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https://www.readbyqxmd.com/read/28822763/activating-transcription-factor-3-regulates-chemokine-expression-in-contracting-c2c12-myotubes-and-in-mouse-skeletal-muscle-after-eccentric-exercise
#1
R Fernández-Verdejo, A M Vanwynsberghe, T Hai, L Deldicque, M Francaux
Activating transcription factor (ATF) 3 regulates chemokine expression in various cell types and tissues. Herein, we studied this regulation in contracting muscle cells in vitro, and in skeletal muscle after muscle-damaging exercise in vivo. C2C12 myotubes with normal or low ATF3 levels (atf3_siRNA) were electrically stimulated (EPS). Also, ATF3-knockout (ATF3-KO) and control mice ran downhill until exhaustion, and muscles were analyzed post-exercise. EPS increased ATF3 levels in myotubes (P < 0.01). Chemokine C-C motif ligand (ccl) 2 mRNA increased post-EPS, but atf3_siRNA attenuated the response (P < 0...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28821775/atf3-negatively-regulates-cellular-antiviral-signaling-and-autophagy-in-the-absence-of-type-i-interferons
#2
Vikas Sood, Kiran Bala Sharma, Vishal Gupta, Dhurjhoti Saha, Parashar Dhapola, Manish Sharma, Utsav Sen, Shigetaka Kitajima, Shantanu Chowdhury, Manjula Kalia, Sudhanshu Vrati
Stringent regulation of antiviral signaling and cellular autophagy is critical for the host response to virus infection. However, little is known how these cellular processes are regulated in the absence of type I interferon signaling. Here, we show that ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. We have identified new targets of ATF3 and show that it binds to the promoter regions of Stat1, Irf9, Isg15 and Atg5 thereby inhibiting cellular antiviral signaling and autophagy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28803237/atf3-dependent-regulation-of-egr1-in-vitro-and-in-vivo
#3
Ilona Schoen, Sabine Koitzsch
BACKGROUND/AIMS: Activating transcription factor 3 (ATF3) and early growth response protein 1 (EGR1) are reported to interact, but their use as prognostic factors in cancer is discussed controversially. METHODS: We measured ATF3 and EGR1 gene expression changes in human mini-organ cultures (MOCs) of healthy nasal epithelia, UM-SCC-22B, and FADUDD cells after acid reflux exposure. Next, ATF3 and EGR1 gene expression was analysed in tumour tissues and related to the median expression of autologous reference tissue samples...
August 12, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28794819/upregulation-of-autophagy-genes-and-the-unfolded-protein-response-in-human-heart-failure
#4
Brian C Jensen, Scott J Bultman, Darcy Holley, Wei Tang, Gustaaf de Ridder, Salvatore Pizzo, Dawn Bowles, Monte S Willis
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1...
2017: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28790348/use-antibiotics-in-cell-culture-with-caution-genome-wide-identification-of-antibiotic-induced-changes-in-gene-expression-and-regulation
#5
Ann H Ryu, Walter L Eckalbar, Anat Kreimer, Nir Yosef, Nadav Ahituv
Standard cell culture guidelines often use media supplemented with antibiotics to prevent cell contamination. However, relatively little is known about the effect of antibiotic use in cell culture on gene expression and the extent to which this treatment could confound results. To comprehensively characterize the effect of antibiotic treatment on gene expression, we performed RNA-seq and ChIP-seq for H3K27ac on HepG2 cells, a human liver cell line commonly used for pharmacokinetic, metabolism and genomic studies, cultured in media supplemented with penicillin-streptomycin (PenStrep) or vehicle control...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28784845/oxidized-low-density-lipoprotein-loading-of-macrophages-downregulates-tlr-induced-proinflammatory-responses-in-a-gene-specific-and-temporal-manner-through-transcriptional-control
#6
Jenny Jongstra-Bilen, Cindy X Zhang, Timothy Wisnicki, Mengyi K Li, Samantha White-Alfred, Ragave Ilaalagan, Dario M Ferri, Ashley Deonarain, Mark H Wan, Sharon J Hyduk, Carolyn L Cummins, Myron I Cybulsky
Hypercholesterolemia is a key risk factor for atherosclerosis and leads to the uptake of native and oxidized low-density lipoprotein (oxLDL) by macrophages (Mϕs) and foam cell formation. Inflammatory processes accompany Mϕ foam cell formation in the artery wall, yet the relationship between Mϕ lipid loading and their response to inflammatory stimuli remains elusive. We investigated proinflammatory gene expression in thioglycollate-elicited peritoneal Mϕs, bone marrow-derived Mϕs and dendritic cells, and RAW264...
August 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28784776/stress-inducible-gene-atf3-in-the-noncancer-host-cells-contributes-to-chemotherapy-exacerbated-breast-cancer-metastasis
#7
Yi Seok Chang, Swati P Jalgaonkar, Justin D Middleton, Tsonwin Hai
Chemotherapy is a double-edged sword. It is anticancer because of its cytotoxicity. Paradoxically, by increasing chemoresistance and cancer metastasis, it is also procancer. However, the underlying mechanisms for chemotherapy-induced procancer activities are not well understood. Here we describe the ability of paclitaxel (PTX), a frontline chemotherapeutic agent, to exacerbate metastasis in mouse models of breast cancer. We demonstrate that, despite the apparent benefit of reducing tumor size, PTX increased the circulating tumor cells in the blood and enhanced the metastatic burden at the lung...
August 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28776714/the-bonding-picture-in-hypervalent-xf3-x%C3%A2-%C3%A2-cl-br-i-at-fluorides-revisited-with-quantum-chemical-topology
#8
Mohamed Amaouch, Dumitru-Claudiu Sergentu, David Steinmetz, Rémi Maurice, Nicolas Galland, Julien Pilmé
Hypervalent XF3 (X = Cl, Br, I, At) fluorides exhibit T-shaped C2V equilibrium structures with the heavier of them, AtF3 , also revealing an almost isoenergetic planar D3h structure. Factors explaining this behavior based on simple "chemical intuition" are currently missing. In this work, we combine non-relativistic (ClF3 ), scalar-relativistic and two-component (X = Br - At) density functional theory calculations, and bonding analyses based on the electron localization function and the quantum theory of atoms in molecules...
August 3, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28765281/p38-mapk-inhibits-nonsense-mediated-rna-decay-in-response-to-persistent-dna-damage-in-non-cycling-cells
#9
Andrew Nickless, Abigael Cheruiyot, Kevin C Flanagan, David Piwnica-Worms, Sheila A Stewart, Zhongsheng You
Persistent DNA damage induces profound alterations in gene expression, which in turn influence tissue homeostasis, tumorigenesis, and cancer treatment outcome. However, the underlying mechanism for the gene expression reprogramming induced by persistent DNA damage remains poorly understood. Here, using a highly effective bioluminescence-based reporter system and other tools, we report that persistent DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, in noncycling cells...
August 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716058/srf-modulates-seizure-occurrence-activity-induced-gene-transcription-and-hippocampal-circuit-reorganization-in-the-mouse-pilocarpine-epilepsy-model
#10
Pascal Lösing, Cristina Elena Niturad, Merle Harrer, Christopher Meyer Zu Reckendorf, Theresa Schatz, Daniela Sinske, Holger Lerche, Snezana Maljevic, Bernd Knöll
A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance...
July 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28714032/atf3-promotes-migration-and-m1-m2-polarization-of-macrophages-by-activating-tenascin%C3%A2-c-via-wnt-%C3%AE-%C3%A2-catenin-pathway
#11
Hao Sha, Dianzhong Zhang, Yunfei Zhang, Yanhua Wen, Yucai Wang
There are different polarization states of macrophages, including the classically activated M1 phenotype and the alternatively activated M2 phenotype. These have different functions in the inflammation process. Activating transcription factor 3 (ATF3) is a key transcriptional regulator that inhibits the inflammatory response. However, the effects of ATF3 on migration and anti‑inflammatory control mechanisms of macrophages have not been thoroughly investigated. The present study investigated the effect of ATF3 on macrophage migration and M1/M2 polarization...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28701342/activating-transcription-factor-3-promotes-loss-of-the-acinar-cell-phenotype-in-response-to-cerulein-induced-pancreatitis-in-mice
#12
Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin
Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). While down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by Next Generation Sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of more than 30% of differentially expressed genes during the initiation of pancreatitis...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28689354/functional-and-molecular-characterization-of-a-novel-traumatic-peripheral-nerve-muscle-injury-model
#13
Renate Wanner, Manuel Gey, Alireza Abaei, Daniela Warnecke, Luisa de Roy, Lutz Dürselen, Volker Rasche, Bernd Knöll
Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice...
July 8, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28686848/transcriptional-regulation-of-endmt-in-cardiac-fibrosis-role-of-mrtf-a-and-atf3
#14
Vibhuti Sharma, Nilambra Dogra, Uma Saikia, Madhu Khullar
The etiology of cardiac fibrogenesis is quite diverse but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined...
July 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28684431/convergent-roles-of-atf3-and-csl-in-chromatin-control-of-cancer-associated-fibroblast-activation
#15
Dong Eun Kim, Maria-Giuseppina Procopio, Soumitra Ghosh, Seung-Hee Jo, Sandro Goruppi, Francesco Magliozzi, Pino Bordignon, Victor Neel, Paolo Angelino, G Paolo Dotto
Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28662411/activating-transcription-factor-3-protects-mice-against-pseudomonas-aeruginosa-induced-acute-lung-injury-by-interacting-with-lipopolysaccharide-binding-protein
#16
Yunfeng Zhao, Xiulin Wu, Lanlan Qian, Liang Guo, Jiangrong Liao, Xueling Wu
Excessive inflammatory response is critical event in the pathogenesis of acute lung injury (ALI). Previous study has shown that activating transcription factor 3 (ATF3) plays a role in downregulate inflammatory responses including ventilation-induced ALI. We hypothesized that ATF3 have a protective effect in ALI induced by pseudomonas aeruginosa. PA was intra-tracheally administrated to ATF3 knock-out (KO) mice to establish ALI model. Inflammatory factors, BALF protein, lung wet to dry ratio, lung injury score and mortality were determined...
June 26, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28662101/specific-gene-expression-signatures-induced-by-the-multiple-oncogenic-alterations-that-occur-within-the-pten-pi3k-akt-pathway-in-lung-cancer
#17
Carmela De Marco, Carmelo Laudanna, Nicola Rinaldo, Duarte Mendes Oliveira, Maria Ravo, Alessandro Weisz, Michele Ceccarelli, Elvira Caira, Antonia Rizzuto, Pietro Zoppoli, Donatella Malanga, Giuseppe Viglietto
Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN...
2017: PloS One
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#18
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28611196/atf3-repression-of-bcl-xl-determines-apoptotic-sensitivity-to-hdac-inhibitors-across-tumor-types
#19
Anderly C Chüeh, Janson W T Tse, Michael Dickinson, Paul Ioannidis, Laura Jenkins, Lars Togel, BeeShin Tan, Ian Luk, Mercedes Davalos-Salas, Rebecca Nightingale, Matthew R Thompson, Bryan R G Williams, Guillaume Lessene, Erinna F Lee, Walter D Fairlie, Amardeep S Dhillon, John M Mariadason
Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in acute myelogenous leukemia, non-small cell lung cancer, and estrogen receptor-positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherapy. However, there is currently no clear strategy to reliably predict HDACi sensitivity. In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28595284/infertility-diagnosis-has-a-significant-impact-on-the-transcriptome-of-developing-blastocysts
#20
Blair R McCallie, Jason C Parks, Darren K Griffin, William B Schoolcraft, Mandy G Katz-Jaffe
STUDY QUESTION: Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF) and unexplained (UE)? SUMMARY ANSWER: The global blastocyst transcriptome was significantly altered in association with a PCO, MF and UE infertility diagnosis. WHAT IS KNOWN ALREADY: Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during preimplantation development...
August 1, 2017: Molecular Human Reproduction
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