Cited by 1,233Cholesterol and Lipid MetabolismSteroid Chemistry and BiochemistryPeroxisome Proliferator-Activated Receptors

Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway

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Lehmann, Jürgen M., Kliewer, Steven A., Moore, Linda B., Smith-Oliver, Tracey A., Oliver, Beverly B., Su, Jui-Lan, Sundseth, Scott S., Winegar, Deborah A. +3 more·1997·Journal of Biological Chemistry

Abstract

Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7alpha-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRalpha and LXRbeta, two orphan members of the nuclear receptor superfamily, are activated by 24(S), 25-epoxycholesterol and 24(S)-hydroxycholesterol at physiologic concentrations. In addition, we have identified an LXR response element in the promoter region of the rat cholesterol 7alpha-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXRs play a critical role in the regulation of cholesterol homeostasis.

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Crossref · 10.1074/jbc.272.6.3137

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Authors
Lehmann, J. M., Kliewer, S. A., Moore, L. B., Smith-Oliver, T. A., Oliver, B. B., Su, J.-L., Sundseth, S. S., Winegar, D. A., Blanchard, D. E., Spencer, T. A., & Willson, T. M.
Affiliations
Dartmouth College (US)
Corresponding author
Lehmann, Jürgen M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-02
Volume
272
Issue
6
Pages
3137-3140
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2135007868
Cited by
1,233
References
3
Citations by year
2026: 17 · 2025: 21 · 2024: 27 · 2023: 32 · 2022: 28 · 2021: 25 · 2020: 33 · 2019: 36 · 2018: 27 · 2017: 33 · 2016: 25 · 2015: 31 · 2014: 35 · 2013: 52 · 2012: 54
FWCI
38.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl052069-04)
  • National Heart, Lung, and Blood Institute (HL52069)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
liver X receptor, liver X receptor alpha, LXRβ, oxysterols, 24S-hydroxycholesterol, CYP7A1, cholesterol homeostasis, bile acid synthesis, transcriptional regulation, nuclear receptors
MeSH terms
Liver X Receptors, Animals, Binding Sites, Cholesterol, Cholesterol 7-alpha-Hydroxylase, DNA-Binding Proteins, Dose-Response Relationship, Drug, Hydroxycholesterols, Promoter Regions, Genetic, Receptors, Cytoplasmic and Nuclear, Rats, Orphan Nuclear Receptors

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