Liver X receptor a

Auboeuf, D., Rieusset, J., Fajas, L., Vallier, P., Frering, V., Riou, J. P., Staels, B., Auw-erx, J., Laville, M., and Vidal, H. (1997). Tissue Distribution and Quantification of the Expression of mRNAS of Peroxisome Proliferator-Activated Receptors and Liver X Receptor a in humans. Diabetes 46, 1319-1327. 

X receptor, famesoid X receptor a, farnesoid X receptor [I, liver X receptor a, liver X receptor [I, and vitamin D receptor. Pharmacological Reviews, 58, 742-759. 

For example, hepatocytes express LXR (liver X receptor), a nuclear receptor that senses the levels of oxysterols. When cellular cholesterol Increases in the liver, oxysterols are generated and activate LXR. Activated LXR stimulates the expression of cholesterol 7ct-hydroxylase, the key rate-limiting enzyme In the hepatic conversion of cholesterol Into bile acids, a major pathway for disposing of excess cholesterol from the body. LXR also stimulates the expression of the ABC proteins that export cholesterol Into the bile (ABCG5/8) or onto lipoproteins in the blood (ABCAl). In... 

The signalling pathways involved in the control of SREBP-lc expression are not clearly understood. However, Protein Kinase B (PKB) (Fleischmann and lynedjian, 2000 Porstmann et al., 2005) and Protein Kinase C X (Matsumoto et al., 2003 Taniguchi et al., 2006) are likely to be involved (Fleischmann and lynedjian, 2000). Moreover, the Liver X Receptor, a nuclear receptor highly expressed in the liver, also contributes to regulate SREBP-lc expression (Peet et al., 1998 Repa et al., 2000). In the last part of this chapter, we will see how PKB and LXR might be involved in the control of SREBP-lc expression in response to the dietary status. 

Several transcription factor-binding sites have been mapped in the CYP7A1 gene promoter, and most of these bind transcription factors that are members of the nuclear receptor superfamily (Table 2). Some of these receptors, notably the liver X receptor a (LXRa NR1H3) and peroxisome proliferator-activated receptor a (PPARa NRICI), bind to their target elements as heterodimers with retinoid X receptor a (RXRa NR2B1). 

Shibahara N, Masunaga Y, Iwano S, Yamazaki H, Kiyotani K, Kamataki T (2011) Human cytochrome P450 1A1 is a novel target gene of liver X receptor a. Drug Metab Pharmacokinet 26 451-457... 

Liver X receptor a bidirectionally transac-tivates human CYPlAl and CYP1A2 through two ci5-elements common to both genes. Toxicol Lett 215 16-24... 

Goodwin B, Watson MA, Kim H, Miao J, Kemper JK, Kliewer SA (2003) Differential regulation of rat and human CYP7A1 by the nuclear oxys-terol receptor liver X receptor-a. Mol Endocrinol 17 386-394... 

Janowski, B.A., Grogan, M.J., Jones, S.A., Wisely, G.B., Kliewer, S.A., Corey, E.J. and Mangelsdorf, D.J. (1999) Structural requirements of ligands for the oxysterol liver X receptors LXRa and LXRp. Proceedings of the National Academy of Sciences of the United States of America, 96, 266-271. 

A., Gustafsson, J.A. and Carlquist, M. (2003) The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands. The Journal of Biological Chemistry, 278, 38821-38828. 

Fukumoto, H., Deng, A., Irizarry, M.C., Fitzgerald, M.L., Rebeck, G.W. (2002) Induction of the cholesterol transport ABCAl in central nervous system cells by liver X receptor agonists increases secreted AP levels. J. Biol. Chem., 277, 48508-48513. 

Another receptor, LXR (Liver X receptor), also exists in alpha and beta forms, and acts as a receptor for cholesterol and its degradation products, which accumulate when cholesterol levels are high. LXRs are expressed in the liver and lower digestive tract, where they regulate cholesterol and bile-acid homeostasis. LXR-beta activates reverse cholesterol transport from the periphery to the liver. LXR-alpha, which is found in the liver, promotes catabolism in the liver and drives catabolism of cholesterol to BAs. Its activation in the liver increases... 

J. Fukuchl, J.M. Kokontls, R.A. Hllpakka, C.P. Chuu, S. Liao, Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells, Cancer Res. 64 (2004) 7686-7689. 

The Streptomyces strain that produces celastramycin A (1212) has also yielded celastramycin B (2166) (1225). Another Streptomyces sp. has afforded bischloro-anthrabenzoxocinone ((-)-BABX) (2167), which has antibacterial activity and inhibits ligand-binding activity of liver X receptors (1937). An example of a rare chlorinated anthraquinone is anthrasesamone C (2168), which was characterized in the Japanese plant Sesamum indicum (1938). The angucycline-type marmycin B... 

Abbreviations. AhR, aromatic hydrocarbon receptor TCDD, tetrachlorodibenzodioxin PXR, pregnenolone-16a-nitrile-X-receptor PCN, pregnenolone-16a-nitrile CAR, constitutive androstane receptor MC, methylcholanthrene PPARa, peroxisome proliferated-activated receptor-a FXR, famesoid-X-receptor LXR, liver-X-receptor RXR, retinod-X-receptor 5-HETE, 5-OH-eicosatetraenoic acid LTB4, leukotriene B4 13-HODE, hydroxyoctadecadienoic acid DMXAA, dimethylxan-thenone-4-acetic acid. 

The ecdysone receptor belongs to the same subfamily of nuclear receptors as the liver X receptor LXR, the famesoid X receptor FXR and the vitamin D receptor VDR [8,[48]. All these receptors bind steroid-related compounds (oxysterol, bile acids and vitamin D). A detailed sequence alignment and a phylogenetic analysis encompassing 19 EcR protein sequences of various arthropods has been perfcxmed by Bonneton et al [46]. We will summarize here the main issues of this study. 

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