Potentiation of the erythropoietin response by dimethyl sulfoxide priming
of erythroleukemia cells: evidence for interaction of two signaling
pathways
Y Chern, S Yonekura and AJ Sytkowski
Laboratory for Cell and Molecular Biology, New England Deaconess Hospital,
Boston, MA 02215.
Erythropoietin (Epo) and dimethyl sulfoxide (DMSO) are believed to induce
the differentiation of transformed erythroid cells by different signal
transduction pathways. We have now obtained evidence for the interaction of
these pathways. We used a Rauscher murine erythroleukemia cell line with a
relatively low (8% to 10%) hemoglobinization response to Epo alone.
Pretreatment of these cells for 1 day with DMSO followed by its removal and
the addition of Epo resulted in a marked enhancement of the Epo specific
hemoglobinization. We have designated this effect "DMSO priming." This
priming effect of DMSO on the Epo response was both time-dependent and DMSO
concentration- dependent. DMSO priming potentiated the Epo response in
three ways. Firstly, DMSO priming increased the total number of Epo
responsive cells from 8% to 10% to 40% to 60%. Secondly, DMSO priming
reduced the time required to reach the optimal Epo-induced response from 4
days to 2 days. Thirdly, the Epo dose-response curve was left-shifted
approximately 20-fold. DMSO priming was also associated with a marked
increase in Epo receptor density characterized by an apparently new
receptor population and by the appearance of positive cooperativity between
receptors. Our results suggest that the DMSO priming effect is due to
potentiation of the Epo signaling pathway, thus resulting in a much more
rapid and dramatic Epo-induced hemoglobinization response.
Volume 76,
Issue 11,
pp. 2204-2209,
12/01/1990
Copyright © 1990 by The American Society of Hematology
