Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin α-subunit in HeLa cells. II. Effect of both agents on mRNA turnover

Dominic E Cosgrove, G. Stanley Cox

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In the accompanying paper it was demonstrated that among several methylxanthine phosphodiesterase inhibitors, only theophylline significantly increased production of the glycoprotein hormone α-subunit in HeLa cells, and that this action was synergistic with that of sodium butyrate. A correlation between α-subunit induction and cAMP concentrations was not evident. In this report we characterized the effect of these two drugs on the metabolism of α-subunit mRNA. Sodium butyrate decreased the apparent half-life of mRNAs encoding α-subunit, β2-microglobulin, and α-tubulin, as well as that of total poly(A)+ RNA and rRNA. Theophylline produced a two- to threefold increase in the apparent half-life of α-subunit mRNA but had no effect on the turnover of β2-microglobulin, α-tubulin, or total poly(A)+ mRNA. An inverse correlation was noted between the apparent half-life of the mRNA and the degree of destabilization elicited by butyrate. It is concluded that α-subunit induction by theophylline is in large part due to mRNA stabilization, and that the concerted effect of theophylline and butyrate results from inhibition by theophylline of the butyrate-mediated destabilization of α-subunit mRNA combined with the elevation in α-subunit gene transcription known to be produced by the fatty acid.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume280
Issue number1
DOIs
StatePublished - Jul 1990

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Butyrates
Chorionic Gonadotropin
Theophylline
HeLa Cells
Messenger RNA
Half-Life
Butyric Acid
Tubulin
Phosphodiesterase Inhibitors
Transcription
Metabolism
Glycoproteins
Fatty Acids
Stabilization
Genes
Hormones
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

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title = "Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin α-subunit in HeLa cells. II. Effect of both agents on mRNA turnover",
abstract = "In the accompanying paper it was demonstrated that among several methylxanthine phosphodiesterase inhibitors, only theophylline significantly increased production of the glycoprotein hormone α-subunit in HeLa cells, and that this action was synergistic with that of sodium butyrate. A correlation between α-subunit induction and cAMP concentrations was not evident. In this report we characterized the effect of these two drugs on the metabolism of α-subunit mRNA. Sodium butyrate decreased the apparent half-life of mRNAs encoding α-subunit, β2-microglobulin, and α-tubulin, as well as that of total poly(A)+ RNA and rRNA. Theophylline produced a two- to threefold increase in the apparent half-life of α-subunit mRNA but had no effect on the turnover of β2-microglobulin, α-tubulin, or total poly(A)+ mRNA. An inverse correlation was noted between the apparent half-life of the mRNA and the degree of destabilization elicited by butyrate. It is concluded that α-subunit induction by theophylline is in large part due to mRNA stabilization, and that the concerted effect of theophylline and butyrate results from inhibition by theophylline of the butyrate-mediated destabilization of α-subunit mRNA combined with the elevation in α-subunit gene transcription known to be produced by the fatty acid.",
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AB - In the accompanying paper it was demonstrated that among several methylxanthine phosphodiesterase inhibitors, only theophylline significantly increased production of the glycoprotein hormone α-subunit in HeLa cells, and that this action was synergistic with that of sodium butyrate. A correlation between α-subunit induction and cAMP concentrations was not evident. In this report we characterized the effect of these two drugs on the metabolism of α-subunit mRNA. Sodium butyrate decreased the apparent half-life of mRNAs encoding α-subunit, β2-microglobulin, and α-tubulin, as well as that of total poly(A)+ RNA and rRNA. Theophylline produced a two- to threefold increase in the apparent half-life of α-subunit mRNA but had no effect on the turnover of β2-microglobulin, α-tubulin, or total poly(A)+ mRNA. An inverse correlation was noted between the apparent half-life of the mRNA and the degree of destabilization elicited by butyrate. It is concluded that α-subunit induction by theophylline is in large part due to mRNA stabilization, and that the concerted effect of theophylline and butyrate results from inhibition by theophylline of the butyrate-mediated destabilization of α-subunit mRNA combined with the elevation in α-subunit gene transcription known to be produced by the fatty acid.

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