Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway
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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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LXR activation induces HDL particle formation through apoe and abca1 expression.
“LXR activation induces HDL particle formation through apoe and abca1 expression (Lehmann et al., 1997; Tall, 2008).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Lehmann et al., 1997
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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
- hybrid
- doi.org
- Licence
- 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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