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Regulation of beta-globin mRNA accumulation by heme in dimethyl sulfoxide
(DMSO)-sensitive and DMSO-resistant murine erythroleukemia cells
Y Fukuda, H Fujita, L Garbaczewski and S Sassa
Rockefeller University, New York, NY 10021.
The level of mRNA encoding beta-globin was examined in dimethyl sulfoxide
(DMSO)-sensitive (DS), and DMSO-resistant (DR) murine erythroleukemia (MEL)
cells. DR cells lack erythroid-specific delta- aminolevulinate (ALA)
synthase (AL-AS-E), and fail to undergo erythroid differentiation following
treatment with DMSO. Treatment of cells with DMSO markedly increased ALAS-E
mRNA in DS cells, while the same treatment downregulated the nonspecific
ALA synthase (ALAS-N) mRNA levels in both DS and DR cells. The levels of
beta-globin mRNA, heme content, and hemoglobin in DS cells increased, while
those in DR cells decreased following treatment with DMSO. Treatment of DR
cells with hemin caused an increase in beta-globin mRNA and hemoglobin, and
partially restored the DMSO-mediated suppression of beta-globin mRNA and
hemoglobin synthesis. DMSO treatment decreased heme oxygenase (HO) mRNA in
hemin-treated DS cells, but not in hemin-treated DR cells. These findings
indicate that heme is necessary for accumulation of the beta-globin
transcript during erythroid differentiation, and that hemin- mediated HO
induction becomes markedly downregulated in differentiated erythroid cells,
presumably because less free heme is available for HO induction by a
greater demand for the synthesis of hemoglobin.
Volume 83,
Issue 6,
pp. 1662-1667,
03/15/1994
Copyright © 1994 by The American Society of Hematology
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