Differential regulation of apolipoprotein A-I gene expression by vitamin D receptor modulators
| Autor: | Michael J. Haas, Ken Ligaray, Angela D. Mazza, Kent R. Wehmeier, Arshag D. Mooradian, Norman C.W. Wong, Sahar B Hachem |
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| Rok vydání: | 2007 |
| Předmět: |
Apolipoprotein B
Biophysics Gene Expression Vitamin D Response Element Biochemistry Calcitriol receptor Calcitriol Gene expression Animals Humans Secretion Intestinal Mucosa Receptor modulator Promoter Regions Genetic Molecular Biology Gene biology Apolipoprotein A-I Promoter Molecular biology Nuclear receptor Gene Expression Regulation biology.protein Hepatocytes Receptors Calcitriol lipids (amino acids peptides and proteins) Caco-2 Cells |
| Zdroj: | Biochimica et biophysica acta. 1780(2) |
| ISSN: | 0006-3002 |
| Popis: | We have found that 1,25-dihydroxy-cholecalciferol (1,25-(OH)(2)D(3)) represses the expression of the apolipoprotein A-I (apo A-I) gene in hepatocytes. In this manuscript we examined the effects of the vitamin D receptor (VDR) modulators EB1089 (EB) and ZK191784 (ZK) on expression of the apo A-I gene in liver (HepG2) and in intestinal (Caco-2) cells. In HepG2 cells, EB and ZK induced apo A-I secretion and gene promoter activity in a dose-dependent manner. This induction did not require the VDR since antisense-mediated inhibition of VDR had no appreciable effect on apo A-I promoter activity in cells treated with EB or ZK. Although repression of apo A-I gene expression by 1,25-(OH)(2)D(3) in hepatocytes required nuclear receptor binding to site A in the promoter, this cis-element was insufficient for induction of apo-AI by EB and ZK. In Caco-2 cells, treatment with 1,25-(OH)(2)D(3) had no effect on apo A-I protein secretion or promoter activity while EB induced and ZK inhibited apo A-I gene expression. Gel shift assays showed that none of the treatments resulted in a change in site A binding activity. These results indicate that VDR modulators in hepatocytes and intestinal cells differentially regulate expression of the apo A-I gene. |
| Databáze: | OpenAIRE |
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