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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/28330718/adult-glucocorticoid-receptor-mrna-expression-volatility-in-response-to-an-acute-stressor-and-juvenile-csf-corticotropin-releasing-factor-a-pilot-neurodevelopmental-study
#1
Shariful A Syed, Eric L P Smith, Olcay Batuman, Leonard A Rosenblum, Michael J Owens, Charles B Nemeroff, Jeremy D Coplan
INTRODUCTION: Early life stress (ELS) has been shown to play a role in establishing persistent maladaptive HPA axis modifications that may contribute to the pathogenesis of mood and anxiety disorders. Central glucocorticoid receptor (GR) messenger RNA (mRNA) expression may facilitate (mal)adaptive responsivity to ELS. The role of adult monocytic GR mRNA expression, a putative CNS proxy, during acute stress exposure was explored as well as the ELS marker, juvenile cerebrospinal fluid (CSF) corticotropin-releasing factor...
March 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28329022/annexin-a1-in-blood-mononuclear-cells-from-patients-with-coronary-artery-disease-its-association-with-inflammatory-status-and-glucocorticoid-sensitivity
#2
Ida Bergström, Anna K Lundberg, Simon Jönsson, Eva Särndahl, Jan Ernerudh, Lena Jonasson
Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS)...
2017: PloS One
https://www.readbyqxmd.com/read/28325773/cue-domain-containing-protein-2-promotes-the-warburg-effect-and-tumorigenesis
#3
Xiuying Zhong, Shengya Tian, Xiang Zhang, Xinwei Diao, Fangting Dong, Jie Yang, Zhaoyong Li, Linchong Sun, Lin Wang, Xiaoping He, Gongwei Wu, Xin Hu, Lihua Wang, Libing Song, Huafeng Zhang, Xin Pan, Ailing Li, Ping Gao
Cancer progression depends on cellular metabolic reprogramming as both direct and indirect consequence of oncogenic lesions; however, the underlying mechanisms are still poorly understood. Here, we report that CUEDC2 (CUE domain-containing protein 2) plays a vital role in facilitating aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we show that CUEDC2 upregulates the two key glycolytic proteins GLUT3 and LDHA via interacting with the glucocorticoid receptor (GR) or 14-3-3ζ, respectively...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28324065/neurod-factors-discriminate-mineralocorticoid-from-glucocorticoid-receptor-dna-binding-in-the-male-rat-brain
#4
Lisa T C M van Weert, Jacobus C Buurstede, Ahmed Mahfouz, Pamela S M Braakhuis, J Annelies E Polman, Hetty C M Sips, Benno Roozendaal, Judit Balog, E Ronald de Kloet, Nicole A Datson, Onno C Meijer
In the limbic brain, mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) both function as receptors for the naturally occurring glucocorticoids (corticosterone/cortisol), but mediate distinct effects on cellular physiology via transcriptional mechanisms. The transcriptional basis for specificity of these MR- versus GR-mediated effects is unknown. To address this conundrum we have identified the extent of MR/GR DNA binding selectivity in the rat hippocampus using chromatin immunoprecipitation followed by sequencing (ChIP-seq)...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#5
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs) including dexamethasone (DEX) are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The glucocorticoid receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX, but still sensitive to its immunosuppressive actions...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323983/autophagic-degradation-of-collagen-1a1-by-cortisol-in-human-amnion-fibroblasts
#6
Yabing Mi, Wangsheng Wang, Chuyue Zhang, Chao Liu, Jiangwen Lu, Wenjiao Li, Rujuan Zuo, Leslie Myatt, Kang Sun
Rupture of fetal membranes can initiate parturition at both term and preterm. Collagen is the crucial factor determining the tensile strength of the membranes. Toward the end of gestation, a feed-forward regeneration of cortisol via 11β-hydroxysteroid dehydrogenase 1 exists in fetal membranes. It remains undetermined whether cortisol contributes to collagen reduction in fetal membranes. Here we have examined whether cortisol accumulation is a causative factor for collagen reduction in human amnion fibroblasts, the major source of collagens in the membranes...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323049/sutherlandia-frutescens-modulates-adrenal-hormone-biosynthesis-displays-anti-mineralocorticoid-and-serga-properties-acting-as-a-dissociated-glucocorticoid
#7
C A Sergeant, D Africander, P Swart, A C Swart
ETHNOPHARMACOLOGICAL RELEVANCE: Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties. AIM OF STUDY: The study aimed at linking anti-stress and anti-inflammatory properties of S. frutescens to its influence on glucocorticoid biosynthesis and the inflammatory response via steroid receptor interaction. MATERIALS AND METHODS: The influence of S...
March 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28321433/transcription-factor-oscillations-in-neural-stem-cells-implications-for-accurate-control-of-gene-expression
#8
REVIEW
Pascal Bielefeld, Marijn Schouten, Paul J Lucassen, Carlos P Fitzsimons
Naturally occurring oscillations in glucocorticoids induce a cyclic activation of the glucocorticoid receptor (GR), a well-characterized ligand-activated transcription factor. These cycles of GR activation/deactivation result in rapid GR exchange at genomic response elements and GR recycling through the chaperone machinery, ultimately generating pulses of GR-mediated transcriptional activity of target genes. In a recent article we have discussed the implications of circadian and high-frequency (ultradian) glucocorticoid oscillations for the dynamic control of gene expression in hippocampal neural stem/progenitor cells (NSPCs) (Fitzsimons et al...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28320277/mechanisms-of-brain-glucocorticoid-resistance-in-stress-induced-psychopathologies
#9
REVIEW
V M Merkulov, T I Merkulova, N P Bondar
Exposure to stress activates the hypothalamic-pituitary-adrenal axis and leads to increased levels of glucocorticoid (GC) hormones. Prolonged elevation of GC levels causes neuronal dysfunction, decreases the density of synapses, and impairs neuronal plasticity. Decreased sensitivity to glucocorticoids (glucocorticoid resistance) that develops as a result of chronic stress is one of the characteristic features of stress-induced psychopathologies. In this article, we reviewed the published data on proposed molecular mechanisms that contribute to the development of glucocorticoid resistance in brain, including changes in the expression of the glucocorticoid receptor (GR) gene, biosynthesis of GR isoforms, and GR posttranslational modifications...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319043/glucocorticoid-receptors-finding-the-middle-ground
#10
Sofie J Desmet, Karolien De Bosscher
Glucocorticoids (GCs; referred to clinically as corticosteroids) are steroid hormones with potent anti-inflammatory and immune modulatory profiles. Depending on the context, these hormones can also mediate pro-inflammatory activities, thereby serving as primers of the immune system. Their target receptor, the GC receptor (GR), is a multi-tasking transcription factor, changing its role and function depending on cellular and organismal needs. To get a clearer idea of how to improve the safety profile of GCs, recent studies have investigated the complex mechanisms underlying GR functions...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28314773/glucocorticoid-receptor-signaling-represses-the-antioxidant-response-by-inhibiting-histone-acetylation-mediated-by-the-transcriptional-activator-nrf2
#11
Md Morshedul Alam, Keito Okazaki, Linh Thi Thao Nguyen, Nao Ota, Hiroshi Kitamura, Shohei Murakami, Hiroki Shima, Kazuhiko Igarashi, Hiroki Sekine, Hozumi Motohashi
NRF2 (nuclear factor erythroid 2-related factor 2) is a key transcriptional activator that mediates the inducible expression of antioxidant genes. NRF2 is normally ubiquitinated by KEAP1 (Kelch-like ECH-associated protein 1) and subsequently degraded by proteasomes. Inactivation of KEAP1 by oxidative stress or electrophilic chemicals allows NRF2 to activate transcription through binding to antioxidant response elements (AREs) and recruiting histone acetyltransferase CBP (CREB-binding protein). While KEAP1-dependent regulation is a major determinant of NRF2 activity, NRF2-mediated transcriptional activation varies from context to context, suggesting other intracellular signaling cascades may impact NRF2 function...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301576/restored-mutant-receptor-corticoid-binding-in-chaperone-complexes-by-trimethylamine-n-oxide
#12
Aaron L Miller, W Austin Elam, Betty H Johnson, Shagufta H Khan, Raj Kumar, E Brad Thompson
Without a glucocorticoid (GC) ligand, the transcription factor glucocorticoid receptor (GR) is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide (TMAO), on a conditions-dependent "activation-labile" mutant GR (GRact/l), which under GR-activating conditions cannot bind GCs in cells or in cell cytosols...
2017: PloS One
https://www.readbyqxmd.com/read/28300583/synthesis-of-new-c-25-and-c-26-steroidal-acids-as-potential-ligands-of-the-nuclear-receptors-daf-12-lxr-and-gr
#13
María V Dansey, María C Del Fueyo, Adriana S Veleiro, Pablo H Di Chenna
A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity...
March 11, 2017: Steroids
https://www.readbyqxmd.com/read/28293120/glucocorticoid-receptor-expression-in-20-solid-tumor-types-using-immunohistochemistry-assay
#14
Thaddeus S Block, Tiffany I Murphy, Pamela N Munster, Dat P Nguyen, Frank J Lynch
BACKGROUND: Glucocorticoid receptor (GR) activity plays a role in many aspects of human physiology and may play a crucial role in chemotherapy resistance in a wide variety of solid tumors. A novel immunohistochemistry (IHC) based assay has been previously developed and validated in order to assess GR immunoreactivity in triple-negative breast cancer. The current study investigates the standardized use of this validated assay to assess GR expression in a broad range of solid tumor malignancies...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28292649/increased-methylation-of-glucocorticoid-receptor-gene-promoter-1f-in-peripheral-blood-of-patients-with-generalized-anxiety-disorder
#15
Wei Wang, Junqin Feng, Cui Ji, Xin Mu, Qingyan Ma, Yajuan Fan, Ce Chen, Chengge Gao, Xian-Cang Ma, Feng Zhu
Previous findings on the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety disorder (GAD) are controversial, and the molecular mechanisms underlying such dysfunction remain unclear. We analyzed the methylation status of the NR3C1 1F promoter and the expression of glucocorticoid receptor-α isoform (GRα) in peripheral blood mononuclear cells (PMBCs), the basal cortisol level in serum, and a functional neuroendocrine marker for GR sensitivity in the PMBCs in 64 patients with current GAD and 85 healthy controls...
March 3, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28291257/integrated-transcriptome-and-methylome-analysis-in-youth-at-high-risk-for-bipolar-disorder-a-preliminary-analysis
#16
G R Fries, J Quevedo, C P Zeni, I F Kazimi, G Zunta-Soares, D E Spiker, C L Bowden, C Walss-Bass, J C Soares
First-degree relatives of patients with bipolar disorder (BD), particularly their offspring, have a higher risk of developing BD and other mental illnesses than the general population. However, the biological mechanisms underlying this increased risk are still unknown, particularly because most of the studies so far have been conducted in chronically ill adults and not in unaffected youth at high risk. In this preliminary study we analyzed genome-wide expression and methylation levels in peripheral blood mononuclear cells from children and adolescents from three matched groups: BD patients, unaffected offspring of bipolar parents (high risk) and controls (low risk)...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28289693/cav1-2-channels-mediate-persistent-chronic-stress-induced-behavioral-deficits-that-are-associated-with-prefrontal-cortex-activation-of-the-p25-cdk5-glucocorticoid-receptor-pathway
#17
Charlotte C Bavley, Delaney K Fischer, Bryant K Rizzo, Anjali M Rajadhyaksha
Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways...
December 2017: Neurobiology of Stress
https://www.readbyqxmd.com/read/28288856/environmental-enrichment-ameliorates-chronic-immobilisation-stress-induced-spatial-learning-deficits-and-restores-the-expression-of-bdnf-vegf-gfap-and-glucocorticoid-receptors
#18
B M Shilpa, V Bhagya, G Harish, M M Srinivas Bharath, B S Shankaranarayana Rao
Severe and prolonged stress is the main environmental factor that precipitates depression, anxiety and cognitive dysfunctions. On the other hand, exposure to environmental enrichment (EE) has been shown to induce progressive plasticity in the brain and improve learning and memory in various neurological and psychiatric disorders. It is not known whether exposure to enriched environment could ameliorate chronic immobilisation stress-induced cognitive deficits and altered molecular markers. Hence, in the present study we aimed to evaluate the effect of enriched environment on chronic immobilisation stress (CIS) associated changes in spatial learning and memory, behavioural measures of anxiety, depression and molecular markers as well as structural alterations...
March 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28287112/glucocorticoid-receptor-promotes-the-function-of-myeloid-derived-suppressor-cells-by-suppressing-hif1%C3%AE-dependent-glycolysis
#19
Yun Lu, Huanrong Liu, Yujing Bi, Hui Yang, Yan Li, Jian Wang, Zhengguo Zhang, Yu Wang, Chunxiao Li, Anna Jia, Linian Han, Ying Hu, Yong Zhao, Ruoning Wang, Guangwei Liu
Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown. Here, we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury (IMH) and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28285561/adverse-parenting-is-associated-with-blunted-salivary-cortisol-awakening-response-and-altered-expression-of-glucocorticoid-receptor-%C3%AE-and-%C3%AE-2-adrenergic-receptor-mrnas-in-leukocytes-in-japanese-medical-students
#20
Tomoko Kawai, Yuki Kuwano, Kiyoshi Masuda, Kinuyo Fujita, Hiroki Tanaka, Tatsuya Nishikawa, Kazuhito Rokutan, Kensei Nishida
Adverse parenting is associated with an increased risk for the development of mood and behavioral disorders. In this study, we assessed the perceived parental bonding of 232 medical students using the parental bonding instrument (PBI) and extracted 22 students who reported their parents' rearing attitudes as affectionless control (LOW; low care, high overprotection). Using the 28-item general health questionnaire, the Zung self-rating depression scale (Zung-SDS), the hospital anxiety and depression scale (HADS), and the Spielberger state-trait-anxiety-inventory (STAI), physical and mental state of the LOW students were compared with those of 30 students who reported their parental bonding as optimal (OPT; high care and low overprotection)...
March 12, 2017: Stress: the International Journal on the Biology of Stress
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