A novel function of apolipoprotein E: upregulation of ATP-binding cassette transporter A1 expression.
A novel function of apolipoprotein E: upregulation of ATP-binding cassette transporter A1 expression.
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DOI：
10.1371/journal.pone.0021453
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Zhao Y;Chen X;Yang H;Zhou L;Okoro EU;Guo Z
尽管载脂蛋白（Apo）E在胆固醇流出中的重要性众所周知，但ApoE对ATP结合盒转运蛋白A1（ABCA 1）表达的影响从未被研究过。本研究的目的是确定ApoE对载脂蛋白B诱导的ABCA 1（一种介导胆固醇流出的蛋白质）表达的影响。我们的数据表明，从野生型和ApoE基因敲除小鼠获得的载脂蛋白B诱导ApoAI介导的小鼠巨噬细胞胆固醇流出，这与增强ABCA 1启动子活性，增加ABCA 1 mRNA和蛋白表达。此外，这些脂蛋白增加了磷酸化特异性蛋白1（Sp1）的水平和与ABCA 1启动子结合的Sp1的量。然而，与野生型脂蛋白处理的细胞相比，所有这些诱导作用在用无ApoE脂蛋白处理的细胞中显著减少。用人ApoE3富集逆转了无ApoE脂蛋白的诱导减少。此外，我们观察到，通过光神霉素A抑制Sp1 DNA结合减少了ABCA1表达和载脂蛋白B脂蛋白诱导的ApoAI介导的胆固醇流出，并且ABCA1启动子区域中Sp1结合基序的突变减少了载脂蛋白B脂蛋白诱导的ABCA1启动子活性。总的来说，这些数据表明，ApoE与载脂蛋白B的脂蛋白具有上调作用的ABCA1的表达，并诱导Sp1磷酸化是一种机制，ApoE上调ABCA1的表达。
Despite the well known importance of apolipoprotein (Apo) E in cholesterol efflux, the effect of ApoE on the expression of ATP-binding cassette transporter A1 (ABCA1) has never been investigated. The objective of this study was to determine the effect of ApoE on ApoB-carrying lipoprotein-induced expression of ABCA1, a protein that mediates cholesterol efflux. Our data demonstrate that ApoB-carrying lipoproteins obtained from both wild-type and ApoE knockout mice induced ApoAI-mediated cholesterol efflux in mouse macrophages, which was associated with an enhanced ABCA1 promoter activity, and an increased ABCA1 mRNA and protein expression. In addition, these lipoproteins increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter. However, all these inductions were significantly diminished in cells treated with ApoE-free lipoproteins, when compared to those treated with wild-type lipoproteins. Enrichment with human ApoE3 reversed the reduced inducibility of ApoE-free lipoproteins. Moreover, we observed that inhibition of Sp1 DNA-binding by mithramycin A diminished ABCA1 expression and ApoAI-mediated cholesterol efflux induced by ApoB-carrying lipoproteins, and that mutation of the Sp1-binding motif in the ABCA1 promoter region diminished ApoB-carrying lipoprotein-induced ABCA1 promoter activity. Collectively, these data suggest that ApoE associated with ApoB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and that induction of Sp1 phosphorylation is a mechanism by which ApoE upregulates ABCA1 expression.
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影响因子：
2.9
作者：
Thymiakou, Efstathia;Zannis, Vassilis I.;Kardassis, Dimitris
通讯作者：
Kardassis, Dimitris
影响因子：
5.5
作者：
Dove, DE;Linton, MF;Fazio, S
通讯作者：
Fazio, S
影响因子：
2.9
作者：
Vedhachalam, Charulatha;Narayanaswami, Vasanthy;Bielicki, John K.
通讯作者：
Bielicki, John K.
影响因子：
5.2
作者：
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通讯作者：
Visvikis, S
影响因子：
8.7
作者：
Huang, ZH;Lin, CY;Mazzone, T
通讯作者：
Mazzone, T