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https://www.readbyqxmd.com/read/29227474/a-proteolytic-fragment-of-histone-deacetylase-4-protects-the-heart-from-failure-by-regulating-the-hexosamine-biosynthetic-pathway
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28940701/a-bioinformatic-algorithm-for-analyzing-cell-signaling-using-temporal-proteomic-data
#14
Chunchao Zhang, Yue Chen, Xinfang Mao, Yin Huang, Sung Yun Jung, Antrix Jain, Jun Qin, Yi Wang
Significance analysis of proteomic data generated by LC-MS/MS is challenging owing to great data variability originated from biological, operational and instrumental variations. Protein quantification by LC-MS/MS either in absolute or relative scale is often highly skewed, which put limitations on model-based statistical inference. For this purpose, we have developed an alternative non-parametric statistical algorithm (named IQR algorithm) for significance analysis of temporal proteomic data and have successfully applied our strategy in finding gefitinib-targeted transcription factors and coregulators in EGF (Epidermal Growth Factor)-stimulated HeLa cells...
September 22, 2017: Proteomics
https://www.readbyqxmd.com/read/28903348/nuclear-receptor-nr4a1-is-a-tumor-suppressor-down-regulated-in-triple-negative-breast-cancer
#15
Hongmei Wu, Jiong Bi, Yan Peng, Lei Huo, Xiaobin Yu, Zhihui Yang, Yunyun Zhou, Li Qin, Yixiang Xu, Lan Liao, Yang Xie, Orla M Conneely, Jos Jonkers, Jianming Xu
The nuclear receptor (NR) superfamily contains hormone-inducible transcription factors that regulate many physiological and pathological processes through regulating gene expression. NR4A1 is an NR family member that still does not have an identified endogenous ligand, and its role in cancer is also currently unclear and controversial. In this study, we aimed to define the expression profiles and specific role of NR4A1 in the highly malignant triple-negative breast cancer (TNBC), which still lacks available targeted therapies...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28860151/myeloid-receptor-cd36-is-required-for-early-phagocytosis-of-myocardial-infarcts-and-induction-of-nr4a1-dependent-mechanisms-of-cardiac-repair
#16
Shirley Dehn, Edward B Thorp
Phagocytosis after myocardial infarction (MI) is a prerequisite to cardiac repair. Recruited monocytes clear necrotic cardiomyocytes and differentiate into cardiac macrophages. Some studies have linked apoptotic cell receptors on cardiac macrophages to tissue repair; however, the contribution of precursor monocyte phagocytic receptors, which are the first to interact with the cardiac parenchyma, is unclear. The scavenger receptor cluster of differentiation (CD)36 protein was detected on cardiac Ly6cHI monocytes, and bone marrow-derived Cd36 was essential for both early phagocytosis of dying cardiomyocytes and for smaller infarct sizes in female and male mice after permanent coronary ligation...
August 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28844671/transcriptional-profiling-of-human-femoral-mesenchymal-stem-cells-in-osteoporosis-and-its-association-with-adipogenesis
#17
Yong Jun Choi, Insun Song, Yilan Jin, Hyun-Seok Jin, Hyung Min Ji, Seon-Yong Jeong, Ye-Yeon Won, Yoon-Sok Chung
Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries...
October 20, 2017: Gene
https://www.readbyqxmd.com/read/28838387/tr3-is-involved-in-hypoxia-induced-apoptosis-resistance-in-lung-cancer-cells-downstream-of-hif-1%C3%AE
#18
Christoph Wohlkoenig, Katharina Leithner, Andrea Olschewski, Horst Olschewski, Andelko Hrzenjak
OBJECTIVES: Lung cancer is the leading cause of cancer death worldwide. Like in all solid tumors, hypoxia is common in lung cancer and contributes to apoptosis, and thus chemotherapy resistance. However, the underlying mechanisms are not entirely clear. TR3 (NR4A1, Nur77) is an orphan nuclear receptor that induces apoptosis and may mediate chemotherapy-induced apoptosis in cancer cells. MATERIALS AND METHODS: We used A549, H23 and H1299 cell lines to investigate how TR3-mediated apoptosis is affected by hypoxia in non-small cell lung cancer (NSCLC) cells...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28834747/triggering-of-nod2-receptor-converts-inflammatory-ly6c-high-into-ly6c-low-monocytes-with-patrolling-properties
#19
Anne-Julie Lessard, Manon LeBel, Benoit Egarnes, Paul Préfontaine, Peter Thériault, Arnaud Droit, Alexandre Brunet, Serge Rivest, Jean Gosselin
The signals that regulate the fate of circulating monocytes remain unknown. In the present study, we demonstrate that triggering of the NOD2 receptor by muramyl dipeptide (MDP) converts inflammatory Ly6C(high) monocytes into patrolling Ly6C(low) monocytes. Administration of MDP to Nr4a1(-/-) mice, which lack Ly6C(low) monocytes, or to Ly6C(low)-depleted mice led to the emergence of blood-patrolling monocytes with a profile similar to that of Ly6C(low) monocytes, including high expression of CX3CR1 and LFA1...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28818208/catecholamine-dependent-%C3%AE-adrenergic-signaling-in-a-pluripotent-stem-cell-model%C3%A2-of-takotsubo-cardiomyopathy
#20
Thomas Borchert, Daniela Hübscher, Celina I Guessoum, Tuan-Dinh D Lam, Jelena R Ghadri, Isabel N Schellinger, Malte Tiburcy, Norman Y Liaw, Yun Li, Jan Haas, Samuel Sossalla, Mia A Huber, Lukas Cyganek, Claudius Jacobshagen, Ralf Dressel, Uwe Raaz, Viacheslav O Nikolaev, Kaomei Guan, Holger Thiele, Benjamin Meder, Bernd Wollnik, Wolfram-Hubertus Zimmermann, Thomas F Lüscher, Gerd Hasenfuss, Christian Templin, Katrin Streckfuss-Bömeke
BACKGROUND: Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. OBJECTIVES: The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS...
August 22, 2017: Journal of the American College of Cardiology
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