FXRE can function as an LXRE in the promoter of human ileal bile acid‐binding protein (I‐BABP) gene

Landrier, Jean‐François; Grober, Jacques; Demydchuk, Julia; Besnard, Philippe

doi:10.1016/s0014-5793(03)01033-0

Cited by 22 publications

(12 citation statements)

References 20 publications

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“…Simultaneously, an LXR agonist influenced the SRE in the LDLR promoter. It is noteworthy that similar data have recently been reported for fatty acid synthase (FAS) [12] and ileal bile acid-binding protein (I-BABP) [13], suggesting that LXRE and SRE independently but additively confer the LXR responsiveness. In fact, we also investigated that T0901317 and pitavastatin can additively activate the LDLR promoter (data not shown).…”

Section: Lxra/rxra Heterodimers Bind Directly To the Lxre In The Ldlrsupporting

confidence: 65%

Identification of human low‐density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

et al. 2006

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Liver X receptor alpha (LXRa) 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 LXRa 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 LXRa/ RXRa (retinoid X receptor alpha) heterodimers in hepatoblastoma cells. These results suggest a novel pathway whereby LXRa might modulate cholesterol metabolism.

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Section: Lxra/rxra Heterodimers Bind Directly To the Lxre In The Ldlrsupporting

confidence: 65%

Identification of human low‐density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

et al. 2006

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“…LXREs have also been reported to be present in introns of target genes such as the ATP-binding cassette transporter G1 (ABCG1; Kennedy et al 2001, Sabol et al 2005. LXRs have been shown to activate gene expression via the IR-1 sequence for genes such as the human ileal bile acid-binding protein and the organic solute transporter (Landrier et al 2003, Okuwaki et al 2007. LXRs induce expression of the mouse Sult2a9 gene through binding to an IR-0 sequence in the promoter (Uppal et al 2007).…”

Section: Transcriptional Regulation By Lxrmentioning

confidence: 99%

Liver X receptor in cholesterol metabolism

Zhao¹,

Dahlman-Wright²

2009

Journal of Endocrinology

370

273

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The liver X receptors (LXRs) are nuclear receptors that are activated by endogenous oxysterols, oxidized derivatives of cholesterol. There are two isoforms of LXR, LXRa (NR1H3) and LXRb (NR1H2). Both LXRa and LXRb regulate gene expression by binding to DNA sequences associated with target genes as heterodimers with isoforms of the retinoid X receptor (RXR), RXRa (NR2B1), RXRb (NR2B2), and RXRg (NR2B3). LXRs act as cholesterol sensors: when cellular oxysterols accumulate as a result of increasing concentrations of cholesterol, LXR induces the transcription of genes that protect cells from cholesterol overload. In this review, we summarize the roles of LXRs in controlling cholesterol homeostasis, including their roles in bile acid synthesis and metabolism/excretion, reverse cholesterol transport, cholesterol biosynthesis and uptake, and cholesterol absorption/excretion in the intestine. The overlapping and distinct roles of the LXRa and LXRb isoforms, and the potential use of LXRs as attractive targets for treatment of cardiovascular disease are also discussed.

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“…In addition, BAs have been reported to activate a G-protein associate receptor, named after the fact G protein-coupled BA receptor 1 (also known as TGR5), which is expressed in many tissues including the gastrointestinal tract [42] . IBABP is also regulated by PPARα/β in humans but not mice [43] , and can also be indirectly up-regulated by cholesterol through the activation of sterol-responsive element-binding protein 1c (SREBP1c) by LXR [44] . ASBT is also regulated by PPARα [45] .…”

Section: Regulation Of Intestinal Ba Transportmentioning

confidence: 99%

Intestinal bile acid physiology and pathophysiology

Martínez‐Augustin¹,

Medina²

2008

WJG

138

114

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Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipathic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

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FXRE can function as an LXRE in the promoter of human ileal bile acid‐binding protein (I‐BABP) gene

Cited by 22 publications

References 20 publications

Identification of human low‐density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

Identification of human low‐density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

Liver X receptor in cholesterol metabolism

Intestinal bile acid physiology and pathophysiology

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