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Molecules 2018, 23(7), 1620; https://doi.org/10.3390/molecules23071620

Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages

1
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan
2
Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei 11490, Taiwan
3
Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
4
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan
5
Department of Applied Chemistry, National Chiayi University, Chiayi City 60004, Taiwan
6
Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan
7
Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
I-Jou Teng and Min-Chien Tsai contribute equally to this work.
Ching-Yuh Chern and Sy-Jou Chen contribute equally to this work.
*
Author to whom correspondence should be addressed.
Received: 22 May 2018 / Revised: 20 June 2018 / Accepted: 29 June 2018 / Published: 3 July 2018
(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)
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Abstract

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. View Full-Text
Keywords: atherosclerosis; cholesterol efflux; ATP-binding cassette transporters A1; chalcone derivative atherosclerosis; cholesterol efflux; ATP-binding cassette transporters A1; chalcone derivative
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Teng, I.-J.; Tsai, M.-C.; Shih, S.-F.; Tsuei, B.-F.; Chang, H.; Chuang, Y.-P.; Lin, C.-S.; Chern, C.-Y.; Chen, S.-J. Chalcone Derivatives Enhance ATP-Binding Cassette Transporters A1 in Human THP-1 Macrophages. Molecules 2018, 23, 1620.

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