Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1970 Apr;49(4):701–707. doi: 10.1172/JCI106282

Stimulation of globin synthesis: relative responsiveness of reticulocytes and nucleated erythroid cells

Herbert S Waxman 1
PMCID: PMC322525  PMID: 5443172

Abstract

The effects of iron, cobalt, hemin, and plasma on hemoglobin synthesis by suspensions of rabbit reticulocytes and nucleated bone marrow cells were studied. L-Leucine-14C and sodium pyruvate-3-14C were employed to measure globin and heme synthesis, respectively. Normal plasma (or serum) was found to stimulate the rate of globin synthesis in both systems. The stimulatory effects of iron and hemin were additive to those of plasma or serum only in the reticulocytes.

Cobaltous ion, at concentrations less than 1.0 mmole/liter, was found to stimulate globin synthesis by reticulocytes as effectively as ferrous ion; cobalt was inhibitory only at concentrations greater than 3.0-5.0 mmoles/liter. Heme synthesis by reticulocytes was inhibited at all concentrations employed (0.2-5.0 mmoles/liter).

In bone marrow nucleated erythroid cells, globin synthesis was markedly enhanced by exogenous hemin. In contrast to reticulocytes, however, bone marrow cells were unresponsive to either cobalt or transferrin-bound iron. Possible implications of these findings on regulation of the rate and mechanism of iron uptake and hemoglobin synthesis in vivo are discussed.

Full text

PDF
701

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson S. D., Herbert E., Kemp S. F. Effects of hemin and other porphyrins on protein synthesis in a reticulocyte lysate cell-free system. J Mol Biol. 1969 Jun 14;42(2):247–258. doi: 10.1016/0022-2836(69)90041-2. [DOI] [PubMed] [Google Scholar]
  2. Armstrong M., Webb M. The reversal of phenylarsenoxide inhibition of keto acid oxidation in mitochondrial and bacterial suspensions by lipoic acid and other disulphides. Biochem J. 1967 Jun;103(3):913–922. doi: 10.1042/bj1030913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BESSIS M. C., BRETON-GORIUS J. Iron metabolism in the bone marrow as seen by electron microscopy: a critical review. Blood. 1962 Jun;19:635–663. [PubMed] [Google Scholar]
  4. BORSOOK H., DEASY C. L., HAAGENSMIT A. J., KEIGHLEY G., LOWY P. H. Incorporation in vitro of labeled amino acids into bone marrow cell proteins. J Biol Chem. 1950 Sep;186(1):297–307. [PubMed] [Google Scholar]
  5. BORSOOK H., DEASY C. L., HAAGENSMIT A. J., KEIGHLEY G., LOWY P. H. Incorporation in vitro of labeled amino acids into proteins of rabbit reticulocytes. J Biol Chem. 1952 May;196(2):669–694. [PubMed] [Google Scholar]
  6. BORSOOK H., FISCHER E. H., KEIGHLEY G. Factors affecting protein synthesis in vitro in rabbit reticulocytes. J Biol Chem. 1957 Dec;229(2):1059–1070. [PubMed] [Google Scholar]
  7. Bates G. W., Billups C., Saltman P. The kinetics and mechanism of iron (3) exchange between chelates and transferrin. I. The complexes of citrate and nitrilotriacetic acid. J Biol Chem. 1967 Jun 25;242(12):2810–2815. [PubMed] [Google Scholar]
  8. Borsook H., Teigler D., Gunderson A. Studies on erythropoiesis. 3. Different patterns of protein and hemoglobin synthesis before and after terminal differentiation in adult rabbit marrow. Arch Biochem Biophys. 1968 May;125(2):429–435. doi: 10.1016/0003-9861(68)90599-7. [DOI] [PubMed] [Google Scholar]
  9. CHODOS R. B., EMERSON C. P., MILLER A., ROSS J. F. Studies of the anemia and iron metabolism in cancer. J Clin Invest. 1956 Nov;35(11):1248–1262. doi: 10.1172/JCI103380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CLARK P., WALSH R. J. Synthesis of haem by circulating blood cells. Nature. 1959 Nov 28;184(Suppl 22):1730–1731. doi: 10.1038/1841730b0. [DOI] [PubMed] [Google Scholar]
  11. DINGLE J. T., WEBB M. INHIBITION OF PYRUVATE METABOLISM IN MITOCHONDRIAL SUSPENSIONS BY COBALT. Nature. 1963 Dec 21;200:1208–1209. doi: 10.1038/2001208b0. [DOI] [PubMed] [Google Scholar]
  12. ERIKSEN L., ERIKSEN N., HAAVALDSEN S. The effect of cobalt ions on the biosynthesis of hemoglobin by rabbit reticulocytes in vitro. Acta Physiol Scand. 1961 Nov-Dec;53:300–307. doi: 10.1111/j.1748-1716.1961.tb02288.x. [DOI] [PubMed] [Google Scholar]
  13. FREIREICH E. J., MILLER A., EMERSON C. P., ROSS J. F. The effect of inflammation on the utilization of erythrocyte and transferrin bound radioiron for red cell production. Blood. 1957 Nov;12(11):972–983. [PubMed] [Google Scholar]
  14. Grayzel A. I., Hörchner P., London I. M. The stimulation of globin synthesis by heme. Proc Natl Acad Sci U S A. 1966 Mar;55(3):650–655. doi: 10.1073/pnas.55.3.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. JANDL J. H., INMAN J. K., SIMMONS R. L., ALLEN D. W. Transfer of iron from serum iron-binding protein to human reticulocytes. J Clin Invest. 1959 Jan 1;38(1 Pt 1):161–185. doi: 10.1172/JCI103786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KASSENAAR A., MORELL H., LONDON I. M. The incorporation of glycine into globin and the synthesis of heme in vitro in duck erythrocytes. J Biol Chem. 1957 Nov;229(1):423–435. [PubMed] [Google Scholar]
  17. KRANTZ S. B., GALLIEN-LARTIGUE O., GOLDWASSER E. THE EFFECT OF ERYTHROPOIETIN UPON HEME SYNTHESIS BY MARROW CELLS IN VITRO. J Biol Chem. 1963 Dec;238:4085–4090. [PubMed] [Google Scholar]
  18. LABBE R. F., NISHIDA G. A new method of hemin isolation. Biochim Biophys Acta. 1957 Nov;26(2):437–437. doi: 10.1016/0006-3002(57)90033-1. [DOI] [PubMed] [Google Scholar]
  19. LAJTHA L. G., SUIT H. D. Uptake of radioactive iron (59Fe) by nucleated red cells in vitro. Br J Haematol. 1955 Jan;1(1):55–61. doi: 10.1111/j.1365-2141.1955.tb05488.x. [DOI] [PubMed] [Google Scholar]
  20. MORELL H., SAVOIE J. C., LONDON I. M. The biosynthesis of heme and the incorporation of glycine into globin in rabbit bone marrow in vitro. J Biol Chem. 1958 Oct;233(4):923–929. [PubMed] [Google Scholar]
  21. MORGAN E. H., LAURELL C. B. STUDIES ON THE EXCHANGE OF IRON BETWEEN TRANSFERRIN AND RETICULOCYTES. Br J Haematol. 1963 Oct;9:471–483. doi: 10.1111/j.1365-2141.1963.tb05471.x. [DOI] [PubMed] [Google Scholar]
  22. MYHRE E. IRON UPTAKE AND HEMOGLOBIN SYNTHESIS BY HUMAN ERYTHROID CELLS IN VITRO. Scand J Clin Lab Invest. 1964;16:212–221. [PubMed] [Google Scholar]
  23. MYHRE E. IRON UPTAKE BY HUMAN ERYTHROID CELLS IN VITRO. Scand J Clin Lab Invest. 1964;16:201–211. [PubMed] [Google Scholar]
  24. Ponka P., Neuwirt J. Regulation of iron entry into reticulocytes. I. Feedback inhibitory effect of heme on iron entry into reticulocytes and on heme synthesis. Blood. 1969 May;33(5):690–707. [PubMed] [Google Scholar]
  25. Rabinovitz M., Waxman H. S. Dependence of polyribosome structure in reticulocytes on iron; implication on the tape theory of haemoglobin synthesis. Nature. 1965 May 29;206(987):897–900. doi: 10.1038/206897a0. [DOI] [PubMed] [Google Scholar]
  26. SHAHIDI N. T., NATHAN D. G., DIAMOND L. K. IRON DEFICIENCY ANEMIA ASSOCIATED WITH AN ERROR OF IRON METABOLISM IN TWO SIBLINGS. J Clin Invest. 1964 Mar;43:510–521. doi: 10.1172/JCI104937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schulman H. M., Jobe A. The inhibition of heme and globin synthesis by cobalt in rabbit reticulocytes and bone marrow. Biochim Biophys Acta. 1968 Nov 20;169(1):241–247. doi: 10.1016/0005-2787(68)90026-9. [DOI] [PubMed] [Google Scholar]
  28. Schwartz E., Nathan D. G. New methods of counting of C-14-labeled hemoglobin and hemin. J Lab Clin Med. 1967 Nov;70(5):841–848. [PubMed] [Google Scholar]
  29. THOMAS E. D. In vitro studies of erythropoiesis. I. The effect of normal serum on heme synthesis and oxygen consumption by bone marrow. Blood. 1955 Jun;10(6):600–611. [PubMed] [Google Scholar]
  30. Tavill A. S., Grayzel A. I., London I. M., Williams M. K., Vanderhoff G. A. The role of heme in the synthesis and assembly of hemoglobin. J Biol Chem. 1968 Oct 10;243(19):4987–4999. [PubMed] [Google Scholar]
  31. WAXMAN H. S., RABINOVITZ M. IRON SUPPLEMENTATION IN VITRO AND THE STATE OF AGGREGATION AND FUNCTION OF RETICULOCYTE RIBOSOMES IN HEMOGLOBIN SYNTHESIS. Biochem Biophys Res Commun. 1965 May 3;19:538–545. doi: 10.1016/0006-291x(65)90159-2. [DOI] [PubMed] [Google Scholar]
  32. Wardle E. N., Israëls M. C. The differential ferrioxamine test in rheumatoid disease, neoplastic and other haematological disorders. Br J Haematol. 1968 Jan;14(1):5–11. doi: 10.1111/j.1365-2141.1968.tb01467.x. [DOI] [PubMed] [Google Scholar]
  33. Waxman H. S., Freedman M. L., Rabinovitz M. Studies with 59Fe-labeled hemin on the control of polyribosome formation in rabbit reticulocytes. Biochim Biophys Acta. 1967 Sep 26;145(2):353–360. doi: 10.1016/0005-2787(67)90053-6. [DOI] [PubMed] [Google Scholar]
  34. Winterhalter K. H., Heywood J. D., Huehns E. R., Finch C. A. The free globin in human erythrocytes. I. Br J Haematol. 1969 Jun;16(6):523–535. doi: 10.1111/j.1365-2141.1969.tb00434.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES