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Science 20 April 1990:
Vol. 248. no. 4953, pp. 378 - 381
DOI: 10.1126/science.2326648

Articles

Science, Vol 248, Issue 4953, 378-381
Copyright © 1990 by American Association for the Advancement of Science


articles

Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells

MJ Koury and MC Bondurant

Division of Hematology, Vanderbilt University Medical Center, Nashville, TN.

The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence of erythropoietin, erythroid progenitor cells accumulated DNA cleavage fragments characteristic of those found in programmed cell death (apoptosis) by 2 to 4 hours and began dying by 16 hours. In the presence of erythropoietin, the progenitor cells survived and differentiated into reticulocytes. Thus, apoptosis is a major component of normal erythropoiesis, and erythropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells.


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Cell Surface Organization of the Erythropoietin Receptor Complex Differs Depending on its Mode of Activation.
K. Tarr, S. S. Watowich, and G. D. Longmore (1997)
J. Biol. Chem. 272, 9099-9107
   Abstract »    Full Text »    PDF »
The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal..
S G Kennedy, A J Wagner, S D Conzen, J Jordan, A Bellacosa, P N Tsichlis, and N Hay (1997)
Genes & Dev. 11, 701-713
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Homodimerization of Erythropoietin Receptor by a Bivalent Monoclonal Antibody Triggers Cell Proliferation and Differentiation of Erythroid Precursors.
H. Schneider, W. Chaovapong, D. J. Matthews, C. Karkaria, R. T. Cass, H. Zhan, M. Boyle, T. Lorenzini, S. G. Elliott, and L. B. Giebel (1997)
Blood 89, 473-482
   Abstract »    Full Text »    PDF »
Interleukin-6 Inhibits Fas-Induced Apoptosis and Stress-Activated Protein Kinase Activation in Multiple Myeloma Cells.
D. Chauhan, S. Kharbanda, A. Ogata, M. Urashima, G. Teoh, M. Robertson, D. W. Kufe, and K. C. Anderson (1997)
Blood 89, 227-234
   Abstract »    Full Text »    PDF »
Transcriptional Activation of the cdc2 Gene Is Associated with Fas-induced Apoptosis of Human Hematopoietic Cells.
Y. Furukawa, S. Iwase, Y. Terui, J. Kikuchi, T. Sakai, M. Nakamura, S. Kitagawa, and M. Kitagawa (1996)
J. Biol. Chem. 271, 28469-28477
   Abstract »    Full Text »    PDF »
Interleukin-3 (IL-3) Inhibits Erythropoietin-induced Differentiation in Ba/F3 Cells via the IL-3 Receptor alpha Subunit.
J. Krosl, J. E. Damen, G. Krystal, and R.K. Humphries (1996)
J. Biol. Chem. 271, 27432-27437
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Protein Kinase C-epsilon Is Necessary for Erythropoietin's Up-regulation of c-myc and for Factor-dependent DNA Synthesis. EVIDENCE FOR DISCRETE SIGNALS FOR GROWTH AND DIFFERENTIATION.
Y. Li, K. L. Davis, and A. J. Sytkowski (1996)
J. Biol. Chem. 271, 27025-27030
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Activation of the Erythropoietin (EPO) Receptor by Bivalent Anti-EPO Receptor Antibodies.
S. Elliott, T. Lorenzini, D. Yanagihara, D. Chang, and G. Elliott (1996)
J. Biol. Chem. 271, 24691-24697
   Abstract »    Full Text »    PDF »
Disrupted Signaling in a Mutant J2E Cell Line That Shows Enhanced Viability, but Does Not Proliferate or Differentiate, with Erythropoietin.
P. A. Tilbrook, T. Bittorf, S. J. Busfield, D. Chappell, and S. P. Klinken (1996)
J. Biol. Chem. 271, 3453-3459
   Abstract »    Full Text »    PDF »
The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis.
P Gonczy and S DiNardo (1996)
Development 122, 2437-2447
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Erythropoietin-dependent Inhibition of Apoptosis Is Supported by Carboxyl-truncated Receptor Forms and Blocked by Dominant-negative Forms of Jak2.
H. Zhuang, Z. Niu, T.-C. He, S. V. Patel, and D. M. Wojchowski (1995)
J. Biol. Chem. 270, 14500-14504
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Erythropoietin-induced Transcription at the Murine beta[IMAGE]-Globin Promoter.
D. J. Taxman and D. M. Wojchowski (1995)
J. Biol. Chem. 270, 6619-6627
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Programmed cell death and the control of cell survival: lessons from the nervous system.
M. Raff, B. Barres, J. Burne, H. Coles, Y Ishizaki, and M. Jacobson (1993)
Science 262, 695-700
   Abstract »    PDF »
Erythropoietin: Biology and Clinical Applications.
I. A. Tabbara (1993)
Arch Intern Med 153, 298-304
   Abstract »    PDF »
Investigating Erythropoietin Resistance.
M. J. Koury (1993)
N. Engl. J. Med. 328, 205-206
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A Truncated Erythropoietin Receptor That Fails to Prevent Programmed Cell Death of Erythroid Cells.
Y. Nakamura, N. Komatsu, and H. Nakauchi (1992)
Science 257, 1138-1141
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