Metabolism of Recombinant Human Erythropoietin in the Rat

  • Jerry L. Spivak
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 271)


Erythropoietin is the only hematopoietic growth factor which behaves like a hormone. Produced primarily in the kidneys and to a small extent in the liver, erythropoietin interacts with primitive erythroid progenitor cells in the bone marrow. Under normal circumstances, the plasma concentracentration of erythropoietin is maintained within narrow limits but is subject to change according to the adequacy of tissue oxygenation. Thus, tissue hypoxia stimulates erythropoietin production while a surfeit of oxygen suppresses it. Erythropoietin, however, is never absent from the plasma since it is an obligatory growth factor for erythroid progenitor cells1.


Sialic Acid Plasma Clearance Dextran Sulfate Recombinant Human Erythropoietin Sialic Acid Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    . Spivak, J.L. 1986. The mechanism of action of erythropoietin. Intl. J. Cell Cloning 4: 139.CrossRefGoogle Scholar
  2. 2.
    . Davis, J.M., T. Arakawa, T.W. Strickland, D.A. Yphantis. 1987. Characterization of recombinant human erythropoietin produced in Chinese hamster ovary cells. Biochemistry 26: 2633.PubMedCrossRefGoogle Scholar
  3. 3.
    . Sasaki, H.B., B. Bothner, A. Dell, M. Fukuda. 1987. Carbohydrate structure of erythropoietin expressed in Chinese hamster ovary cells by human erythropoietin cDNA. J. Biol. Chem. 262: 12059.PubMedGoogle Scholar
  4. 4.
    . Goldwasser, E., CK-H. Kung. 1968. Progress in the purification of erythropoietin. Ann. N.Y. Acad. Sci. 149: 49.PubMedCrossRefGoogle Scholar
  5. 5.
    . Lukowsky, W.A., R.H. Painter. 1972. Studies on the role of sialic acid in the physical and biological properties of erythropoietin. Canad. J. Biochem. 50: 909.Google Scholar
  6. 6.
    . Goldwasser, E., CK-H. Kung, J. Eliason. 1974. On the mechanism of erythropoietin-induced differentiation. J. Biol. Chem. 249: 4202.PubMedGoogle Scholar
  7. 7.
    . Marchalonis, J.J. 1969. An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem. J. 113: 299.PubMedGoogle Scholar
  8. 8.
    . Spivak, J.L., B.B. Hogans. 1989. The in vivo metabolism of recombinant human erythropoietin in the rat. Blood 73: 90.PubMedGoogle Scholar
  9. 9.
    . Krystal, G. 1983. A simple microassay for erythropoietin based on 3H-thymidine incorporation into spleen cells from phenylhydra-zine-treated mice. Exper. Hematol. 20: 649.Google Scholar
  10. 10.
    . Spiro, R.G. 1963. Periodate oxidation of the glycoprotein fetuin. J. Biol. Chem. 239: 567.Google Scholar
  11. 11.
    . Regoeczi, E. 1975. Hepatic uptake of asialoglycoproteins in vivo: quantification using a dual-isotope technique. J. Nucl. Biol. Med. 19: 149.PubMedGoogle Scholar
  12. 12.
    . Emmanouel, D.S., E. Goldwasser, and A.I. Katz. 1984. Metabolism of pure human erythropoietin in the rat. Amer. J. Physiol. 247: F168.Google Scholar
  13. 13.
    . Steinberg, S.E., J.F. Garcia, G.R. Matzke, and J. Mladenovic. 1986. Erythropoietin kinetics in rats: generation and clearance. Blood 67: 646.PubMedGoogle Scholar
  14. 14.
    . Seglen, P.O. 1976. Preparation of isolated rat liver cells. _In Methods in Cell Biology, vol. 13, D.M. Prescott (ed), Academic Press, New York, p. 29.Google Scholar
  15. 15.
    . Baenziger, J.U. 1985. The role of glycosylation in protein recognition. Amer. J. Pathol. 121: 382.Google Scholar
  16. 16.
    . Lee, Y.C., R.R. Townsend, M.R. Hardy, J. Lonngren, J. Arnarp, M. Haraldsson, and H. Lonn. 1983. Binding of synthetic oligosaccharides to the hepatic gal/galNAc lectin. J. Biol. Chem. 258: 199.PubMedGoogle Scholar
  17. 17.
    Schooley, J.C., and L.J. Mahlmann. 1972. Evidence for the de novo synthesis of erythropoietin in hypoxic rats. Blood 40: 662.Google Scholar
  18. 18.
    . Bondurant, M.C., and M.J. Koury. 1986. Anemia induces accumulation of erythropoietin mRNA in the kidney and liver. Molec. Cell Biol. 6: 2731.Google Scholar
  19. 19.
    . Beru, N., J. McDonald, C. Lacombe, and E. Goldwasser. 1986. Expression of erythropoietin gene. Molec. Cell Biol. 6: 2571.Google Scholar
  20. 20.
    . Katoaka, M., and M. Tavassoli. 1985. Identification of lectin-like substances recognizing galactosyl residues of glycoconjugates on the plasma membrane of marrow sinus endothelium. Blood 65: 1163.Google Scholar
  21. 21.
    . Regoeczi, E., P.A. Chindemi, M.C.W. Hatton, and L.R. Berry. 1980. Galactose specific elimination of human asialotransferins by the bone marrow in the rabbit. Arch. Biochem. Biophys. 205: 76.Google Scholar
  22. 22.
    . Dube, S., N. Lin, R. Manger, J.W. Fisher, and J.S. Powell. 1987. Erythropoietin (EP) requires specific addition of carbohydrate (CHO) side chains for intracellular processing and secretion. Blood 70: 170a.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Jerry L. Spivak
    • 1
  1. 1.Division of Hematology Department of MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations