Regulation of human apolipoprotein A-I expression in Caco-2 and HepG2 cells by all-trans and 9-cis retinoic acids.
Retinoids are reported to stimulate apolipoprotein (apo) A-I gene promoter activity (Rottman et al. 1991. Mol. Cell. Biol. 11: 3814-3820) and apoA-I protein secretion by monkey hepatocytes (Kaptein et al. 1993. Arterioscler. Thromb. 13: 1505-1514). In this study we have assessed the effects of retinoids on parameters of apoA-I biosynthesis in human cell lines. Caco-2 and HepG2 cells (human intestinal and hepatoma cell lines, respectively, both known to express and secrete apoA-I) were stably transfected with a reporter gene construct containing 1.3 kb of the 5-'flanking region of the human apoA-I gene linked to the firefly luciferase coding region. These cells were incubated for 48 h with 10 microM all-trans retinoic acid (RA) or 9-cis RA. The cells were then assayed for luciferase activity, for apoA-I mRNA level, and for secretion of apoA-I protein in the medium. Secretion of apoB was monitored as well. In Caco-2 cells, all-trans and 9-cis RA increased luciferase activity, mRNA content, and protein secretion by 40% to 80% above control. Strikingly, in HepG2 cells all-trans and 9-cis RA caused a more marked stimulation of luciferase activity (by 100-150%) but a weaker increase of mRNA content and protein secretion (by 25-30%). In contrast, apoB secretion was inhibited by the two retinoids in Caco-2 cells and not changed in HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Giller
T
T
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Hennes
U
U
Kempen
H J
HJ
D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics; D001055:Apolipoproteins B / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012176:Retinoids / Q000494:pharmacology*; D013237:Stereoisomerism; D013268:Stimulation, Chemical; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D012176:Retinoids; D014212:Tretinoin; D008156:Luciferases