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.
Tamura
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Department of Biochemistry, University of Nebraska Medical Center, Omaha 68198-4525.
Cox
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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