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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/27903902/role-of-the-chromatin-landscape-and-sequence-in-determining-cell-type-specific-genomic-glucocorticoid-receptor-binding-and-gene-regulation
#1
Michael I Love, Matthew R Huska, Marcel Jurk, Robert Schöpflin, Stephan R Starick, Kevin Schwahn, Samantha B Cooper, Keith R Yamamoto, Morgane Thomas-Chollier, Martin Vingron, Sebastiaan H Meijsing
The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903230/glucocorticoid-receptor-interacting-co-regulators-putative-candidates-for-future-drug-targeting-therapy
#2
Alessia Di Silvestre, Marianna Lucafò, Sara De Iudicibus, Alessandro Ventura, Stefano Martelossi, Gabriele Stocco, Giuliana Decorti
Glucocorticoids (GCs) are largely used in different inflammatory, autoimmune and proliferative diseases. To date their mechanism of action is not completely clear and more studies are necessary, in particular to explain the great interindividual variability in clinical response. In this panorama the glucocorticoid receptor (GR) has an important role: in fact it regulates the pharmacological response thanks to the capability to interact with different molecules (DNA, RNA, ncRNA and proteins) that are known to influence its activity...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27901049/glucocorticoid-receptor-and-histone-deacetylase-6-mediate-the-differential-effect-of-dexamethasone-during-osteogenesis-of-mesenchymal-stromal-cells-mscs
#3
Marilyn G Rimando, Hao-Hsiang Wu, Yu-An Liu, Chien-Wei Lee, Shu-Wen Kuo, Yin-Ping Lo, Kuo-Fung Tseng, Yi-Shiuan Liu, Oscar Kuang-Sheng Lee
Lineage commitment and differentiation of mesenchymal stromal cells (MSCs) into osteoblasts in vitro is enhanced by a potent synthetic form of glucocorticoid (GC), dexamethasone (Dex). Paradoxically, when used chronically in patients, GCs exert negative effects on bone, a phenomenon known as glucocorticoid-induced osteoporosis in clinical practice. The mechanism on how GC differentially affects bone precursor cells to become mature osteoblasts during osteogenesis remains elusive. In this study, the dose and temporal regulation of Dex on MSC differentiation into osteoblasts were investigated...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897427/structure-based-drug-design-of-mineralocorticoid-receptor-antagonists-to-explore-oxosteroid-receptor-selectivity
#4
Anneli Nordqvist, Gavin O'Mahony, Maria Fridén-Saxin, Marlene Fredenwall, Anders Hogner, Kenneth L Granberg, Anna Aagaard, Stefan Bäckström, Anders Gunnarsson, Tim Kaminski, Yafeng Xue, Anita Dellsén, Eva Hansson, Pia Hansson, Ida Ivarsson, Ulla Karlsson, Krister Bamberg, Majlis Hermansson, Jennie Georgsson, Bo Lindmark, Karl Edman
The mineralocorticoid receptor (MR) is a nuclear hormone receptor involved in regulation of body fluid and electrolyte homeostasis. In this study we explore selectivity triggers for a series of non-steroidal MR antagonists to improve selectivity over other members of the oxosteroid receptor family. A biaryl sulfonamide compound was identified in a high-throughput screening (HTS) campaign. The compound bound to MR with a pKi=6.6, but displayed poor selectivity over the glucocorticoid receptor (GR) and the progesterone receptor (PR)...
November 29, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27895155/investigations-of-glucocorticoid-action-in-gn
#5
Christoph Kuppe, Claudia van Roeyen, Katja Leuchtle, Nazanin Kabgani, Michael Vogt, Marc Van Zandvoort, Bart Smeets, Jürgen Floege, Hermann-Josef Gröne, Marcus J Moeller
For several decades, glucocorticoids have been used empirically to treat rapid progressive GN. It is commonly assumed that glucocorticoids act primarily by dampening the immune response, but the mechanisms remain incompletely understood. In this study, we inactivated the glucocorticoid receptor (GR) specifically in kidney epithelial cells using Pax8-Cre/GR(fl/fl) mice. Pax8-Cre/GR(fl/fl) mice did not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic serum to induce crescentic nephritis (rapidly progressive GN), this genetic inactivation of the GR in kidney epithelial cells exerted renal benefits, including inhibition of albuminuria and cellular crescent formation, similar to the renal benefits observed with high-dose prednisolone in control mice...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27889894/glucocorticoid-induced-leucine-zipper-in-central-nervous-system-health-and-disease
#6
REVIEW
Mythily Srinivasan, Debomoy K Lahiri
The central nervous system (CNS) is a large network of intercommunicating cells that function to maintain tissue health and homeostasis. Considerable evidence suggests that glucocorticoids exert both neuroprotective and neurodegenerative effects on the CNS. Glucocorticoids act by binding two related receptors in the cytoplasm, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The glucocorticoid receptor complex mediates cellular responses by transactivating target genes and by protein: protein interactions...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27888798/mir-103-inhibits-proliferation-and-sensitizes-hemopoietic-tumor-cells-for-glucocorticoid-induced-apoptosis
#7
Shlomit Kfir-Erenfeld, Noa Haggiag, Moshe Biton, Polina Stepensky, Nathalie Assayag-Asherie, Eitan Yefenof
Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888447/the-regulation-of-the-mitochondrial-apoptotic-pathway-by-glucocorticoid-receptor-in-collaboration-with-bcl-2-family-proteins-in-developing-t-cells
#8
Lilla Prenek, Ferenc Boldizsár, Réka Kugyelka, Emese Ugor, Gergely Berta, Péter Németh, Timea Berki
Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity...
November 26, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27883019/17-oxo-dha-displays-additive-anti-inflammatory-effects-with-fluticasone-propionate-and-inhibits-the-nlrp3-inflammasome
#9
Chiara Cipollina, Serena Di Vincenzo, Liboria Siena, Caterina Di Sano, Mark Gjomarkaj, Elisabetta Pace
Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function associated with increased local and systemic inflammatory markers, such as TNFα and IL-1β. Glucocorticoids are used to treat this chronic disease, however their efficacy is low and new drugs are very much required. 17-oxo-DHA is a cyclooxygenase-2-dependent, electrophilic, α,β-unsaturated keto-derivative of docosahexaenoic acid with anti-inflammatory properties. We evaluated the action of 17-oxo-DHA alone or in combination with the steroid fluticasone propionate (FP) in peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy individuals exposed to lipopolysaccharide...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27878281/etomidate-inhibits-nuclear-factor-%C3%AE%C2%BAb-through-decreased-expression-of-glucocorticoid-receptor-in-septic-rats
#10
Yu Zhang, Ruo-Meng Li, Chun Wang, Na Liu, Shen Lv, Jun-Yu Xiong
The present study aimed to investigate the effect of etomidate administered prior to or following cecal ligation and puncture (CLP) on the expression of glucocorticoid receptor (GR) and lymphocyte apoptosis in septic rats. Right jugular vein catheterization was performed on female Sprague‑Dawley rats under isoflurane anesthesia, and CLP surgery was performed to induce sepsis 3 days following catheterization. The rats were randomly divided into five groups. All groups were infused with 2 ml of either etomidate or 5‰ dimethyl sulfoxide (DMSO) at 1 ml/h for 2 h from 6 h post‑surgery...
November 16, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27874237/tactile-stimulation-during-different-developmental-periods-modifies-hippocampal-bdnf-and-gr-affecting-memory-and-behavior-in-adult-rats
#11
Caren T D Antoniazzi, Vinícia G Metz, Karine Roversi, Daniele L Freitas, Luciana T Vey, Verônica T Dias, Hecson J Segat, Marta M M F Duarte, Marilise Escobar Bürger
Recent studies have shown that tactile stimulation (TS) in pups is able to prevent and/or minimize fear, anxiety behaviors, and addiction to psychostimulant drugs in adult rats. In these studies, animals have been exposed to handling from postnatal day (PND) 1 to 21. The present study was designed to precisely establish which period of preweaning development has a greater influence of TS on neuronal development. After birth, male pups were exposed to TS from PND1 to 7, PND8 to 14, and PND15 to 21. In adulthood, the different periods of postnatal TS were assessed through behavioral, biochemical and molecular assessments...
November 22, 2016: Hippocampus
https://www.readbyqxmd.com/read/27864677/glucocorticoids
#12
Ian M Adcock, Sharon Mumby
The most effective anti-inflammatory drugs used to treat patients with airways disease are topical glucocorticosteroids (GCs). These act on virtually all cells within the airway to suppress airway inflammation or prevent the recruitment of inflammatory cells into the airway. They also have profound effects on airway structural cells to reverse the effects of disease on their function. Glucorticosteroids act via specific receptors-the glucocorticosteroid receptor (GR)-which are a member of the nuclear receptor family...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27857212/gr-independent-down-modulation-on-gm-csf-bone-marrow-derived-dendritic-cells-by-the-selective-glucocorticoid-receptor-modulator-compound-a
#13
Andres E Barcala Tabarrozzi, Luz Andreone, Julie Deckers, Carla N Castro, María L Gimeno, Laura Ariolfo, Paula M Berguer, María Antunica-Noguerol, Ana C Liberman, Sabine Vettorazzi, Jan P Tuckermann, Karolien De Bosscher, Marcelo J Perone
Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856527/role-of-glucocorticoid-receptor-and-pregnane-x-receptor-in-dexamethasone-induction-of-rat-hepatic-aryl-hydrocarbon-receptor-nuclear-translocator-and-nadph-cytochrome-p450-oxidoreductase
#14
Sarah R Hunter, Alex Vonk, Anne K Mullen Grey, David S Riddick
The aryl hydrocarbon receptor (AHR) nuclear translocator (ARNT), as the AHR's heterodimerization partner, and NADPH-cytochrome P450 oxidoreductase (POR), as the key electron donor for all microsomal P450s, are independent and indispensable components in the adaptive and toxic responses to polycyclic aromatic hydrocarbons. Expression of both ARNT and POR in rat liver is induced by dexamethasone (DEX), a synthetic glucocorticoid known to activate both the glucocorticoid receptor (GR) and the pregnane X receptor (PXR)...
November 16, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27849648/amygdala-mediated-mechanisms-regulate-visceral-hypersensitivity-in-adult-females-following-early-life-stress-importance-of-the-glucocorticoid-receptor-and-corticotropin-releasing-factor
#15
Dawn K Prusator, Beverley Greenwood-Van Meerveld
Alterations in amygdala activity are apparent in women who report a history of early life stress (ELS) as well as those diagnosed with chronic pain disorders. Chronic stress in adulthood induces visceral hypersensitivity via alterations in glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF) expression within the central amygdala (CeA). Here we hypothesized that unpredictable ELS, previously shown to induce visceral hypersensitivity in adult female rats, alters GR and CRF expression in the CeA...
November 14, 2016: Pain
https://www.readbyqxmd.com/read/27849045/deletion-of-neurotrophin-signaling-through-the-glucocorticoid-receptor-pathway-causes-tau-neuropathology
#16
Margarita Arango-Lievano, Camille Peguet, Matthias Catteau, Marie-Laure Parmentier, Synphen Wu, Moses V Chao, Stephen D Ginsberg, Freddy Jeanneteau
Glucocorticoid resistance is a risk factor for Alzheimer's disease (AD). Molecular and cellular mechanisms of glucocorticoid resistance in the brain have remained unknown and are potential therapeutic targets. Phosphorylation of glucocorticoid receptors (GR) by brain-derived neurotrophic factor (BDNF) signaling integrates both pathways for remodeling synaptic structure and plasticity. The goal of this study is to test the role of the BDNF-dependent pathway on glucocorticoid signaling in a mouse model of glucocorticoid resistance...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27846806/gen3va-aggregation-and-analysis-of-gene-expression-signatures-from-related-studies
#17
Gregory W Gundersen, Kathleen M Jagodnik, Holly Woodland, Nicholas F Fernandez, Kevin Sani, Anders B Dohlman, Peter Man-Un Ung, Caroline D Monteiro, Avner Schlessinger, Avi Ma'ayan
BACKGROUND: Genome-wide gene expression profiling of mammalian cells is becoming a staple of many published biomedical and biological research studies. Such data is deposited into data repositories such as the Gene Expression Omnibus (GEO) for potential reuse. However, these repositories currently do not provide simple interfaces to systematically analyze collections of related studies. RESULTS: Here we present GENE Expression and Enrichment Vector Analyzer (GEN3VA), a web-based system that enables the integrative analysis of aggregated collections of tagged gene expression signatures identified and extracted from GEO...
November 15, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27845381/fasting-and-feeding-signals-control-the-oscillatory-expression-of-angptl8-to-modulate-lipid-metabolism
#18
Fabin Dang, Rong Wu, Pengfei Wang, Yuting Wu, Md Shofiul Azam, Qian Xu, Yaqiong Chen, Yi Liu
Emerging evidence implies a key role of angiopoietin-like protein 8 (Angptl8) in the metabolic transition between fasting and feeding, whereas much less is known about the mechanism of its own expression. Here we show that hepatic Angptl8 is rhythmically expressed, which involving the liver X receptor alpha (LXRα) and glucocorticoid receptor (GR) modulation during feeding and fasting periods, respectively. In addition, Angptl8 mRNA is very unstable, which contributes to the nature of its daily rhythmicity by rapidly responding to fasting/feeding transition...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27835038/family-matters-collaboration-and-conflict-among-the-steroid-receptors-raises-a-need-for-group-therapy
#19
Matthew J Sikora
Antiestrogen therapies targeting the function of estrogen receptor (ER) have been the cornerstone of therapy for ER+ breast cancer for decades. However, as long as these therapies have been in use, it has also been evident that response to antiestrogen therapy is not based solely on ER expression but that other factors modify breast cancer antiestrogen response. Such factors may include ER's relatives in the steroid hormone receptor (HR) family, androgen receptor (AR), progesterone receptor (PR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR)...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27834851/negative-glucocorticoid-response-like-element-from-the-first-intron-of-the-chicken-growth-hormone-gene-represses-gene-expression-in-the-rat-pituitary-tumor-cell-line
#20
Jing-E Ma, Qian-Qian Lang, Feng-Fang Qiu, Li Zhang, Xiang-Guang Li, Wen Luo, Juan Wang, Xing Wang, Xi-Ran Lin, Wen-Sheng Liu, Qing-Hua Nie, Xi-Quan Zhang
The effects of introns, especially the first intron, on the regulation of gene expression remains unclear. Therefore, the objective of the present study was to investigate the transcriptional regulatory function of intron 1 on the chicken growth hormone (cGH) gene in the rat pituitary tumor cell line (GH4-C1). Transient transfection using first-intron-inserted cGH complete coding sequences (CDSs) and non-intron-inserted cGH CDS plasmids, quantitative RT-PCR (qRT-PCR) and western blot assays were used to detect the expression of cGH...
November 9, 2016: International Journal of Molecular Sciences
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