Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway

Jürgen M. Lehmann; Steven A. Kliewer; Linda B. Moore; Tracey A. Smith-Oliver; Beverly B. Oliver; Jui Lan Su; Scott S. Sundseth; Deborah A. Winegar; Daniel E. Blanchard; Thomas A. Spencer; Timothy M. Willson

doi:10.1074/jbc.272.6.3137

Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway

Jürgen M. Lehmann, Steven A. Kliewer, Linda B. Moore, Tracey A. Smith-Oliver, Beverly B. Oliver, Jui Lan Su, Scott S. Sundseth, Deborah A. Winegar, Daniel E. Blanchard, Thomas A. Spencer, Timothy M. Willson

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

1073 Scopus citations

Abstract

Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7α-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRα and LXRβ, 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 7α-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXR play a critical role in the regulation of cholesterol homeostasis.

Original language	English (US)
Pages (from-to)	3137-3140
Number of pages	4
Journal	Journal of Biological Chemistry
Volume	272
Issue number	6
DOIs	https://doi.org/10.1074/jbc.272.6.3137
State	Published - 1997

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway",

abstract = "Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7α-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRα and LXRβ, 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 7α-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXR play a critical role in the regulation of cholesterol homeostasis.",

author = "Lehmann, {J{\"u}rgen M.} and Kliewer, {Steven A.} and Moore, {Linda B.} and Smith-Oliver, {Tracey A.} and Oliver, {Beverly B.} and Su, {Jui Lan} and Sundseth, {Scott S.} and Winegar, {Deborah A.} and Blanchard, {Daniel E.} and Spencer, {Thomas A.} and Willson, {Timothy M.}",

year = "1997",

doi = "10.1074/jbc.272.6.3137",

language = "English (US)",

volume = "272",

pages = "3137--3140",

journal = "Journal of Biological Chemistry",

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T1 - Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway

AU - Lehmann, Jürgen M.

AU - Kliewer, Steven A.

AU - Moore, Linda B.

AU - Smith-Oliver, Tracey A.

AU - Oliver, Beverly B.

AU - Su, Jui Lan

AU - Sundseth, Scott S.

AU - Winegar, Deborah A.

AU - Blanchard, Daniel E.

AU - Spencer, Thomas A.

AU - Willson, Timothy M.

PY - 1997

Y1 - 1997

N2 - Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7α-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRα and LXRβ, 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 7α-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXR play a critical role in the regulation of cholesterol homeostasis.

AB - Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7α-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRα and LXRβ, 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 7α-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXR play a critical role in the regulation of cholesterol homeostasis.

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Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway

Abstract

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