Fenofibric acid modulates the human apolipoprotein A-IV gene expression in HepG2 cells.
The influence of the hypolipidemic drug, fenofibric acid, on the regulation of apolipoprotein A-IV (apoA-IV) gene expression was investigated in two human cell lines, HepG2 and Caco-2. As shown in the present report, fenofibric acid induces a strong dose-dependent increase of the apoA-IV mRNA level in HepG2 cells, while other apolipoproteins mRNA levels are only slightly modified. In Caco-2 cells, no modification is observed, except for a 2-fold increase of the apoE mRNA level. The increase of the apoA-IV mRNA level could be correlated with a clear enhancement of DNase I hypersensitive sites in the 5' flanking region of the gene in nuclei of HepG2 cells treated with fenofibric acid. Thus, fenofibric acid may act by facilitating the interaction of nuclear regulatory proteins with the DNA in the control regions of the apoA-IV gene.
Bovard-Houppermans
S
S
Unité d'Expression des Gènes Eucaryotes-Institut Pasteur-28, Paris, France.
Ochoa
A
A
Fruchart
J C
JC
Zakin
M M
MM
D001053:Apolipoproteins / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics*; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014407:Tumor Cells, Cultured
D001053:Apolipoproteins; D001054:Apolipoproteins A; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; C006012:fenofibric acid; D011345:Fenofibrate