Early transient suppression of c-myb mRNA levels and induction of differentiation in Friend erythroleukemia cells by the [Ca2+](i)-increasing agents cyclopiazonic acid and thapsigargin

A. Schaefer, M. Magocsi, U. Stocker, F. Kosa, H. Marquardt

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Abstract

Cyclopiazonic acid and thapsigargin, inhibitors of the endoplasmic reticulum Ca2+ pump were shown to elevate [Ca2+](i) in Friend erythroleukemia cells, line F4-6, at concentrations of 1-5 μM and 0.5-2 nM, respectively. At the same concentrations, these agents induced a strong suppression of c-myb mRNA levels within 3 h, whereas c-myc expression remained unaffected. The c-myb expression recovered and approached pretreatment levels at 9-12 h of incubation. The decrease in c-myb mRNA was prevented in Ca2+-free medium. Treatment of F4-6 cells with EGTA led to a transient increase in c-myb mRNA with the same kinetics as the Ca2+ pump inhibitor-induced suppression, indicating that c-myb expression is bidirectionally regulated by changes in [Ca2+](i). Studies on the differentiation status of F4-6 cells following cyclopiazonic acid or thapsigargin exposure demonstrated a marked increase in β-globin mRNA synthesis at 60h and in hemoglobin production at 96 h. These results provide further evidence that a rise in the cytosolic Ca2+ concentration is capable, in Friend erythroleukemia cells, of inducing an early transient suppression of c-myb mRNA levels, which is followed by terminal erythroid differentiation.

Original languageEnglish
Pages (from-to)8786-8791
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number12
Publication statusPublished - Jan 1 1994

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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