Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells.
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.
Koury
M J
MJ
Division of Hematology, Vanderbilt University Medical Center, Nashville, TN.
Bondurant
M C
MC
D000818:Animals; D002454:Cell Differentiation; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D004260:DNA Repair; D004905:Erythrocyte Aging / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008970:Molecular Weight
D004921:Erythropoietin; D004247:DNA