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Nr4a1

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https://www.readbyqxmd.com/read/29470798/nr4a1-contributes-to-high-fat-associated-endothelial-dysfunction-by-promoting-camkii-parkin-mitophagy-pathways
#1
Pei Li, Yuzhi Bai, Xia Zhao, Tian Tian, Liying Tang, Jing Ru, Yun An, Jing Wang
Parkin-related mitophagy is vital for endothelial cell viability and the development of atherosclerosis, although the upstream regulatory factor underlying Parkin-mediated mitophagy in endothelial apoptosis and atherosclerosis progression remains unknown. In the present study, we demonstrated that nuclear receptor subfamily 4 group A member 1 (NR4A1) is actually expressed in aortic endothelial cells (AECs) under oxidized low-density lipoprotein (ox-LDL) treatment in vitro or isolated from high-fat treated mice in vivo...
February 22, 2018: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29454296/effect-of-multiple-low-dose-pgf-2-%C3%AE-injections-on-the-mature-corpus-luteum-in-non-pregnant-bitches
#2
Eyyup H Ucar, Hayrettin Cetin, Mehmet O Atli
This study investigated molecular regulation in the canine corpus luteums/corpora lutea (CL) following multiple low-dose prostaglandin F 2 alpha (PGF 2 α) injections in non-pregnant bitches around 30-35 days after ovulation. The CL were obtained by ovariohysterectomy 1 h after the last PGF 2 α injection. The subjects were divided into the following groups: control (no PGF 2 α injection, n = 4), one PGF 2 α injection (injection at 0 h, 1PGF, n = 4), two PGF 2 α injection (injection at 0 and 8 h, 2PGF, n = 4), and three PGF 2 α injection (injection at 0, 8 and 24 h, 3PGF, n = 4)...
February 14, 2018: Theriogenology
https://www.readbyqxmd.com/read/29409832/the-tumor-suppressor-cholesterol-metabolite-dendrogenin-a-is-a-new-class-of-lxr-modulator-activating-lethal-autophagy-in-cancers
#3
REVIEW
Marc Poirot, Sandrine Silvente-Poirot
Dendrogenin A (DDA) is a mammalian cholesterol metabolite recently identified that displays tumor suppressor properties. The discovery of DDA has revealed the existence in mammals of a new metabolic branch in the cholesterol pathway centered on 5,6α-epoxycholesterol and bridging cholesterol metabolism with histamine metabolism. Metabolic studies showed a drop in DDA levels in cancer cells and tumors compared to normal cells, suggesting a link between DDA metabolism deregulation and oncogenesis. Importantly, complementation of cancer cells with DDA induced 1) cancer cell re-differentiation, 2) blockade of 6-oxo-cholestan-3β,5α-diol (OCDO) production, an endogenous tumor promoter and 3) lethal autophagy in tumors...
January 31, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29371962/overexpression-of-nr4a1-is-associated-with-tumor-recurrence-and-poor-survival-in-non-small-cell-lung-carcinoma
#4
Bing Zhu, Jian-Ru Yang, Yang Jia, Pei Zhang, Lin Shen, Xiao-Long Li, Jing Li, Bing Wang
The expression level and clinical significance of NR4A1 are presently unknown in the non-small-cell lung carcinoma (NSCLC). This study aimed to explore the expression, prognostic value, and function of NR4A1 in NSCLC. METHODS: Clinicopathological parameters of 167 NSCLC patients who received radical surgery from January 2007 and December 2012 were retrospectively reviewed. The NR4A1 expression in NSCLC tumors and the adjacent matched para-carcinoma specimens were examined, and the association between NR4A1 expression and clinical variables was explored...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29343483/nr4a1-and-nr4a3-restrict-hsc-proliferation-via-reciprocal-regulation-of-c-ebp%C3%AE-and-inflammatory-signaling
#5
Pablo R Freire, Orla M Conneely
Members of the NR4A subfamily of nuclear receptors have complex, overlapping roles during hematopoietic cell development and also function as tumor suppressors of hematological malignancies. We previously identified NR4A1 and NR4A3 as functionally redundant suppressors of AML development. However, their role in hematopoietic stem cell (HSC) homeostasis remains to be disclosed. Using a conditional Nr4a1/Nr4a3 knockout mouse (CDKO), we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis including loss of HSC quiescence, accumulation of oxidative stress and DNA damage while maintaining stem cell regenerative and differentiation capacity...
January 17, 2018: Blood
https://www.readbyqxmd.com/read/29295823/the-stress-induced-transcription-factor-nr4a1-adjusts-mitochondrial-function-and-synapse-number-in-prefrontal-cortex
#6
Freddy Jeanneteau, Christian Barrère, Mariska Vos, Carlie Jm De Vries, Claude Rouillard, Daniel Levesque, Yann Dromard, Marie-Pierre Moisan, Vanja Duric, Tina C Franklin, Ronald S Duman, David A Lewis, Stephen D Ginsberg, Margarita Arango-Lievano
The energetic costs of behavioral chronic stress are unlikely to be sustainable without neuronal plasticity. Mitochondria have the capacity to handle synaptic activity up to a limit before energetic depletion occurs. Protective mechanisms driven by the induction of neuronal genes likely evolved to buffer the consequences of chronic stress on excitatory neurons in prefrontal cortex (PFC), as this circuitry is vulnerable to excitotoxic insults. Little is known about the genes involved in mitochondrial adaptation to the build up of chronic stress...
January 2, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29282309/identification-of-a-multipotent-progenitor-population-in-the-spleen-that-is-regulated-by-nr4a1
#7
Melanie D Mumau, Ashley N Vanderbeck, Elizabeth D Lynch, Sophia B Golec, Stephen G Emerson, Jennifer A Punt
The developmental fate of hematopoietic stem and progenitor cells is influenced by their physiological context. Although most hematopoietic stem and progenitor cells are found in the bone marrow of the adult, some are found in other tissues, including the spleen. The extent to which the fate of stem cells is determined by the tissue in which they reside is not clear. In this study, we identify a new progenitor population, which is enriched in the mouse spleen, defined by cKit+CD71lowCD24high expression. This previously uncharacterized population generates exclusively myeloid lineage cells, including erythrocytes, platelets, monocytes, and neutrophils...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29227474/a-proteolytic-fragment-of-histone-deacetylase-4-protects-the-heart-from-failure-by-regulating-the-hexosamine-biosynthetic-pathway
#8
Lorenz H Lehmann, Zegeye H Jebessa, Michael M Kreusser, Axel Horsch, Tao He, Mariya Kronlage, Matthias Dewenter, Viviana Sramek, Ulrike Oehl, Jutta Krebs-Haupenthal, Albert H von der Lieth, Andrea Schmidt, Qiang Sun, Julia Ritterhoff, Daniel Finke, Mirko Völkers, Andreas Jungmann, Sven W Sauer, Christian Thiel, Alexander Nickel, Michael Kohlhaas, Michaela Schäfer, Carsten Sticht, Christoph Maack, Norbert Gretz, Michael Wagner, Ali El-Armouche, Lars S Maier, Juan E Camacho Londoño, Benjamin Meder, Marc Freichel, Hermann-Josef Gröne, Patrick Most, Oliver J Müller, Stephan Herzig, Eileen E M Furlong, Hugo A Katus, Johannes Backs
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP)...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29207128/nr4a1-induced-increase-in-the-sensitivity-of-a-human-gastric-cancer-line-to-tnf%C3%AE-mediated-apoptosis-is-associated-with-the-inhibition-of-jnk-parkin-dependent-mitophagy
#9
Hongzhu Yan, Feng Xiao, Jue Zou, Chengmin Qiu, Weiwei Sun, Minmin Gu, Li Zhang
Tumor necrosis factor α (TNFα)-based immunotherapy is the vital host defense system against the progression of gastric cancer (GC) as a pro-inflammatory and pro-apoptotic cytokine. However, resistance limits its therapeutic efficiency. Therefore, an increasing number of studies are focusing on the development of drugs or methods with which to enhance the treatment efficacy of TNFα. Nuclear receptor subfamily 4 group A member 1 (NR4A1) has been shown to exert antitumor effects through several mechanisms, such as by inhibiting proliferation, as well as pro-apoptotic and potent pro-oxidant effects...
December 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29175309/altered-neuro-inflammatory-gene-expression-in-hippocampus-in-major-depressive-disorder
#10
Gouri J Mahajan, Eric J Vallender, Michael R Garrett, Lavanya Challagundla, James C Overholser, George Jurjus, Lesa Dieter, Maryam Syed, Damian G Romero, Hamed Benghuzzi, Craig A Stockmeier
Major Depressive Disorder (MDD) is a common psychiatric disorder for which available medications are often not effective. The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. Decreased hippocampal volume with increasing duration of depression suggests altered gene expression or even a decrease in neurogenesis. Tissue punches from the dentate gyrus were collected postmortem from 23 subjects with MDD and 23 psychiatrically-normal control subjects...
November 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29165597/gsta1-expression-is-correlated-with-aldosterone-level-in-kcnj5-mutated-adrenal-aldosterone-producing-adenoma
#11
Xintao Li, Baojun Wang, Lu Tang, Yu Zhang, Luyao Chen, Liangyou Gu, Fan Zhang, Jinzhi Ouyang, Xu Zhang
Context: KCNJ5 mutation is a major cause of aldosterone-producing adenoma (APA). The development of APA apart from KCNJ5 mutation is less investigated. Objective: To investigate other mechanisms affecting aldosterone secretion apart from KCNJ5. Patients and Methods: Six pairs of KCNJ5-mutated, high and low aldosterone-secreting APAs, five non-KCNJ5-mutated APAs and four normal adrenal glands were assayed by Affymetrix Genechip Human Transcriptome Array 2...
November 20, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#12
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29105655/pre-metastatic-cancer-exosomes-induce-immune-surveillance-by-patrolling-monocytes-at-the-metastatic-niche
#13
Michael P Plebanek, Nicholas L Angeloni, Elena Vinokour, Jia Li, Anna Henkin, Dalia Martinez-Marin, Stephanie Filleur, Reshma Bhowmick, Jack Henkin, Stephen D Miller, Igal Ifergan, Yesung Lee, Iman Osman, C Shad Thaxton, Olga V Volpert
Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These "non-metastatic" exosomes stimulate an innate immune response through the expansion of Ly6C(low) patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29097167/high-fat-diet-exposure-regardless-of-induction-of-obesity-is-associated-with-altered-expression-of-genes-critical-to-normal-ovulatory-function
#14
Natalie M Hohos, Kirstin J Cho, Delaney C Swindle, Malgorzata E Skaznik-Wikiel
We evaluated the impact of high-fat diet (HFD) on ovarian gene expression. Female 5-week-old C57BL/6J mice were fed a 60% HFD or standard chow for 10 weeks. HFD-fed mice were then separated into obese (HF-Ob) and lean (HF-Ln) based on body weight. HFD exposure led to impairment of the estrous cycle, changes in hormones affecting reproduction, and decreased primordial follicles regardless of the development of obesity. RNA-sequencing of whole ovaries identified multiple genes with altered expression after HFD, with 25 genes displaying decreased expression in both HF-Ln and HF-Ob mice compared to the chow-fed controls (q < 0...
October 30, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29053748/treatment-with-the-nr4a1-agonist-cytosporone-b-controls-influenza-virus-infection-and-improves-pulmonary-function-in-infected-mice
#15
Benoit Egarnes, Marie-Renée Blanchet, Jean Gosselin
The transcription factor NR4A1 has emerged as a pivotal regulator of the inflammatory response and immune homeostasis. Although contribution of NR4A1 in the innate immune response has been demonstrated, its role in host defense against viral infection remains to be investigated. In the present study, we show that administration of cytosporone B (Csn-B), a specific agonist of NR4A1, to mice infected with influenza virus (IAV) reduces lung viral loads and improves pulmonary function. Our results demonstrate that administration of Csn-B to naive mice leads to a modest production of type 1 IFN...
2017: PloS One
https://www.readbyqxmd.com/read/29041844/reduced-expression-of-nr4a1-activates-glycolytic-pathway-in-acute-promyelocytic-leukemia-cells
#16
Flávia Adolfo Corrocher, Luciana Bueno de Paiva, Adriana Silva Santos Duarte, Karla Priscila Ferro, Leonardo Dos Reis Silveira, Tanes Iamamura de Lima, Sara Teresinha Olalla Saad, Mariana Lazarini
No abstract text is available yet for this article.
October 17, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28981157/effects-of-melatonin-on-fatty-liver-disease-the-role-of-nr4a1-dna-pkcs-p53-pathway-mitochondrial-fission-and-mitophagy
#17
Hao Zhou, Wenjuan Du, Ye Li, Chen Shi, Nan Hu, Sai Ma, Weihu Wang, Jun Ren
Mitochondrial dysfunction has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through poorly defined mechanisms. Melatonin supplementation has been found to protect liver function in diabetes and obesity. Here, we intensively explored the role and mechanism of melatonin in the development of NAFLD. We demonstrated that the onset of diet-induced NAFLD greatly caused NR4A1 upregulation in hepatocytes, leading to the activation of DNA-PKcs and p53. On the one hand, p53 aided Drp1 migration in the mitochondria and consequently drove mitochondrial fission...
October 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28980305/ly6c-high-monocytes-facilitate-transport-of-murid-herpesvirus-68-into-inflamed-joints-of-arthritic-mice
#18
Manon LeBel, Benoit Egarnes, Alexandre Brunet, Patricia Lacerte, Alexandre Paré, Steve Lacroix, Jacques P Brown, Jean Gosselin
Viruses, particularly the Epstein-Barr virus (EBV) has long been suspected to exacerbate acute arthritic symptoms. However, the cell populations that contribute to import viruses into the inflamed tissues remain to be identified. In the present study, we have investigated the role of monocytes in the transport of Murid herpesvirus 68 (MHV-68), a mouse virus closely related to EBV, using the serum transfer-induced arthritis (STIA) model. We found compelling evidence that MHV-68 infection markedly increased disease severity in NR4A1-/- mice, which are deficient for Ly6C(low) monocytes...
October 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28962999/nr4a1-plays-a-crucial-modulatory-role-in-th1-th17-cell-responses-and-cns-autoimmunity
#19
Li-Mei Wang, Yuan Zhang, Xing Li, Ming-Liang Zhang, Lin Zhu, Guang-Xian Zhang, Yu-Ming Xu
Nuclear receptor4 group A1 (Nr4a1), an orphan nuclear receptor, is down-regulated in peripheral blood mononuclear cells (MNCs) of individuals with multiple sclerosis (MS), and Nr4a1 deficiency results in severe experimental autoimmune encephalomyelitis (EAE), an animal model of MS, caused by increased macrophage infiltration into the central nervous system (CNS). However, the role of Nr4a1 in macrophage phenotype and T cell responses remains poorly understood. In the present study we show that macrophages/microglia of Nr4a1(-/-) mice, which exhibited earlier onset and more severe clinical EAE, were polarized to an enhanced type 1 (M1) phenotype and produced higher levels of IL-12 and TNF-α than wild type mice...
September 26, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28951217/assessing-molecular-initiating-events-mies-key-events-kes-and-modulating-factors-mfs-for-styrene-responses-in-mouse-lungs-using-whole-genome-gene-expression-profiling-following-1-day-and-multi-week-exposures
#20
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Patrick D McMullen
Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP2F2(-/-) transgenic containing human CYP2F1, 2A13 and 2B6). Exposures were for 1-day and 1, 4 and 26weeks. After 1-day exposures at 1, 5, 10, 20, 40 and 120ppm significant increases in differentially expressed genes (DEGs) occurred only in parental strain lungs where there was already an increase in DEGs at 5ppm and then many thousands of DEGs by 120ppm...
November 15, 2017: Toxicology and Applied Pharmacology
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