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https://www.readbyqxmd.com/read/29695779/a-dual-role-for-glucocorticoid-induced-leucine-zipper-in-glucocorticoid-function-tumor-growth-promotion-or-suppression
#1
Emira Ayroldi, Lorenza Cannarile, Domenico V Delfino, Carlo Riccardi
Glucocorticoids (GCs), important therapeutic tools to treat inflammatory and immunosuppressive diseases, can also be used as part of cancer therapy. In oncology, GCs are used as anticancer drugs for lymphohematopoietic malignancies, while in solid neoplasms primarily to control the side effects of chemo/radiotherapy treatments. The molecular mechanisms underlying the effects of GCs are numerous and often overlapping, but not all have been elucidated. In normal, cancerous, and inflammatory tissues, the response to GCs differs based on the tissue type...
April 26, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29681857/a-synthesized-glucocorticoid-induced-leucine-zipper-peptide-inhibits-retinal-m%C3%A3-ller-cell-gliosis
#2
Ruiping Gu, Xinyi Ding, Wenyi Tang, Boya Lei, Chen Jiang, Gezhi Xu
Purpose: The anti-inflammatory activities of protein glucocorticoid-induced leucine zipper (GILZ) have been demonstrated in vivo and in vitro . Here, we examined the potential effect of a synthetic peptide derived from the leucine zipper motif and proline-rich region of GILZ on suppressing inflammatory responses in primary cultured rat Müller cells. Methods: Peptides were selected from amino acids 98-134 of the GILZ protein (GILZ-p). Solid-phase peptide synthesis was used to generate the cell-penetrating peptide TAT, which was bound to the amino terminus of GILZ-p...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29670697/imidazo-2-1-b-benzothiazol-derivatives-as-potential-allosteric-inhibitors-of-the-glucocorticoid-receptor
#3
Michael S Christodoulou, Federico Dapiaggi, Francesca Ghiringhelli, Stefano Pieraccini, Maurizio Sironi, Marianna Lucafò, Debora Curci, Giuliana Decorti, Gabriele Stocco, Chandra Sekhar Chirumamilla, Wim Vanden Berghe, Patrick Balaguer, Benoît Y Michel, Alain Burger, Egle M Beccalli, Daniele Passarella, Nadine Martinet
Glucocorticoid receptor (GCR) transactivation reporter gene assays were used as an initial high-throughput screening on a diversified library of 1200 compounds for their evaluation as GCR antagonists. A class of imidazo[2,1- b ]benzothiazole and imidazo[2,1- b ]benzoimidazole derivatives were identified for their ability to modulate GCR transactivation and anti-inflammatory transrepression effects utilizing GCR and NF-κB specific reporter gene assays. Modeling studies on the crystallographic structure of the GCR ligand binding domain provided three new analogues bearing the tetrahydroimidazo[2,1- b ]benzothiazole scaffold able to antagonize the GCR in the presence of dexamethasone (DEX) and also defined their putative binding into the GCR structure...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29467389/long-glucocorticoid-induced-leucine-zipper-regulates-human-thyroid-cancer-cell-proliferation
#4
Emira Ayroldi, Maria Grazia Petrillo, Maria Cristina Marchetti, Lorenza Cannarile, Simona Ronchetti, Erika Ricci, Luigi Cari, Nicola Avenia, Sonia Moretti, Efisio Puxeddu, Carlo Riccardi
Long glucocorticoid-induced leucine zipper (L-GILZ) has recently been implicated in cancer cell proliferation. Here, we investigated its role in human thyroid cancer cells. L-GILZ protein was highly expressed in well-differentiated cancer cells from thyroid cancer patients and differentiated thyroid cancer cell lines, but poorly expressed in anaplastic tumors. A fusion protein containing L-GILZ, when overexpressed in an L-GILZ-deficient 8505C cell line derived from undifferentiated human thyroid cancer tissue, inhibited cellular proliferation in vitro...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29385519/genomic-dissection-of-enhancers-uncovers-principles-of-combinatorial-regulation-and-cell-type-specific-wiring-of-enhancer-promoter-contacts
#5
Verena Thormann, Maika C Rothkegel, Robert Schöpflin, Laura V Glaser, Petar Djuric, Na Li, Ho-Ryun Chung, Kevin Schwahn, Martin Vingron, Sebastiaan H Meijsing
Genomic binding of transcription factors, like the glucocorticoid receptor (GR), is linked to the regulation of genes. However, as we show here, GR binding is a poor predictor of GR-dependent gene regulation even when taking the 3D organization of the genome into account. To connect GR binding sites to the regulation of genes in the endogenous genomic context, we turned to genome editing. By deleting GR binding sites, individually or in combination, we uncovered how cooperative interactions between binding sites contribute to the regulation of genes...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29347214/quantum-hamiltonian-daemons-unitary-analogs-of-combustion-engines
#6
Eike P Thesing, Lukas Gilz, James R Anglin
Hamiltonian daemons have recently been defined classically as small, closed Hamiltonian systems which can exhibit secular energy transfer from high-frequency to low-frequency degrees of freedom (steady downconversion), analogous to the steady transfer of energy in a combustion engine from the high terahertz frequencies of molecular excitations to the low kilohertz frequencies of piston motion [L. Gilz, E. P. Thesing, and J. R. Anglin, Phys. Rev. E 94, 042127 (2016)2470-004510.1103/PhysRevE.94.042127]. Classical daemons achieve downconversion within a small, closed system by exploiting nonlinear resonances; the adiabatic theorem permits their operation but imposes nontrivial limitations on their efficiency...
July 2017: Physical Review. E
https://www.readbyqxmd.com/read/29344311/gilz-activin-a-as-a-novel-signaling-axis-orchestrating-mesenchymal-stem-cell-and-th17-cell-interplay
#7
Patricia Luz-Crawford, Gabriel Espinosa-Carrasco, Natacha Ipseiz, Rafael Contreras, Gautier Tejedor, Daniel A Medina, Ana-Maria Vega-Letter, Devi Ngo, Eric F Morand, Jérôme Pène, Javier Hernandez, Christian Jorgensen, Farida Djouad
Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive. Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO2 secreted by MSC...
2018: Theranostics
https://www.readbyqxmd.com/read/29319166/long-non-coding-rna-tcons_00041960-enhances-osteogenesis-and-inhibits-adipogenesis-of-rat-bone-marrow-mesenchymal-stem-cell-by-targeting-mir-204-5p-and-mir-125a-3p
#8
Guowei Shang, Yadong Wang, Yan Xu, Shanfeng Zhang, Xiaoya Sun, Hongya Guan, Xuefeng Zhao, Yisheng Wang, Yuebai Li, Guoqiang Zhao
A growing number of long non-coding RNAs (lncRNAs) have been found to be involved in diverse biological processes such as cell cycle regulation, embryonic development, and cell differentiation. However, limited knowledge is available concerning the underlying mechanisms of lncRNA functions. In this study, we found down-regulation of TCONS_00041960 during adipogenic and osteogenic differentiation of glucocorticoid-treated bone marrow mesenchymal stem cells (BMSCs). Furthermore, up-regulation of TCONS_00041960 promoted expression of osteogenic genes Runx2, osterix, and osteocalcin, and anti-adipogenic gene glucocorticoid-induced leucine zipper (GILZ)...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29278648/clock-represses-preadipocytes-adipogenesis-via-gilz
#9
Zhu Zhu, Lirong Xu, Tingting Cai, Gongsheng Yuan, Ning Sun, Chao Lu, Ruizhe Qian
Adiposity is a worldwide health threat that needs to be prevented. Circadian gene Clock (circadian locomotor output cycles kaput) is closely correlated to adiposity; for example, weight gain, adipocytes size expansion, and serum lipid level rise in ClockΔ19 mice compared to C57BL/6J mice. However, the precise role of Clock during adipogenic differentiation is unknown. Herein, the circadian gene Clock is shown to regulate adipogenesis mediated by GILZ. Clock-mediated attenuation and upregulation influenced lipid synthesis and affected the levels of adipogenic transcriptional factors, C/EBP-β, C/EBP-α, PPAR-γ, and FABP4, both in vivo and in vitro (primary adipose-derived stromal cells and 3T3-L1 cells)...
December 26, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29190094/active-glucocorticoids-have-a-range-of-important-adverse-developmental-and-physiological-effects-on-developing-zebrafish-embryos
#10
Raffael Alois Willi, Susanne Faltermann, Timm Hettich, Karl Fent
Glucocorticoids in aquatic systems originating from natural excretion and medical use may pose a risk to fish. Here, we analyzed physiological and transcriptional effects of clobetasol propionate (CLO), cortisol and cortisone in zebrafish embryos as single compounds and binary mixtures. CLO and cortisol, but not cortisone showed a concentration-dependent decrease in muscle contraction, increase in heart rate, and accelerated hatching. CLO also induced immobilization and edema at high concentrations. Transcription analysis covering up to 26 genes showed that mostly genes related to glucose metabolism, immune system and development were differentially expressed at 91 ng/L and higher...
January 16, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29146236/infectious-bursal-disease-virus-protein-vp4-suppresses-type-i-interferon-expression-via-inhibiting-k48-linked-ubiquitylation-of-glucocorticoid-induced-leucine-zipper-gilz
#11
Zhiyuan He, Xiang Chen, Mengjiao Fu, Jun Tang, Xiaoqi Li, Hong Cao, Yongqiang Wang, Shijun J Zheng
Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-β expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-β expression and GILZ ubiquitylation...
April 2018: Immunobiology
https://www.readbyqxmd.com/read/29059216/protective-effect-of-dexamethasone-on-5-fu-induced-oral-mucositis-in-hamsters
#12
Susana Barbosa Ribeiro, Aurigena Antunes de Araújo, Raimundo Fernandes de Araújo Júnior, Gerly Anne de Castro Brito, Renata Carvalho Leitão, Maisie Mitchele Barbosa, Vinicius Barreto Garcia, Aldo Cunha Medeiros, Caroline Addison Carvalho Xavier de Medeiros
Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4...
2017: PloS One
https://www.readbyqxmd.com/read/28916285/profiling-of-bisphenol-s-towards-nuclear-receptors-activities-in-human-reporter-cell-lines
#13
Ondrej Zenata, Zdenek Dvorak, Radim Vrzal
Bisphenol S (BPS) is heat-stable structural analog of bisphenol A (BPA), a known endocrine disruptor. Due to the effort to replace BPA with BPS, it is essential to know if BPS is suitable non-toxic replacement without reported deleterious effects of BPA. Since most of the BPA effects are ascribed to its ability to activate nuclear receptors, we screened some prominent members of this family in order to confirm or refute some recent findings. We found that BPS insignificantly activated aryl hydrocarbon receptor (AhR) in reporter gene assay and no induction of AhR target gene CYP1A1 was observed in human hepatocytes (HH)...
November 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28884339/altered-expression-of-circadian-clock-genes-in-polyglandular-autoimmune-syndrome-type-iii
#14
Anna Angelousi, Narjes Nasiri-Ansari, Eliana Spilioti, Emilia Mantzou, Vasiliki Kalotyxou, George Chrousos, Gregory Kaltsas, Eva Kassi
PURPOSE: Circadian timing system is a highly conserved, ubiquitous molecular "clock" which creates internal circadian rhythmicity. Dysregulation of clock genes expression is associated with various diseases including immune dysregulation. In this study we investigated the circadian pattern of Clock-related genes in patients with polyglandular autoimmune syndrome type III (PAS type III). METHODS: Nineteen patients diagnosed with PAS type III and 12 healthy controls were enrolled...
January 2018: Endocrine
https://www.readbyqxmd.com/read/28806151/establishment-of-a-monoclonal-antibody-against-chgilz
#15
Zhiyuan He, Yongqiang Wang
The chicken glucocorticoid-induced leucine zipper (chGILZ) participates in the inflammation of avian immunosuppressive diseases. We aimed to establish a monoclonal antibody (MAb) against chGILZ and to investigate its distribution in clinical diagnosis. A gene cloned from chicken embryo fibroblast (CEF) cell was inserted into the expression vector pET-28a and pGEX-6p-1. The recombinant expression vectors were transformed into Escherichia coli BL21 (DE3). Then the recombinant proteins His-chGILZ and GST-chGILZ were successfully expressed and purified...
August 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28771604/role-of-glucocorticoid-induced-leucine-zipper-gilz-in-inflammatory-bone-loss
#16
Nianlan Yang, Babak Baban, Carlos M Isales, Xing-Ming Shi
TNF-α plays a key role in the development of rheumatoid arthritis (RA) and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs) also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ), a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg) by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3...
2017: PloS One
https://www.readbyqxmd.com/read/28754349/effect-of-steviol-steviol-glycosides-and-stevia-extract-on-glucocorticoid-receptor-signaling-in-normal-and-cancer-blood-cells
#17
Christina Panagiotou, Chrysovalantou Mihailidou, George Brauhli, Olga Katsarou, Paraskevi Moutsatsou
The use of steviol glycosides as non-caloric sweeteners has proven to be beneficial for patients with type 2 diabetes mellitus (T2D), obesity, and metabolic syndrome. However, recent data demonstrate that steviol and stevioside might act as glucocorticoid receptor (GR) agonists and thus correlate with adverse effects on metabolism. Herein, we evaluated the impact of steviol, steviol glycosides, and a Greek-derived stevia extract on a number of key steps of GR signaling cascade in peripheral blood mononuclear cells (PBMCs) and in Jurkat leukemia cells...
January 15, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28729456/mechanistic-multi-tissue-modeling-of-glucocorticoid-induced-leucine-zipper-regulation-integrating-circadian-gene-expression-with-receptor-mediated-corticosteroid-pharmacodynamics
#18
Vivaswath S Ayyar, Debra C DuBois, Richard R Almon, William J Jusko
The glucocorticoid-induced leucine zipper (GILZ) is an important mediator of anti-inflammatory corticosteroid action. The pharmacokinetic/pharmacodynamic/pharmacogenomic effects of acute and chronic methylprednisolone (MPL) dosing on the tissue-specific dynamics of GILZ expression were examined in rats. A mechanism-based model was developed to investigate and integrate the role of MPL and circadian rhythms on the transcriptional enhancement of GILZ in multiple tissues. Animals received a single 50-mg/kg intramuscular bolus or a 7-day 0...
October 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28728173/glucocorticoid-induced-leucine-zipper-protects-the-retina-from-light-induced-retinal-degeneration-by-inducing-bcl-xl-in-rats
#19
Ruiping Gu, Wenyi Tang, Boya Lei, Xinyi Ding, Cheng Jiang, Gezhi Xu
Purpose: The aim of the present study was to investigate the neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ) in a light-induced retinal degeneration model and to explore the underlying mechanisms. Methods: Intravitreal injection of recombinant GILZ-overexpressing lentivirus (OE-GILZ-rLV) and short hairpin RNA targeting GILZ recombinant lentivirus (shRNA-GILZ-rLV) was performed to up- and downregulate retinal GILZ, respectively. Three days after stable transduction, rats were exposed to continuous bright light (5000 lux) for 2 days...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28649452/glucocorticoid-receptor-expression-on-circulating-leukocytes-differs-between-healthy-male-and-female-adults
#20
Kim D Lu, Shlomit Radom-Aizik, Fadia Haddad, Frank Zaldivar, Monica Kraft, Dan M Cooper
INTRODUCTION: The glucocorticoid receptor (GR) is a key receptor involved in inflammatory responses and is influenced by sex steroids. This study measured GR expression on circulating leukocyte subtypes in males and females. METHODS: A total of 23 healthy adults (12 female) participated in this study. GR expression was measured in leukocyte subtypes using flow cytometry. Peripheral blood mononuclear cell (PBMC) gene expression of GR (NR3C1), GR β, TGF-β1 and 2, and glucocorticoid-induced leucine zipper (GILZ) were determined by real-time polymerase chain reaction...
April 2017: Journal of Clinical and Translational Science
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