Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages
Atherosclerosis is a process of imbalanced lipid metabolism in the vascular walls. The underlying pathology mainly involves the deposition of oxidized lipids in the endothelium and the accumulation of cholesterol in macrophages. Macrophages export excessive cholesterol (cholesterol efflux) through A...
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MDPI AG
2018-07-01
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| Series: | Molecules |
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| author | I-Jou Teng Min-Chien Tsai Shao-Fu Shih Bi-Feng Tsuei Hsin Chang Yi-Ping Chuang Chin-Sheng Lin Ching-Yuh Chern Sy-Jou Chen |
| author_facet | I-Jou Teng Min-Chien Tsai Shao-Fu Shih Bi-Feng Tsuei Hsin Chang Yi-Ping Chuang Chin-Sheng Lin Ching-Yuh Chern Sy-Jou Chen |
| author_sort | I-Jou Teng |
| collection | DOAJ |
| description | Atherosclerosis is a process of imbalanced lipid metabolism in the vascular walls. The underlying pathology mainly involves the deposition of oxidized lipids in the endothelium and the accumulation of cholesterol in macrophages. Macrophages export excessive cholesterol (cholesterol efflux) through ATP-binding cassette transporter A1 (ABCA1) to counter the progression of atherosclerosis. We synthesized novel chalcone derivatives and assessed their effects and the underlying mechanisms on ABCA1 expression in macrophages. Human THP-1 macrophages were treated with synthetic chalcone derivatives for 24 h. In Western blot and flow cytometry analyses, a chalcone derivative, (E)-1-(3,4-diisopropoxyphenyl)-3-(4-isopropoxy-3-methoxyphenyl)prop- 2-en-1-one (1m), was observed to significantly enhance ABCA1 protein expression in THP-1 cells (10 µM, 24 h). Levels of mRNA of ABCA1 and liver X receptor alpha (LXRα) were quantified using a real-time quantitative polymerase chain reaction technique and were found to be significantly increased after treatment with the novel chalcone derivative 1m. Several microRNAs, including miR155, miR758, miR10b, miR145, miR33, and miR106b, which functionally inhibit ABCA1 expression were suppressed after treatment with 1m. Collectively, 1m increases ABCA1 expression in human THP-1 macrophages. The mechanisms involve the activation of the LXRα-ABCA1 pathway and suppression of certain microRNAs that regulate ABCA1 expression. |
| first_indexed | 2024-12-21T17:17:03Z |
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| language | English |
| last_indexed | 2024-12-21T17:17:03Z |
| publishDate | 2018-07-01 |
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| series | Molecules |
| spelling | doaj.art-62b6b6fbb12946089ab4bd56fa785a6f2022-12-21T18:56:15ZengMDPI AGMolecules1420-30492018-07-01237162010.3390/molecules23071620molecules23071620Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 MacrophagesI-Jou Teng0Min-Chien Tsai1Shao-Fu Shih2Bi-Feng Tsuei3Hsin Chang4Yi-Ping Chuang5Chin-Sheng Lin6Ching-Yuh Chern7Sy-Jou Chen8Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei 11490, TaiwanDivision of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Applied Chemistry, National Chiayi University, Chiayi City 60004, TaiwanDepartment and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, TaiwanDivision of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Applied Chemistry, National Chiayi University, Chiayi City 60004, TaiwanDepartment of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanAtherosclerosis is a process of imbalanced lipid metabolism in the vascular walls. The underlying pathology mainly involves the deposition of oxidized lipids in the endothelium and the accumulation of cholesterol in macrophages. Macrophages export excessive cholesterol (cholesterol efflux) through ATP-binding cassette transporter A1 (ABCA1) to counter the progression of atherosclerosis. We synthesized novel chalcone derivatives and assessed their effects and the underlying mechanisms on ABCA1 expression in macrophages. Human THP-1 macrophages were treated with synthetic chalcone derivatives for 24 h. In Western blot and flow cytometry analyses, a chalcone derivative, (E)-1-(3,4-diisopropoxyphenyl)-3-(4-isopropoxy-3-methoxyphenyl)prop- 2-en-1-one (1m), was observed to significantly enhance ABCA1 protein expression in THP-1 cells (10 µM, 24 h). Levels of mRNA of ABCA1 and liver X receptor alpha (LXRα) were quantified using a real-time quantitative polymerase chain reaction technique and were found to be significantly increased after treatment with the novel chalcone derivative 1m. Several microRNAs, including miR155, miR758, miR10b, miR145, miR33, and miR106b, which functionally inhibit ABCA1 expression were suppressed after treatment with 1m. Collectively, 1m increases ABCA1 expression in human THP-1 macrophages. The mechanisms involve the activation of the LXRα-ABCA1 pathway and suppression of certain microRNAs that regulate ABCA1 expression.http://www.mdpi.com/1420-3049/23/7/1620atherosclerosischolesterol effluxATP-binding cassette transporters A1chalcone derivative |
| spellingShingle | I-Jou Teng Min-Chien Tsai Shao-Fu Shih Bi-Feng Tsuei Hsin Chang Yi-Ping Chuang Chin-Sheng Lin Ching-Yuh Chern Sy-Jou Chen Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages Molecules atherosclerosis cholesterol efflux ATP-binding cassette transporters A1 chalcone derivative |
| title | Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages |
| title_full | Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages |
| title_fullStr | Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages |
| title_full_unstemmed | Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages |
| title_short | Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages |
| title_sort | chalcone derivatives enhance atp binding cassette transporters a1 in human thp 1 macrophages |
| topic | atherosclerosis cholesterol efflux ATP-binding cassette transporters A1 chalcone derivative |
| url | http://www.mdpi.com/1420-3049/23/7/1620 |
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