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Identification of novel human high-density lipoprotein receptor Up-regulators using a cell-based high-throughput screening assay.

Authors
  • Yang, Yuan
  • Zhang, Zhongbing
  • Jiang, Wei
  • Gao, Lei
  • Zhao, Guiyu
  • Zheng, Zhihui
  • Wang, Min
  • Si, Shuyi
  • Hong, Bin
Type
Published Article
Journal
Journal of Biomolecular Screening
Publisher
SAGE Publications
Publication Date
Mar 01, 2007
Volume
12
Issue
2
Pages
211–219
Identifiers
PMID: 17259591
Source
Medline
License
Unknown

Abstract

Scavenger receptor class B type I (SR-BI) is the high-affinity high-density lipoprotein (HDL) receptor, and CLA-1 is the human homologue of the murine SR-BI. CLA-1/SR-BI receptor has been suggested as a new preventative and/or therapeutic target for atherosclerosis due to its pivotal role in overall HDL cholesterol (HDL-C) metabolism and its antiatherogenic activity in vivo. To search for active compounds that can increase CLA-1 transcription, a novel cell-based assay was developed for application in high-throughput screening (HTS). Human hepatoma HepG2 cells were transfected with a CLA-1-promoter-luciferase reporter gene construct, and the stable transfected cell line was selected and named CLAp-LUC HepG2. With rosiglitazone as a positive control, this stable cell line was used to establish a specific CLA-1 gene expression assay in a 96-well microplate format. The evaluating parameter Z' value of 0.64 showed that this cell-based HTS assay was robust and reliable. Screening of 6000 microbial secondary metabolite crude extracts identified 8 positive strains. Between 2 identified CLA-1 up-regulators produced by actinomycete strain 04-4776, 4776B may stimulate not only the expression of CLA-1 on the transcriptional and translational levels but also the activity of CLA-1 to uptake the HDL-C in HepG2 cells. The active compounds originated from this HTS assay may be developed to drug candidates or lead compounds for new antiatherosclerosis agents.

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