title: Identification of human low-density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha.
abstract: Liver X receptor alpha (LXRalpha) 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 LXRalpha 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 LXRalpha/RXRalpha (retinoid X receptor alpha) heterodimers in hepatoblastoma cells. These results suggest a novel pathway whereby LXRalpha might modulate cholesterol metabolism.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishimoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tachibana
authors.forename: Mikako
authors.initials: M
authors.lastname: Sumitomo
authors.forename: Shiho
authors.initials: S
authors.lastname: Omote
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hanano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamasaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Takefumi
authors.initials: T
authors.lastname: Doi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D047490:Retinoid X Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D047490:Retinoid X Receptor alpha; D002784:Cholesterol