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.
ASJC Scopus subject areas
- Molecular Biology