Identification of upregulators of human ATP-binding cassette transporter A1 via high-throughput screening of a synthetic and natural compound library

J Biomol Screen. 2008 Aug;13(7):648-56. doi: 10.1177/1087057108320545. Epub 2008 Jul 1.


The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by mediating the cellular efflux of cholesterol and phospholipids to lipid-poor apolipoprotein A-I. Therefore, identification of a novel upregulator of ABCA1 would be beneficial for atherosclerosis prevention and/or therapy because of its pivotal role in cholesterol homeostasis and HDL metabolism. In this study, a high-throughput assay method for ABCA1 upregulators was developed and used for screening a synthetic and natural compound library. The cell-based high-throughput screen is conducted in a 96-well format using the human hepatoma HepG2 cells stably transfected with ABCA1 promoter-luciferase construct and calibrated with reference ABCA1 upregulators (oxysterols, 9-cis-retinoic acid, thiazolidinediones, cyclic adenosine monophosphate, verapamil, fenofibrate, and oncostatin M). Among 2600 compounds, 4 microbial compounds (pyrromycin, aclarubicin, daidzein, and pratensein) were picked up as hits by the high-throughput screening assay, and those compounds were further identified as upregulators of ABCA1 expression by real-time quantitative reverse transcription-polymerase chain reaction and Western blot analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / biosynthesis*
  • Atherosclerosis / therapy
  • Cell Line, Tumor
  • Combinatorial Chemistry Techniques
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Membrane Transport Proteins
  • Models, Chemical
  • Peptide Library
  • Plasmids / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Technology, Pharmaceutical / methods
  • Transcription, Genetic
  • Transfection
  • Up-Regulation*


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Membrane Transport Proteins
  • Peptide Library