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https://www.readbyqxmd.com/read/29242753/activating-transcription-factor-3-in-immune-response-and-metabolic-regulation
#1
Kavita Jadhav, Yanqiao Zhang
Activating transcription factor 3 (ATF3) is a member of the ATF/cAMP-response element binding protein (CREB) family of transcription factors. In response to stress stimuli, ATF3 forms dimers to activate or repress gene expression. Further, ATF3 modulates the immune response, atherogenesis, cell cycle, apoptosis, and glucose homeostasis. Recent studies have shown that ATF3 may also be involved in pathogenesis of other diseases. However, more studies are needed to determine the role of ATF3 in metabolic regulation...
September 2017: Liver Research
https://www.readbyqxmd.com/read/29242405/digitalis-like-compounds-restore-hnis-expression-and-iodide-uptake-capacity-in-anaplastic-thyroid-cancer
#2
Marika H Tesselaar, Thomas Crezee, Imke Schuurmans, Danny Gerrits, James Nagarajah, Otto C Boerman, Ilse van Engen-van Grunsven, Johannes W A Smit, Romana T Netea-Maier, Theo S Plantinga
Purpose: Anaplastic thyroid cancer (ATC) is a rare malignancy that accounts for 1-2% of all thyroid cancers. ATC is one of the most aggressive human cancers, with rapid growth, tumor invasion and development of distant metastases. The median survival is only 5 months and the 1-year survival is less than 20%. Moreover, as a result of severe dedifferentiation including the loss of human sodium iodide symporter (hNIS) expression, radioactive iodide (RAI) therapy is ineffective. Recently, we have demonstrated beneficial effects of autophagy activating digitalis-like compounds (DLCs) on redifferentiation and concomitant restoration of iodide uptake in RAI-refractory papillary and follicular thyroid cancer cell lines...
December 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29225035/cockayne-s-syndrome-a-and-b-proteins-regulate-transcription-arrest-after-genotoxic-stress-by-promoting-atf3-degradation
#3
Alexey Epanchintsev, Federico Costanzo, Marc-Alexander Rauschendorf, Manuela Caputo, Tao Ye, Lise-Marie Donnio, Luca Proietti-de-Santis, Frederic Coin, Vincent Laugel, Jean-Marc Egly
Cockayne syndrome (CS) is caused by mutations in CSA and CSB. The CSA and CSB proteins have been linked to both promoting transcription-coupled repair and restoring transcription following DNA damage. We show that UV stress arrests transcription of approximately 70% of genes in CSA- or CSB-deficient cells due to the constitutive presence of ATF3 at CRE/ATF sites. We found that CSB, CSA/DDB1/CUL4A, and MDM2 were essential for ATF3 ubiquitination and degradation by the proteasome. ATF3 removal was concomitant with the recruitment of RNA polymerase II and the restart of transcription...
November 30, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29210072/chemical-hypoxia-induced-integrated-stress-response-activation-in-oligodendrocytes-is-mediated-by-the-transcription-factor-nuclear-factor-erythroid-derived-2-like-2-nrf2
#4
Nico Teske, Annette Liessem, Felix Fischbach, Tim Clarner, C Beyer, Christoph Wruck, Athanassios Fragoulis, Simone C Tauber, Marion Victor, Markus Kipp
The extent of remyelination in multiple sclerosis (MS) lesions is often incomplete. Injury to oligodendrocyte progenitor cells can be a contributing factor for such incomplete remyelination. The precise mechanisms underlying insufficient repair remain to be defined, but oxidative stress appears to be involved. Here, we used immortalized oligodendrocyte cell lines as model systems to investigate a causal relation of oxidative stress and endoplasmic reticulum stress signaling cascades. OLN93 and OliNeu cells were subjected to chemical hypoxia by blocking the respiratory chain at various levels...
December 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29203210/indoxyl-sulfate-upregulates-the-cannabinoid-type-1-receptor-gene-via-an-atf3-c-jun-complex-mediated-signaling-pathway-in-the-model-of-uremic-cardiomyopathy
#5
Yu-Juei Hsu, Shih-Che Hsu, Yung-Lung Chang, Shih-Ming Huang, Chun-Che Shih, Chien-Sung Tsai, Chih-Yuan Lin
BACKGROUND: The risk of cardiovascular disease is notably increased in patients with chronic kidney disease (CKD) and cannabinoid receptor type 1 (CB1R) plays an important role in the development of uremic cardiomyopathy. However, the molecular mechanism underlying the uremic toxin-induced upregulation of CB1R remains elusive. METHODS: The expression of the ATF3/c-Jun complex and CB1R in both in vivo and in vitro models of CKD were measured. We also determined the impact of the ATF3/c-Jun complex on CB1R expression by transfecting H9c2 cells with dominant negative mutants of ATF3 or c-Jun...
December 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29176329/inflammatory-processes-during-acute-respiratory-distress-syndrome-a-complex-system
#6
Lucy K Reiss, Andreas Schuppert, Stefan Uhlig
PURPOSE OF REVIEW: ARDS is a severe pulmonary disease characterized by inflammation. However, inflammation-directed therapies have yet failed to improve the outcome in ARDS patients. One of the reasons may be the underestimated complexity of inflammation. Here, we summarize recent insights into the complex interrelations between inflammatory circuits. RECENT FINDINGS: Gene expression analysis from animal models or from patients with ARDS, sepsis or trauma show an enormous number of differentially expressed genes with highly significant overlaps between the various conditions...
November 15, 2017: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/29175029/depletion-of-d3-dopamine-receptor-affects-methamphetamine-induced-expression-patterns-of-pde4b-and-atf3
#7
Yanjiong Chen, Cuo Yang, Li Zhu, Jiaqi Li, Fanglin Guan, Teng Chen
The role of the D3 dopamine receptor (D3R) and the specific molecular mechanisms underlying the regulation of D3R via the cAMP signaling pathway in methamphetamine (METH) addiction are still unclear. Here, we measured changes in Pde4b and Atf3 in the cAMP signaling pathway of dopaminergic system components, including the nucleus accumbens (NAc), caudate putamen (CPu) and hippocampus (Hip), in D3R knockout mice(D3R-/-) 1h and 24h after METH-induced behavioral sensitization. We found that knocking out D3R attenuated METH-induced behavioral sensitization, and Pde4b and Atf3 exhibited different expression patterns in brain regions in response to METH...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29163428/hhv-6a-6b-infection-of-nk-cells-modulates-the-expression-of-mirnas-and-transcription-factors-potentially-associated-to-impaired-nk-activity
#8
Roberta Rizzo, Irene Soffritti, Maria D'Accolti, Daria Bortolotti, Dario Di Luca, Elisabetta Caselli
Natural killer (NK) cells have a critical role in controlling virus infections, and viruses have evolved several mechanisms to escape NK cell functions. In particular, Human herpesvirus 6 (HHV-6) is associated with diseases characterized by immune dysregulation and has been reported to infect NK cells. We recently found that HHV-6 in vitro infection of human thyroid follicular epithelial cells and T-lymphocytes modulates several miRNAs associated with alterations in immune response. Since miRNAs are key regulators of many immune pathways, including NK cell functions, we aimed to study the impact of HHV-6A and -6B in vitro infection on the intracellular mediators correlated to NK cell function...
2017: Frontiers in Microbiology
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
#9
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/29109091/transcriptomic-profiling-of-mda-mb-231-cells-exposed-to-boswellia-serrata-and-3-o-acetyl-b-boswellic-acid-er-upr-mediated-programmed-cell-death
#10
REVIEW
Elizabeth A Mazzio, Charles A Lewis, Karam F A Soliman
BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptors (estrogen, progesterone and human epidermal growth factor receptor-2) and a relatively poor prognosis due to inefficacy of hormone receptor-based chemotherapies. It is imperative that we continue to explore natural products with potential to impede growth and metastasis of TNBC. In this study, we screened over 1,000 natural products for capacity to induce cell death in TNBC (MDA-MB -231) cells...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29107625/activation-of-erk-creb-pathway-in-noradrenergic-neurons-contributes-to-hypernociceptive-phenotype-in-h4-receptor-knockout-mice-after-nerve-injury
#11
Maria Domenica Sanna, Tommaso Mello, Emanuela Masini, Nicoletta Galeotti
G-protein coupled receptor H4 (H4R) is a histamine receptor subtype that is involved in a condition of pathological chronic pain, but its pathophysiological function is unknown. Here, we investigate the role of H4R in a model of traumatic nerve injury. H4R knockout (H4R(-)/(-)) mice exposed to spared nerve injury (SNI) developed a more prominent mechanical and thermal hypersensitivity than wild type mice. Western blotting and immunofluorescence were used to characterize the cellular mechanisms. Nerve injury increased phosphorylated pERK MAPK expression in the spinal cord that was further promoted in H4R(-)/(-) genotype...
October 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29106982/distinct-trka-and-ret-modulated-negative-and-positive-neuropathic-behaviors-in-a-mouse-model-of-resiniferatoxin-induced-small-fiber-neuropathy
#12
Yu-Lin Hsieh, Hung-Wei Kan, Hao Chiang, Yi-Chen Lee, Sung-Tsang Hsieh
Neurotrophic factors and their corresponding receptors play key roles in the maintenance of different phenotypic dorsal root ganglion (DRG) neurons, the axons of which degenerate in small fiber neuropathy, leading to various neuropathic manifestations. Mechanisms underlying positive and negative symptoms of small fiber neuropathy have not been systematically explored. This study investigated the molecular basis of these seemingly paradoxical neuropathic behaviors according to the profiles of TrkA and Ret with immunohistochemical and pharmacological interventions in a mouse model of resiniferatoxin (RTX)-induced small fiber neuropathy...
October 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29102675/rna-seq-revealed-atf3-regulated-inflammation-induced-by-silica
#13
Judy Y W Chan, Joseph C C Tsui, Patrick T W Law, Winnie K W So, Doris Y P Leung, Michael M K Sham, Stephen K W Tsui, Carmen W H Chan
BACKGROUND: Millions of workers are exposed to dust containing silica. Chronic and over-exposure to silica will lead to silicosis, which is an irreversible and sometimes fatal lung disease. The disordered physiological processes of silicosis consist of accumulation of silica particles in the alveoli of the lung. Then, the ingestion of the silica particles by macrophages was followed by an inflammatory response. Up till now, the chest radiographs remain the key tool in diagnosing and assessing the extent of silicosis...
November 2, 2017: Toxicology
https://www.readbyqxmd.com/read/29093367/-novel-anticancer-strategy-targeting-switch-mechanisms-in-two-types-of-cell-death-necrosis-and-apoptosis
#14
Akira Sato
 Two types of cell death, necrosis and apoptosis, are defined in terms of cell death morphological features. We have been studying the mechanisms by which cell death processes are switched during the treatment of mouse tumor FM3A with anticancer, 5-fluoro-2'-deoxyuridine (FUdR): it induces original clone F28-7 to necrosis, but its sub-clone F28-7-A to apoptosis. We identified several such switch regulators of cell death: heat shock protein 90 (HSP90), lamin-B1, cytokeratin-19, and activating transcription factor 3 (ATF3), by using transcriptomic, proteomic analyses and siRNA screening...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29093345/cytosolic-prostaglandin-e-synthase-is-involved-in-c-fos-expression-in-rat-fibroblastic-3y1-cells
#15
Yoshihito Nakatani, Yuki Miyazaki, Shuntaro Hara
Cytosolic prostaglandin (PG) E synthase (cPGES/p23) plays a role in the biosynthesis of PGE2 and in the molecular chaperone machinery. Studies of knockout mice lacking cPGES/p23 have demonstrated that cPGES/p23 is essential in fetal mouse development. A cDNA microarray analysis revealed that a lack of cPGES/p23 decreases the expression of some immediate early genes, such as c-fos and activating transcription factor 3 (ATF3). Here we report the involvement of cPGES/p23 in c-Fos expression. A stable knockdown of cPGES/p23 in cultured fibroblasts not only reduced serum-induced c-Fos expression, but also decreased the phosphorylation of extracellular signal regulated kinase (ERK)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29061384/motoneuron-degeneration-in-the-trigeminal-motor-nucleus-innervating-the-masseter-muscle-in-dystonia-musculorum-mice
#16
M Ibrahim Hossain, Masao Horie, Nozomu Yoshioka, Masayuki Kurose, Kensuke Yamamura, Hirohide Takebayashi
Dystonia musculorum (dt) mice, which have a mutation in the Dystonin (Dst) gene, are used as animal models to investigate the human disease known as hereditary sensory and autonomic neuropathy type VI. Massive neuronal cell death is observed, mainly in the peripheral nervous system (PNS) of dt mice. We and others have recently reported a histopathological feature of these mice that neurofilament (NF) accumulates in various areas of the central nervous system (CNS), including motor pathways. Although dt mice show motor disorder and growth retardation, the causes for these are still unknown...
October 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29038896/inducible-atf3-nfat-axis-aggravates-podocyte-injury
#17
Hong Zhang, Shun Liang, Yue Du, Ruizhao Li, Chaosheng He, Wenjian Wang, Shuangxin Liu, Zhiming Ye, Xinling Liang, Wei Shi, Bin Zhang
Podocyte injury and loss contribute to proteinuria, glomerulosclerosis, and eventually kidney failure. Activating transcription factor 3 (ATF3) is a stress inducible transcription factor that is transiently expressed following stimulation. However, we show for the first time an induction of ATF3 in podocytes from patients with chronic kidney disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetic nephropathy. The role of ATF3 induction in podocytes under chronic conditions is currently unknown...
October 16, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29017144/anxiolytic-effect-of-fatty-acids-and-terpenes-fraction-from-aloysia-triphylla-serotoninergic-gabaergic-and-glutamatergic-implications
#18
Enrique Jiménez-Ferrer, Mayra Alejandra Santillán-Urquiza, Elian Alegría-Herrera, Alejandro Zamilpa, Carmen Noguerón-Merino, Jaime Tortoriello, Victor Navarro-García, Margarita Avilés-Flores, Macrina Fuentes-Mata, Maribel Herrera-Ruiz
Aloysia triphylla (Verbenaceae) is an aromatic medicinal plant, and it is used for the treatment of "nervous" problems as, "sadness" and "nervousness". While, there are no reports about its pharmacological activity in animal models. The objective of this work was to evaluate the anxiolytic effect of the extracts and fractions of this species and to measure the interaction of the most active fraction with serotonergic, glutamatergic and GABAergic drugs. An elevated plus maze test was carried ought where the methanol (AtM), dicloromethane (AtD) and hexanic (AtH) extracts presented anxiolytic activity in mice when exposed to the test...
October 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28985996/tlr-induced-secretion-of-novel-cytokine-il-27-is-defective-in-newly-diagnosed-type-2-diabetic-subjects
#19
Haridoss Madhumitha, Viswanathan Mohan, Subash Babu, Vivekanandhan Aravindhan
Toll-like receptors (TLRs), the innate immune receptors, act as sentinels bridging both innate and adaptive arms of immunity. In the present study, we estimated TLR-induced secretion of IL-27, IL-12, IL-23, IL-8, IP-10, IL-17, IL-6 and TNF-α (by ELISA) and expression of Human Leukocyte Antigen- (Human Leukocyte Antigen - antigen D Related (HLA-DR), CD69, CD80 (also known asB7-1) (by flowcytometry) and Activating Transcription Factor 3(ATF3) (by qRT-PCR) in whole blood cultures of control and type-2 diabetic (both newly diagnosed/NDD and known/KDM) subjects...
October 3, 2017: Cytokine
https://www.readbyqxmd.com/read/28982115/tlr4-as-a-negative-regulator-of-keratinocyte-proliferation
#20
Guergana Iotzova-Weiss, Sandra N Freiberger, Pål Johansen, Jivko Kamarachev, Emmanuella Guenova, Piotr J Dziunycz, Guillaume A Roux, Johannes Neu, Günther F L Hofbauer
TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC) of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro...
2017: PloS One
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