Ac‑hE‑18A‑NH2, a novel dual‑domain apolipoprotein mimetic peptide, inhibits apoptosis in macrophages by promoting cholesterol efflux

Xie,Qiong; Li,Feng; Zhao,Shui‑Ping

doi:10.3892/mmr.2014.2056

Ac‑hE‑18A‑NH2, a novel dual‑domain apolipoprotein mimetic peptide, inhibits apoptosis in macrophages by promoting cholesterol efflux

Authors:
- Qiong Xie
- Feng Li
- Shui‑Ping Zhao
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Affiliations: Department of Cardiology, Hunan Provincial People's Hospital, Changsha, Hunan 410005, P.R. China, Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: March 14, 2014 https://doi.org/10.3892/mmr.2014.2056
Pages: 1851-1856

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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.

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