Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element
Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element
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DOI：
10.1016/j.atherosclerosis.2006.04.018
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发表时间：
2007-03-01
期刊：
影响因子：
5.3
通讯作者：
Saku, Keijiro
中科院分区：
文献类型：
--
作者：
Uehara, Yoshinari;Miura, Shin-ichiro;Saku, Keijiro
ATP结合盒转运蛋白（ABC）G1和ABCA 1是膜胆固醇转运蛋白，并已被牵连到介导胆固醇流出细胞的存在下，高密度脂蛋白和其主要蛋白质成分载脂蛋白A-I，分别。我们以前证明，不饱和脂肪酸抑制氧化固醇和类维生素A对ABCA 1基因转录的刺激作用。我们在这里证明，不饱和脂肪酸可显着抑制氧化固醇和类维生素A对ABCG 1 mRNA和蛋白质表达以及野生型人ABCG 1启动子和ABCA 1活性的刺激作用。突变或删除的DR 4元件内的ABCG 1或ABCA 1的启动子，转录诱导剂LXR和RXR结合，废除了不饱和脂肪酸的抑制作用。我们的观察提供了第一个证据，不饱和脂肪酸抑制ABCG 1基因表达的机制，涉及LXR/RXR的启动子的结合。ABCA 1和ABCG 1基因的抑制可能表明，不饱和脂肪酸不仅抑制胆固醇流出到apoA-I，从而抑制新生HDL形成，而且抑制HDL依赖性胆固醇从血管细胞流出。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
ATP-binding cassette transporters (ABC) G1 and ABCA1 are membrane cholesterol transporters and have been implicated to mediate cholesterol efflux from cells in the presence of high density lipoproteins and its major protein constituent apolipoprotein A-I, respectively. We previously demonstrated that unsaturated fatty acids suppress the stimulatory effects of oxysterols and retinoids on ABCA1 gene transcription. We here demonstrate that unsaturated fatty acids significantly suppress the stimulatory effects of oxysterols and retinoids on the expression of ABCG1 mRNA and protein and the activity of the wild-type human ABCG1 promoter as well as ABCA1. Mutation or deletion of the DR4 element within the ABCG1 or ABCA1 promoters, to which the transcriptional inducers LXR and RXR bind, abolished the suppressive effects of unsaturated fatty acids. Our observations provide the first evidence that unsaturated fatty acids suppress ABCG1 gene expression by a mechanism which involves the binding of LXR/RXR to the promoters. Suppression of both the ABCA1 and ABCG1 genes may indicate that unsaturated fatty acids suppress not only cholesterol efflux to apoA-I and thereby nascent HDL formation but also HDL-dependent cholesterol efflux from vascular cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.