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Erythropoietins

Erythropoietin is a glycoprotein hormone that regulates red blood cell production in a feedback loop manner between kidney and bone marrow based on oxygen tension. It consists of 165 amino acids and has a molecular weight of 30,000-34,000 approximately 30% is accounted for by covalently linked carbohydrate. Erythropoietin is produced by the fetal liver and shortly after birth production switches from the liver to the kidney. In the fetus, erythropoietin functions in a paracrine-endocrine fashion because liver is the site of erythropoietin synthesis as well as ery-thropoiesis. The mechanism of this developmental switch is unclear. In the liver, erythropoietin synthesis occurs in [Pg.656]

Recombinant human erythropoietin has been used in the correction of anemia of chronic renal failure. It has also been used in other disorders of anemia such as anemia [Pg.656]

The cardioprotective effect of EPO has also been demonstrated in animal models. EPO administration at the time of reperfusion significantly reduced infarct size and apoptosis (assessed by TUNEL staining) in a rabbit model of acute coronary occlusion and reperfusion.36 This effect was accompanied by increased activation of ERK and Akt in the unstressed myocardium.36 Similarly, EPO administration throughout the period of low-flow ischemia reduced apoptosis and improved recovery of left ventricular pressure in perfused rat hearts.34 [Pg.81]

EPO is an additional haemopoietic growth factor. It is primarily responsible for stimulating and regulating erythropoiesis (i.e. erythrogenesis, the production of red blood cells) in mammals. [Pg.272]

Incomplete (N-linked) glycosylation prompts decreased in vivo activity due to more rapid hepatic clearance of the EPO molecule. Enzymatic removal of terminal sialic acid sugar residues from oligosaccharides exposes otherwise hidden galactose residues. These residues are then free to bind specific hepatic lectins, which promote EPO removal from the plasma. The reported plasma tm value for native EPO is 4-6 h. The tm for desialated EPO is 2 min. Comparison of native human EPO with its recombinant form produced in CHO cells reveals very similar glycosylation patterns. [Pg.273]

EPO in the human adult is synthesized almost exclusively by specialized kidney cells (peritubular interstitial cells of the kidney cortex and upper medulla). Minor quantities are also synthesized in the liver, which represents the primary EPO-producing organ of the foetus. [Pg.273]

EPO is present in serum and (at very low concentrations) in urine, particularly of anaemic individuals. This cytokine/hormone was first purified in 1971 from the plasma of anaemic sheep, and small quantities of human EPO were later purified (in 1977) from over 2500 1 of urine collected from anaemic patients. Large-scale purification from native sources was thus impractical. The isolation (in 1985) of the human EPO gene from a genomic DNA library facilitated its transfection into CHO cells. This now facilitates large-scale commercial production of the recombinant human product (rhEPO), which has found widespread medical application. [Pg.274]

The EPO receptor is a member of the haemopoietic cytokine receptor superfamily. Its intracellular domain displays no known catalytic activity, but it appears to couple directly to the JAK2 kinase (Chapter 8) that likely promotes the early events of EPO signal transduction. Other studies have implicated additional possible signalling mechanisms, including the involvement of G proteins, protein kinase C and Ca2+. The exact molecular events underlining EPO signal transduction remain to be elucidated in detail. [Pg.274]

SCHEME 11.20 Chemical synthesis of EPO having a complex-type sialyloligosaccharide. [Pg.286]

Fmoc-SPPS and convergent coupling Fmoc-SPPS and convergent coupling [Pg.287]

SCHEME 11.21 Synthesis of EPO bearing three N-linked chitobioses and an O-linked tetrasaccharide. [Pg.287]

Department of Chemistry, Indian Institute ofTechnology-Bombay, Mumbai, India [Pg.293]

Glycochemical Synthesis Strategies and Applications, First Edition. [Pg.293]


Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of ah biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic semm, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. [Pg.83]

As of early 1992, the market for ceU culture-derived products approached 1 billion per year. The market is expected to grow substantially throughout the 1990s. CeU culture products include erythropoietin, 1991 sales of approximately 400 million, for the treatment of anemia associated with kidney dialysis, and tissue plasminogen activator, 1991 sales approximately 200 million, for treating heart attack victims with blocked arteries (see Cardiovascularagents). [Pg.234]

In addition to being involved in the formation of urine, the kidney acts as an endocrine organ secreting renin, erythropoietin, prostaglandins (qv), and kinins it is also capable of synthesizing substances such as la,25-dihydroxycholecalciferol [32222-06-3] One of the principal functions of the... [Pg.202]

IP Boissel, WR Lee, SR Presnell, EE Cohen, HP Bunn. Erythropoietin stiaicture-function relationships. Mutant proteins that test a model of tertiary stiaicture. I Biol Chem 268 15983-15993, 1993. [Pg.305]

Phage display of random peptide libraries identified agonists of erythropoietin receptor... [Pg.364]

Figure 17.12 Ribbon diagram of EMPl bound to the extracellular domain of the erythropoietin receptor (EBP). Binding of EMPl causes dimerization of erythropoietin receptor. The x-ray crystal structure of the EMPl-EBP complex shows a nearly symmetrical dimer complex in which both peptide monomers interact with both copies of EBP. Recognition between the EMPl peptides and EBP utilizes more than 60% of the EMPl surface and four of six loops in the erythropoietin-binding pocket of EBP. Figure 17.12 Ribbon diagram of EMPl bound to the extracellular domain of the erythropoietin receptor (EBP). Binding of EMPl causes dimerization of erythropoietin receptor. The x-ray crystal structure of the EMPl-EBP complex shows a nearly symmetrical dimer complex in which both peptide monomers interact with both copies of EBP. Recognition between the EMPl peptides and EBP utilizes more than 60% of the EMPl surface and four of six loops in the erythropoietin-binding pocket of EBP.
In particular, three residues thought to be critical for binding erythropoietin (Phe 93, Met ISO, and Phe 205) are fully buried in the structure of the peptide-receptor complex. (From J.A. Wells, Science 273 449-450, 1996.)... [Pg.365]

Wrighton, N.C., et al. Small peptides as potent mimetics of the protein hormone erythropoietin. Science 273 458-463, 1996. [Pg.372]

There are undifferentiated stem cells of the blood elements in the bone marrow that differentiate and mature into erythrocytes, (red blood cells), thrombocytes (platelets), and white blood cells (leukocytes and lymphocytes). The production of erythrocytes is regulated by a hormone, erythropoietin (see the section on kidney toxicity), that is synthetized and excreted by the kidney. An increase in the number of premature erythrocytes is an indication of stimulation of erythropoiesis, i.e., increased production of erythrocytes in anemia due to continuous bleeding. [Pg.306]

Hematopoietic cytokines/colony-stimulating factors IL-3, IL-5, IL-6, IL-7, erythropoietin, GM-CSF, G-CSF, M-CSF, thrombo-poietin... [Pg.410]

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. [Pg.411]

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. [Pg.483]

Macdougall IC (2005) CERA (Continuous Erythropoietin Receptor Activator) a new erythropoiesis-stimulating agent for the treatment of anemia. Curr Hematol Rep 4 436-440... [Pg.581]

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... [Pg.1238]

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). [Pg.434]

Epoetin alfa (erythropoietin EPO) and darbepoetin alfa are usually well tolerated. The most common adverse reactions include hypertension, headache, tachycardia, nausea, vomiting, diarrhea, skin rashes, fever, myalgia, and skin reaction at tlie injection site. See the Summary Drug Table Drug Used in the Treatment of Anemia for more information on these drug. [Pg.434]

Erythropoietin pro ait with chronic renal tachycardia, nausea, vomiting, 50—100 U/kg (3 times... [Pg.435]


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Anemia cancer-related, erythropoietin

Antibodies against erythropoietin

Biologic response modifiers erythropoietin

Cytokine erythropoietin (EPO

Drug delivery erythropoietin

Epoetin alfa [erythropoietin, EPO

Epoetin alfa [erythropoietin, EPO Epogen, Procrit)

Erythropoiesis Erythropoietin

Erythropoietin (EPO)

Erythropoietin , anemia

Erythropoietin , anemia management

Erythropoietin , cytokine signaling

Erythropoietin Epoetin

Erythropoietin Epogen

Erythropoietin Procrit

Erythropoietin [epoetin alfa

Erythropoietin absorption

Erythropoietin activation

Erythropoietin administration

Erythropoietin adverse effects

Erythropoietin and

Erythropoietin androgen effects

Erythropoietin as hormone

Erythropoietin assay

Erythropoietin bioactivity

Erythropoietin bioassays

Erythropoietin biological activities

Erythropoietin cardiovascular effect

Erythropoietin case study

Erythropoietin cells targeted

Erythropoietin chemistry

Erythropoietin composition

Erythropoietin concentrations

Erythropoietin deficiency

Erythropoietin description

Erythropoietin distribution

Erythropoietin doping control

Erythropoietin dosing

Erythropoietin efficacy

Erythropoietin expression

Erythropoietin function

Erythropoietin gene induction

Erythropoietin glycosylated

Erythropoietin hormone

Erythropoietin hypertension with

Erythropoietin increase

Erythropoietin inhibition

Erythropoietin intraperitoneal

Erythropoietin is effective for the treatment of anemia associated with chronic renal failure

Erythropoietin marrow

Erythropoietin metabolism

Erythropoietin molecular mass

Erythropoietin monitoring

Erythropoietin oxidation

Erythropoietin periodate oxidation

Erythropoietin pharmacokinetics

Erythropoietin plasma concentrations

Erythropoietin preparations

Erythropoietin production

Erythropoietin production-oxyhemoglobin concentration

Erythropoietin protein production

Erythropoietin purification

Erythropoietin reaction with lectins

Erythropoietin reaction with serum

Erythropoietin receptor

Erythropoietin receptor agonists

Erythropoietin receptor dimerization

Erythropoietin recombinant type

Erythropoietin regulation

Erythropoietin resistance

Erythropoietin serum

Erythropoietin stimulating agent

Erythropoietin structure

Erythropoietin structure function

Erythropoietin therapeutic applications

Erythropoietin therapy

Erythropoietin use

Erythropoietin variants

Erythropoietin with stem cell factor

Erythropoietin-Epoetin Alpha

Erythropoietin-receptor activators

Erythropoietin-stimulating protein

Erythropoietin-stimulating protein NESP)

Glycoprotein hormone erythropoietin

Glycoproteins erythropoietin

Growth Erythropoietin

Human erythropoietin

Iron deficiency during erythropoietin therapy

Kidney disease, chronic erythropoietin

Oxyhemoglobin relationship, erythropoietin

Patents erythropoietin

Peptides recombinant human erythropoietin

Protein erythropoietin

Recombinant erythropoietin

Recombinant erythropoietin (epoetin

Recombinant human erythropoietin

Recombinant human erythropoietin (rhuEPO

Recombinant human erythropoietin glycoforms

Renal erythropoietin production

Therapeutic applications of erythropoietin

Uremia Erythropoietin

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