Yang Hong, Zhang Ningya, Guo Zhongmao
Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, USA.
Cardiovasc Dis Med. 2020;1(1). doi: 10.47496/nl.cdm.2020.01.02. Epub 2020 Nov 13.
Apolipoprotein A-I (apoAI) upregulates ATP-binding cassette transport A1 (ABCA1) in various cell types. ABCA1 has been shown to induce the redistribution of raft-associated proteins and lipids to the non-raft membrane. This report investigated the effect of apoAI on ABCA1 expression and raft cholesterol and protein distribution, as well as the effect of ABCA1 knockdown on apoAI-induced changes in mouse aortic endothelial cells (MAECs). Our data demonstrated that ABCA1 was distributed in both the lipid raft and non-raft membranes and was coimmunoprecipitated with caveolin-1 (CAV1). ApoAI treatment significantly increased the mRNA and protein levels of ABCA1 and reduced the percentage of ABCA1 in the raft membrane. Our data also showed that free cholesterol (FC) and CAV1 were concentrated in the raft-like detergent-resistant membranes (DRMs) under the control conditions. ApoAI treatment did not alter the cellular level of FC and CAV1 significantly but reduced the percentage of FC and CAV1 in the DRMs. Knockdown of ABCA1 attenuated apoAI-induced redistribution of FC and CAV1. The percentage of FC and CAV1 in the DRMs was correlated inversely with the cellular level of ABCA1, suggesting that apoAI induces relocation of CAV1 and FC from the raft to the non-rail membrane via a mechanism involving upregulation of ABCA1.
载脂蛋白A-I(apoAI)可上调多种细胞类型中的ATP结合盒转运体A1(ABCA1)。已有研究表明,ABCA1可诱导脂筏相关蛋白和脂质重新分布至非脂筏膜。本报告研究了apoAI对ABCA1表达、脂筏胆固醇及蛋白分布的影响,以及敲低ABCA1对apoAI诱导的小鼠主动脉内皮细胞(MAECs)变化的影响。我们的数据表明,ABCA1分布于脂筏和非脂筏膜中,并与小窝蛋白-1(CAV1)共免疫沉淀。apoAI处理显著增加了ABCA1的mRNA和蛋白水平,并降低了脂筏膜中ABCA1的百分比。我们的数据还显示,在对照条件下,游离胆固醇(FC)和CAV1集中在类似脂筏的耐去污剂膜(DRMs)中。apoAI处理并未显著改变细胞内FC和CAV1的水平,但降低了DRMs中FC和CAV1的百分比。敲低ABCA1可减弱apoAI诱导的FC和CAV1重新分布。DRMs中FC和CAV1的百分比与细胞内ABCA1水平呈负相关,这表明apoAI通过一种涉及上调ABCA1的机制诱导CAV1和FC从脂筏重新定位至非脂筏膜。