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Nr4a1

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https://www.readbyqxmd.com/read/29678743/the-orphan-nuclear-receptor-nr4a1-attenuates-oxidative-stress-induced-%C3%AE-cells-apoptosis-via-up-regulation-of-glutathione-peroxidase-1
#1
Yingfeng Yang, Fangyu Xie, Dandan Qin, Chen Zong, Feng Han, Zeqing Pu, Dong Liu, Xia Li, Yuchao Zhang, Yuantao Liu, Xiangdong Wang
AIMS: Our previous study showed that NR4A1 protects against oxidative stress-induced cell apoptosis. However, the targets downstream of NR4A1 are incompletely known. Glutathione peroxidase 1 (GPX1) is the most common antioxidant enzyme in the glutathione peroxidase class. In this study, we aimed to investigate whether GPX1 is a mediator of the protective effects of NR4A1 in pancreatic β cells. MAIN METHODS: A pancreatic β cell line, MIN6, was used to generate NR4A1 over-expression cell line...
April 17, 2018: Life Sciences
https://www.readbyqxmd.com/read/29669342/nr4a1-is-involved-in-fibrogenesis-in-ovarian-endometriosis
#2
Xinliu Zeng, Zhang Yue, Ying Gao, Guosong Jiang, Fuqing Zeng, Ying Shao, Jiayu Huang, Minuo Yin, Yajie Li
BACKGROUND/AIMS: Excess fibrosis may lead to chronic pain, scarring, and infertility as endometriosis develops and progresses. The pathogenesis of endometriosis has been linked to transforming growth factor-β (TGF-β), the most potent promoter of fibrosis. METHODS: Levels of NR4A1 and P-NR4A1 protein in human endometrial and endometriotic tissue were assessed by western blotting and immunohistochemistry. The expression levels of fibrotic markers in stromal cells were evaluated by real-time PCR...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29559474/inhibition-of-nr4a-receptors-enhances-anti-tumor-immunity-by-breaking-treg-mediated-immune-tolerance
#3
Sana Hibino, Shunsuke Chikuma, Taisuke Kondo, Minako Ito, Hiroko Nakatsukasa, Setsuko Omata-Mise, Akihiko Yoshimura
Enhanced infiltration of regulatory T (Treg) cells into tumor tissue is detrimental to cancer patients and closely associated with poor prognosis as they create an immunosuppressive state that suppresses anti-tumor immune responses. Therefore, breaking Treg-mediated immune tolerance is important when considering cancer immunotherapy. Here we show that the Nr4a nuclear receptors, key transcription factors maintaining Treg cell genetic programs, contribute to Treg-mediated suppression of anti-tumor immunity in the tumor microenvironment...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29538345/transcriptomic-profiles-of-brain-provide-insights-into-molecular-mechanism-of-feed-conversion-efficiency-in-crucian-carp-carassius-auratus
#4
Meixia Pang, Weiwei Luo, Beide Fu, Xiaomu Yu, Ying Zhou, Jingou Tong
Feed efficiency is an economically crucial trait for cultured animals, however, progress has been scarcely made in the genetic analyses of feed conversion efficiency (FCE) in fish because of the difficulties in measurement of trait phenotypes. In the present investigation, we present the first application of RNA sequencing (RNA-Seq) combined with differentially expressed genes (DEGs) analysis for identification of functional determinants related to FCE at the gene level in an aquaculture fish, crucian carp ( Carassius auratus )...
March 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29530712/genetic-disruption-of-the-nuclear-receptor-nur77-nr4a1-in-rat-reduces-dopamine-cell-loss-and-l-dopa-induced-dyskinesia-in-experimental-parkinson-s-disease
#5
Claude Rouillard, Joanie Baillargeon, Brigitte Paquet, Michel St-Hilaire, Jérôme Maheux, Catherine Lévesque, Noémie Darlix, Simon Majeur, Daniel Lévesque
Parkinson's disease (PD) is an idiopathic progressive neurodegenerative disorder characterized by the loss of midbrain dopamine neurons. Levodopa (l-dopa) is the main pharmacological approach to relieve PD motor symptoms. However, chronic treatment with l-Dopa is inevitably associated with the generation of abnormal involuntary movements (l-Dopa-induced dyskinesia). We have previously shown that Nr4a1 (Nur77), a transcription factor of the nuclear receptor family, is closely associated with dopamine neurotransmission in the mature brain...
March 9, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29498706/new-drug-candidate-targeting-the-4a1-orphan-nuclear-receptor-for-medullary-thyroid-cancer-therapy
#6
Lei Zhang, Wen Liu, Qun Wang, Qinpei Li, Huijuan Wang, Jun Wang, Tieshan Teng, Mingliang Chen, Ailing Ji, Yanzhang Li
Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29470798/nr4a1-contributes-to-high-fat-associated-endothelial-dysfunction-by-promoting-camkii-parkin-mitophagy-pathways
#7
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
#8
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
#9
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...
February 1, 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
#10
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
#11
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 hematologic malignancies. We previously identified NR4A1 and NR4A3 (NR4A1/3) as functionally redundant suppressors of acute myeloid leukemia (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...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29295823/the-stress-induced-transcription-factor-nr4a1-adjusts-mitochondrial-function-and-synapse-number-in-prefrontal-cortex
#12
Freddy Jeanneteau, Christian Barrère, Mariska Vos, Carlie J M 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 buildup of chronic stress...
February 7, 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
#13
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+ CD71low CD24high expression. This previously uncharacterized population generates exclusively myeloid lineage cells, including erythrocytes, platelets, monocytes, and neutrophils...
February 1, 2018: 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
#14
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)...
January 2018: 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
#15
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...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29175309/altered-neuro-inflammatory-gene-expression-in-hippocampus-in-major-depressive-disorder
#16
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...
March 2, 2018: 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
#17
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
#18
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 45Ca2+ influx by 2-fold that was abolished by L-type voltage-gated Ca2+ channel blocker nicardipine, but it was resistant to Na+ /Ca2+ exchanger inhibitor KB-R7943. To study the role of Ca2+ -mediated signaling in the expression of Na+ i /K+ i -sensitive genes we used intracellular Ca2+ chelator BAPTA and incubated RVSMC in Ca2+ -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
#19
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 Ly6Clow 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
#20
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
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