Establishment of a drug screening model for identifying up-regulator of human high density lipoprotein receptor.
- Author:
Xiao-hui LIU
1
;
Bin HONG
;
Li-fei WANG
;
Yuan YANG
;
Shu-yi SI
;
Yuan LI
Author Information
- Publication Type:Journal Article
- MeSH: CD36 Antigens; Cholesterol Esters; metabolism; Drug Evaluation, Preclinical; methods; Gene Expression Regulation; drug effects; Humans; Hypolipidemic Agents; chemical synthesis; pharmacology; Lipoproteins, HDL; genetics; metabolism; RNA, Messenger; metabolism; RNA-Binding Proteins; Receptors, Immunologic; genetics; Receptors, Lipoprotein; genetics; Receptors, Scavenger; Scavenger Receptors, Class B; Transcription, Genetic; drug effects; Up-Regulation
- From: Acta Academiae Medicinae Sinicae 2004;26(4):354-358
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo establish a new drug screening model based on transcriptional regulation of human high density lipoprotein (HDL) receptor gene CD36 and LIMPII analogous-1 (CLA-1) for discovering up-regulator of this receptor.
METHODSThe upstream regulatory sequence of CLA-1 was obtained by polymerase chain reaction. A recombinant reporter plasmid pGL3-CLAP was constructed by inserting the regulatory sequence upstream of luciferase gene of pGL3-Basic. Human hepatoma cell line BEL-7402 was transfected with pGL3-CLAP. Samples were detected by testing luciferase activity of transfected BEL-7402 cells in microtiter wells.
RESULTSThe drug screening model was established and optimized. Significant difference was present between pGL3-CLAP and pGL3-Basic transfected BEL-7402 cells (P< 0.001), and coefficient of variation was less than 10%. After primary and secondary screening, 1 compounds and 3 fermentation extracts had up-regulating activities.
CONCLUSIONThis new drug screening model may be efficiently used to screen up-regulators of human HDL receptor expression, which might become lead compounds for new anti-atherosclerosis drugs.
