title: Lp-PLA2 silencing protects against ox-LDL-induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages.
abstract: Atherosclerosis is a disease of the large- and medium-size arteries that is characterized by the formation of atherosclerotic plaques, in which foam cells are the characteristic pathological cells. However, the key underlying pathomechanisms are still not fully elucidated. In this study, we investigated the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in ox-LDL-induced oxidative stress and cell apoptosis, and further, elucidated the potential machanisms in human THP1 macrophages. Flow cytometry and western blot analyses showed that both cell apoptosis and Lp-PLA2 expression were dose-dependently elevated after ox-LDL treatment for 24 h and also time-dependently increased after 50 mg/L ox-LDL incubation in THP1 macrophages. In addition, Lp-PLA2 silencing decreased ox-LDL-induced Lp-PLA2 and CD36 expression in THP1 macrophages. We also found that the levels of oil red O-staining, triglyceride (TG) and total cholesterol (TC) were significantly upregulated in ox-LDL-treated THP1 cells, but inhibited by Lp-PLA2 silencing. Furthermore, ox-LDL treatment resulted in significant increases of ROS and MDA but a marked decrease of SOD, effects that were reversed by Lp-PLA2 silencing in THP1 cells. Lp-PLA2 silencing reduced ox-LDL-induced cell apoptosis and caspase-3 expression in THP1 cells. Moreover, Lp-PLA2 siRNA transfection dramatically lowered the elevated levels of p-Akt and p-mTOR proteins in ox-LDL-treated THP1 cells. Both PI3K inhibitor LY294002 and mTOR inhibitor rapamycin decreased the augmented caspase-3 expression and TC content induced by ox-LDL, respectively. Taken together, these results revealed that Lp-PLA2 silencing protected against ox-LDL-induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages.
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710004, Shaanxi, PR China; Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China. Electronic address: zhd239@hotmail.com.
authors.forename: HuaDong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710004, Shaanxi, PR China.
authors.forename: DaJiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710004, Shaanxi, PR China.
authors.forename: XiaoJuan
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710004, Shaanxi, PR China.
authors.forename: WeiLin
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710004, Shaanxi, PR China.
authors.forename: YingNa
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710004, Shaanxi, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China. Electronic address: liuenqi@mail.xjtu.edu.cn.
authors.forename: EnQi
authors.initials: E
authors.lastname: Liu
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D020868:Gene Silencing; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
keywords: Cell apoptosis; Lp-PLA2; Macrophage; Oxidative stress; ox-LDL