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Retinoid X Receptor

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https://www.readbyqxmd.com/read/28923935/retinoid-x-receptor-suppresses-a-metastasis-promoting-transcriptional-program-in-myeloid-cells-via-a-ligand-insensitive-mechanism
#1
Mate Kiss, Zsolt Czimmerer, Gergely Nagy, Pawel Bieniasz-Krzywiec, Manuel Ehling, Attila Pap, Szilard Poliska, Pal Boto, Petros Tzerpos, Attila Horvath, Zsuzsanna Kolostyak, Bence Daniel, Istvan Szatmari, Massimiliano Mazzone, Laszlo Nagy
Retinoid X receptor (RXR) regulates several key functions in myeloid cells, including inflammatory responses, phagocytosis, chemokine secretion, and proangiogenic activity. Its importance, however, in tumor-associated myeloid cells is unknown. In this study, we demonstrate that deletion of RXR in myeloid cells enhances lung metastasis formation while not affecting primary tumor growth. We show that RXR deficiency leads to transcriptomic changes in the lung myeloid compartment characterized by increased expression of prometastatic genes, including important determinants of premetastatic niche formation...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28895119/fxr-controls-chop-expression-in-steatohepatitis
#2
Claudia D Fuchs, Thierry Claudel, Hubert Scharnagl, Tatjana Stojakovic, Michael Trauner
The farnesoid X receptor (FXR) and C/EBP homologous protein (CHOP) have critical functions in hepatic lipid metabolism. Here, we aimed to explore a potential relationship between FXR and CHOP. We fed wild-type (WT) and FXR KO mice a MCD-diet (model of steatohepatitis) and found that Chop mRNA expression is upregulated in WT but not FXR KO mice. Absence of FXR aggravates hepatic inflammation after MCD feeding. In HepG2 cells, we found that Chop expression is regulated in a FXR/Retinoid X receptor (RXR)-dependent manner...
September 12, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28890360/synergistic-regulation-of-coregulator-nuclear-receptor-interaction-by-ligand-and-dna
#3
Ian Mitchelle S de Vera, Jie Zheng, Scott Novick, Jinsai Shang, Travis S Hughes, Richard Brust, Paola Munoz-Tello, William J Gardner, David P Marciano, Xiangming Kong, Patrick R Griffin, Douglas J Kojetin
Nuclear receptor (NR) transcription factors bind various coreceptors, small-molecule ligands, DNA response element sequences, and transcriptional coregulator proteins to affect gene transcription. Small-molecule ligands and DNA are known to influence receptor structure, coregulator protein interaction, and function; however, little is known on the mechanism of synergy between ligand and DNA. Using quantitative biochemical, biophysical, and solution structural methods, including (13)C-detected nuclear magnetic resonance and hydrogen/deuterium exchange (HDX) mass spectrometry, we show that ligand and DNA cooperatively recruit the intrinsically disordered steroid receptor coactivator-2 (SRC-2/TIF2/GRIP1/NCoA-2) receptor interaction domain to peroxisome proliferator-activated receptor gamma-retinoid X receptor alpha (PPARγ-RXRα) heterodimer and reveal the binding determinants of the complex...
August 23, 2017: Structure
https://www.readbyqxmd.com/read/28886987/consequences-of-the-natural-retinoid-retinoid-x-receptor-ligands-action-in-human-breast-cancer-mda-mb-231-cell-line-focus-on-functional-proteomics
#4
D Flodrova, L Toporova, M Lastovickova, D Macejova, L Hunakova, J Brtko, J Bobalova
The main intention of this study was the investigation of impact of natural biologically active ligands of nuclear retinoid/retinoid X receptors (all-trans and 9-cis retinoic acid) on proteomic pattern in human estrogen receptor negative breast cancer cell line MDA-MB-231. For this purpose, proteomic strategies based on bottom-up method were applied. The total cell proteins were extracted utilizing a commercially Radio-Immunoprecipitation Assay (RIPA) buffer and separated on 2D sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE)...
September 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28854753/proteomic-identification-of-turkey-meleagris-gallopavo-seminal-plasma-proteins
#5
M Slowinska, J Nynca, G J Arnold, T Fröhlich, J Jankowski, K Kozlowski, A Mostek, A Ciereszko
SDS-PAGE combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 2-dimensional electrophoresis (2DE) combined with matrix-assisted laser desorption/ionization time of flight/time of flight mass spectrometry (MALDI TOF/TOF) were applied to characterize the turkey seminal plasma proteome. LC-MS/MS led to the identification of 175 proteins, which were classified according to their function and to corresponding biochemical pathways. Using 2DE and MALDI TOF/TOF, 34 different turkey seminal plasma proteins could be identified, of which 20 were found in more than one spot, indicating different proteoforms of these proteins...
September 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28846104/berberine-binds-rxr%C3%AE-to-suppress-%C3%AE-catenin-signaling-in-colon-cancer-cells
#6
H Ruan, Y Y Zhan, J Hou, B Xu, B Chen, Y Tian, D Wu, Y Zhao, Y Zhang, X Chen, P Mi, L Zhang, S Zhang, X Wang, H Cao, W Zhang, H Wang, H Li, Y Su, X K Zhang, T Hu
Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28843100/differential-tissue-regulation-of-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-and-cannabinoid-receptor-1-cb1-gene-transcription-pathways-by-diethylene-glycol-dibenzoate-degb-preliminary-observations-in-a-seabream-sparus-aurata-in-vivo-model
#7
Paolo Cocci, Matteo Mozzicafreddo, Mauro Angeletti, Gilberto Mosconi, Francesco Alessandro Palermo
Today a variety of endocrine disrupting chemicals (EDCs) are recognized in the group of metabolic disruptors, a wide range of environmental contaminants that alter energy balance regulation by affecting the peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor (RXR) pathway. Herein, we investigated the effect of diethylene glycol dibenzoate (DEGB), a dibenzoate-based plasticizer used as alternative to phthalates, on the expression of key genes involved in lipid metabolism and energy balance by using Sparus aurata juveniles as models...
August 19, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28836501/effects-of-natural-ligands-and-synthetic-triorganotin-compounds-of-nuclear-retinoid-x-receptors-in-human-mcf-7-breast-cancer-cell-line
#8
Dana Macejova, Lucia Toporova, Julius Brtko
In the present study, we analyzed in vitro effects of natural and synthetic triorganotin ligands of nuclear retinoid X receptors in human MCF-7 breast cancer cells. Our data has shown that all-trans retinoic acid significantly reduced expression of RXRalpha mRNA, Bcl2 and enhanced expression of BAX proteins. Tributyltin bromide markedly decreased mRNA level of RXRalpha and RXRbeta. Significantly reduced levels of both RXRs proteins were observed after treatment with tributyltin chloride (TBT-Cl) but not after treatment with triphenyltin chloride (TPT-Cl) for RXRbeta protein...
August 24, 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/28816564/cytotoxicity-screening-and-cytokine-profiling-of-nineteen-nanomaterials-enables-hazard-ranking-and-grouping-based-on-inflammogenic-potential
#9
Kunal Bhattacharya, Gözde Kiliç, Pedro M Costa, Bengt Fadeel
Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free...
August 17, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28815487/benzophenone-3-impairs-autophagy-alters-epigenetic-status-and-disrupts-retinoid-x-receptor-signaling-in-apoptotic-neuronal-cells
#10
Agnieszka Wnuk, Joanna Rzemieniec, Władysław Lasoń, Wojciech Krzeptowski, Małgorzata Kajta
Benzophenone-3 (BP-3) is the most widely used compound among UV filters for the prevention of photodegradation. Population studies have demonstrated that it penetrates through the skin and crosses the blood-brain barrier. However, little is known about the impact of BP-3 on the nervous system and its possible adverse effects on the developing brain. We demonstrated that the neurotoxic effects of BP-3 were accompanied by the induction of apoptosis, as evidenced by apoptosis-related caspase-3 activation and apoptotic body formation as well as the inhibition of autophagy, as determined by the downregulation of autophagy-related genes, decreased autophagosome formation, and reduced LC3B-to-LC3A ratio...
August 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28804273/influence-of-the-number-of-axial-bexarotene-ligands-on-the-cytotoxicity-of-pt-iv-analogs-of-oxaliplatin
#11
Yulia N Nosova, Ilia V Zenin, Varvara P Maximova, Ekaterina M Zhidkova, Kirill I Kirsanov, Ekaterina A Lesovaya, Anna A Lobas, Mikhail V Gorshkov, Olga N Kovaleva, Elena R Milaeva, Markus Galanski, Bernhard K Keppler, Alexey A Nazarov
We present the synthesis and cytotoxic potencies of new Pt(IV) complexes with bexarotene, an anticancer drug that induces cell differentiation and apoptosis via selective activation of retinoid X receptors. In these complexes bexarotene is positioned as an axial ligand. The complex of one bexarotene ligand attached to Pt(IV) oxaliplatin moiety was potent whereas its counterpart carrying two bexarotene ligands was inactive.
2017: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/28800627/suppressive-effects-of-rxr-agonist-pa024-on-adrenal-cyp11b2-expression-aldosterone-secretion-and-blood-pressure
#12
Dai Suzuki, Akiko Saito-Hakoda, Ryo Ito, Kyoko Shimizu, Rehana Parvin, Hiroki Shimada, Erika Noro, Susumu Suzuki, Ikuma Fujiwara, Hiroyuki Kagechika, William E Rainey, Shigeo Kure, Sadayoshi Ito, Atsushi Yokoyama, Akira Sugawara
The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells...
2017: PloS One
https://www.readbyqxmd.com/read/28790326/intestinal-toxicity-of-the-type-b-trichothecene-mycotoxin-fusarenon-x-whole-transcriptome-profiling-reveals-new-signaling-pathways
#13
Imourana Alassane-Kpembi, Juliana Rubira Gerez, Anne-Marie Cossalter, Manon Neves, Joëlle Laffitte, Claire Naylies, Yannick Lippi, Martine Kolf-Clauw, Ana Paula L Bracarense, Philippe Pinton, Isabelle P Oswald
The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774779/extensive-and-functional-overlap-of-the-stat6-and-rxr-cistromes-in-the-active-enhancer-repertoire-of-human-cd14-monocyte-derived-differentiating-macrophages
#14
Zsolt Czimmerer, Zsuzsanna S Nagy, Gergely Nagy, Attila Horvath, Timea Silye-Cseh, Agnes Kriston, David Jonas, Sascha Sauer, Laszlo Steiner, Bence Daniel, Jean-Francois Deleuze, Laszlo Nagy
Macrophages are able to differentiate into classically polarized (M1) or alternatively polarized (M2) states upon encountering pro-inflammatory cytokines such as interferon (IFN) γ or anti-inflammatory cytokines such as interleukin (IL) -4/IL-13, respectively. Moreover, macrophages are known to regulate lipid metabolism via multiple members of the nuclear hormone receptor family, including the retinoid X receptors (RXR). It has been also documented that cytokines are able to modulate macrophage responses to lipid signals but the nature of these interactions and the underlying mechanisms of these processes especially at the level of the chromatinized genome are not well understood...
July 31, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28754339/interleukin-1-receptor-knockout-mice-develop-epidermal-cysts-and-show-an-altered-innate-immune-response-following-exposure-to-ultraviolet-b-radiation
#15
Nikhil N Kulkarni, Christopher A Adase, Ling-Juan Zhang, Andrew W Borkowski, Fengwu Li, James A Sanford, Daniel J Coleman, Carlos Aguilera, Arup K Indra, Richard L Gallo
In this study, we observed that mice lacking the interleukin 1 receptor (IL1r(-/-)), or deficient in interleukin 1-beta (IL1-β), developed multiple epidermal cysts after chronic ultraviolet B (UVB) exposure. Cysts that developed in IL1r(-/-) mice were characterized by the presence of the hair follicle marker Sox 9, keratins (K10 and K14) and normal melanocyte distribution and retinoid X receptor α (RXR α) expression. The increased incidence of cysts in IL1r(-/-) mice was associated with less skin inflammation as characterized by decreased recruitment of macrophages, and their skin also maintained epidermal barrier function compared to wild-type mice...
July 25, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28753292/synthesis-of-11-c-labeled-rxr-partial-agonist-1-3-5-5-8-8-pentamethyl-5-6-7-8-tetrahydronaphthalen-2-yl-amino-benzotriazole-5-carboxylic-acid-cbt-pmn-by-direct-11-c-carbon-dioxide-fixation-via-organolithiation-of-trialkyltin-precursor-and-pet-imaging-thereof
#16
Osamu Shibahara, Masaki Watanabe, Shoya Yamada, Masaru Akehi, Takanori Sasaki, Akiya Akahoshi, Takahisa Hanada, Hiroyuki Hirano, Shunsuke Nakatani, Hiromi Nishioka, Yasuo Takeuchi, Hiroki Kakuta
The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([(11)C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1...
August 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28740157/potentiation-of-17%C3%AE-estradiol-synthesis-in-the-brain-and-elongation-of-seizure-latency-through-dietary-supplementation-with-docosahexaenoic-acid
#17
Yasuhiro Ishihara, Kouichi Itoh, Miki Tanaka, Mayumi Tsuji, Toshihiro Kawamoto, Suguru Kawato, Christoph F A Vogel, Takeshi Yamazaki
Several studies have shown that docosahexaenoic acid (DHA) attenuates epileptic seizures; however, the molecular mechanism by which it achieves this effect is still largely unknown. DHA stimulates the retinoid X receptor, which reportedly regulates the expression of cytochrome P450 aromatase (P450arom). This study aimed to clarify how DHA suppresses seizures, focusing on the regulation of 17β-estradiol synthesis in the brain. Dietary supplementation with DHA increased not only the expression of P450arom, but also 17β-estradiol in the cerebral cortex...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714476/modulation-of-nongenomic-activation-of-pi3k-signalling-by-tetramerization-of-n-terminally-cleaved-rxr%C3%AE
#18
Liqun Chen, Alexander E Aleshin, Gulimiran Alitongbieke, Yuqi Zhou, Xindao Zhang, Xiaohong Ye, Mengjie Hu, Gaoang Ren, Ziwen Chen, Yue Ma, Duo Zhang, Shuai Liu, Weiwei Gao, Lijun Cai, Lingjuan Wu, Zhiping Zeng, Fuquan Jiang, Jie Liu, Hu Zhou, Gregory Cadwell, Robert C Liddington, Ying Su, Xiao-Kun Zhang
Retinoid X receptor-alpha (RXRα) binds to DNA either as homodimers or heterodimers, but it also forms homotetramers whose function is poorly defined. We previously discovered that an N-terminally-cleaved form of RXRα (tRXRα), produced in tumour cells, activates phosphoinositide 3-kinase (PI3K) signalling by binding to the p85α subunit of PI3K and that K-80003, an anti-cancer agent, inhibits this process. Here, we report through crystallographic and biochemical studies that K-80003 binds to and stabilizes tRXRα tetramers via a 'three-pronged' combination of canonical and non-canonical mechanisms...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28709983/sn-and-ge-triorganometallics-exert-different-cytotoxicity-and-modulation-of-migration-in-triple-negative-breast-cancer-cell-line-mda-mb-231
#19
COMPARATIVE STUDY
Luba Hunakova, Julius Brtko
Among a variety of metal containing organic compounds, tin derivatives are enjoying an increasing interest and appear to be very promising as potential drug candidates. We studied eight organometallic derivatives, nuclear retinoid X receptor (RXR) ligands and two germanium containing derivates that do not serve as RXR ligands. Tributylgermanium chloride (TBGe) and triphenylgermanium chloride (TPGe) did not inhibit growth of human triple negative MDA-MB-231 breast cancer cells. On the other hand, the tributyltin derivatives were highly, the triphenyltin derivatives less cytotoxic, both groups with IC50 values of nanomolar range...
September 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28708516/peroxisome-proliferator-activated-receptor-ppar-isoforms-are-differentially-expressed-in-peri-implantation-porcine-conceptuses
#20
Agnieszka Blitek, Magdalena Szymanska
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of ligand-dependent transcription factors. PPARs are critical regulators of glucose homeostasis and lipid metabolism, and affect cell proliferation and differentiation. In the current study, we examined (1) the profiles of PPARA, PPARD, and PPARG mRNA expression and DNA binding activity in porcine conceptuses collected on Days 10-11 (spherical and tubular conceptuses), 11-12 (filamentous conceptuses), 13-14, and 15-16 (elongated conceptuses) of pregnancy, (2) the presence of PPARA, PPARD, and PPARG proteins in Days 10, 12, and 15 conceptuses...
June 13, 2017: Theriogenology
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