LXR (liver X receptor) and HNF-4 (hepatocyte nuclear factor-4): key regulators in reverse cholesterol transport.

Details

Serval ID
serval:BIB_6E860B1D0861
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
LXR (liver X receptor) and HNF-4 (hepatocyte nuclear factor-4): key regulators in reverse cholesterol transport.
Journal
Biochemical Society transactions
Author(s)
Crestani M., De Fabiani E., Caruso D., Mitro N., Gilardi F., Vigil Chacon A.B., Patelli R., Godio C., Galli G.
ISSN
0300-5127 (Print)
ISSN-L
0300-5127
Publication state
Published
Issued date
02/2004
Peer-reviewed
Oui
Volume
32
Number
Pt 1
Pages
92-96
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
Cholesterol homoeostasis is the result of the fine tuning between intake and disposal of this molecule. High levels of cholesterol in the blood are detrimental as they may lead to excessive accumulation in vessel walls, a condition predisposing to the development of atherosclerotic lesions. Cholesterol is removed from the vessel wall and transported to the liver through a process called reverse cholesterol transport. Nuclear receptors are among the most important transcription factors regulating genes involved in different steps of reverse cholesterol transport. Here, we discuss the role of the nuclear receptors LXR (liver X receptor) and HNF-4alpha (hepatocyte nuclear factor-4alpha) in different steps of reverse cholesterol transport. LXR controls the transcription of crucial genes in cholesterol efflux from macrophages and its transport to the liver, such as ABCA1 (ATP binding cassette A1), CYP27A1 (sterol 27-hydroxylase), CLA-1 (scavenger receptor type B1) and apolipoprotein E. Some oxysterols present in oxidized low-density lipoproteins and proinflammatory cytokines modulate the activity of LXR by antagonizing the effect of activators of this receptor, thus contributing to cholesterol accumulation in macrophages. Bile acid synthesis, which represents the final step of reverse cholesterol transport, is transcriptionally regulated by several nuclear receptors at the level of the liver-specific cytochrome P450 cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme of this metabolic pathway. Bile acids returning to the liver through the enterohepatic circulation down-regulate CYP7A1 transcription via the bile acid sensors farnesoid X receptor and HNF-4alpha. Based on this evidence, these nuclear receptors are candidate targets of new drugs for the treatment and prevention of atherosclerotic disease.
Keywords
Animals, Biological Transport, Cholesterol/metabolism, DNA-Binding Proteins/metabolism, Hepatocyte Nuclear Factor 4, Humans, Liver/metabolism, Phosphoproteins/metabolism, Receptors, Cytoplasmic and Nuclear/metabolism, Transcription Factors/metabolism
Pubmed
Web of science
Create date
21/03/2019 11:29
Last modification date
20/02/2020 6:26
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