标题：Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway
作者：Yao S.; Tian H.; Zhao L.; Li J.; Yang L.; Yue F.; Li Y.; Jiao P.;等 更多 作者机构：[Yao, S] Key Laboratory of Atherosclerosis, Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China, College 更多
通讯作者地址：[Qin, A.S] Key Laboratory of Atherosclerosis, Universities of Shandong, Institute of Atherosclerosis, Taishan Medical UniversityChina;
来源：Journal of Lipid Research
关键词：Atherosclerosis; CCAATenhancer-binding protein homologous protein; Oxidative stress; Supplementary endoplasmic reticulum stress
摘要：Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress- CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. As with tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and upregulation of glucose-regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL isolated from patients with metabolic syndrome induced macrophage apoptosis, oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway in macrophages via enhanced oxidative stress and that this pathway may be mediated by TLR4.- Yao, S., H. Tian, L. Zhao, J. Li, L. Yang, F. Yue, Y. Li, P. Jiao, N. Yang, Y. Wang, X. Zhang, and S. Qin. Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway J. © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.