Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1780, Issue 2, Pages 264-273Publisher
ELSEVIER
DOI: 10.1016/j.bbagen.2007.11.008
Keywords
apolipoprotein A-I; vitamin D; gene expression; receptor modulator
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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. (C) 2007 Elsevier B.V. All rights reserved.
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