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Retinoid X Receptor

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https://www.readbyqxmd.com/read/28627642/effect-of-retinoid-x-receptor-%C3%AE-nuclear-export-inhibition-on-apoptosis-of-neurons-in%C3%A2-vivo-and-in%C3%A2-vitro
#1
Yingchun Liu, Jiangguo Tang, Xiaoxiao Gao, Min Wang, Jie Shen, Xiaoqing You
Alzheimer's disease (AD), which is characte-rized by excessive apoptosis of neurons, is considered to be a global public health crisis. Retinoid-induced apoptosis is dependent on the orphan nuclear receptor Nur77, a transcription factor that is expressed predominantly in brain tissues. Nur77 nuclear export requires retinoid X receptor‑α (RXRα) as a carrier. However, the involvement of Nur77 in mediating β‑amyloid (Aβ)‑induced neuronal apoptosis has not yet been elucidated. The primary aim of the present study was to investigate the potential of Nur77 in Aβ‑induced neuron apoptosis, and to evaluate the effect of RXRα nuclear export inhibition on neuronal apoptosis...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28611979/impact-of-preferentially-expressed-antigen-of-melanoma-on-the-prognosis-of-hepatocellular-carcinoma
#2
Kenji Oyama, Keita Kanki, Hiroki Shimizu, Yohei Kono, Junya Azumi, Kan Toriguchi, Etsuro Hatano, Goshi Shiota
BACKGROUND: Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. METHODS: PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection...
March 2017: Gastrointestinal Tumors
https://www.readbyqxmd.com/read/28611266/retinoid-x-receptor-%C3%AE-dependent-hbv-minichromosome-remodeling-and-viral-replication
#3
Yan Zhang, Song He, Jin-Jun Guo, Hong Peng, Jia-Hao Fan, Qing-Ling Li
BACKGROUND AND AIM: The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. MATERIAL AND METHODS: This study investigated RXRα involvement in HBV cccDNA epigenetic modifications...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28601022/nrf2-induces-lipocyte-phenotype-via-a-socs3-dependent-negative-feedback-loop-on-jak2-stat3-signaling-in-hepatic-stellate-cells
#4
Chunfeng Lu, Wenxuan Xu, Jiangjuan Shao, Feng Zhang, Anping Chen, Shizhong Zheng
Hepatic stellate cells (HSCs) are universally acknowledged to play a core role in the pathogenesis of hepatic fibrosis. HSCs when activated are characterized by dramatic loss of intracellular lipid droplets. Accumulative evidence has suggested that recovery of lipid droplets could suppress HSC activation. However, the underlying molecular mechanisms still remain largely unclear. In this study, we found that the expression and activity of nuclear factor (erythroid-derived 2) - like 2 (Nrf2) were decreased in activated HSCs and negatively correlated with hepatic fibrosis severity in human liver specimens...
June 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28560450/upregulation-of-socs3-in-lung-cd4-t-cells-in-a-mouse-model-of-chronic-pa-lung-infection-and-suppression-of-th17%C3%A2-mediated-neutrophil-recruitment-in-exogenous-socs3-transfer-in-vitro
#5
Feng-Ming Ding, Ruo-Min Liao, Yu-Qing Chen, Guo-Gang Xie, Peng-Yu Zhang, Ping Shao, Min Zhang
Neutrophilic airway inflammation in chronic lung infections caused by Pseudomonas aeruginosa (PA) is associated with T helper (Th)17 responses. Suppressor of cytokine signaling 3 (SOCS3) is the major negative modulator of Th17 function through the suppression of signal transducer and activator of transcription (STAT)3 activation. The aim of the present study was to investigate the expression of SOCS3 in lung CD4+ T cells in a mouse model of chronic PA lung infection and the effect of exogenous SOCS3 on Th17‑mediated neutrophil recruitment in vitro...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28560446/prediction-of-marker-genes-associated-with-hypertension-by-bioinformatics-analyses
#6
Yuan Gao, Guo-Xian Qi, Zhi-Mei Jia, Ying-Xian Sun
This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses. A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed...
May 25, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28551182/identification-and-functional-analysis-of-bull-bos-taurus-cauda-epididymal-fluid-proteome
#7
B Westfalewicz, M A Dietrich, A Mostek, A Partyka, W Bielas, W Niżański, A Ciereszko
Despite recent advances in bull epididymal fluid proteome research, significant numbers of proteins secreted to epididymal lumen remain unidentified. The objective of this study was to expand the number of identified cauda epididymal fluid proteins in bulls and to contextualize them in a broader view of their mutual interactions and involvement in biological processes and pathways, to fully elucidate the ways in which epididymal fluid proteins are involved in storage and maturation of spermatozoa in epididymis...
May 24, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28535483/cloning-and-functional-characterization-of-a-retinoid-x-receptor-orthologue-in-platynereis-dumerilii-an-evolutionary-and-toxicological-perspective
#8
Ana André, Raquel Ruivo, Ana Capitão, Elsa Froufe, Inês Páscoa, Luís Filipe Costa Castro, Miguel Machado Santos
In the present work we provide the first isolation and functional characterization of a RXR orthologue in an annelid species, the Platynereis dumerilii. Using an in vitro luciferase reporter assay we evaluated the annelid receptor ability to respond to ligand 9-cis-retinoic acid, TBT and TPT. Our results show that the annelid RXR responds to 9-cis-retinoic acid and to the organotins by activating reporter gene transcription. The findings suggest a conserved mode of action of the receptor in response to a common signaling molecule and modulation by organotin compounds between vertebrates and Lophotrochozoans...
May 20, 2017: Chemosphere
https://www.readbyqxmd.com/read/28534485/pseudoexfoliation-syndrome-associated-genetic-variants-affect-transcription-factor-binding-and-alternative-splicing-of-loxl1
#9
Francesca Pasutto, Matthias Zenkel, Ursula Hoja, Daniel Berner, Steffen Uebe, Fulvia Ferrazzi, Johannes Schödel, Panah Liravi, Mineo Ozaki, Daniela Paoli, Paolo Frezzotti, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Shinichi Manabe, Erika Salvi, Paolo Manunta, Daniele Cusi, Christian Gieger, Heinz-Erich Wichmann, Tin Aung, Chiea Chuen Khor, Friedrich E Kruse, André Reis, Ursula Schlötzer-Schrehardt
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534193/antagonist-perturbation-mechanism-for-activation-function-2-fixed-motifs-active-conformation-and-docking-mode-of-retinoid-x-receptor-antagonists
#10
Motonori Tsuji
HX531, which contains a dibenzodiazepine skeleton, is one of the first retinoid X receptor (RXR) antagonists. Functioning via RXR-PPARγ heterodimer, this compound is receiving a lot of attention as a therapeutic drug candidate for diabetic disease controlling differentiation of adipose tissue. However, the active conformation of HX531 for RXRs is not well established. In the present study, quantum mechanics calculations and molecular mechanical docking simulations were carried out to precisely study the docking mode of HX531 with the human RXRα ligand-binding domain, as well as to provide a new approach to drug design using a structure-based perspective...
May 22, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28506627/rxrb-is-a-mhc-encoded-susceptibility-gene-associated-with-anti-topoisomerase-i-antibody-positive-systemic-sclerosis
#11
Akira Oka, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Masataka Kuwana, Yasushi Kawaguchi, Toshiyuki Yamamoto, Hiroki Takahashi, Daisuke Goto, Hirahito Endo, Masatoshi Jinnin, Shuhei Mano, Kazuyoshi Hosomichi, Tomotaka Mabuchi, Mahoko Takahashi Ueda, So Nakagawa, Stephan Beck, Seiamak Bahram, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn
Systemic sclerosis (SSc) is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen (HLA) locus. However, the functional relationship between HLA gene(s) and disease development remains unknown. To elucidate major histocompatibility complex (MHC)-linked SSc genetics, we performed genotyping of MHC-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed 2 MHC haplotypes associated with SSc...
May 12, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28503816/xanthophylls-increased-hdlc-level-and-nuclear-factor-ppar%C3%AE-rxr%C3%AE-and-rar%C3%AE-expression-in-hens-and-chicks
#12
Y-Y Gao, L Jin, H Peng, L-H Xu, Q-X Wang, J Ji, C-K Wang, Y-Z Bi
This study was designed to investigate effects of xanthophylls on serum lipid profile (triglyceride, TG; cholesterol, CHO; high-density lipoprotein cholesterol, HDLC; and low-density lipoprotein cholesterol, LDLC) and nuclear factor (peroxisome proliferator-activated receptor gamma, PPARγ; PPAR gamma coactivator 1 alpha, PGC1α; retinoid X receptor gamma, RXRγ; and retinoic acid receptor alpha, RARα) gene expression of breeding hens and chicks. In experiment 1, 432 hens were divided into three groups and fed diets supplemented with 0 (as control group), 20 or 40 mg/kg xanthophylls...
May 15, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28488421/retinoic-acid-modulates-lipid-accumulation-glucose-concentration-dependently-through-inverse-regulation-of-srebp-1-expression-in-3t3l1-adipocytes
#13
Mabrouk Attia Abd Eldaim, Shinya Matsuoka, Yuko Okamatsu-Ogura, Akihiro Kamikawa, Mohamed Mohamed Ahmed, Akira Terao, Kei-Ichi Nakajima, Kazuhiro Kimura
It is well known that retinoic acid (RA) suppresses adipogenesis, although there are some contradicting reports. In this study, we examined the effect of extracellular glucose on RA-induced suppression of adipogenesis in 3T3L1 cell culture. When the cells were cultured in normal glucose medium (NG), the addition of RA suppressed lipid accumulation. However, when cultured in high glucose medium (HG), addition of RA to the cells enhanced lipid accumulation. These changes were accompanied by parallel alterations in fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1 gene expression...
May 10, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28465486/overexpression-of-sphk2-contributes-to-atra-resistance-in-colon-cancer-through-rapid-degradation-of-cytoplasmic-rxr%C3%AE-by-k48-k63-linked-polyubiquitination
#14
Wen-Na Shi, Shu-Xiang Cui, Zhi-Yu Song, Shu-Qing Wang, Shi-Yue Sun, Xin-Feng Yu, Ye Li, Yu-Hang Zhang, Zu-Hua Gao, Xian-Jun Qu
The resistance mechanisms that limit the efficacy of retinoid therapy in cancer are poorly understood. Sphingosine kinase 2 (SphK2) is a highly conserved enzyme that is mainly located in the nucleus and endoplasmic reticulum. Unlike well-studied sphingosine kinase 1 (SphK1) located in the cytosol, little has yet understood the functions of SphK2. Here we show that SphK2 overexpression contributes to the resistance of all-trans retinoic acid (ATRA) therapy in colon cancer through rapid degradation of cytoplasmic retinoid X receptor α (RXRα) by lysine 48 (K48)- and lysine 63 (K63)-based polyubiquitination...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465354/egfr-inhibition-by-epigallocatechin-3-gallate-and-iif-treatments-reduces-breast-cancer-cell-invasion
#15
Fulvia Farabegoli, Marzia Govoni, Enzo Spisni, Alessio Papi
Epidermal growth factor receptor (EGFR) expression is an important marker in breast carcinoma pathology and is considered a pivotal molecule for cancer cell proliferation, invasion and metastasis. We investigated the effects of epigallocatechin-3-gallate (EGCG), the most active green tea catechin, in combination with 6-OH-11-O-hydroxyphenanthrene (IIF), a synthetic retinoid X receptor-γ (RXRγ) agonist, on three breast carcinoma cell lines: MCF-7, MCF-7TAM and MDA-MB-231. EGFR and AKT activation and molecular markers of cell motility and migration (CD44, extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMPs)) were studied after EGCG and IIF treatments...
June 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28427429/vitamin-d-receptor-retinoid-x-receptor-and-peroxisome-proliferator-activated-receptor-%C3%AE-are-overexpressed-in-brca1-mutated-breast-cancer-and-predict-prognosis
#16
Sabine Heublein, Doris Mayr, Alfons Meindl, Alexandra Kircher, Udo Jeschke, Nina Ditsch
BACKGROUND: BRCA1 mutated breast cancers are commonly diagnosed as negative for classical hormone receptors i.e. estrogen receptor, progesterone receptor and/or Her2. Due to these common targets being absent the application of anti-endocrine therapies is rather limited and a certain focus has been set on discovering alternative target molecules. We recently highlighted thyroid hormone receptors (TRs) to predict prognosis in breast cancer patients that had been diagnosed a BRCA1 germline mutation...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28426724/cloning-retinoid-and-peroxisome-proliferator-activated-nuclear-receptors-of-the-pacific-oyster-and-in-silico-binding-to-environmental-chemicals
#17
Susanne Vogeler, Tamara S Galloway, Michail Isupov, Tim P Bean
Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor's functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species...
2017: PloS One
https://www.readbyqxmd.com/read/28420144/retinoids-regulate-adipogenesis-involving-the-tgf%C3%AE-smad-and-wnt-%C3%AE-catenin-pathways-in-human-bone-marrow-mesenchymal-stem-cells
#18
Jun Cao, Yuhong Ma, Weiqi Yao, Xiaoye Zhang, Dongcheng Wu
Retinoids may regulate cell differentiation as ligands of retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein β (C/EBPβ) in the early stages, but blocked adipogenesis at a later stage in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted adipogenesis at all time points in hBMSCs. The effect of RAR agonists was mediated mainly by the RARβ subtype. RAR agonists, in contrast to RXR agonists, significantly promoted the expression of RARβ...
April 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28407400/designed-spiroketal-protein-modulation
#19
Marcel Scheepstra, Sebastian A Andrei, M Yagiz Unver, Anna K H Hirsch, Seppe Leysen, Christian Ottmann, Luc Brunsveld, Lech-Gustav Milroy
Spiroketals are structural motifs found in many biologically active natural products, which has stimulated considerable efforts toward their synthesis and interest in their use as drug lead compounds. Despite this, the use of spiroketals, and especially bisbenzanulated spiroketals, in a structure-based drug discovery setting has not been convincingly demonstrated. Herein, we report the rational design of a bisbenzannulated spiroketal that potently binds to the retinoid X receptor (RXR) thereby inducing partial co-activator recruitment...
May 8, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28394474/proteomic-identification-of-rainbow-trout-blood-plasma-proteins-and-their-relationship-to-seminal-plasma-proteins
#20
Joanna Nynca, G J Arnold, T Fröhlich, A Ciereszko
The characterization of fish blood proteomes is important for comparative studies of seminal and blood proteins as well as for the analysis of fish immune mechanisms and pathways. In this study LC-MS/MS and 2D DIGE were applied to compare rainbow trout seminal (SP) and blood plasma (BP) proteomes. The 54 differentially abundant proteins identified in SP are involved in a variety of signalling pathways, including protein ubiquitination, liver X receptor/retinoid X receptor (LXR/RXR) and farnesoid X receptor (FXR)/RXR activation, cell cycle and acute phase signalling...
April 10, 2017: Proteomics
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