RRC ID 6517
Author Iwamoto N, Abe-Dohmae S, Sato R, Yokoyama S.
Title ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis.
Journal J. Lipid Res.
Abstract ABCA7 is highly homologous to ABCA1 and mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro. However, expression of ABCA7 was downregulated by increased cellular cholesterol while ABCA1 was upregulated, and the results were consistent by forced expression or downregulation of sterol-responsive/regulatory element (SRE) binding proteins (SREBPs). We analyzed the promoter of the ABCA7 gene and identified the new exon encoding 96 bp (mouse) and 95 bp (human) of the 5' untranslated region and the transcription start site at 1,122 bp (mouse) and 1,260 bp (human) upstream of the initiation methionine codon. At 5' upstream of this exon is the ABCA7 proximal promoter containing multiple binding sites of transcription factors for hematopoiesis and SRE of 9 bp at 212 bp (mouse) and 179 bp (human) upstream of the new exon. The apolipoprotein A-I-mediated lipid release was not influenced by suppression of the endogenous ABCA7 with small interfering RNA in mouse fibroblasts or by its increase in ABCA1-deficient mouse cells. In contrast, phagocytic activity was altered in parallel to the ABCA7 expression in these cells. When phagocytosis was induced, the messages increased for SREBP2, ABCA7, and other SREBP2-regulated proteins. The ABCA1 message decreased in this condition. We conclude that the ABCA7 gene is regulated by sterol in the opposite direction to ABCA1 through SRE/SREBP2 and that expression of ABCA7 by this regulation is associated with phagocytic activity.
Volume 47(9)
Pages 1915-27
Published 2006-9
DOI 10.1194/jlr.M600127-JLR200
PII M600127-JLR200
PMID 16788211
MeSH 3T3 Cells ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Animals Base Sequence Blotting, Western / methods Caco-2 Cells Cell Line Cholesterol / pharmacology* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Gene Expression Regulation / drug effects HeLa Cells Humans Mice Microscopy, Fluorescence / methods Molecular Sequence Data Phagocytosis / physiology* Promoter Regions, Genetic / genetics Protein Binding RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction / methods Sequence Homology, Nucleic Acid Signal Transduction / drug effects Sterol Regulatory Element Binding Protein 2 / genetics Sterol Regulatory Element Binding Protein 2 / metabolism* Transcription Factors / genetics Transcription Factors / metabolism
IF 4.743
Times Cited 44
Human and Animal Cells