Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells
Autor: | Xue-Mei Hu, Xiao-Juan Fan, Huijun Hu, Yuanbo Liu, Yongquan Pan, Wen-Quan Zhou, Min-Wen Peng, Cai-Hong Gu, Wei-Wen Zou, Xiaolong Lin |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Peroxisome proliferator-activated receptor allicin 030204 cardiovascular system & hematology Biology Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Genetics Humans Disulfides RNA Messenger Liver X receptor Foam cell Liver X Receptors chemistry.chemical_classification Allicin Macrophages Lipid metabolism General Medicine Transfection Articles Lipid Metabolism Sulfinic Acids foam cells Cell biology Up-Regulation PPAR gamma 030104 developmental biology Cholesterol chemistry ABCA1 biology.protein lipids (amino acids peptides and proteins) ATP binding cassette transporter A1 atherosclerosis ATP Binding Cassette Transporter 1 Signal Transduction |
Zdroj: | International Journal of Molecular Medicine |
ISSN: | 1791-244X 1107-3756 |
Popis: | Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) in THP‑1 macrophage-derived foam cells. THP‑1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP‑1 macrophage-derived foam cells. |
Databáze: | OpenAIRE |
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