Docosahexaenoic acid suppresses apolipoprotein A-I gene expression through hepatocyte nuclear factor-3ß  

Oleh:

Kuang, Yu-Lin ; Paulson, K. Eric ; Lichtenstein, Alice H. ; Matthan, Nirupa R. ; Lamon-Fava, Stefania

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The American Journal of Clinical Nutrition vol. 94 no. 02 (Aug. 2011), page 594-600 .
Topik: Dietary Fish-Oil; Gene-Nutrient Interactions
Fulltext: Am J Clin Nutr-2011-Kuang-594-600.pdf (257.51KB)

Ketersediaan

Perpustakaan FK Nomor Panggil: A07.K.2011.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Background: Dietary fish-oil supplementation has been shown in human kinetic studies to lower the production rate of apolipoprotein (apo) A-I, the major protein component of HDL. The underlying mechanism responsible for this effect is not fully understood. Objective: We investigated the effect and the mechanism of action of the very-long-chain n-3 (omega-3) polyunsaturated fatty acid docosahexaenoic acid (DHA), relative to the saturated fatty acid palmitic acid (PA), on the hepatic expression of apo A-I in HepG2 cells. Design: HepG2 cells were treated with different doses of DHA and PA (0–200 µmol/L). mRNA expression levels of apo A-I were assessed by real-time polymerase chain reaction, and apo A-I protein concentrations were measured by immunoassay. DHA dose-dependently suppressed apo A-I mRNA levels and also lowered apo A-I protein concentrations in the media, with maximum effects at 200 µmol/L. This concentration of fatty acids was used in all subsequent experiments. Results: To elucidate the mechanism mediating the reduction in apo A-I expression by DHA, transfection experiments were conducted with plasmid constructs containing serial deletions of the apo A-I promoter. The DHA-responsive region was mapped to the -185 to -148 nucleotide region of the apo A-I promoter, which binds the hepatocyte nuclear factor (HNF)-3ß. Nuclear extracts from cells treated with DHA or PA had a similar nuclear abundance of HNF-3ß. However, electrophoresis mobility shift assays showed less binding of HNF-3ß to the -180 to -140 sequence of the apo A-I promoter than did PA-treated cells. As shown by chromatin immunoprecipitation analysis, less HNF-3ß was recruited to the apo A-I promoter in DHA-treated cells than in PA-treated cells, which supports the concept of an interference of DHA with the binding of HNF-3ß to the apo A-I promoter. Conclusion: These findings suggest that, in human hepatoma HepG2 cells, DHA inhibits the binding of HNF-3ß to the apo A-I promoter, resulting in the repression of apo A-I promoter transactivity and thus a reduction in apo A-I expression.

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