in hematocrit and is marked by elevated cytosolic [Ca+2] and nitric oxide (NO) resistance. The present study was done to determine the effect of EPO on NO production and endothelial NO synthase (eNOS) expression by endothelial cells. Human coronary artery endothelial cells were cultured to subconfluence and then were incubated for 24 hours in the presence of either EPO (0, 5, and 20 U/mL) alone or EPO plus the calcium channel blocker felodipine. The experiments were carried out with quiescent (0.5% FCS) and proliferating (5% FCS) cells. Total nitrate and nitrite, eNOS protein, DNA synthesis (thymidine incorporation), and cell proliferation (cell count) were determined. In addition, NO production in response to acetylcholine stimulation was tested. EPO resulted in a dose-dependent inhibition of basal and acetylcholine-stimulated NO production and eNOS protein expression and also led to a significant dose-dependent stimulation of DNA synthesis in endothelial cells. The inhibitory effects of EPO on NO production and eNOS expression were reversed by felodipine. Thus, EPO downregulates basal and acetylcholine-stimulated NO production, depresses eNOS expression, and stimulates proliferation in isolated human endothelial cells. The suppressive effects of EPO on NO production and on eNOS expression are reversed by calcium channel blockade.  (+info)

Expression of the erythropoietin receptor by trophoblast cellsin the human placenta. (8/3892)

Nonclassical sites of erythropoietin (EPO) and erythropoietin receptor (EPO-R) expression have been described that suggest new physiological roles for this hormone unrelated to erythropoiesis. The recent finding of EPO expression by trophoblast cells in the human placenta prompted us to consider whether these cells also express EPO-R. With use of immunocytochemistry, EPO-R was identified in villous and extravillous cytotrophoblast cells, as well as in the syncytiotrophoblast at all gestational ages. EPO-R was also expressed by cells within the villous core, including endothelial cells of fetoplacental blood vessels. Placental tissues and isolated and immunopurified trophoblast cells, as well as trophoblast-derived choriocarcinoma Jar cells, expressed immunoreactive EPO-R on Western blot. EPO-R mRNA was also detected in the same placental tissues and trophoblast cells by nested-primer reverse transcription-polymerase chain reaction. Finally, EPO-R was functional insofar as the receptor was phosphorylated on tyrosine residues in response to exogenous EPO treatment of cultured trophoblast or Jar cells. Thus, the present findings support the hypothesis that trophoblast cells of the human placenta express EPO-R. In view of these results, taken together with previous work demonstrating EPO expression by the same cells, an autocrine role for this hormone in the survival, proliferation, or differentiation of placental trophoblast cells is proposed.  (+info)

  • abstract = "Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. (
  • abstract = "A sensitive radioimmunoassay (RIA) for the detection of erythropoietin (EPO) was developed using antibody directed against EPO from human urine. (
  • A European randomized, placebo-controlled trial confirmed these QOL results, and a meta-analysis of other randomized clinical trials firmly supports the role of erythropoietin therapy in improving hemoglobin levels and reducing transfusion requirements. (
  • This glycoprotein demonstrates anti-anemic capabilities and has a longer terminal half-life than erythropoietin. (
  • The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. (
  • Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. (
  • misc{etde_22121055, title = {Recovery of the Erythropoietin-Sensitive Stem-Cell Population following Total-Body X-Irradiation} author = {Byron, J. W.} abstractNote = {Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. (
  • have developed a differentiation protocol for erythropoietin-producing cells from human and mouse iPSCs and ESCs. (
  • Erythropoietin, a hormone produced in the adult kidney, controls erythrocyte production. (
  • Methods: Darbepoetin alfa (DA) and carbamylated nonerythropoietic derivative of erythropoietin (CEPO) protective effects were evaluated in a model of I/R injury after kidney transplantation in both syngeneic and allogeneic combinations. (
  • The gene for erythropoietin ( EPO ), which boosts red blood cells thereby raising blood oxygen and endurance, presents another possibility. (
  • To study the variability of cell and donor sources, we compared different primary human cells as candidates for gene therapy-mediated delivery of human erythropoietin (hEpo). (
  • Their research demonstrated that the gene for erythropoietin encoded the production of EPO in mammalian cells that is biologically active in vitro and in vivo. (
  • Regulation of expression of the erythropoietin gene. (
  • We have a limited understanding of the factors governing the tissue specificity of erythropoietin gene expression but considerable progress has been made toward understanding the mechanisms that increase erythropoietin gene expression in response to hypoxia. (
  • Animals were killed 24 hr or 7 days after transplant and kidneys were processed for histological analysis, immunohistochemistry assessment of erythropoietin receptor (EPOR) and β-common chain receptor expression, granulocyte infiltration, nitrotyrosine staining, p-Akt expression, peritubular capillary (PTC) density, apoptosis, antioxidant, and antiapoptotic gene expression. (
  • The source of circulating erythropoietin (EPO), the mediators and the mechanisms involved in the upregulation of EPO gene expression during acute-phase reaction are still poorly understood. (
  • Specifically, the colony forming unit-erythroid (CFU-E) is completely dependent on erythropoietin. (
  • This effect may be used in polycythaemic mice to estimate changes in the erythropoietin-sensitive stem-cell population following total-body irradiation (TBR). (
  • Subgroup analysis showed that patients with observed to predicted (O/P) serum erythropoietin levels ≤0.9 and responders to chemotherapy benefited from erythropoietin administration in contrast to patients with O/P >0.9 or non-responders. (
  • These cells produced and secreted functional erythropoietin protein in a hypoxia-dependent manner. (
  • Rosenbaum, Daniel M. / Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury . (
  • From the perspective of basic research, erythropoietin-producing cells may be a useful tool for investigating the molecular mechanisms of erythropoietin production and secretion. (
  • Those substances included undetectable steroids and the blood-boosting erythropoietin (EPO). (
  • Chronic treatment with asialo erythropoietin (ASIALO-EPO) or carbamylated erythropoietin (CEPO) improved motor behavior and reduced motoneuron loss and astrocyte and microglia activation in the cervical spinal cord of wobbler mice, an animal model of amyotrophic lateral sclerosis, but had no effect on hematocrit values. (
  • Another nonerythropoietic EPO derivative is asialo erythropoietin (ASIALO-EPO), which, although it binds to the classic homodimeric EPOR, has a short half-life in vivo and does not increase the hematocrit (an activity that requires persistent circulating levels of EPO) but also retains neuroprotective activities in vivo ( 16 ). (
  • Thirty-two patients with a hematocrit of 25% or less received erythropoietin at the dose of 4500 IU/week, by the intravenous route for 8 weeks. (
  • On account of patent protection, widespread use of biologics in the treatment of chronic kidney diseases, the biologics erythropoietin drugs segment emerged as the leader with a 73.69% share of market revenue in 2017. (
  • Due to being the first US FDA approved biologic erythropoietin drug that is available for the treatment of anemia caused by the chemotherapy, HIV AIDS, chronic kidney disease and other similar diseases Epotin alpha product segment emerged as the largest with a 39.48% share of revenue in 2017. (
  • Even though increasing prevalence of chronic kidney disease, HIV AIDS and anemia diseases and rising use of biosimilar erythropoietin are driving the global erythropoietin drugs market. (
  • Does erythropoietin slow progression of chronic kidney disease? (
  • Vogel, M , Thomas, A , Schänzer, W & Thevis, M 2015, Detection of Erythropoietin Mimetic Peptide-Based Drugs from Human Urine by means of EPOR-purification and LC/MS/MS determination . (
  • Background: The present study was designed to evaluate the homing potential of mouse embryonic stem cells (ESC) treated with erythropoietin (EPO) in hematopoietic organs such as spleen and liver after transplantation using morphological and immuno-histochemical techniques. (
  • Erythropoietin (EPO), a hematopoietic growth factor, is neuroprotective in different models of neurodegenerative disease, including experimental autoimmune encephalomyelitis (EAE) ( 4 , 5 ), cerebral ischemia ( 6 ), and diabetic neuropathy ( 7 ). (
  • On account of widespread utilization of erythropoietin drugs for the treatment of the cancer patients undergoing chemotherapy, the cancer segment is anticipated to grow at an accelerated CAGR of 13.97% over the forecasted period. (
  • RLS patients were examined for clinical picture and laboratory markers including erythropoietin levels. (
  • Our results confirm previously published lower age at symptom onset in familial RLS and provide the first evidence of lower erythropoietin levels in RLS patients. (
  • Cost-effectiveness of recombinant human erythropoietin for reducing red blood cells transfusions in critically ill patients. (
  • Preoperative recombinant human erythropoietin in anemic surgical patients. (
  • We investigated whether treatment of anemic hemodialysis patients with a low dose of recombinant human erythropoietin (erythropoietin) for a short period would increase their blood pressure. (
  • Circadian variation of blood pressure (nocturnal fall and diurnal rise) had been attenuated in the patients of the pressor group before erythropoietin treatment and erythropoietin decreased the nocturnal fall of blood pressure further more. (
  • Although the pressor effect of erythropoietin treatment for 8 weeks at the dose of 4500 IU/week was not evident on clinic blood pressure measurements, any increase in blood pressure determined by ambulatory blood pressure should be treated carefully to reduce the risk of a cardiovascular complication in patients receiving hemodialysis. (
  • The regulatory mechanism responsible for a paradoxal, rapid drop in the erythropoietin (EPO) plasma level seen 2 to 4 days after acute, phlebotomy-induced anemia was investigated in seven adult sheep. (
  • Erythropoietin is a well-known erythroid differentiation and growth factor, but the mechanism of its action is not well understood. (
  • In this work, we have examined its mechanism of action on the erythropoietin-responsive murine erythroleukemia cells (TSA8). (
  • On account of its improved efficacy and longer shelf life, the Epoetin beta segment also accounted for a significant share of global erythropoietin drugs market in 2017. (
  • Jantzie LL, Miller RH, Robinson S. Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury. (
  • Beigi Boroujeni M, Salehnia M, Rezazadeh Valojerdi M, Forouzandeh Moghadam M. Transplantation and Homing of Mouse Embryonic Stem Cells Treated with Erythropoietin in Spleen and Liver of irradiated mice. (
  • Growing investments on research and development of biosimilars, robust product pipeline and rise in collaborations between hospitals and manufactures for the adoption of erythropoietin biosimilars are some of the factors that are expected to drive the growth of the biosimilar segment. (
  • The log of erythropoietin focus was plotted versus the log of optical denseness for the typical curve. (
  • Alternatives to blood product transfusion in the critically ill: erythropoietin. (
  • Using a mouse model that overexpresses recombinant human erythropoietin (EPO) in the CNS, we observed stimulation of the postnatal maturation of GABAergic transmission in the hippocampus, notably accelerated maturation of parvalbumin (PV)+ interneurons, enhanced glutamatergic inputs onto these interneurons, and enhanced IPSCs onto pyramidal cells. (
  • TSA8 cells become responsive to erythropoietin after induction with DMSO. (
  • cAMP analogues themselves show no stimulatory effect on TSA8 cells, nor does erythropoietin increase cAMP level in the cells. (
  • Like erythropoietin, Mircera works by increasing the number of red blood cells and the haemoglobin level in your blood. (
  • Extracts from The Cochrane Library: Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer. (
  • This installment features a Cochrane Review entitled "Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer," which concludes that erythropoietin should not be administered as an addition to radiation therapy outside the experimental setting. (
  • Compared to other erythropoietin medicines, Mircera can stay in your body longer, therefore requiring fewer injections for your treatment. (
  • Stimulatory effects on erythropoietin response are observed with the addition of compounds affecting the cAMP level such as forskolin, phophodiesterase inhibitor and cholera toxin only in the presence of erythropoietin. (
  • Therefore, the increase in blood pressure induced by erythropoietin was detected more reliably by ambulatory blood pressure monitoring. (
  • Artificial erythropoietin is used by athletes to increase the capacity of their blood to carry oxygen in their body and thereby increase their stamina. (
  • It is an 80 - 85 kDa protein that consists of an N-terminal domain with homology to Erythropoietin (Epo) and a C-terminal domain that contains multiple N-linked and O-linked glycosylation sites (4, 5). (
  • Erythropoietin levels in the familial cases were significantly lower than in the reference population (median -2.26 SDs from the mean). (