Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin alpha-subunit in HeLa cells. I. Lack of correlation with cAMP.
The glycoprotein hormone common alpha-subunit can be induced in HeLa and other nontrophoblastic tumor cell lines by sodium butyrate. This report demonstrates that production of alpha-subunit can be further modulated by theophylline, especially in conjunction with butyrate. This synergism was not observed with other phosphodiesterase inhibitors such as xanthine, caffeine, theobromine, or methylisobutylxanthine. Induction by a combination of the short chain fatty acid plus the methylxanthine results from a decrease in the lag time after effector addition as well as a change in the rate of subunit accumulation. The increase in alpha-subunit is correlated with an increase in the levels of alpha-subunit mRNA, suggesting that induction is manifest at a pretranslational stage. The production of alpha-subunit was only marginally affected in cultures treated with 8-Br-cAMP or forskolin. Intracellular levels of cAMP were increased approximately threefold by methylisobutylxanthine, twofold by theophylline, fourfold by forskolin, and about 50% by butyrate, yet significant induction was achieved only by butyrate and theophylline. Taken together, these data suggest that the synergism between butyrate and theophylline is not mediated by cAMP.
Department of Biochemistry, University of Nebraska Medical Center, Omaha 68198-4525.
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D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013806:Theophylline / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
D002087:Butyrates; D015292:Glycoprotein Hormones, alpha Subunit; D014970:Xanthines; D020148:Butyric Acid; D005576:Colforsin; D013806:Theophylline; D000469:Alkaline Phosphatase