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https://www.readbyqxmd.com/read/29888229/nuclear-receptors-and-neuroinflammation-in-schizophrenia
#1
Shan-Yuan Tsai, Vibeke S Catts, Janice M Fullerton, Susan M Corley, Stuart G Fillman, Cynthia Shannon Weickert
Introduction: Several nuclear receptor family members have been associated with schizophrenia and inflammation. Vitamins A and D exert anti-inflammatory actions, but their receptors (mainly nuclear receptors) have not been extensively studied in either schizophrenia brains or in association with neuroinflammation. We examined the expression of vitamin A (RARs and RXRs) and vitamin D and protein disulphide-isomerase A3 (PDIA3) receptors, as well as nuclear orphan receptors (NR4As), in the context of elevated cytokine expression in the dorsolateral prefrontal cortex (DLPFC)...
May 2018: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29861853/oxidized-analogs-of-di-1-h-indol-3-yl-methyl-4-substituted-benzenes-are-nr4a1-dependent-upr-inducers-with-potent-and-safe-anti-cancer-activity
#2
Marisa Sanchez, Zebin Xia, Elizabeth Rico-Bautista, Xihua Cao, Michael Cuddy, David J Castro, Ricardo G Correa, Liqun Chen, Jinghua Yu, Andrey Bobkov, Vivian Ruvolo, Michael Andreeff, Robert G Oshima, Shu-Ichi Matsuzawa, John C Reed, Xiao-Kun Zhang, Donna Hansel, Dieter A Wolf, Marcia I Dawson
Di(1 H -indol-3-yl)(4-trifluoromethylphenyl)methane (DIM-Ph-4-CF3 ) is an analog of orphan nuclear receptor 4A1 (NR4A1) ligand cytosporone B. We have synthesized several oxidation products of DIM-Ph-4-CF3 , focusing on analogs with electron-withdrawing or donating groups at their phenyl ring 4-positions, and examined their anti-cancer activity and mechanism-of-action. Mesylates (DIM-Ph-4-X+ OMs- s) having CF3 , CO2 Me and Cl groups were more effective inhibitors of cancer cell viability than their precursors...
May 18, 2018: Oncotarget
https://www.readbyqxmd.com/read/29859287/molecular-network-pathway-and-functional-analysis-of-time-dependent-gene-changes-related-to-cathepsin-g-exposure-in-neonatal-rat-cardiomyocytes
#3
Sanket Kumar Shukla, Kunal Sikder, Amrita Sarkar, Sankar Addya, Khadija Rafiq
The molecular pathways activated in response to acute cathepsin G (CG) exposure, as well as the mechanisms involved in activation of signaling pathways that culminate in myocyte detachment and apoptosis remain unclear. This study aimed to determine the changes in gene expression patterns associated with time dependent CG exposure to neonatal rat cardiomyocytes (NRCMs). Microarray analysis revealed a total of 451, 572 and 1127 differentially expressed genes after CG exposure at 1, 4 and 8 h respectively. A total of 54 overlapped genes at each time point were mapped by Ingenuity Pathway Analysis (IPA)...
May 30, 2018: Gene
https://www.readbyqxmd.com/read/29846361/deficiency-of-the-transcription-factor-nr4a1-enhances-bacterial-clearance-and-prevents-lung-injury-during-escherichia-coli-pneumonia
#4
Ping Cui, Shuijing Wu, Xia Xu, Hui Ye, Jinchao Hou, Xu Liu, Haihong Wang, Xiangming Fang
BACKGROUND: Bacterial pneumonia is one of the most common diagnoses and a leading cause of death in the intensive care unit. NR4A1 is an early response gene that has been identified as a vital regulator of immune and inflammatory responses. This study aims to explore the role of NR4A1 in Escherichia coli (E. coli) pneumonia. METHODS: Alveolar macrophages (AMs) were isolated from Wide type (WT) and NR4A1 knock out (Nr4a1) mice, and the NR4A1 expression and phagocytic capacity against E...
May 24, 2018: Shock
https://www.readbyqxmd.com/read/29752062/single-cell-rna-sequencing-of-lymph-node-stromal-cells-reveals-niche-associated-heterogeneity
#5
Lauren B Rodda, Erick Lu, Mariko L Bennett, Caroline L Sokol, Xiaoming Wang, Sanjiv A Luther, Ben A Barres, Andrew D Luster, Chun Jimmie Ye, Jason G Cyster
Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19lo TRCs, likely including cholesterol-25-hydroxylase+ cells located at the T-zone perimeter, Cxcl9+ TRCs in the T-zone and interfollicular region, CD34+ SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase+ SCs in the medullary cords, and Nr4a1+ SCs in several niches...
April 26, 2018: Immunity
https://www.readbyqxmd.com/read/29744594/nr4a1-aggravates-the-cardiac-microvascular-ischemia-reperfusion-injury-through-suppressing-fundc1-mediated-mitophagy-and-promoting-mff-required-mitochondrial-fission-by-ck2%C3%AE
#6
Hao Zhou, Jin Wang, Pingjun Zhu, Hong Zhu, Sam Toan, Shunying Hu, Jun Ren, Yundai Chen
Mitochondrial fission and mitophagy are considered key processes involved in the pathogenesis of cardiac microvascular ischemia reperfusion (IR) injury although the upstream regulatory mechanism for fission and mitophagy still remains unclear. Herein, we reported that NR4A1 was significantly upregulated following cardiac microvascular IR injury, and its level was positively correlated with microvascular collapse, endothelial cellular apoptosis and mitochondrial damage. However, NR4A1-knockout mice exhibited resistance against the acute microvascular injury and mitochondrial dysfunction compared with the wild-type mice...
May 9, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29739797/epigenetic-regulation-of-aldosterone-synthase-gene-by-sodium-and-angiotensin-ii
#7
Yoshimichi Takeda, Masashi Demura, Fen Wang, Shigehiro Karashima, Takashi Yoneda, Mitsuhiro Kometani, Atsushi Hashimoto, Daisuke Aono, Shin-Ichi Horike, Makiko Meguro-Horike, Masakazu Yamagishi, Yoshiyu Takeda
BACKGROUND: DNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene ( CYP11B2 ). METHODS AND RESULTS: DNA methylation of CYP11B2 was analyzed in aldosterone-producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels...
May 8, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29726098/mef2-induction-of-the-immediate-early-gene-hr38-nr4a-is-terminated-by-sirt1-to-promote-ethanol-tolerance
#8
Pratik Adhikari, Donnoban Orozco, Harpreet Randhawa, Fred W Wolf
Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors...
May 3, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29700293/dna-methylation-through-dnmt1-has-an-essential-role-in-the-development-of-gastrointestinal-smooth-muscle-cells-and-disease
#9
Brian G Jorgensen, Robyn M Berent, Se Eun Ha, Kazuhide Horiguchi, Kent C Sasse, Laren S Becker, Seungil Ro
DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMCs) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMCs are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency...
April 27, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29680662/insulin-sensitivity-linked-skeletal-muscle-nr4a1-dna-methylation-is-programmed-by-the-maternal-diet-and-modulated-by-voluntary-exercise-in-mice
#10
Juliane Kasch, Isabel Kanzleiter, Sophie Saussenthaler, Annette Schürmann, Jaap Keijer, Evert van Schothorst, Susanne Klaus, Sara Schumann
Perinatal maternal high-fat consumption is known to increase the obesity and type 2 diabetes susceptibility and to impair exercise performance in the offspring. We hypothesize that epigenetic modifications in the skeletal muscle are partly responsible for this phenotype. To detect skeletal muscle genes affected by maternal nutrition, male offspring of low-fat (LF) and high-fat (HF) diet fed dams (BL6 mice) received LF diet upon weaning and were sacrificed at 6 or 25 weeks of age. Gene expression of Musculus quadriceps was investigated by microarray analysis revealing an up-regulation of the nuclear receptor Nr4a1 by maternal HF feeding...
March 21, 2018: Journal of Nutritional Biochemistry
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
#11
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...
June 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29669342/nr4a1-is-involved-in-fibrogenesis-in-ovarian-endometriosis
#12
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...
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
#13
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
#14
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
#15
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...
June 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29498706/new-drug-candidate-targeting-the-4a1-orphan-nuclear-receptor-for-medullary-thyroid-cancer-therapy
#16
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
#17
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
#18
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 F2 alpha (PGF2 α) injections in non-pregnant bitches around 30-35 days after ovulation. The CL were obtained by ovariohysterectomy 1 h after the last PGF2 α injection. The subjects were divided into the following groups: control (no PGF2 α injection, n = 4), one PGF2 α injection (injection at 0 h, 1PGF, n = 4), two PGF2 α injection (injection at 0 and 8 h, 2PGF, n = 4), and three PGF2 α injection (injection at 0, 8 and 24 h, 3PGF, n = 4)...
June 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
#19
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
#20
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
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