Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells
Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells
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Gly[14]-人素抑制 ox-LDL 摄取并刺激巨噬细胞衍生泡沫细胞中的胆固醇流出
DOI：
10.1016/j.bbrc.2016.10.138
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发表时间：
2017-01-01
影响因子：
3.1
通讯作者：
Zhang，Yan-lin
中科院分区：
文献类型：
--
作者：
Zhu，Wa-wa;Wang，Shu-rong;Zhang，Yan-lin
巨噬细胞不平衡的胆固醇内流和外流导致泡沫细胞的形成，在动脉粥样硬化的发生发展中起着重要作用。人蛋白(Human in，HN)是一种线粒体来源的多肽，可防止氧化型低密度脂蛋白(OX-LDL)诱导的人主动脉内皮细胞产生活性氧和细胞死亡，对动脉粥样硬化早期患者具有保护作用。然而，HN对RAW 264.7巨噬细胞胆固醇代谢的调节作用尚不清楚。本研究旨在探讨[Gly14]-人(HNG)在RAW 264.7巨噬细胞脂质摄取和胆固醇外流中的作用。流式细胞仪和活细胞成像结果显示，HNG减少了原始264.7巨噬细胞中Dil-ox-LDL的积聚。通过测量细胞胆固醇含量，脂肪积累也得到了类似的结果。Western印迹分析表明，ox-LDL处理不仅上调了介导ox-LDL内吞的CD36和LOX-1的蛋白表达，而且上调了介导ox-LDL外流的ATP结合盒转运体A1和Abcg1的蛋白表达。HNG可抑制氧化低密度脂蛋白诱导的CD36和LOX-1水平的上调，促进ABCA1和Abcg1水平的上调。因此，我们得出结论，HNG可以抑制ox-LDL诱导的巨噬细胞源性泡沫细胞的形成，这是由于巨噬细胞的脂质摄取减少和胆固醇外流增加所致。
Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264.7 macrophages are still unknown. This study was designed to investigate the role of [Gly14]-humanin (HNG) in lipid uptake and cholesterol efflux in RAW 264.7 macrophages. Flow cytometry and live cell imaging results showed that HNG reduced Dil-ox-LDL accumulation in the RAW 264.7 macrophages. A similar result was obtained for lipid accumulation by measuring cellular cholesterol content. Western blot analysis showed that ox-LDL treatment upregulated not only the protein expression of CD36 and LOX-1, which mediate ox-LDL endocytosis, but also ATP-binding cassette (ABC) transporter A1 and ABCG1, which mediate ox-LDL exflux. HNG pretreatment inhibited the upregulation of CD36 and LOX-1 levels, prompting the upregulation of ABCA1 and ABCG1 levels induced by ox-LDL. Therefore we concluded that HNG could inhibit ox-LDL-induced macrophage-derived foam cell formation, which occurs because of a decrease in lipid uptake and an increase in cholesterol efflux from macrophage cells.