Rapamycin Promotes the Autophagic Degradation of Oxidized Low-Density Lipoprotein in Human Umbilical Vein Endothelial Cells
Rapamycin Promotes the Autophagic Degradation of Oxidized Low-Density Lipoprotein in Human Umbilical Vein Endothelial Cells
复制标题
雷帕霉素促进人脐静脉内皮细胞氧化低密度脂蛋白自噬降解
DOI：
10.1159/000441143
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发表时间：
2015-12
影响因子：
1.7
通讯作者：
Han Qiao
中科院分区：
文献类型：
--
作者：
Zhang Yanlin;Han Qiao;You Shoujiang;Cao Yongjun;Zhang Xia;Liu Huihui;Hu Lifang;Liu Chunfeng;Han Qiao
背景/目的：氧化低密度脂蛋白（ox-LDL）广泛参与动脉粥样硬化的发生。我们之前的研究报道了ox-LDL可以激活人脐静脉内皮细胞（HUVECs）的自噬。因此，后续研究旨在阐明自噬诱导剂雷帕霉素在内皮细胞ox-LDL降解中的可能作用。方法：采用组织总胆固醇测定试剂盒测定细胞内胆固醇含量。流式细胞术分析内皮细胞内ox-LDL运输。Western blot检测自噬过程中参与蛋白微管相关蛋白1轻链3 （MAP1-LC3）、溶酶体相关膜蛋白1 （LAMP1）、Beclin 1和p62的表达水平。结果：我们发现雷帕霉素可以降低HUVECs中ox-LDL在3小时时间点的含量。雷帕霉素还介导了dil标记的ox-LDL (Dil-ox-LDL)/LC3和Dil-ox-LDL/LAMP1共定位的明显增加，这被自噬抑制剂3-甲基腺苷（3-MA）抑制。此外，在雷帕霉素预处理的细胞中，LC3和LAMP1发生了显著的共定位。在雷帕霉素存在下，p62水平降低，自噬通量增强。结论：这些数据表明，雷帕霉素激活自噬-溶酶体途径可能加速ox-LDL的降解。
Background/Aims: Oxidized low-density lipoprotein (ox-LDL) has been extensively implicated in the initiation of atherosclerosis. Our previous studies reported that ox-LDL could activate autophagy in human umbilical vein endothelial cells (HUVECs). Because of this, subsequent studies were designed to elucidate the possible role of the autophagic inducer, rapamycin, on ox-LDL degradation in endothelial cells. Methods: Intracellular cholesterol content was measured using a tissue total cholesterol assay kit. ox-LDL trafficking within endothelial cells was analyzed by flow cytometry. Levels of proteins involved in the autophagic process, microtubule-associated protein 1 light chain 3 (MAP1-LC3), lysosome-associated membrane protein 1 (LAMP1), Beclin 1 and p62, were assessed by Western blot analysis. Results: We discovered that rapamycin could decrease the ox-LDL content in HUVECs at the 3-hour time point. Rapamycin also mediated an obvious increase in Dil-labeled ox-LDL (Dil-ox-LDL)/LC3 and Dil-ox-LDL/LAMP1 co-localization, which was inhibited by 3-methyladenine (3-MA), an autophagic inhibitor. In addition, significant co-localization of LC3 and LAMP1 occurred in cells pretreated with rapamycin. In the presence of rapamycin, p62 levels were reduced, and autophagic flux was enhanced. Conclusion: These data demonstrate that the activation of the autophagy-lysosome pathway by rapamycin may accelerate ox-LDL degradation.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
DOI：
--
发表时间：
2007
期刊：
--
影响因子：
--
作者：
I. Tabas;K. Williams;J. Borén
通讯作者：
I. Tabas;K. Williams;J. Borén
DOI：
10.1016/j.biocel.2004.05.009
发表时间：
2004-12
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Tanida I;Ueno T;Kominami E
通讯作者：
Kominami E
影响因子：
4.8
作者：
Mietus-Snyder, M;Gowri, MS;Pitas, RE
通讯作者：
Pitas, RE
影响因子：
64.5
作者：
Nakatogawa, Hitoshi;Ichimura, Yoshinobu;Ohsumi, Yoshinori
通讯作者：
Ohsumi, Yoshinori