Oxidized LDL upregulated ATP binding cassette transporter-1 in THP-1 macrophages.
OBJECTIVE
To study the effect of oxidized low density lipoprotein (ox-LDL) on ATP binding cassette transporter A1 (ABCA1) in THP-1 macrophages.


METHODS
After exposing the cultured THP-1 macrophages to ox-LDL for different periods, cholesterol efflux was determined by FJ-2107P type liquid scintillator. ABCA1 mRNA and protein level were determined by reverse trancriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The cholesterol level in THP-1 macrophage foam cells was detected by high performance liquid chromatography.


RESULTS
ox-LDL elevated ABCA1 in both protein and mRNA levels and increased apolipoprotein (apo) A-I-mediated cholesterol efflux in a time- and dose-dependent manner. 22(R)-hydroxycholesterol and 9-cis-retinoic acid did significantly increase cholesterol efflux in THP-1 macrophage foam cells (P<0.05), respectively. Both of them further promoted cholesterol efflux (P<0.01). As expected, liver X receptor (LXR) agonist decreased content of esterified cholesterol in the macrophage foam cells compared with control, whereas only a slight decrease of free cholesterol was observed. LXR activity was slightly increased by oxidized LDL by 12 % at 12 h compared with 6 h. However, LXR activity was increased about 1.8 times at 24 h, and oxidized LDL further increased LXR activity by about 2.6 times at 48 h.


CONCLUSIONS
ABCA1 gene expression was markedly increased in cholesterol-loaded cells as a result of activation of LXR/RXR. ABCA1 plays an important role in the homeostasis of cholesterol in the macrophages.
Tang
Chao-ke
CK
Institute of Cardiovascular Disease of Nanhua University, Hengyang 421001, China.
Yi
Guang-hui
GH
Yang
Jun-hao
JH
Liu
Lu-shan
LS
Wang
Zuo
Z
Ruan
Chang-geng
CG
Yang
Yong-zong
YZ
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000077556:Alitretinoin; D016632:Apolipoprotein A-I / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D057093:Orphan Nuclear Receptors; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C099252:oxidized low density lipoprotein; C003585:22-hydroxycholesterol; D000077556:Alitretinoin; D014212:Tretinoin; D002784:Cholesterol