Identification of human low-density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

Abstract 

Liver X receptor alpha (LXRα) is a member of the nuclear receptor superfamily that is activated by oxysterols, and plays a pivotal role in regulating the metabolism, transport and uptake of cholesterol. Here, we demonstrate that LXRα also regulates the low-density lipoprotein receptor (LDLR) gene, which mediates the endocytic uptake of LDL cholesterol in the liver. An LXR agonist induced the expression of LDLR in cultured hepatoblastoma cells. Moreover, the LDLR promoter contained an LXR response element that was recognized by LXRα/RXRα (retinoid X receptor alpha) heterodimers in hepatoblastoma cells. These results suggest a novel pathway whereby LXRα might modulate cholesterol metabolism.

Abbreviations: LDLR, low-density lipoprotein, LXR, liver X receptor, RXR, retinoid X receptor, SRE, sterol-regulatory element, SREBP, SRE-binding protein, HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A, DR4, direct repeat 4, LXRE, LXR response element, ABC, ATP-binding cassette, CYP7A, cholesterol 7α-hydoroxylase, LPDS, lipoprotein-deficient serum, 25-HC, 25-hydroxycholesterol, PCR, polymerase chain reaction, DMEM, Dulbecco’s Modified Eagle Medium, DMSO, dimethyl sulfoxide, CMV, cytomegalovirus

Keywords: Liver X receptor, Low-density lipoprotein receptor, Cholesterol, LXR response element, Nuclear receptor, SREBP