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Glucocorticoid receptor

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https://www.readbyqxmd.com/read/28528409/polychlorinated-biphenyl-related-alterations-of-the-expression-of-essential-genes-in-harbour-seals-phoca-vitulina-from-coastal-sites-in-canada-and-the-united-states
#1
Marie Noël, Neil Dangerfield, Steve Jeffries, Dyanna Lambourn, Monique Lance, Caren Helbing, Michel Lebeuf, Peter S Ross
As long-lived marine mammals found throughout the temperate coastal waters of the North Pacific and Atlantic Oceans, harbour seals (Phoca vitulina) have become an invaluable sentinel of food-web contamination. Their relatively high trophic position predisposes harbour seals to the accumulation of harmful levels of persistent organic pollutants (POPs). We obtained skin/blubber biopsy samples from live-captured young harbour seals from various sites in the northeastern Pacific (British Columbia, Canada, and Washington State, USA) as well as the northwestern Atlantic (Newfoundland and Quebec, Canada)...
May 20, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28527915/methylparaben-and-butylparaben-alter-multipotent-mesenchymal-stem-cell-fates-towards-adipocyte-lineage
#2
Pan Hu, Haley Overby, Emily Heal, Shu Wang, Jiangang Chen, Chwan-Li Shen, Ling Zhao
Paraben esters and their salts are widely used as preservatives in cosmetics, personal care products, pharmaceuticals, and foods. We previously reported that parabens promoted adipocyte differentiation in vitro and increased adiposity but suppressed serum marker of bone formation in vivo. Here, we investigated the effects of parabens (methylparaben and butylparaben) on modulating cell fate of multipotent stem cell line C3H10T1/2. Both parabens modulated adipogenic, osteogenic, and chondrogenic differentiation of C3H10T1/2 cells in vitro...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527581/nuclear-receptors-in-skeletal-homeostasis
#3
Hao Zuo, Yihong Wan
Nuclear receptors are a family of transcription factors that can be activated by lipophilic ligands. They are fundamental regulators of development, reproduction, and energy metabolism. In bone, nuclear receptors enable bone cells, including osteoblasts, osteoclasts, and osteocytes, to sense their dynamic microenvironment and maintain normal bone development and remodeling. Our views of the molecular mechanisms in this process have advanced greatly in the past decade. Drugs targeting nuclear receptors are widely used in the clinic for treating patients with bone disorders such as osteoporosis by modulating bone formation and resorption rates...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527108/increased-expression-of-brain-derived-neurotrophic-factor-transcripts-i-and-vi-camp-response-element-binding-and-glucocorticoid-receptor-in-the-cortex-of-patients-with-temporal-lobe-epilepsy
#4
G A Martínez-Levy, L Rocha, F Rodríguez-Pineda, M A Alonso-Vanegas, A Nani, R M Buentello-García, M Briones-Velasco, D San-Juan, J Cienfuegos, C S Cruz-Fuentes
A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic...
May 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28524007/the-proinflammatory-cytokine-gitrl-contributes-to-trail-mediated-neurotoxicity-in-the-hcn-2-human-neuronal-cell-line
#5
Giulia Di Benedetto, Salvatore Saccone, Laurence Lempereur, Nicole Ronsisvalle, Giuseppe Nocentini, Rodolfo Bianchini, Carlo Riccardi, Renato Bernardini, Giuseppina Cantarella
Cytokines belonging to the TNF superfamily play a relevant role in neurodegenerative processes. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), released during neuronal injury, has proven to potently mediate and sustain neurotoxic processes leading to neuronal death. Similarly to TRAIL, the cytokine Glucocorticoid-induced TNF receptor ligand (GITRL) is able to transduce proapoptotic signals. In spite of the array of reports suggesting relationships between TRAIL and other cytokines, scanty data are, so far, available about a GITRL/TRAIL crosstalk...
May 18, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#6
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28523546/histone-modifications-in-major-depressive-disorder-and-related-rodent-models
#7
Jan M Deussing, Mira Jakovcevski
Major depressive disorder (MDD) is a multifactorial disease, weakly linked to multiple genetic risk factors. In contrast to that, environmental factors and "gene × environment" interaction between specific risk genes and environmental factors, such as severe or early stress exposure, have been strongly linked to MDD vulnerability. Stressors can act on the interface between an organism and the environment, the epigenome. The molecular foundation for the impact of stressors on the risk to develop MDD is based on the hormonal stress response itself: the glucocorticoid receptor (GR, encoded by NR3C1)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523344/role-of-g3bp1-in-glucocorticoid-receptor-mediated-microrna-15b-and-microrna-23a-biogenesis-in-endothelial-cells
#8
Hoi-Hin Kwok, Po-Ying Poon, Kylie Hin-Man Mak, Lin-Yao Zhang, Pei Liu, Huoming Zhang, Nai-Ki Mak, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28523300/prenatal-glucocorticoid-administration-persistently-increased-the-immunohistochemical-expression-of-type-1-metabotropic-glutamate-receptor-and-purkinje-cell-dendritic-growth-in-the-cerebellar-cortex-of-the-rat
#9
Rodrigo Pascual, Odra Santander, Isabel Cuevas, Martina Valencia
Several studies have indicated that abnormal prenatal changes in the circulating glucocorticoids (GCs), induced by either maternal stress or exogenous GC administration, significantly alter the development of Purkinje cells (PCs). Among the suggested mechanisms that could mediate this GC-dependent PC susceptibility are changes in the expression of type-1 metabotropic glutamate receptors (mGluR1). In the current study, we analyzed whether a single course of prenatally administered betamethasone phosphate (BET) in pregnant rats increased the immunohistochemical expression of mGluR1 in PCs and decreased PC dendritic growth...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28523069/crosstalk-between-aryl-hydrocarbon-receptor-and-glucocorticoid-receptor-in-human-retinal-pigment-epithelial-cells
#10
Hong Lan Jin, Yujin Choi, Kwang Won Jeong
The aryl hydrocarbon receptor (AHR) is known to mediate the cellular reaction involved in processing environmental contaminants and, ultimately, preventing accumulation of unfavorable extra lipids and proteins. Glucocorticoid receptor (GR) mediates the expression of genes associated with anti-inflammatory properties. Because AHR and GR are closely related in lipid metabolic dysregulation and inflammation, we speculate that AHR and GR may play a crucial role in AMD pathogenesis and focus on their crosstalk in human retinal pigment epithelial cells (ARPE-19)...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28521279/chronic-stress-impairs-the-local-immune-response-during-cutaneous-repair-in-gilthead-sea-bream-sparus-aurata-l
#11
Ana Patrícia Mateus, Liliana Anjos, João R Cardoso, Deborah M Power
Scale removal in fish triggers a damage-repair program to re-establish the lost epidermis and scale and an associated local immune response. In mammals, chronic stress is known to delay wound healing and to modulate the cutaneous stress axis, but this is unstudied in teleost fish the most successful extant vertebrates. The present study was designed to test the hypothesis that chronic stress impairs cutaneous repair in teleost fish as a consequence of suppression of the immune response. The hypothesis was tested by removing the scales and damaging the skin on one side of the body of fish previously exposed for 4 weeks to a chronic crowding stress and then evaluating cutaneous repair for 1 week...
May 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28515473/placental-o-glcnac-transferase-expression-and-interactions-with-the-glucocorticoid-receptor-are-sex-specific-and-regulated-by-maternal-corticosterone-exposure-in-mice
#12
Marie Pantaleon, Sarah E Steane, Kathryn McMahon, James S M Cuffe, Karen M Moritz
Maternal stress programs offspring disease in a sexually dimorphic manner with males often more adversely affected. Previous studies of maternal glucocorticoid exposure suggest male vulnerability may derive from placental alterations. The hexosamine signalling pathway and O-linked glycosylation (O-GlcNAcylation) are part of an essential adaptive survival response in healthy cells. The key enzyme involved is O-linked-N-acetylglucosamine transferase (OGT), a gene recently identified as a sex-specific placental biomarker of maternal stress...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515280/airway-epithelial-cells-are-crucial-targets-of-glucocorticoids-in-a-mouse-model-of-allergic-asthma
#13
Carina Klaßen, Anna Karabinskaya, Lien Dejager, Sabine Vettorazzi, Justine Van Moorleghem, Fred Lühder, Sebastiaan H Meijsing, Jan P Tuckermann, Hanibal Bohnenberger, Claude Libert, Holger M Reichardt
Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28515208/glucocorticoid-responsive-lymphocytic-parathyroiditis-and-hypocalciuric-hypercalcemia-due-to-autoantibodies-against-the-calcium-sensing-receptor-a-case-report-and-literature-review
#14
Li Song, Liping Liu, R Tyler Miller, Shirley X Yan, Nancy Jackson, Shelby A Holt, Naim M Maalouf
OBJECTIVE: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with autoantibodies against the calcium-sensing receptor (anti-CaSR) are rare and poorly understood conditions. Here, we describe a patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with associated hypocalciuria, found to have true lymphocytic parathyroiditis on histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND METHODS: A 64-year-old woman was referred to our clinic for persistent hypercalcemia after a subtotal parathyroidectomy...
July 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28514613/kit-inhibition-by-imatinib-in-patients-with-severe-refractory-asthma
#15
Katherine N Cahill, Howard R Katz, Jing Cui, Juying Lai, Shamsah Kazani, Allison Crosby-Thompson, Denise Garofalo, Mario Castro, Nizar Jarjour, Emily DiMango, Serpil Erzurum, Jennifer L Trevor, Kartik Shenoy, Vernon M Chinchilli, Michael E Wechsler, Tanya M Laidlaw, Joshua A Boyce, Elliot Israel
BACKGROUND: Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma...
May 18, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28510246/molecular-cloning-and-differential-expression-of-the-glucocorticoid-receptorgene-in-the-estuarine-tapertail-anchovy-coilia-nasus
#16
F K Du, G C Xu, Y Li, Z J Nie, P Xu
To understand the regulation of the glucocorticoid receptor gene (Gcr) during loading and transport stress in fish, the Gcr gene of Coilia nasus was cloned. Gcr in C. nasus is expressed strongly in the liver and muscle, and less stronglyin the gills, brain, spleen, intestine, trunk kidney, and head kidney. Gcr expression in both the liver and muscle was increased by loading and transport stress. NaCl reduced the death rate caused by loading and transport stress, and the expression of Gcr in liver and muscle differed significantly between the NaCl and non-NaCl groups...
May 10, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28507805/generation-and-functional-characterization-of-mdsc-like-cells
#17
Annkristin Heine, Stefanie Andrea Erika Held, Jonas Schulte-Schrepping, Julia Friederike Andrea Wolff, Kathrin Klee, Thomas Ulas, Niklas Arndt Schmacke, Solveig Nora Daecke, Kati Riethausen, Joachim L Schultze, Peter Brossart
Myeloid-derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with interleukin (IL)-10 during their differentiation to monocyte-derived dendritic cells (moDCs) results in the generation of an APC population with a CD14(+)HLA-DR(low)phenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to moDC caused a reduction of DC-induced T-cell proliferation, of the expression of maturation markers, and of secreted cytokines and chemokines such as TNF-α, IL-6, MIP-1α and Rantes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506584/development-of-nonsteroidal-glucocorticoid-receptor-modulators-based-on-n-benzyl-n-4-phenoxyphenyl-benzenesulfonamide-scaffold
#18
Hiromasa Yoshioka, Ayumi Yamada, Yuko Nishiyama, Hiroyuki Kagechika, Yuichi Hashimoto, Shinya Fujii
N-Benzyl-N-(4-phenoxyphenyl)benzenesulfonamide derivatives were developed as a novel class of nonsteroidal glucocorticoid receptor (GR) modulators, which are promising drug candidates for treating immune-related disorders. Focusing on the similarity of the GR and progesterone receptor (PR) ligand-binding domain (LBD) structures, we adopted our recently developed PR antagonist 10 as a lead compound and synthesized a series of derivatives. We found that the N-(4-phenoxyphenyl)benzenesulfonamide skeleton serves as a versatile scaffold for GR antagonists...
April 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28504720/a-clinical-drug-library-screen-identifies-clobetasol-propionate-as-an-nrf2-inhibitor-with-potential-therapeutic-efficacy-in-keap1-mutant-lung-cancer
#19
E-J Choi, B-J Jung, S-H Lee, H-S Yoo, E-A Shin, H-J Ko, S Chang, S-Y Kim, S-M Jeon
The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28502880/maternal-care-modulates-the-febrile-response-to-lipopolysaccharide-through-differences-in-glucocorticoid-receptor-sensitivity-in-the-rat
#20
Carine Parent, Huy-Binh Nguyen, Xianglan Wen, Josie Diorio, Michael J Meaney, Tie Yuan Zhang
Early life adversity increases the risk for later infection. The febrile response is a potent mechanism to combat infection. We found that variations in maternal care influence the febrile response to 50 µg/kg lipopolysaccharide (LPS) challenge in adult male rats. Offspring from low-licking/grooming (LG) mothers had an increased febrile response compared to offspring from high-LG mothers challenged with LPS. Low-LG offspring had reduced plasma IL-6 at one and two hours post challenge compared to high-LG offspring...
May 10, 2017: Brain, Behavior, and Immunity
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