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Retinoid X Receptor

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https://www.readbyqxmd.com/read/28506627/rxrb-is-a-mhc-encoded-susceptibility-gene-associated-with-anti-topoisomerase-i-antibody-positive-systemic-sclerosis
#1
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
#2
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
#3
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
#4
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...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465354/egfr-inhibition-by-epigallocatechin-3-gallate%C3%A2-and-iif-treatments-reduces-breast-cancer-cell-invasion
#5
Fulvia Farabegoli, Marzia Govoni, Enzo Spisni, Alessio Papi
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 EGCG, the most active green tea catechin, in combination with 6-OH-11-O-hydroxyphenantrene (IIF), a synthetic retinoid X receptor-g (RXRg) 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, EMMPRIN, MMP-2, MMP-9 and TIMPs) were studied after EGCG and IIF treatments...
May 2, 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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28370539/rar%C3%AE-rxr-synergism-potentiates-retinoid-responsiveness-in-cutaneous-t-cell-lymphoma-cell-lines
#11
Lei Wang, Sebastian S DeMarco, Mary Stuart Peaks, Abigail L Maiorana-Boutilier, JianMing Chen, Miranda J Crouch, Brian M Shewchuk, Saame Raza Shaikh, Charles M Phillips, Lance C Bridges
Retinoids, natural and synthetic derivatives of vitamin A, induce cellular changes by activating nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Although the ability of retinoids to govern gene expression is exploited clinically for cancer therapeutics, the full benefit of retinoid-based strategies is unrealized due to detrimental side effects. Delineating the receptors that prompt cellular outcomes is critical to advancing retinoid-based approaches. Here we identify the receptors that evoke multiple responses in cutaneous T cell lymphoma (CTCL)...
March 31, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28348207/nurr1-rxr%C3%AE-heterodimer-activation-as-monotherapy-for-parkinson-s-disease
#12
Athanasios D Spathis, Xenophon Asvos, Despina Ziavra, Theodoros Karampelas, Stavros Topouzis, Zoe Cournia, Xiaobing Qing, Pavlos Alexakos, Lisa M Smits, Christina Dalla, Hardy J Rideout, Jens Christian Schwamborn, Constantin Tamvakopoulos, Demosthenes Fokas, Demetrios K Vassilatis
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the gradual depletion of dopamine (DA). Current treatments replenish the DA deficit and improve symptoms but induce dyskinesias over time, and neuroprotective therapies are nonexistent. Here we report that Nuclear receptor-related 1 (Nurr1):Retinoid X receptor α (RXRα) activation has a double therapeutic potential for PD, offering both neuroprotective and symptomatic improvement...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#13
Giuseppe Gallone, Wilfried Haerty, Giulio Disanto, Sreeram V Ramagopalan, Chris P Ponting, Antonio J Berlanga-Taylor
Large numbers of statistically significant associations between sentinel SNPs and case-control status have been replicated by genome-wide association studies. Nevertheless, few underlying molecular mechanisms of complex disease are currently known. We investigated whether variation in binding of a transcription factor, the vitamin D receptor (VDR), whose activating ligand vitamin D has been proposed as a modifiable factor in multiple disorders, could explain any of these associations. VDR modifies gene expression by binding DNA as a heterodimer with the Retinoid X receptor (RXR)...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28286734/identifying-the-receptor-subtype-selectivity-of-retinoid-x-and-retinoic-acid-receptors-via-quantum-mechanics
#14
Motonori Tsuji, Koichi Shudo, Hiroyuki Kagechika
Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28267642/fundamental-studies-of-adrenal-retinoid-x-receptor-protein-isoform-tissue-expression-subcellular-distribution-and-ligand-availability
#15
Behling Cheng, Fatema H Al-Shammari, Isra'a A Ghader, Fatima Sequeira, Jitendra Thakkar, Thazhumpal C Mathew
Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions...
March 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28262136/support-for-the-association-between-rora-gene-polymorphisms-and-the-dsm-5-posttraumatic-stress-disorder-symptoms-in-male-earthquake-survivors-in-china
#16
Chengqi Cao, Li Wang, Xing Cao, Chongya Dong, Ping Liu, Shu Luo, Hong Cui, Jun Yang, Jianxin Zhang
BACKGROUND: This study examined the association between interaction of retinoid-related orphan receptor alpha (RORA) (rs8042149) genotype x trauma exposure and post-traumatic stress disorder (PTSD) symptoms. METHODS: A total of 1196 Chinese adults who suffered from a deadly 2008 Wenchuan earthquake participated in this study. PTSD symptoms were measured with the PTSD Checklist for DSM-5 (PCL-5). A custom-by-design 2×48-Plex SNPscan™Kit were used to genotype the RORA rs8042149 SNP...
February 2017: Asian Journal of Psychiatry
https://www.readbyqxmd.com/read/28257826/structural-aspects-of-vitamin-d-endocrinology
#17
Natacha Rochel, Ferdinand Molnár
1α,25-Dihydroxvitamin D3 (1,25(OH)2D3) is the hormonally active form of vitamin D3. Its synthesis and its metabolites, their transport and elimination as well as action on transcriptional regulation involves the harmonic cooperation of diverse proteins with vitamin D binding capacities such as vitamin D binding protein (DBP), cytochrome P450 enzymes or the nuclear vitamin receptor (VDR). The genomic mechanism of 1,25(OH)2D3 action involves its binding to VDR that functionally acts as a heterodimer with retinoid X receptor...
February 28, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28254816/rxr-ligands-negatively-regulate-thrombosis-and-hemostasis
#18
Amanda J Unsworth, Gagan D Flora, Parvathy Sasikumar, Alexander P Bye, Tanya Sage, Neline Kriek, Marilena Crescente, Jonathan M Gibbins
OBJECTIVE: Platelets have been found to express intracellular nuclear receptors including the retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2; however, the effects on responses to other platelet agonists and the underlying mechanism have not been fully characterized. APPROACH AND RESULTS: The effect of 9-cis-retinoic acid, docosahexaenoic acid and methoprene acid on collagen receptor (glycoprotein VI [GPVI]) agonists and thrombin-stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilization, integrin αIIbβ3 outside-in signaling and thrombus formation in vitro and in vivo were determined...
May 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28251414/molecular-dynamics-simulations-and-molecular-flooding-studies-of-the-retinoid-x-receptor-ligand-binding-domain
#19
Geoffrey M Gray, Ning Ma, Carl E Wagner, Arjan van der Vaart
Bexarotene is an FDA approved retinoid X-receptor (RXR) agonist for the treatment of cutaneous T-cell lymphoma, and its use in other cancers and Alzheimer's disease is being investigated. The drug causes serious side effects, which might be reduced by chemical modifications of the molecule. To rationalize known agonists and to help identify sites for potential substitutions we present molecular simulations in which the RXR ligand-binding domain was flooded with a large number of drug-like molecules, and molecular dynamics simulations of a series of bexarotene-like ligands bound to the RXR ligand-binding domain...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28249598/the-prognostic-utility-of-the-transcription-factor-srf-in-docetaxel-resistant-prostate-cancer-in-vitro-discovery-and-in-vivo-validation
#20
D J Lundon, A Boland, M Prencipe, G Hurley, A O'Neill, E Kay, S T Aherne, P Doolan, S F Madden, M Clynes, C Morrissey, J M Fitzpatrick, R W Watson
BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel...
March 1, 2017: BMC Cancer
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