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Retinoid X Receptor

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https://www.readbyqxmd.com/read/28205585/neuronally-directed-effects-of-rxr-activation-in-a-mouse-model-of-alzheimer-s-disease
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28099842/brown-adipogenic-reprogramming-induced-by-a-small-molecule
#12
Baoming Nie, Tao Nie, Xiaoyan Hui, Ping Gu, Liufeng Mao, Kuai Li, Ran Yuan, Jiashun Zheng, Haixia Wang, Ke Li, Shibing Tang, Yu Zhang, Tao Xu, Aimin Xu, Donghai Wu, Sheng Ding
Brown adipose tissue (BAT) has attracted considerable research interest because of its therapeutic potential to treat obesity and associated metabolic diseases. Augmentation of brown fat mass and/or its function may represent an attractive strategy to enhance energy expenditure. Using high-throughput phenotypic screening to induce brown adipocyte reprogramming in committed myoblasts, we identified a retinoid X receptor (RXR) agonist, bexarotene (Bex), that efficiently converted myoblasts into brown adipocyte-like cells...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28089347/virtual-screening-and-experimental-validation-identify-novel-modulators-of-nuclear-receptor-rxr%C3%AE-from-drugbank-database
#13
Dan Xu, Lijun Cai, Shangjie Guo, Lei Xie, Meimei Yin, Ziwen Chen, Hu Zhou, Ying Su, Zhiping Zeng, Xiaokun Zhang
Retinoid X receptor alpha (RXRα), an important ligand-dependent transcription factor, plays a critical role in the development of various cancers and metabolic and neurodegenerative diseases. Therefore, RXRα represents one of the most important targets in modern drug discovery. In this study, Drugbank 2.0 with 1280 old drugs were virtually screened by Glide according to the crystal structure of ligand-binding domain (LBP) of RXRα. 15 compounds selected were tested for their binding and transcriptional activity toward RXRα by Biacore and reporter gene assay, respectively...
December 26, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28088372/nanoformulation-of-dual-bexarotene-tailed-phospholipid-conjugate-with-high-drug-loading
#14
Ruiyu He, Yawei Du, Longbing Ling, Muhammad Ismail, Yongpeng Hou, Chen Yao, Xinsong Li
Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotene-tailed phospholipid (DBTP) conjugate based nanovesicles were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method...
March 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28069388/vitamin-d-receptor-deficit-induces-activation-of-renin-angiotensin-system-via-sirt1-modulation-in-podocytes
#15
Nirupama Chandel, Kamesh Ayasolla, Hongxiu Wen, Xiqian Lan, Shabirul Haque, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
Vitamin D receptor (VDR) deficient status has been shown to be associated with the activation of renin angiotensin system (RAS). We hypothesized that lack of VDR would enhance p53 expression in podocytes through down regulation of SIRT1; the former would enhance the transcription of angiotensinogen (Agt) and angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, and AT1R. In vitro studies, VDR knockout podocytes not only displayed up regulation p53 but also displayed enhanced expression of Agt, renin and AT1R...
January 6, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28054069/challenge-and-perspective-the-relevance-of-ultraviolet-uv-radiation-and-the-vitamin-d-endocrine-system-vdes-for-psoriasis-and-other-inflammatory-skin-diseases
#16
Jörg Reichrath, Roman Saternus, Thomas Vogt
During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites...
January 5, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28041731/analysis-of-bull-bos-taurus-seminal-vesicle-fluid-proteome-in-relation-to-seminal-plasma-proteome
#17
B Westfalewicz, M A Dietrich, A Mostek, A Partyka, W Bielas, W Niżański, A Ciereszko
The existing knowledge on the bull seminal vesicle proteome, a major seminal plasma constituent, and its relationship with seminal plasma is limited. This knowledge is prerequisite for a better understanding of seminal plasma variability, which is linked to semen quality. The objective of this study was to characterize the proteomes of seminal vesicle fluid and seminal plasma and to compare them to better understand the origin of seminal plasma proteins. We collected ejaculates and seminal vesicle fluid postmortem from 6 mature Holstein Friesian bulls...
March 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28007475/mechanisms-of-retinoic-acid-signaling-during-cardiogenesis
#18
REVIEW
Sonia Stefanovic, Stéphane Zaffran
Substantial experimental and epidemiological data have highlighted the interplay between nutritional and genetic factors in the development of congenital heart defects. Retinoic acid (RA), a derivative of vitamin A, plays a key role during vertebrate development including the formation of the heart. Retinoids bind to RA and retinoid X receptors (RARs and RXRs) which then regulate tissue-specific genes. Here, we will focus on the roles of RA signaling and receptors in gene regulation during cardiogenesis, and the consequence of deregulated retinoid signaling on heart formation and congenital heart defects...
December 19, 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/28003731/a-regulatory-sequence-from-the-retinoid-x-receptor-%C3%AE-gene-directs-expression-to-horizontal-cells-and-photoreceptors-in-the-embryonic-chicken-retina
#19
Maria K E Blixt, Finn Hallböök
PURPOSE: Combining techniques of episomal vector gene-specific Cre expression and genomic integration using the piggyBac transposon system enables studies of gene expression-specific cell lineage tracing in the chicken retina. In this work, we aimed to target the retinal horizontal cell progenitors. METHODS: A 208 bp gene regulatory sequence from the chicken retinoid X receptor γgene (RXRγ208) was used to drive Cre expression. RXRγ is expressed in progenitors and photoreceptors during development...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27993043/mechanisms-of-action-of-compounds-that-enhance-storage-lipid-accumulation-in-daphnia-magna
#20
Rita Jordão, Bruno Campos, Benjamín Piña, Romà Tauler, Amadeu M V M Soares, Carlos Barata
Accumulation of storage lipids in the crustacean Daphnia magna can be altered by a number of exogenous and endogenous compounds, like 20-hydroxyecdysone (natural ligand of the ecdysone receptor, EcR), methyl farnesoate, pyrirproxyfen (agonists of the methyl farnesoate receptor, MfR), and tributyltin (agonist of the retinoid X acid receptor, RXR). This effect, analogous to the obesogenic disruption in mammals, alters Daphnia's growth and reproductive investment. Here we propose that storage lipid accumulation in droplets is regulated in Daphnia by the interaction between the nuclear receptor heterodimer EcR:RXR and MfR...
December 20, 2016: Environmental Science & Technology
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