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

Kenji Ishimoto; Keisuke Tachibana; Mikako Sumitomo; Shiho Omote; Ikuko Hanano; Daisuke Yamasaki; Yuichiro Watanabe; Toshiya Tanaka; Takao Hamakubo; Juro Sakai; Tatsuhiko Kodama; Takefumi Doi

doi:10.1016/j.febslet.2006.08.010

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

Kenji Ishimoto, Keisuke Tachibana, Mikako Sumitomo, Shiho Omote, Ikuko Hanano, Daisuke Yamasaki, Yuichiro Watanabe, Toshiya Tanaka, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Takefumi Doi

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4929-4933
Number of pages	5
Journal	FEBS Letters
Volume	580
Issue number	20
DOIs	https://doi.org/10.1016/j.febslet.2006.08.010
Publication status	Published - 2006 Sep 4
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2006.08.010

Cite this

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title = "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.",

keywords = "Cholesterol, LXR response element, Liver X receptor, Low-density lipoprotein receptor, Nuclear receptor, SREBP",

author = "Kenji Ishimoto and Keisuke Tachibana and Mikako Sumitomo and Shiho Omote and Ikuko Hanano and Daisuke Yamasaki and Yuichiro Watanabe and Toshiya Tanaka and Takao Hamakubo and Juro Sakai and Tatsuhiko Kodama and Takefumi Doi",

note = "Funding Information: We thank Dr. David J. Mangelsdorf of the Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center for kindly providing the human LXRα expression vector. We also thank Dr. Yoshiharu Matsuura of Research Institute for Microbial Diseases at Osaka University for kindly providing FLC4 cells. This study was supported by the Program of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), by Focus 21 project of New Energy and Industrial Technology development Organization (NEDO) and by Special Coordination Fund for Science and Technology from Ministry of Education, Culture, Sports, Science and Technology.",

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doi = "10.1016/j.febslet.2006.08.010",

language = "English",

volume = "580",

pages = "4929--4933",

journal = "FEBS Letters",

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T1 - Identification of human low-density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

AU - Ishimoto, Kenji

AU - Tachibana, Keisuke

AU - Sumitomo, Mikako

AU - Omote, Shiho

AU - Hanano, Ikuko

AU - Yamasaki, Daisuke

AU - Watanabe, Yuichiro

AU - Tanaka, Toshiya

AU - Hamakubo, Takao

AU - Sakai, Juro

AU - Kodama, Tatsuhiko

AU - Doi, Takefumi

N1 - Funding Information: We thank Dr. David J. Mangelsdorf of the Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center for kindly providing the human LXRα expression vector. We also thank Dr. Yoshiharu Matsuura of Research Institute for Microbial Diseases at Osaka University for kindly providing FLC4 cells. This study was supported by the Program of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), by Focus 21 project of New Energy and Industrial Technology development Organization (NEDO) and by Special Coordination Fund for Science and Technology from Ministry of Education, Culture, Sports, Science and Technology.

PY - 2006/9/4

Y1 - 2006/9/4

N2 - 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.

AB - 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.

KW - Cholesterol

KW - LXR response element

KW - Liver X receptor

KW - Low-density lipoprotein receptor

KW - Nuclear receptor

KW - SREBP

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

Abstract

Keywords

ASJC Scopus subject areas

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