147 Noble Research Center, Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA.
Mol Cell Biochem. 2010 Oct;343(1-2):115-24. doi: 10.1007/s11010-010-0505-7. Epub 2010 Jun 10.
Adipose tissue is a major reservoir of cholesterol and, as such, it may play a significant role in cholesterol homeostasis. The aims of this study were to obtain a quantitative characterization of apolipoprotein A-I (apoA-I)-dependent lipid efflux from adipocytes and examine the role of ATP-binding cassette transporter A1 (ABCA1) in this process. The rates of apoA-I-induced cholesterol and phospholipid efflux were determined and normalized by cellular protein or ABCA1 levels. In order to allow a comparative analysis, parallel experiments were also performed in macrophages. These studies showed that apoA-I induces cholesterol efflux from adipocytes at similar rates as from macrophages. Enhancement of the expression of ABCA1 increased the rates of cholesterol efflux from both adipocytes and macrophages. The results also suggested that a non-ABCA1-dependent mechanism could make significant contributions to the rate of apoA-I-dependent cholesterol efflux when the expression levels of ABCA1 are low. Furthermore, the study of the effect of inhibitors of lipid efflux showed that glyburide and brefeldin A, which affect ABCA1 function, exerted strong and similar inhibitory effects on lipid efflux from both adipocytes and macrophages, whereas BLT1, an SRB-I inhibitor, only exerted a moderate inhibition. Overall these studies suggest that ABCA1 plays a major role in apoA-I-dependent lipid efflux from adipocytes and showed high similarities between the abilities of adipocytes and macrophages to release cholesterol in an apoA-I-dependent fashion.
脂肪组织是胆固醇的主要储存库，因此它可能在胆固醇稳态中发挥重要作用。本研究的目的是获得载脂蛋白 A-I（apoA-I）依赖性脂肪细胞脂质外排的定量特征，并研究 ATP 结合盒转运体 A1（ABCA1）在该过程中的作用。测定了 apoA-I 诱导的胆固醇和磷脂外排的速率，并通过细胞蛋白或 ABCA1 水平进行了归一化。为了进行比较分析，还在巨噬细胞中进行了平行实验。这些研究表明，apoA-I 诱导脂肪细胞和巨噬细胞中的胆固醇外排速率相似。ABCA1 表达的增强增加了胆固醇从脂肪细胞和巨噬细胞中外排的速率。结果还表明，当 ABCA1 的表达水平较低时，非 ABCA1 依赖性机制可能对 apoA-I 依赖性胆固醇外排速率做出重大贡献。此外，对脂质外排抑制剂作用的研究表明，影响 ABCA1 功能的格列本脲和布雷非德菌素 A 对脂肪细胞和巨噬细胞中脂质外排均具有强烈且相似的抑制作用，而 SRB-I 抑制剂 BLT1 仅产生适度抑制。总体而言，这些研究表明 ABCA1 在 apoA-I 依赖性脂肪细胞脂质外排中起主要作用，并显示脂肪细胞和巨噬细胞以 apoA-I 依赖性方式释放胆固醇的能力具有高度相似性。
