Erythropoietin Retards DNA Breakdown and Prevents Programmed Death in Erythroid Progenitor Cells

• Published in: Science (American Association for the Advancement of Science) 1990-04, Vol.248 (4953), p.378-381
• Main Authors: Koury, Mark J., Bondurant, Maurice C.
• Format: Article
• Language: English
• Subjects: 3T3 cells; Analytical, structural and metabolic biochemistry; ANIMALS; AZINES; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BIOLOGICAL FUNCTIONS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; Cell culture techniques; Cell death; CELL DIFFERENTIATION; Cellular biology; CLEAVAGE; CRYSTAL STRUCTURE; Cultured cells; DNA; DNA - biosynthesis; DNA - drug effects; DNA - metabolism; DNA cleavage; DNA REPAIR; DNA REPLICATION; Epics; Erythrocyte Aging - drug effects; Erythroid cells; Erythroid Precursor Cells - cytology; Erythroid Precursor Cells - drug effects; Erythroid Precursor Cells - metabolism; Erythroid progenitor cells; Erythropoiesis; ERYTHROPOIETIN; Erythropoietin - pharmacology; Friend murine leukemia virus; FUNCTIONS; Fundamental and applied biological sciences. Psychology; Gels; Glycoproteins; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; INHIBITION; ISOTOPE APPLICATIONS; Leukemia, Erythroblastic, Acute; MAMMALS; MICE; MICROSTRUCTURE; MITOGENS; Molecular Weight; NUCLEIC ACID REPLICATION; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; Physiological aspects; PROTEINS; PYRIMIDINES; RECOVERY; REPAIR; RIBOSIDES; RODENTS; Stem cells; THYMIDINE; TRACER TECHNIQUES; TRITIUM COMPOUNDS; VERTEBRATES 550201 > Biochemistry-- Tracer Techniques
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2326648

The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [$^3$H]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.