Induction of alcohol dehydrogenase activity and mRNA in hepatoma cells by dexamethasone.
Liver alcohol dehydrogenase activity was present in rat H4IIE hepatoma cells. Dexamethasone increased the enzyme activity two- to fourfold in these cells, but not in HepG2 cells. Enzyme induction was observed at dexamethasone concentrations as low as 10(-9) M, and the induction was maximal at 3 days. The increase in enzyme activity was accompanied by an increase in alcohol dehydrogenase mRNA on Northern blots and a two- to fourfold increase in alcohol dehydrogenase mRNA levels as estimated from cytoplasmic dot blots. There was no effect of dexamethasone on alpha-tubulin mRNA levels. Insulin, triiodothyronine, and growth hormone had no effect on alcohol dehydrogenase activity or mRNA levels. The induction of alcohol dehydrogenase mRNA by dexamethasone could be blocked by actinomycin D, but not by protein synthesis inhibitors. Superinduction of the mRNA (approximately twofold) was observed with dexamethasone in the presence of cycloheximide. Southern blots of genomic DNA from rat liver and H4IIE cells revealed no differences in alcohol dehydrogenase gene structure. The induction of alcohol dehydrogenase activity and mRNA levels by dexamethasone may be due to an increase in the rate of transcription of the alcohol dehydrogenase gene.
Wolfla
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Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Ross
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Crabb
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D000426:Alcohol Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats
D012333:RNA, Messenger; D003907:Dexamethasone; D000426:Alcohol Dehydrogenase