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Atherosclerosis. 1994 Feb;105(2):235-43.

Regulation of apolipoprotein A-I gene expression by phenobarbital in the human hepatocarcinoma cell line, Hep3B.

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Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.


Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoprotein (HDL), which has been suggested to play a protective role against the development of atherosclerosis. The effect of phenobarbital on apo A-I mRNA and protein levels was studied in the human hepatoma cell line, Hep3B. Exposure of Hep3B cells to the drug (200 micrograms/ml) for 16 h resulted in a 4-fold and 8-fold increase in apo A-I mRNA and secreted protein levels, respectively. The induction of apo A-I mRNA level caused by phenobarbital could be due to increased rates of transcription and/or alteration in mRNA stability. To test these possibilities, nuclear run-off transcription assays and pulse-chase deinduction experiments were performed. We have demonstrated that phenobarbital treatment is associated with a 2-fold induction in apo A-I transcriptional activity. The estimated half-lives for apo A-I mRNA are 2 h and 3.6 h in the absence or presence of phenobarbital, respectively. The combination of increase in apo A-I transcription rate and mRNA stabilization could explain the 4-fold induction in apo A-I mRNA levels caused by phenobarbital treatment. However, these events could not be solely responsible for the 8-fold increase in secreted apo A-I protein level observed. The results suggest that the mechanism(s) by which phenobarbital induces apo A-I production operate at both pre- and either co- or post-translational mechanisms. The induction of apo A-I is specific since no significant alteration in apo E mRNA and proteins was observed in drug-treated cells.

[Indexed for MEDLINE]

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