机构：[1]Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China,[2]Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China,[3]Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
Background Lectin-like oxidized low-density lipoprotein-1 (LOX-1) is the major receptor for oxidized low density lipoprotein (ox-LDL) uptake in human umbilical vein endothelial cells (HUVECs). Previously, we found that rapamycin inhibited ox-LDL accumulation in HUVECs, and this effect was related to its role in increasing the activity of autophagy-lysosome pathway. In this study, we determined whether rapamycin could also reduce ox-LDL uptake in HUVECs and investigated the underlying signaling mechanisms. Results Flow cytometry and live cell imaging showed that rapamycin reduced Dil-ox-LDL accumulation in HUVECs. Furthermore, rapamycin reduced the ox-LDL-induced increase in LOX-1 mRNA and protein levels. Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and I kappa B alpha phosphorylation triggered by ox-LDL. Flow cytometry implied that mTOR, NF-kappa B knockdown and NF-kappa B inhibitors significantly reduced Dil-ox-LDL uptake. Moreover, immunofluorescent staining showed that rapamycin reduced the accumulation of p65 in the nucleus after ox-LDL treatment for 30 h. mTOR knockdown decreased LOX-1 protein production and I kappa B alpha phosphorylation induced by ox-LDL. NF-kappa B knockdown and NF-kappa B inhibitors reduced LOX-1 protein production, but did not inhibit mTOR phosphorylation stimulated by ox-LDL. Conclusions These findings demonstrate that rapamycin reduce mTOR phosphorylation and subsequently inhibit NF-kappa B activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs.
基金：
This work was supported by grants from
the PhD Programs Foundation of the Ministry of
Education of China (20113201120016), the Natural
Science Foundation of Jiangsu Province
(BK2012172), the National Natural Science
Foundation of China (81200894, 81471195), the
Suzhou Foundation of Science and Technology
Development Plan (SYSD2012083, SDFEYGJ1106),
the Suzhou Social Development project
(SYS201548), and the second affiliated hospital of Soochow university preponderant clinic discipline
group project (XKQ2015002).
第一作者机构：[1]Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China,[2]Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China,
推荐引用方式(GB/T 7714)：
Yan-De Zhou,Xue-Qin Cao,Zhi-Hua Liu,et al.Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-kappa B/LOX-1 Pathway[J].PLOS ONE.2016,11(1):e0146777.doi:10.1371/journal.pone.0146777.
APA：
Yan-De Zhou,Xue-Qin Cao,Zhi-Hua Liu,Yong-Jun Cao,Chun-Feng Liu...&Ying Xie.(2016).Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-kappa B/LOX-1 Pathway.PLOS ONE,11,(1)
MLA：
Yan-De Zhou,et al."Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-kappa B/LOX-1 Pathway".PLOS ONE 11..1(2016):e0146777
