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Transcriptional regulation of apolipoprotein A‐I expression in Hep G2 cells by phorbol ester
Author(s) -
Vandenbrouck Yves,
Lambert Gilles,
Janvier Brigitte,
Girlich Delphine,
Bereziat Gilbert,
Mangeney-Andreani Marise
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01252-x
Subject(s) - phorbol ester , apolipoprotein b , chemistry , phorbol , microbiology and biotechnology , biochemistry , biology , protein kinase c , signal transduction , cholesterol
The regulation of apolipoprotein A‐I (apo A‐I) gene expression by 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA) was investigated in the human hepatoma cell line Hep G2. TPA treatment decreased apo A‐I mRNA levels in a time‐dependent manner, by up to 50% versus control cells within 24 h. Nuclear run‐on transcription assays demonstrated a transcriptional effect of TPA. Using transfection analysis with a plasmid construct containing the −1378/+11 apo A‐I promoter fused to the secreted placental alkaline phosphatase (SPAP) reporter gene, we showed that the SPAP activity was decreased to 50% when Hep G2 cells were incubated in the presence of TPA. The inhibitory effect of TPA was still maintained when fragment −253 to −4 of apo A‐I promoter was linked to the CAT reporter gene. These data indicate that transcriptional modulation of apolipoprotein A‐I gene expression following phorbol ester treatment is transduced by gene elements located between −253 and −4 of the apo A‐I promoter.