title: Ac‑hE‑18A‑NH2, a novel dual‑domain apolipoprotein mimetic peptide, inhibits apoptosis in macrophages by promoting cholesterol efflux.
abstract: A novel synthetic dual-domain apolipoprotein (apo)-mimetic peptide, Ac-hE-18A-NH2, has been proposed to possess several apo A-I- and apo E-mimetic properties. This study investigated the protective effect of this peptide on oxidized low-density lipoprotein (ox-LDL)-induced apoptosis in RAW264.7 cells. For this purpose, RAW264.7 cells were exposed to 50 µg/ml ox-LDL for 48 h, and then incubated with the peptide Ac-hE-18A-NH2 at various concentrations. Apoptosis was detected using annexin V-fluorescein isothiocyanate staining and flow cytometric analysis. The study revealed that the peptide Ac-hE-18A-NH2 (1, 10 and 50 µg/ml) inhibited ox-LDL-mediated apoptosis, and this was accompanied by an increased rate of intracellular cholesterol efflux, and decreased total cholesterol levels in the cells in a concentration-dependent manner. The peptide also decreased caspase-3 activity and increased B-cell lymphoma 2 protein (Bcl-2) expression in macrophages in a dose-dependent manner. Moreover, blockage of cholesterol efflux by brefeldin A decreased the protective effect of Ac-hE-18A-NH2 against ox-LDL induced apoptosis, while increasing the cholesterol efflux by β-cyclodextrin administration led to a marked decrease in the rate of apoptosis of the cells. These findings demonstrate that the apo-mimetic peptide Ac-hE-18A-NH2 exerts a protective effect against apoptosis by reducing the accumulation of cholesterol.
authors.affiliation: Department of Cardiology, Hunan Provincial People's Hospital, Changsha, Hunan 410005, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020126:Brefeldin A / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D008074:Lipoproteins / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: C478448:Ac-hE18A-NH(2); D008074:Lipoproteins; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D047392:beta-Cyclodextrins; D020126:Brefeldin A; D002784:Cholesterol; D053148:Caspase 3