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Stimulation of erythropoietin gene transcription during hypoxia and cobalt
exposure
SJ Schuster, EV Badiavas, P Costa-Giomi, R Weinmann, AJ Erslev and J Caro
Cardeza Foundation for Hematologic Research, Department of Medicine,
Philadelphia, PA 19107.
Erythropoietin, a plasma glycoprotein produced primarily by the kidney, is
a growth and differentiation factor for erythroid progenitor cells.
Production of renal erythropoietin is regulated by modulation of mRNA
levels in response to changes in tissue oxygenation. Exposure to cobalt, a
nonphysiologic stimulus for erythropoietin production, also acts by
inducing mRNA accumulation. To determine whether variations in
erythropoietin mRNA levels result from enhanced transcription of the
erythropoietin gene, in vitro transcription reactions were performed using
isolated rat kidney cell nuclei. Quantitation of specific nuclear RNAs
labeled during in vitro transcription revealed active erythropoietin gene
transcription in kidney nuclei from anemic-hypoxic and cobalt-treated
animals while erythropoietin transcriptional activity was undetectable in
normal kidney nuclei. Time course studies showed that stimulation of
transcription begins between two and four hours following cobalt treatment
and parallels the kinetics of mRNA and plasma erythropoietin accumulation.
These results indicate that tissue hypoxia and cobalt exposure specifically
enhance erythropoietin gene expression. This increase in erythropoietin
production is regulated at least in part at the level of gene
transcription.
Volume 73,
Issue 1,
pp. 13-16,
01/01/1989
Copyright © 1989 by The American Society of Hematology
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