Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan.
Phytomedicine. 2012 Mar 15;19(5):383-8. doi: 10.1016/j.phymed.2011.10.007. Epub 2012 Feb 2.
The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by regulating the cellular efflux of cholesterol. Since ABCA1 plays a pivotal role in cholesterol homeostasis and HDL metabolism, identification of a novel substance that is capable of increasing its expression would be beneficial for the prevention and therapy of atherosclerosis. In the present study, we studied the effects of ethanolic extracts of Brazilian red propolis (EERP) on ABCA1 expression and cholesterol efflux in THP-1 macrophages. EERP enhanced PPARγ and liver X receptor (LXR) transcriptional activity at 5-15μg/ml, which was associated with upregulation of PPARγ and LXRα expression. It was also found that EERP increase the activity of the ABCA1 promoter, which is positively regulated by LXR. Consistent with these findings, treatment with EERP increased both mRNA and protein expression of ABCA1. Finally, EERP upregulated ApoA-I-mediated cholesterol efflux. Our results showed that EERP promote ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression via induction of PPARγ/LXR.
三磷酸腺苷结合盒转运体 A1（ABCA1）是一种膜转运蛋白，通过调节细胞内胆固醇的流出，直接参与高密度脂蛋白（HDL）的生成。由于 ABCA1 在胆固醇稳态和 HDL 代谢中发挥着关键作用，因此鉴定一种能够增加其表达的新型物质将有助于动脉粥样硬化的预防和治疗。在本研究中，我们研究了巴西红蜂胶（EERP）的乙醇提取物对 THP-1 巨噬细胞中 ABCA1 表达和胆固醇流出的影响。EERP 在 5-15μg/ml 时增强了 PPARγ 和肝 X 受体（LXR）的转录活性，这与 PPARγ 和 LXRα 表达的上调有关。还发现，EERP 增加了 ABCA1 启动子的活性，而 LXR 正向调节该启动子。与这些发现一致的是，EERP 处理增加了 ABCA1 的 mRNA 和蛋白表达。最后，EERP 上调了 ApoA-I 介导的胆固醇流出。我们的结果表明，EERP 通过诱导 PPARγ/LXR 增加 ABCA1 的表达，促进 ApoA-I 介导的巨噬细胞内胆固醇流出。
