机构:[a]Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou , China[b]Institute of Neuroscience, Soochow University, Suzhou , China[c]Department of Neurology, Suzhou Hospital of Traditional Chinese Medicine, Suzhou , China
Background/Aims: Oxidized low-density lipoprotein (oxLDL) 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-oxLDL)/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.
基金:
This work was supported by a grant from the PhD Programs
Foundation of the Ministry of Education of China
(20113201120016), the Province Natural Science Fund of Jiangsu
of China (BK2012172), the National Natural Science Fund of China
(81200894, 81471195) and a project funded by the Priority Academic
Program Development of Jiangsu Higher Education Institutions
第一作者机构:[a]Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou , China
通讯作者:
通讯机构:[*1]Department of Neurology,Second Affiliated Hospital of Soochow University ,1055 Sanxiang Road, Suzhou 215004
推荐引用方式(GB/T 7714):
Yanlin Zhang,Qiao Han,Shoujiang You,et al.Rapamycin Promotes the Autophagic Degradation of Oxidized Low-Density Lipoprotein in Human Umbilical Vein Endothelial Cells[J].JOURNAL OF VASCULAR RESEARCH.2015,52(3):210-9.doi:10.1159/000441143.
APA:
Yanlin Zhang,Qiao Han,Shoujiang You,Yongjun Cao,Xia Zhang...&Chun-Feng Liu.(2015).Rapamycin Promotes the Autophagic Degradation of Oxidized Low-Density Lipoprotein in Human Umbilical Vein Endothelial Cells.JOURNAL OF VASCULAR RESEARCH,52,(3)
MLA:
Yanlin Zhang,et al."Rapamycin Promotes the Autophagic Degradation of Oxidized Low-Density Lipoprotein in Human Umbilical Vein Endothelial Cells".JOURNAL OF VASCULAR RESEARCH 52..3(2015):210-9