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. 1979 Oct;76(10):5321–5325. doi: 10.1073/pnas.76.10.5321

Uroporphyrinogen I synthase induction in normal human bone marrow cultures: an early and quantitative response of erythroid differentiation.

S Sassa, A Urabe
PMCID: PMC413134  PMID: 291949

Abstract

Uroporphyrinogen I (URO) synthase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] activity increased when cultures of normal human bone marrow cells were incubated with erythropoietin. The increase of URO synthase activity was a linear function of erythropoietin concentration in the culture medium and was proportional to the extent of heme synthesis as determined by 55Fe incorporation into heme. The onset of the increase in URO synthase activity, which occurred on day 4 of incubation with erythropoietin, preceded by 3 days the appearance of hemoglobin in colonies derived from erythroid progenitor cells. These results indicate that induction of URO synthase in normal human bone marrow cells incubated with erythropoietin is an early event and that URO synthase activity is a useful quantitative index of erythroid differentiation.

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Selected References

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

  1. Dabney B. J., Beaudet A. L. Increase in globin chains and globin mRNA in erythroleukemia cells in response to hemin. Arch Biochem Biophys. 1977 Feb;179(1):106–112. doi: 10.1016/0003-9861(77)90092-3. [DOI] [PubMed] [Google Scholar]
  2. Freshney R. I., Paul J. The activities of three enzymes of haem synthesis during hepatic erythropoiesis in the mouse embryo. J Embryol Exp Morphol. 1971 Oct;26(2):313–322. [PubMed] [Google Scholar]
  3. Granick J. L., Sassa S. Hemin control of heme biosynthesis in mouse Friend virus-transformed erythroleukemia cells in culture. J Biol Chem. 1978 Aug 10;253(15):5402–5406. [PubMed] [Google Scholar]
  4. Gregory C. J., Eaves A. C. Human marrow cells capable of erythropoietic differentiation in vitro: definition of three erythroid colony responses. Blood. 1977 Jun;49(6):855–864. [PubMed] [Google Scholar]
  5. Iscove N. N., Sieber F. Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol. 1975 Jan;3(1):32–43. [PubMed] [Google Scholar]
  6. Iscove N. N., Sieber F., Winterhalter K. H. Erythroid colony formation in cultures of mouse and human bone marrow: analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose-concanavalin A. J Cell Physiol. 1974 Apr;83(2):309–320. doi: 10.1002/jcp.1040830218. [DOI] [PubMed] [Google Scholar]
  7. Ogawa M., Grush O. C., O'Dell R. F., Hara H., MacEachern M. D. Circulating erythropoietic precursors assessed in culture: characterization in normal men and patients with hemoglobinopathies. Blood. 1977 Dec;50(6):1081–1092. [PubMed] [Google Scholar]
  8. Ogawa M., Parmley R. T., Bank H. L., Spicer S. S. Human marrow erythropoiesis in culture. I. Characterization of methylcellulose colony assay. Blood. 1976 Sep;48(3):407–417. [PubMed] [Google Scholar]
  9. Porter P. N., Meints R. H., Mesner K. Enhancement of erythroid colony growth in culture by hemin. Exp Hematol. 1979 Jan;7(1):11–16. [PubMed] [Google Scholar]
  10. Ross J., Sautner D. Induction of globin mRNA accumulation by hemin in cultured erythroleukemic cells. Cell. 1976 Aug;8(4):513–520. doi: 10.1016/0092-8674(76)90219-1. [DOI] [PubMed] [Google Scholar]
  11. Rutherford T. R., Weatherall D. J. Deficient heme synthesis as the cause of noninducibility of hemoglobin synthesis in a Friend erythroleukemia cell line. Cell. 1979 Feb;16(2):415–423. doi: 10.1016/0092-8674(79)90017-5. [DOI] [PubMed] [Google Scholar]
  12. Rutherford T., Thompson G. G., Moore M. R. Heme biosynthesis in Friend erythroleukemia cells: control by ferrochelatase. Proc Natl Acad Sci U S A. 1979 Feb;76(2):833–836. doi: 10.1073/pnas.76.2.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sassa S., Bernstein S. E. Levels of delta-aminolevulinate dehydratase, uroporphyrinogen-I synthase, and protoporphyrin IX in erythrocytes from anemic mutant mice. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1181–1184. doi: 10.1073/pnas.74.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sassa S., Granick J. L., Granick S., Kappas A., Levere R. D. Studies in lead poisoning. I. Microanalysis of erythrocyte protoporphyrin levels by spectrophotometry in the detection of chronic lead intoxication in the subclinical range. Biochem Med. 1973 Aug;8(1):135–148. doi: 10.1016/0006-2944(73)90017-3. [DOI] [PubMed] [Google Scholar]
  15. Sassa S., Granick S., Bickers D. R., Bradlow H. L., Kappas A. A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease. Proc Natl Acad Sci U S A. 1974 Mar;71(3):732–736. doi: 10.1073/pnas.71.3.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sassa S., Granick S., Kappas A. Sequential induction of enzymes in the heme biosynthetic pathway during erythroid differentiation. Nihon Ketsueki Gakkai Zasshi. 1975 Dec;38(6):715–722. [PubMed] [Google Scholar]
  17. Sassa S., Kappas A. Induction of aminolevulinate synthase and porphyrins in cultured liver cells maintained in chemically defined medium. Permissive effects of hormones on induction process. J Biol Chem. 1977 Apr 10;252(7):2428–2436. [PubMed] [Google Scholar]
  18. Sassa S. Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells. J Exp Med. 1976 Feb 1;143(2):305–315. doi: 10.1084/jem.143.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tepperman A. D., Curtis J. E., McCulloch E. A. Erythropietic colonies in cultures of human marrow. Blood. 1974 Nov;44(5):659–669. [PubMed] [Google Scholar]
  20. Tien W., White D. C. Linear sequential arrangement of genes for the biosynthetic pathway of protoheme in Staphylococcus aureus. Proc Natl Acad Sci U S A. 1968 Dec;61(4):1392–1398. doi: 10.1073/pnas.61.4.1392. [DOI] [PMC free article] [PubMed] [Google Scholar]

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