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Retinoid X Receptor

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https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#1
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)...
March 9, 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
#2
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
#3
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
#4
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
#5
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
#6
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 synthetic ligand for RXR, methoprene acid on collagen receptor (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...
March 2, 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
#7
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
#8
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
https://www.readbyqxmd.com/read/28243223/retinoid-x-receptors-intersect-the-molecular-clockwork-in-the-regulation-of-liver-metabolism
#9
REVIEW
Salvatore De Cosmo, Gianluigi Mazzoccoli
Liver metabolic pathways are driven by the biological clock, and appropriate timing of 24-h patterns of metabolic gene expression as well as anabolic/catabolic processes with wake-related activity/feeding and sleep-related resting/fasting cycles preserves hepatic healthiness. The interplay among the liver metabolic pathways and the molecular clockwork is geared by the nuclear receptors, and ligand-dependent transcription factors that gauge the cellular nutritional status and redox balance, bind hormones and metabolites, and modulate the transcription of thousands target genes through their DNA-binding domain...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28205585/neuronally-directed-effects-of-rxr-activation-in-a-mouse-model-of-alzheimer-s-disease
#10
M M Mariani, T Malm, R Lamb, T R Jay, L Neilson, B Casali, L Medarametla, G E Landreth
Alzheimer's disease (AD) is characterized by extensive neuron loss that accompanies profound impairments in memory and cognition. We examined the neuronally directed effects of the retinoid X receptor agonist bexarotene in an aggressive model of AD. We report that a two week treatment of 3.5 month old 5XFAD mice with bexarotene resulted in the clearance of intraneuronal amyloid deposits. Importantly, neuronal loss was attenuated by 44% in the subiculum in mice 4 months of age and 18% in layer V of the cortex in mice 8 months of age...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186459/bioactivity-of-carotenoids-chasms-of-knowledge
#11
Torsten Bohn
Carotenoid dietary intake, especially within fruits/vegetables and their plasma levels have been associated in many epidemiological studies with a reduced risk of several chronic diseases, including type-2 diabetes, cardiovascular diseases, several types of cancer, and agerelated macular degeneration. However, intervention trials with isolated carotenoids (as supplements) have fallen short of fulfi lling the hopes that were placed in these lipophilic pigments, often producing no positive or even adverse effects, such as increased lung cancer rate or total mortality...
February 10, 2017: International Journal for Vitamin and Nutrition Research. Journal International de Vitaminologie et de Nutrition
https://www.readbyqxmd.com/read/28174130/identification-and-expression-of-nuclear-receptor-genes-and-ecdysteroid-titers-during-nymphal-development-in-the-spider-agelena-silvatica
#12
Yoshiko Honda, Wataru Ishiguro, Mari H Ogihara, Hiroshi Kataoka, DeMar Taylor
Ecdysteroids play an essential role in the regulation of the molting processes of arthropods. Nuclear receptors of the spider Agelena silvatica that showed high homology with other arthropods especially in the functional domains were identified, two isoforms of ecdysone receptor (AsEcRA, AsEcRB), retinoid X receptor (AsRXR) and two isoforms of E75 (AsE75A, AsE75D). AsEcR and AsRXR mRNA did not show major changes in expression but occurred throughout the third instar nymphal stage. AsE75DBD was low or non-existent at first then showed a sudden increase from D7 to D10...
February 4, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28167758/microrna-10a-is-crucial-for-endothelial-response-to-different-flow-patterns-via-interaction-of-retinoid-acid-receptors-and-histone-deacetylases
#13
Ding-Yu Lee, Ting-Er Lin, Chih-I Lee, Jing Zhou, Yi-Hsuan Huang, Pei-Ling Lee, Yu-Tsung Shih, Shu Chien, Jeng-Jiann Chiu
Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic factors in the regulation of vascular physiology. This study aimed to elucidate the relationship between HDACs and miRs in the hemodynamic modulation of endothelial cell (EC) dysfunction. We found that miR-10a has the lowest expression among all examined shear-responsive miRs in ECs under oscillatory shear stress (OS), and a relatively high expression under pulsatile shear stress (PS). PS and OS alter EC miR-10a expression to regulate the expression of its direct target GATA6 and downstream vascular cell adhesion molecule (VCAM)-1...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28161411/structural-basis-for-the-inhibition-of-akr1b10-by-the-c3-brominated-ttnpb-derivative-uvi2008
#14
Francesc X Ruiz, Isidro Crespo, Susana Álvarez, Sergio Porté, Joan Giménez-Dejoz, Alexandra Cousido-Siah, André Mitschler, Ángel R de Lera, Xavier Parés, Alberto Podjarny, Jaume Farrés
UVI2008, a retinoic acid receptor (RAR) β/γ agonist originated from C3 bromine addition to the parent RAR pan-agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), is also a selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10). Thus, it might become a lead drug for the design of compounds targeting both activities, as an AKR1B10 inhibitor and RAR agonist, which could constitute a novel therapeutic approach against cancer and skin-related diseases...
February 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28129653/rxr%C3%AE-ligand-z-10-induces-pml-rar%C3%AE-cleavage-and-apl-cell-apoptosis-through-disrupting-pml-rar%C3%AE-rxr%C3%AE-complex-in-a-camp-independent-manner
#15
Lin Xu, Zhiping Zeng, Weidong Zhang, Gaoang Ren, Xiaobin Ling, Fengyu Huang, Peizhen Xie, Ying Su, Xiao-Kun Zhang, Hu Zhou
The major oncogenic driver of acute promyelocytic leukemia (APL) is the fusion protein PML-RARα originated from the chromosomal translocation t(15;17). All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARα. However, major issues including the resistance of ATRA and arsenic therapy still remain in APL clinical management. Here we showed that compound Z-10, a nitro-ligand of retinoid X receptor α (RXRα), strongly promoted the cAMP-independent apoptosis of both ATRA- sensitive and resistant NB4 cells via the induction of caspase-mediated PML-RARα degradation...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115699/similarities-and-differences-in-the-transcriptional-control-of-expression-of-the-mouse-tslp-gene-in-skin-epidermis-and-intestinal-epithelium
#16
Krishna Priya Ganti, Atish Mukherji, Milan Surjit, Mei Li, Pierre Chambon
We previously reported that selective ablation of the nuclear receptors retinoid X receptor (RXR)-α and RXR-β in mouse epidermal keratinocytes (RXR-αβ(ep-/-)) or a topical application of active vitamin D3 (VD3) and/or all-trans retinoic acid (RA) on wild-type mouse skin induces a human atopic dermatitis-like phenotype that is triggered by an increased expression of the thymic stromal lymphopoietin (TSLP) proinflammatory cytokine. We demonstrate here that in epidermal keratinocytes, unliganded heterodimers of vitamin D receptor (VDR)/RXR-α and retinoic acid receptor-γ (RAR-γ)/RXR-β are bound as repressing complexes to their cognate DNA-binding sequence(s) (DBS) in the TSLP promoter regulatory region...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28114934/effect-of-a-retinoid-x-receptor-partial-agonist-on-airway-inflammation-and-hyperresponsiveness-in-a-murine-model-of-asthma
#17
Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Naohiro Oda, Daisuke Morichika, Etsuko Murakami, Hikari Nakayama, Koichi Waseda, Mikio Kataoka, Hiroki Kakuta, Mitsune Tanimoto, Arihiko Kanehiro
BACKGROUND: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners-e.g., retinoic acid receptors (RARs), vitamin D receptors (VDRs), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). The NR family was recently associated with allergic diseases, but the role of RXRs in allergen-induced airway responses is not well defined...
January 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28111285/the-interrelationship-between-bile-acid-and-vitamin-a-homeostasis
#18
REVIEW
Ali Saeed, Mark Hoekstra, Martijn Oscar Hoeke, Janette Heegsma, Klaas Nico Faber
Vitamin A is a fat-soluble vitamin important for vision, reproduction, embryonic development, cell differentiation, epithelial barrier function and adequate immune responses. Efficient absorption of dietary vitamin A depends on the fat-solubilizing properties of bile acids. Bile acids are synthesized in the liver and maintained in an enterohepatic circulation. The liver is also the main storage site for vitamin A in the mammalian body, where an intimate collaboration between hepatocytes and hepatic stellate cells leads to the accumulation of retinyl esters in large cytoplasmic lipid droplet hepatic stellate cells...
January 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28105491/the-multi-faceted-role-of-retinoid-x-receptor-in-bone-remodeling
#19
REVIEW
María P Menéndez-Gutiérrez, Mercedes Ricote
Retinoid X receptors (RXRs) form a unique subclass within the nuclear receptor (NR) superfamily of ligand-dependent transcription factors. RXRs are obligatory partners for a number of other NRs, placing RXRs in a coordinating role at the crossroads of multiple signaling pathways. In addition, RXRs can function as self-sufficient homodimers. Recent advances have revealed RXRs as novel regulators of osteoclastogenesis and bone remodeling. This review outlines the versatility of RXR action in the control of transcription of bone-forming osteoblasts and bone-resorbing osteoclasts, both through heterodimerization with other NRs and through RXR homodimerization...
January 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28105175/analysis-of-transcription-profile-to-reveal-altered-signaling-pathways-following-the-overexpression-of-human-desumoylating-isopeptidase-2-in-pancreatic-cancer-cells
#20
Yu-Yin Fu, Yu-Huan Kang, Cong-Cong Shen, Rui-Xue Wang, Lin Yu, Xin-Yue Li, Dan-Dan Cui, Jin-Liang Yang, Yu-Qin Yao, Lan-Tu Gou
Human desumoylating isopeptidase 2 (DESI-2) is a member of the DESI family and contains a conserved PPPDE1 domain. Previous studies have demonstrated that DESI-2 overexpression may induce cell apoptosis. In the present study, differentially expressed genes were analyzed using a transcription microarray in DESI-2 overexpressing PANC-1 pancreatic cancer cells. A total of 45,033 genes were examined by microarray, which identified 1,766 upregulated and 1,643 downregulated genes. A series of altered signaling pathways were analyzed, in which certain essential signaling factors, including retinoid X receptor (RXR), BH3 interacting-domain death agonist, Ras homolog gene family member A (RhoA) and Rho-associated protein kinase, were further investigated at the protein level...
December 2016: Oncology Letters
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