Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages.
The critical initiating event in atherogenesis involves the invasion of monocytes through the endothelial wall of arteries, and their transformation from macrophages into foam cells. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and can then be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). We previously reported that adipocyte lipid binding protein (ALBP/aP2) is a gene that is highly up-regulated in foam cells in response to oxLDL. Here, we showed that overexpression of the ALBP gene using a lentiviral construct in macrophage foam cells enhanced the accumulations of cholesterol and triglyceride, probably due to an increased expression of the scavenger receptor type AI (SR-AI), which plays an important role in cell lipid metabolism. Moreover, we determined that the expression of acyl-coenzyme A: cholesterol-acyltransferase 1 (ACAT1) gene was up-regulated by the overexpression of ALBP gene, and on the other hand, the ATP-binding cassette A1 (ABCA1) gene and hormone sensitive lipase (HSL) gene, which mediate separately cholesterol efflux and cholesterol ester hydrolysis in the macrophage cells, were down-regulated by the overexpression of ALBP gene in these cells. Finally, our data indicated that oxLDL regulates expression of ALBP related to two peroxisome proliferator-responsive elements (PPREs) which are located in ALBP promoter region. These results have determined that ALBP gene expression accelerates cholesterol and triglyceride accumulation in macrophage foam cells and affects some key gene expression for lipid metabolism, suggesting some pivotal roles of ALBP in lipid metabolism for macrophage foam cell formation.
Fu
Yuchang
Y
Department of Nutrition Sciences, University of Alabama at Birmingham, 1675 University Boulevard, Birmingham, AL 35294-3360, USA. yfu@uab.edu
Luo
Liehong
L
Luo
Nanlan
N
Garvey
W Timothy
WT
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005487:Foam Cells / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000378:metabolism; D020218:Response Elements; D051117:Scavenger Receptors, Class A / Q000235:genetics; D002787:Sterol Esterase / Q000235:genetics; D002785:Sterol O-Acyltransferase / Q000235:genetics; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008077:Lipoproteins, LDL; D020025:Peroxisome Proliferators; D051117:Scavenger Receptors, Class A; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1; D002787:Sterol Esterase