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https://www.readbyqxmd.com/read/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#1
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27913641/translation-repression-by-maternal-rna-binding-protein-zar1-is-essential-for-early-oogenesis-in-zebrafish
#2
Liyun Miao, Yue Yuan, Feng Cheng, Junshun Fang, Fang Zhou, Weirui Ma, Yan Jiang, Xiahe Huang, Yingchun Wang, Lingjuan Shan, Dahua Chen, Jian Zhang
Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27912076/activating-transcription-factor-3-is-essential-for-cigarette-smoke-induced-mucin-expression-via-interaction-with-activator-protein-1
#3
Yan-Ping Wu, Yin-Fang Wu, Chao Zhang, Hong-Bin Zhou, Chao Cao, Miao Li, Chen Zhu, Song-Min Ying, Zhi-Hua Chen, Hua-Hao Shen, Wen Li
Mucus hypersecretion is an important pathologic feature of chronic obstructive pulmonary disease. Activating transcription factor 3 (ATF3) is an adaptive-response gene that participates in various cellular processes. However, little is known about its role in cigarette smoke (CS)-induced mucus hyperproduction. This study aimed to investigate the role and molecular mechanisms of ATF3 in CS-induced Mucin 5AC (MUC5AC) expression. ATF3 was elevated in lung tissues of mice exposed to CS for 12 weeks. Treatment with CS extract significantly induced ATF3 expression and MUC5AC production in human bronchial epithelial cells, NCI-H292, and mouse tracheal epithelial cells...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27902739/degenerative-suspensory-ligament-desmitis-dsld-in-peruvian-paso-horses-is-characterized-by-altered-expression-of-tgf%C3%AE-signaling-components-in-adipose-derived-stromal-fibroblasts
#4
Wei Luo, John Sandy, Katie Trella, Daniel Gorski, Shuguang Gao, Jun Li, Sabrina Brounts, Jorge Galante, Anna Plaas
Equine degenerative suspensory ligament desmitis (DSLD) in Peruvian Paso horses typically presents at 7-15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding) we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs) from six DSLD-affected and five unaffected Paso horses...
2016: PloS One
https://www.readbyqxmd.com/read/27902686/genomic-characterization-of-metformin-hepatic-response
#5
Marcelo R Luizon, Walter L Eckalbar, Yao Wang, Stacy L Jones, Robin P Smith, Megan Laurance, Lawrence Lin, Paul J Gallins, Amy S Etheridge, Fred Wright, Yihui Zhou, Cliona Molony, Federico Innocenti, Sook Wah Yee, Kathleen M Giacomini, Nadav Ahituv
Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27895723/cisplatin-induced-regulation-of-signal-transduction-pathways-and-transcription-factors-in-p53-mutated-subclone-variants-of-hepatoma-cells-potential-application-for-therapeutic-targeting
#6
Jinn-Rung Kuo, Hung-Sheng Shang, Chun-Te Ho, Kun-Goung Lai, Tsan-Zon Liu, Yin-Ju Chen, Jeng-Fong Chiou
Cisplatin is commonly recognized as a DNA-damaging drug; however, its versatile antitumor effects have been demonstrated to extend beyond this narrow functional attribute. The present study determined how cisplatin regulates alternative pathways and transcription factors to exert its additional antitumor actions. Cisplatin was observed to be able to trigger an endoplasmic reticulum stress response through aggravated nitrosative stress coupled to perturbed mitochondrial calcium (Ca(2+)) homeostasis, which substantially downregulated glucose-regulated protein (GRP) 78 expression by suppressing the cleavage of activating transcription factor (ATF) 6α (90 kDa) to its active 50 kDa subunit...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27888615/unconjugated-secondary-bile-acids-activate-the-unfolded-protein-response-and-induce-golgi-fragmentation-via-a-src-kinase-dependant-mechanism
#7
Ruchika Sharma, Francis Quilty, John F Gilmer, Aideen Long, Anne-Marie Byrne
Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27871156/kahweol-from-coffee-induces-apoptosis-by-upregulating-activating-transcription-factor-3-in-human-colorectal-cancer-cells
#8
Gwang Hun Park, Hun Min Song, Jin Boo Jeong
Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells...
November 25, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27870968/the-cardiac-maladaptive-atf3-dependent-cross-talk-between-cardiomyocytes-and-macrophages-is-mediated-by-the-ifn%C3%AE-cxcl10-cxcr3-axis
#9
L Koren, U Barash, Y Zohar, N Karin, A Aronheim
RATIONAL: Pressure overload induces adaptive and maladaptive cardiac remodeling processes in the heart. Part of the maladaptive process is the cross-talk between cardiomyocytes and macrophages which is dependent on the function of the Activating Transcription Factor 3, ATF3. Yet, the molecular mechanism involved in cardiomyocytes-macrophages communication leading to macrophages recruitment to the heart and cardiac maladaptive remodeling is currently unknown. METHODS AND RESULTS: Isolated peritoneal macrophages from either wild type or ATF3-KO mice were cultured in serum free medium to collect conditioned medium (CM)...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27856557/activating-transcription-factor-3-attenuates-chemokine-and-cytokine-expression-in-mouse-skeletal-muscle-after-exercise-and-facilitates-molecular-adaptation-to-endurance-training
#10
Rodrigo Fernández-Verdejo, Aline M Vanwynsberghe, Ahmed Essaghir, Jean-Baptiste Demoulin, Tsonwin Hai, Louise Deldicque, Marc Francaux
Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Skeletal muscles of ATF3-knockout (ATF3-KO) and control mice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type...
November 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27829167/atf3-modulates-calcium-signaling-in-osteoclast-differentiation-and-activity-by-associating-with-c-fos-and-nfatc1-proteins
#11
Byung-Chul Jeong, Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Nacksung Kim
Activating transcription factor 3 (ATF3), a member of the ATF/cAMP response element-binding protein family of transcription factors, has been implicated in the regulation of cell proliferation and differentiation. However, whether ATF3 is involved in osteoclast differentiation and activity has not been well-studied. In the present study, we examined the role of ATF3 in osteoclast differentiation and function. ATF3 expression was down-regulated during RANKL-induced osteoclast differentiation. Overexpression of ATF3 in bone marrow-derived monocyte/macrophage lineage cells (BMMs) promoted osteoclast differentiation and activity and strongly induced the expression of osteoclast genes encoding nuclear factor of activated T-cells c1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP) compared to that in the control group...
November 6, 2016: Bone
https://www.readbyqxmd.com/read/27797824/a-genome-wide-analysis-of-gene-caffeine-consumption-interaction-on-basal-cell-carcinoma
#12
Xin Li, Marilyn C Cornelis, Liming Liang, Fengju Song, Immaculata De Vivo, Edward Giovannucci, Jean Y Tang, Jiali Han
Animal models have suggested that oral or topical administration of caffeine could inhibit ultraviolet-induced carcinogenesis via the ataxia telangiectasia and rad3 (ATR)-related apoptosis. Previous epidemiological studies have demonstrated that increased caffeine consumption is associated with reduced risk of basal cell carcinoma (BCC). To identify common genetic markers that may modify this association, we tested gene-caffeine intake interaction on BCC risk in a genome-wide analysis. We included 3383 BCC cases and 8528 controls of European ancestry from the Nurses' Health Study and Health Professionals Follow-up Study...
December 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27791078/asbel-tcf3-complex-is-required-for-the-tumorigenicity-of-colorectal-cancer-cells
#13
Kenzui Taniue, Akiko Kurimoto, Yasuko Takeda, Takeshi Nagashima, Mariko Okada-Hatakeyama, Yuki Katou, Katsuhiko Shirahige, Tetsu Akiyama
Wnt/β-catenin signaling plays a key role in the tumorigenicity of colon cancer. Furthermore, it has been reported that lncRNAs are dysregulated in several steps of cancer development. Here we show that β-catenin directly activates the transcription of the long noncoding RNA (lncRNA) ASBEL [antisense ncRNA in the ANA (Abundant in neuroepithelium area)/BTG3 (B-cell translocation gene 3) locus] and transcription factor 3 (TCF3), both of which are required for the survival and tumorigenicity of colorectal cancer cells...
October 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27791037/orthopedic-surgery-modulates-neuropeptides-and-bdnf-expression-at-the-spinal-and-hippocampal-levels
#14
Ming-Dong Zhang, Swapnali Barde, Ting Yang, Beilei Lei, Lars I Eriksson, Joseph P Mathew, Thomas Andreska, Katerina Akassoglou, Tibor Harkany, Tomas G M Hökfelt, Niccolò Terrando
Pain is a critical component hindering recovery and regaining of function after surgery, particularly in the elderly. Understanding the role of pain signaling after surgery may lead to novel interventions for common complications such as delirium and postoperative cognitive dysfunction. Using a model of tibial fracture with intramedullary pinning in male mice, associated with cognitive deficits, we characterized the effects on the primary somatosensory system. Here we show that tibial fracture with pinning triggers cold allodynia and up-regulates nerve injury and inflammatory markers in dorsal root ganglia (DRGs) and spinal cord up to 2 wk after intervention...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27786393/the-pleiotropic-transcriptional-regulator-nlpr-contributes-to-the-modulation-of-nitrogen-metabolism-lipogenesis-and-triacylglycerol-accumulation-in-oleaginous-rhodococci
#15
Martín A Hernández, Julia Lara, Gabriela Gago, Hugo Gramajo, Héctor M Alvarez
The regulatory mechanisms involved in lipogenesis and triacylglycerol (TAG) accumulation are largely unknown in oleaginous rhodococci. In this study we identified a regulatory protein (here called NlpR: Nitrogen lipid Regulator), which contributes to the modulation of nitrogen metabolism, lipogenesis and triacylglycerol accumulation in oleaginous rhodococci. Under nitrogen deprivation conditions, in which TAG accumulation is stimulated, the nlpR gene was significantly upregulated, whereas a significant decrease of its expression and TAG accumulation occurred when cerulenin was added...
October 27, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27780541/atf3-is-a-negative-regulator-of-inflammation-in-human-fetal-membranes
#16
Ratana Lim, Gillian Barker, Stella Liong, Caitlyn Nguyen-Ngo, Stephen Tong, Tu'uhevaha Kaitu'u-Lino, Martha Lappas
INTRODUCTION: Infection and inflammation stimulate pro-inflammatory cytokines, prostaglandins and matrix metalloproteinase (MMP)-9, which play a central role in myometrial contractions and rupture of fetal membranes. In human and mouse immune cells, activating transcription factor 3 (ATF3) is a negative regulator of inflammation. No studies have examined the role of ATF3 in human labour. METHODS: Primary amnion cells were used to determine the effect of interleukin (IL)-1β and the bacterial product fibroblast-stimulating lipopeptide (fsl-1) on ATF3 expression, and the effect of ATF3 siRNA on pro-labour mediators...
November 2016: Placenta
https://www.readbyqxmd.com/read/27740623/tm7sf3-a-novel-p53-regulated-homeostatic-factor-attenuates-cellular-stress-and-the-subsequent-induction-of-the-unfolded-protein-response
#17
Roi Isaac, Ido Goldstein, Noa Furth, Neta Zilber, Sarina Streim, Sigalit Boura-Halfon, Eytan Elhanany, Varda Rotter, Moshe Oren, Yehiel Zick
Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27679973/nur77-exacerbates-pc12-cellular-injury-in-vitro-by-aggravating-mitochondrial-impairment-and-endoplasmic-reticulum-stress
#18
Huimin Gao, Zhaoyu Chen, Yongmei Fu, Xiaoyan Yang, Ruihui Weng, Rui Wang, Jianjun Lu, Mengqiu Pan, Kunlin Jin, Chris McElroy, Beisha Tang, Ying Xia, Qing Wang
The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27659012/induction-of-activating-transcription-factor-3-is-associated-with-cisplatin-responsiveness-in-non-small-cell-lung-carcinoma-cells
#19
Jair Bar, Mohamed S Hasim, Tabassom Baghai, Nima Niknejad, Theodore J Perkins, David J Stewart, Harmanjatinder S Sekhon, Patrick J Villeneuve, Jim Dimitroulakos
Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer deaths, with platin-based combination chemotherapy the most efficacious therapies. Gains in overall survival are modest, highlighting the need for novel therapeutic approaches including the development of next-generation platin combination regimens. The goal of this study was to identify novel regulators of platin-induced cytotoxicity as potential therapeutic targets to further enhance platin cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their cisplatin-resistant sublines, Calu6cisR1 and H23cisR1, activating transcription factor 3 (ATF3) was robustly induced in cisplatin-treated parental sensitive cell lines but not their resistant sublines, and in three of six tumors evaluated, but not in their corresponding normal adjacent lung tissue (0/6)...
September 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27629805/progranulin-overexpression-in-sensory-neurons-attenuates-neuropathic-pain-in-mice-role-of-autophagy
#20
Christine Altmann, Stefanie Hardt, Caroline Fischer, Juliana Heidler, Hee-Young Lim, Annett Häussler, Boris Albuquerque, Béla Zimmer, Christine Möser, Christian Behrends, Frank Koentgen, Ilka Wittig, Mirko H H Schmidt, Albrecht M Clement, Thomas Deller, Irmgard Tegeder
Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis...
September 11, 2016: Neurobiology of Disease
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