Glucocorticoids inhibit the coordinated translation of α- and β-globin mRNAs in friend erythroleukemia cells

John Papaconstantinou, James A. Stewart, Jeffrey P. Rabek, Patrick R. McClintock, Edith Y. Wong

Research output: Contribution to journalArticle

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Abstract

The dimethylsulfoxide (Me2SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10-5 to 10-8 m inhibits by 90-30% and fluocinolone acetonide at concentrations of 10-8 to 10-11 m shows a greater than 90% inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the a- and β-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and that the expression of some of these, in addition to α- and β-globin, is affected by glucocorticoids. The levels of α- and β-globin mRNAs are very close to fully induced levels and preclude transcription as a major site for glucocorticoid control. In addition, it has been shown that glucocorticoids inhibit the translation of α- and β-globin mRNAs, that the level of this inhibition is concentration dependent, and that the translation of β-globin mRNA is slightly more sensitive to inhibition than the translation of α-globin mRNA. It is concluded that, although the translation of α- and β-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of α- and β-globin synthesized. Thus, part of this mechanism may involve a differential sensitivity of α- and β-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.

Original languageEnglish (US)
Pages (from-to)542-551
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume227
Issue number2
DOIs
StatePublished - 1983

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Leukemia, Erythroblastic, Acute
Globins
Protein Biosynthesis
Glucocorticoids
Messenger RNA
Fluocinolone Acetonide
Hydrocortisone
Hemoglobins
Cell growth
Transcription
Dimethyl Sulfoxide
Dexamethasone
Cell Differentiation
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Glucocorticoids inhibit the coordinated translation of α- and β-globin mRNAs in friend erythroleukemia cells. / Papaconstantinou, John; Stewart, James A.; Rabek, Jeffrey P.; McClintock, Patrick R.; Wong, Edith Y.

In: Archives of Biochemistry and Biophysics, Vol. 227, No. 2, 1983, p. 542-551.

Research output: Contribution to journalArticle

Papaconstantinou, John ; Stewart, James A. ; Rabek, Jeffrey P. ; McClintock, Patrick R. ; Wong, Edith Y. / Glucocorticoids inhibit the coordinated translation of α- and β-globin mRNAs in friend erythroleukemia cells. In: Archives of Biochemistry and Biophysics. 1983 ; Vol. 227, No. 2. pp. 542-551.
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abstract = "The dimethylsulfoxide (Me2SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10-5 to 10-8 m inhibits by 90-30{\%} and fluocinolone acetonide at concentrations of 10-8 to 10-11 m shows a greater than 90{\%} inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the a- and β-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and that the expression of some of these, in addition to α- and β-globin, is affected by glucocorticoids. The levels of α- and β-globin mRNAs are very close to fully induced levels and preclude transcription as a major site for glucocorticoid control. In addition, it has been shown that glucocorticoids inhibit the translation of α- and β-globin mRNAs, that the level of this inhibition is concentration dependent, and that the translation of β-globin mRNA is slightly more sensitive to inhibition than the translation of α-globin mRNA. It is concluded that, although the translation of α- and β-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of α- and β-globin synthesized. Thus, part of this mechanism may involve a differential sensitivity of α- and β-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.",
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