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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cholesterol / metabolism
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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Gene Expression Regulation*
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Humans
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Liver X Receptors
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Orphan Nuclear Receptors
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Promoter Regions, Genetic
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, LDL / genetics
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Receptors, LDL / metabolism*
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Retinoid X Receptor alpha / chemistry
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Retinoid X Receptor alpha / genetics
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Retinoid X Receptor alpha / metabolism
Substances
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DNA-Binding Proteins
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Liver X Receptors
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NR1H3 protein, human
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear
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Receptors, LDL
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Retinoid X Receptor alpha
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Cholesterol