Nicotinate-Curcumin Impedes Foam Cell Formation from THP-1 Cells through Restoring Autophagy Flux.
Nicotinate-Curcumin Impedes Foam Cell Formation from THP-1 Cells through Restoring Autophagy Flux.
复制标题
烟酸姜黄素通过恢复自噬通量阻止 THP-1 细胞形成泡沫细胞
DOI：
10.1371/journal.pone.0154820
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Liao DF
中科院分区：
文献类型：
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作者：
Gu HF;Li HZ;Tang YL;Tang XQ;Zheng XL;Liao DF
我们前期的研究表明，一种新型的姜黄素衍生物烟酸酯-姜黄素（NC）具有预防动脉粥样硬化的作用，但其确切机制尚不完全清楚。鉴于自噬调节脂质代谢，本研究旨在研究NC是否通过恢复氧化低密度脂蛋白（ox-LDL）处理的THP-1细胞中的自噬通量来减少泡沫细胞形成。我们的结果表明，ox-LDL（100 μg/ml）在THP-1细胞中积累，并损害自噬流量。自噬抑制剂氯喹（CQ）可增强氧化低密度脂蛋白诱导的自噬损伤，自噬诱导剂雷帕霉素可挽救氧化低密度脂蛋白诱导的自噬损伤。CQ可增加ox-LDL的聚集性，而雷帕霉素可降低ox-LDL的聚集性。此外，ox-LDL组脂滴与LC 3-II的共定位明显减少。相比之下，NC（10 μM）通过显着增加ox-LDL处理的THP-1细胞中LC 3-II的水平、自噬溶酶体的数量和p62的降解来挽救受损的自噬通量。抑制PI 3 K-Akt-mTOR信号传导是NC拯救的自噬通量所需的。值得注意的是，我们的结果表明，NC显着促进脂滴与自噬溶酶体的共定位，增加胆固醇的流出，并减少THP-1细胞中ox-LDL的积累。然而，3-甲基腺嘌呤（3-MA）或CQ处理降低了NC对脂质积累的保护作用。总的来说，研究结果表明，NC通过恢复自噬流量减少THP-1细胞中的脂质积累，并进一步暗示NC可能是一种潜在的治疗剂，以逆转动脉粥样硬化。
Our previous studies have indicated that a novel curcumin derivate nicotinate-curcumin (NC) has beneficial effects on the prevention of atherosclerosis, but the precise mechanisms are not fully understood. Given that autophagy regulates lipid metabolism, the present study was designed to investigate whether NC decreases foam cell formation through restoring autophagy flux in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells. Our results showed that ox-LDL (100 μg/ml) was accumulated in THP-1 cells and impaired autophagy flux. Ox-LDL-induced impairment of autophagy was enhanced by treatment with the autophagy inhibitor chloroquine (CQ) and rescued by the autophagy inducer rapamycin. The aggregation of ox-LDL was increased by CQ, but decreased by rapamycin. In addition, colocalization of lipid droplets with LC3-II was remarkably reduced in ox-LDL group. In contrast, NC (10 μM) rescued the impaired autophagy flux by significantly increasing level of LC3-II, the number of autophagolysosomes, and the degradation of p62 in ox-LDL-treated THP-1 cells. Inhibition of the PI3K-Akt-mTOR signaling was required for NC-rescued autophagy flux. Notably, our results showed that NC remarkably promoted the colocalization of lipid droplets with autophagolysosomes, increased efflux of cholesterol, and reduced ox-LDL accumulation in THP-1 cells. However, treatment with 3-methyladenine (3-MA) or CQ reduced the protective effects of NC on lipid accumulation. Collectively, the findings suggest that NC decreases lipid accumulation in THP-1 cells through restoring autophagy flux, and further implicate that NC may be a potential therapeutic reagent to reverse atherosclerosis.