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Retinoid X Receptor

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https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#1
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29133527/interaction-of-the-phosphorylated-dna-binding-domain-in-nuclear-receptor-car-with-its-ligand-binding-domain-regulates-car-activation
#2
Ryota Shizu, Jungki Min, Mack Sobhany, Lars C Pedersen, Shingo Mutoh, Masahiko Negishi
The nuclear protein constitutive active/androstane receptor (CAR or NR1I3) regulates several liver functions such as drug and energy metabolism and cell growth or death, which are often involved in the development of diseases such as diabetes and hepatocellular carcinoma. CAR undergoes a conversion from inactive homodimers to active heterodimers with retinoid X receptor alpha (RXRα), and phosphorylation of the DNA-binding domain (DBD) at Thr-38 in CAR regulates this conversion. Here, we uncovered the molecular mechanism by which this phosphorylation regulates the intramolecular interaction between CARs DBD and ligand-binding domain (LBD), enabling the homodimer-heterodimer conversion...
November 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29128212/liver-proteomic-analysis-of-postpartum-holstein-cows-exposed-to-heat-stress-or-cooling-conditions-during-the-dry-period
#3
Amy L Skibiel, Maya Zachut, Bruno C do Amaral, Yishai Levin, Geoffrey E Dahl
Heat stress negatively affects cow performance, compromises immune function, and increases susceptibility to metabolic disorders, particularly during the dry period and as cows transition from gestation to lactation. Metabolic adaptations of the liver are critical for successful transition, yet it is unclear how heat stress affects metabolic pathways within the liver at the proteomic level. The objective of this study was to investigate the liver proteome of postpartum cows that were cooled or heat stressed during the dry period to gain insight into how protein expression is altered by prior heat stress and may contribute to performance and disease outcomes...
November 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29127736/liver-x-receptor-activation-inhibits-sglt2-mediated-glucose-transport-in-human-renal-proximal-tubular-cells
#4
Pattira Chonlaket, Teerasak Wongwan, Sunhapas Soodvilai
Liver X receptors (LXRs) are members of a nuclear receptor family consisting of two isoforms, LXR-α and LXR-β. They play a major role in energy metabolism including lipid and glucose metabolism. Recent studies reported LXRs regulate plasma glucose although the mechanism is still uncertain. The present study investigated whether LXR activation regulates sodium glucose cotransporter2 (SGLT2) in human renal proximal tubular cells. LXR agonists, T0901317 and GW3965, inhibited SGLT2-mediated glucose uptake in concentration-dependent manners...
November 11, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29127362/functional-analysis-of-vdr-gene-mutation-r343h-in-a-child-with-vitamin-d-resistant-rickets-with-alopecia
#5
Min-Hua Tseng, Shih-Ming Huang, Fu-Sung Lo, Jing-Long Huang, Chih-Jen Cheng, Hwei-Jen Lee, Shih-Hua Lin
The functional study of different mutations on vitamin D receptor (VDR) gene causing hereditary vitamin D-resistant rickets (HVDRR) remains limited. This study was to determine the VDR mutation and the mechanisms of this mutation-causing phenotype in a family with HVDRR and alopecia. Phenotype was analyzed, and in vitro functional studies were performed. The proband and his affected sister exhibited typical HVDRR with alopecia, and their biochemical and radiographic abnormalities but not alopecia responded to supraphysiological doses of active vitamin D3...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29126514/structural-and-functional-evidences-for-the-interactions-between-nuclear-hormone-receptors-and-endocrine-disruptors-at-low-doses
#6
Patrick Balaguer, Vanessa Delfosse, Marina Grimaldi, William Bourguet
Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities...
September 2017: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/29121869/ablation-of-epidermal-rxr%C3%AE-in-cooperation-with-activated-cdk4-and-oncogenic-nras-generates-spontaneous-and-acute-neonatal-uvb-induced-malignant-metastatic-melanomas
#7
Sharmeen Chagani, Rong Wang, Evan L Carpenter, Christiane V Löhr, Gitali Ganguli-Indra, Arup K Indra
BACKGROUND: Understanding the underlying molecular mechanisms involved in the formation of cutaneous malignant melanoma is critical for improved diagnosis and treatment. Keratinocytic nuclear receptor Retinoid X Receptor α (RXRα) has a protective role against melanomagenesis and is involved in the regulation of keratinocyte and melanocyte homeostasis subsequent acute ultraviolet (UV) irradiation. METHODS: We generated a trigenic mouse model system (RXRα (ep-/-) | Tyr-NRAS (Q61K) | CDK4 (R24C/R24C) ) harboring an epidermal knockout of Retinoid X Receptor α (RXRα (ep-/-) ), combined with oncogenic NRAS (Q61K) (constitutively active RAS) and activated CDK4 (R24C/R24C) (constitutively active CDK4)...
November 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29120899/association-of-a-3-untranslated-region-polymorphism-in-proprotein-convertase-subtilisin-kexin-type-9-with-hiv-viral-load-and-cd4-levels-in-hiv-hepatitis-c-virus-coinfected-women
#8
Mark H Kuniholm, Hua Liang, Kathryn Anastos, Deborah Gustafson, Seble Kassaye, Marek Nowicki, Beverly E Sha, Emilia J Pawlowski, Stephen J Gange, Bradley E Aouizerat, Tatiana Pushkarsky, Michael I Bukrinsky, Vinayaka R Prasad
OBJECTIVE: To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. DESIGN: Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. METHODS: We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women...
November 28, 2017: AIDS
https://www.readbyqxmd.com/read/29119384/tributyltin-advancing-the-science-on-assessing-endocrine-disruption-with-an-unconventional-endocrine-disrupting-compound
#9
Laurent Lagadic, Ioanna Katsiadaki, Ron Biever, Patrick D Guiney, Natalie Karouna-Renier, Tamar Schwarz, James P Meador
Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA...
November 9, 2017: Reviews of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/29105092/ultraviolet-a-eye-irradiation-ameliorates-atopic-dermatitis-via-p53-and-clock-gene-proteins-in-nc-nga-mice
#10
Keiichi Hiramoto, Yurika Yamate, Satoshi Yokoyama
Atopic dermatitis (AD) is a widespread chronic skin condition that severely affects quality of life and can lead to more serious complications. Although ultraviolet (UV)A eye irradiation can exert various effects on the skin, it is unknown whether UVA can affect AD. To investigate potential associations, we used an NC/Nga mouse model of AD to study the effects of UVA eye irradiation. The eyes of mice were irradiated with a UVA dose of 100 kJ/m(2) using a FL20SBLB-A lamp. Our histological data demonstrated that AD symptoms could be ameliorated by UVA eye irradiation...
November 4, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29089448/endogenous-retinoid-x-receptor-ligands-in-mouse-hematopoietic-cells
#11
Haixia Niu, Hideji Fujiwara, Orsola di Martino, Gayla Hadwiger, Thomas E Frederick, María P Menéndez-Gutiérrez, Mercedes Ricote, Gregory R Bowman, John S Welch
The retinoid X receptor α (RXRA) has been implicated in diverse hematological processes. To identify natural ligands of RXRA that are present in hematopoietic cells, we adapted an upstream activation sequence-green fluorescent protein (UAS-GFP) reporter mouse to detect natural RXRA ligands in vivo. We observed reporter activity in diverse types of hematopoietic cells in vivo. Reporter activity increased during granulocyte colony-stimulating factor (G-CSF)-induced granulopoiesis and after phenylhydrazine (PHZ)-induced anemia, suggesting the presence of dynamically regulated natural RXRA ligands in hematopoietic cells...
October 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/29074825/-update-on-recent-progress-in-vitamin-d-research-vitamin-d-receptor-and-the-nuclear-receptor-superfamily
#12
Makoto Makishima
The vitamin D receptor(VDR)is a ligand-dependent transcription factor of the nuclear receptor superfamily. VDR belongs to the NR1I subfamily along with other nuclear receptors involved in xenobiotic metabolism, such as pregnane X receptor. The oxysterol receptors liver X receptors α/β and the bile acid receptor farnesoid X receptor belong to the NR1H subfamily, which are closely related to the NR1I subfamily. NR1I and NR1H nuclear receptors form heterodimers with retinoid X receptor. The active form of vitamin D, 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], acts as a physiological VDR ligand, and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity, and cardiovascular function...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29072505/profiling-of-anthocyanidins-against-transcriptional-activities-of-steroid-and-nuclear-receptors
#13
Barbora Pastorková, Petr Illés, Zdeněk Dvořák
The aim of current study was to evaluate the effect of the most common anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) on the transcriptional activity of steroid and nuclear receptors. The activities of steroid receptors - progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and nuclear receptors - vitamin D receptor (VDR), retinoid X receptor (RXR), retinoic acid receptor (RAR), pregnane X receptor (PXR), and thyroid receptor (TR) were assessed using either stable transfected luciferase gene reporter cell lines or transiently transfected cell lines...
October 26, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29057944/linked-magnolol-dimer-as-a-selective-ppar%C3%AE-agonist-structure-based-rational-design-synthesis-and-bioactivity-evaluation
#14
Dominik Dreier, Simone Latkolik, Lukas Rycek, Michael Schnürch, Andrea Dymáková, Atanas G Atanasov, Angela Ladurner, Elke H Heiss, Hermann Stuppner, Daniela Schuster, Marko D Mihovilovic, Verena M Dirsch
The nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and its hetero-dimerization partner retinoid X receptor α (RXRα) are considered as drug targets in the treatment of diseases like the metabolic syndrome and diabetes mellitus type 2. Effort has been made to develop new agonists for PPARγ to obtain ligands with more favorable properties than currently used drugs. Magnolol was previously described as dual agonist of PPARγ and RXRα. Here we show the structure-based rational design of a linked magnolol dimer within the ligand binding domain of PPARγ and its synthesis...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030554/hdx-reveals-the-conformational-dynamics-of-dna-sequence-specific-vdr-co-activator-interactions
#15
Jie Zheng, Mi Ra Chang, Ryan E Stites, Yong Wang, John B Bruning, Bruce D Pascal, Scott J Novick, Ruben D Garcia-Ordonez, Keith R Stayrook, Michael J Chalmers, Jeffrey A Dodge, Patrick R Griffin
The vitamin D receptor/retinoid X receptor-α heterodimer (VDRRXRα) regulates bone mineralization via transcriptional control of osteocalcin (BGLAP) gene and is the receptor for 1α,25-dihydroxyvitamin D3 (1,25D3). However, supra-physiological levels of 1,25D3 activates the calcium-regulating gene TRPV6 leading to hypercalcemia. An approach to attenuate this adverse effect is to develop selective VDR modulators (VDRMs) that differentially activate BGLAP but not TRPV6. Here we present structural insight for the action of a VDRM compared with agonists by employing hydrogen/deuterium exchange...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29017757/effects-of-retinoic-acid-signaling-on-extraocular-muscle-myogenic-precursor-cells-in-vitro
#16
Sadie L Hebert, Krysta R Fitzpatrick, Samantha A McConnell, Anja Cucak, Ching Yuan, Linda K McLoon
One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would differ in leg muscle. The two muscle groups expressed differential retinoic acid receptor (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2-positive cells but not with those expressing Pax7...
October 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28989932/mutations-in-liver-x-receptor-alpha-that-impair-dimerization-and-ligand-dependent-transactivation
#17
Shimpi Bedi, Heather A Hostetler, Stanley Dean Rider
Liver X receptor alpha (LXRα) is crucial for the maintenance of lipid and cholesterol homeostasis. Ligand binding and dimerization with retinoid X receptor (RXR) or peroxisome proliferator-activated receptor (PPAR) is required for forming active DNA binding complexes leading to gene regulation. Structure based prediction and solvent accessibility of LXRα LBD shows that residues H383, E387, H390, L414, and R415 which are located in helices 9 and 10 may be critical for mediating protein-protein interactions...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28981706/insights-into-interplay-between-rexinoid-signaling-and-myogenic-regulatory-factor-associated-chromatin-state-in-myogenic-differentiation
#18
Munerah Hamed, Saadia Khilji, Katherine Dixon, Alexandre Blais, Ilya Ioshikhes, Jihong Chen, Qiao Li
While skeletal myogenesis is tightly coordinated by myogenic regulatory factors including MyoD and myogenin, chromatin modifications have emerged as vital mechanisms of myogenic regulation. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor (RXR), promotes the specification and differentiation of skeletal muscle lineage. Here, we examine the genome-wide impact of rexinoids on myogenic differentiation through integral RNA-seq and ChIP-seq analyses. We found that bexarotene promotes myoblast differentiation through the coordination of exit from the cell cycle and the activation of muscle-related genes...
September 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977589/retinoid-x-receptor-activation-alters-the-chromatin-landscape-to-commit-mesenchymal-stem-cells-to-the-adipose-lineage
#19
Bassem M Shoucri, Eric S Martinez, Timothy J Abreo, Victor T Hung, Zdena Moosova, Toshi Shioda, Bruce Blumberg
Developmental exposure to environmental factors has been linked to obesity risk later in life. Nuclear receptors are molecular sensors that play critical roles during development and, as such, are prime candidates to explain the developmental programming of disease risk by environmental chemicals. We have previously characterized the obesogen tributyltin (TBT), which activates the nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor (RXR) to increase adiposity in mice exposed in utero...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28943908/expression-of-chicken-ovalbumin-upstream-promoter-transcription-factor-ii-and-liver-x-receptor-as-prognostic-indicators-for-human-colorectal-cancer
#20
Seong-Hoon Yun, Min-Gyoung Park, Yu-Mi Kim, Mee-Sook Roh, Joo-In Park
Cholesterol increases the risk of colorectal cancer. Liver X receptor (LXR), retinoid X receptor (RXR)α and sterol regulatory element binding protein (SREBP)-1c are transcriptional regulators of lipid metabolism. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) serves an essential role in angiogenesis and development, but its role in cancer is controversial. The expression of COUP-TFII, LXR, RXRα and SREBP-1c in colorectal cancer, as well as their association with clinicopathologic features, was assessed, and their utility as prognostic indicators in colorectal cancer evaluated...
October 2017: Oncology Letters
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