Screening and identification of the upregulators of ATP-binding cassette transporter A1.
- Author:
Yan-Ni XU
1
;
Jie GAO
;
Yang XU
;
Ji-Kai LIU
;
Fang-Fang LAI
;
Ye-Xiang WU
;
Bin HONG
;
Shu-Yi SI
Author Information
1. National Center for Drug (Microbiology) Screening Laboratory, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter 1;
ATP-Binding Cassette Transporters;
genetics;
metabolism;
Animals;
Anticholesteremic Agents;
administration & dosage;
chemistry;
pharmacology;
Apolipoprotein A-I;
metabolism;
Benzaldehydes;
administration & dosage;
chemistry;
pharmacology;
Biological Transport;
Cells, Cultured;
Cholesterol;
secretion;
Dose-Response Relationship, Drug;
Hep G2 Cells;
High-Throughput Screening Assays;
Humans;
Lipid Metabolism;
Lipids;
analysis;
Macrophages, Peritoneal;
cytology;
metabolism;
Mice;
Molecular Structure;
RNA, Messenger;
Up-Regulation;
drug effects
- From:
Acta Pharmaceutica Sinica
2012;47(4):446-451
- CountryChina
- Language:Chinese
-
Abstract:
ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I (apoA-I), and plays a key role in the initial steps of the whole process of reverse cholesterol transport (RCT). Upregulation of ABCA1 is beneficial for atherosclerosis (AS) prevention and/or therapy, which indicated that ABCA1 was a target for anti-AS drug development. In the previous study, a high-throughput screening method was established using ABCA1p-LUC HepG2 cell line to find the upregulators of ABCA1. In the present study, compound 2030421B was found using this method, with EC50 of 0.50 microg x mL(-1). The compound was further identified as an upregulator of ABCA1 expression by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis. Studies also showed that the 2030421B could induce apoA-I-mediated cholesterol efflux and inhibit lipids uptake into mouse peritoneal macrophages RAW264.7.
