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https://www.readbyqxmd.com/read/29446045/effects-of-extracellular-orotic-acid-on-acute-contraction-induced-adaptation-patterns-in-c2c12-cells
#1
Thomas Beiter, Jens Hudemann, Christof Burgstahler, Andreas M Nieß, Barbara Munz
Dietary administration of orotic acid (OA), an intermediate in the pyrimidine biosynthetic pathway, is considered to provide a wide range of beneficial effects, including cardioprotection and exercise adaptation. Its mechanisms of action, when applied extracellularly, however, are barely understood. In this study, we evaluated potential effects of OA on skeletal muscle using an in vitro contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By analyzing a subset of genes representing inflammatory, metabolic, and structural adaptation pathways, we could show that OA supplementation diminishes the EPS-provoked expression of inflammatory transcripts (interleukin 6, Il6; chemokine (C-X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of nuclear receptor subfamily 4 group A member 3 (Nr4A3), early growth response 1 (Egr1), activating transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA isoform (Myh2)...
February 14, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29425209/retinal-genes-are-differentially-expressed-in-areas-of-primary-versus-secondary-degeneration-following-partial-optic-nerve-injury
#2
Wissam Chiha, Chrisna J LeVaillant, Carole A Bartlett, Alex W Hewitt, Phillip E Melton, Melinda Fitzgerald, Alan R Harvey
BACKGROUND: Partial transection (PT) of the optic nerve is an established experimental model of secondary degeneration in the central nervous system. After a dorsal transection, retinal ganglion cells (RGCs) with axons in ventral optic nerve are intact but vulnerable to secondary degeneration, whereas RGCs in dorsal retina with dorsal axons are affected by primary and secondary injuries. Using microarray, we quantified gene expression changes in dorsal and ventral retina at 1 and 7 days post PT, to characterize pathogenic pathways linked to primary and secondary degeneration...
2018: PloS One
https://www.readbyqxmd.com/read/29413899/regulation-of-the-atf3-gene-by-a-single-promoter-in-response-to-amino-acid-availability-and-endoplasmic-reticulum-stress-in-human-primary-hepatocytes-and-hepatoma-cells
#3
Jaclyn N Hayner, Jixiu Shan, Michael S Kilberg
Activating transcription factor 3 (ATF3) is a highly regulated protein that is implicated in a wide range of pathological conditions including inflammation and transformation. Transcription from the ATF3 gene is induced by several stress-induced signaling pathways, including amino acid limitation (amino acid response, AAR) and ER stress (unfolded protein response, UPR). Induction of ATF3 transcription by these pathways is mediated by ATF4 and cJUN recruitment to enhancer elements within the ATF3 gene. Although a canonical promoter (promoter A) has been studied by numerous laboratories, a second promoter activity (promoter A1), 43 kb upstream of the first, has been reported to respond to stress-induced signaling and to be critical for ATF3 expression in certain transformed cells...
February 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29382334/novel-evidence-for-a-piwi-interacting-rna-pirna-as-an-oncogenic-mediator-of-disease-progression-and-a-potential-prognostic-biomarker-in-colorectal-cancer
#4
Wenhao Weng, Na Liu, Yuji Toiyama, Masato Kusunoki, Takeshi Nagasaka, Toshiyoshi Fujiwara, Qing Wei, Huanlong Qin, Haifan Lin, Yanlei Ma, Ajay Goel
BACKGROUND: Emerging evidence suggests that PIWI-interacting RNAs (piRNAs) may be important epigenetic regulators of gene expression in human cancers; however, their functional and clinical significance in colorectal cancer (CRC) remains unknown. METHODS: We performed piRNA expression profiling in paired cancer and normal tissues through small RNA-sequencing. The clinical significance of candidate piRNAs was investigated, and independently validated in 771 CRC patients from three independent cohorts...
January 30, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29378244/atf3-is-positively-involved-in-particulate-matter-induced-airway-inflammation-in-vitro-and-in-vivo
#5
Fugui Yan, Yinfang Wu, Huiwen Liu, Yanping Wu, Huahao Shen, Wen Li
Airborne particulate matter (PM) has been reported to be associated with a wide range of respiratory disorders. However, the mechanisms underlying PM-induced airway inflammation remain largely unknown. Generally, ATF3 negatively regulates pro-inflammatory cytokines production in response to TLR4 signaling. Here we first showed ATF3 has promoting effects in PM-induced airway inflammation in vitro an in vivo. We demonstrated PM significantly upregulated ATF3 expression in HBE cells and in mouse lung tissues. ATF3 siRNA markedly inhibited, while ATF3-recombinant over-expression plasmid significantly increased PM-induced IL-6 expression in cultured HBE cells, and PM-induced IL-6, CXCL2 expression as well as neutrophil infiltration, mucus over-production in the lung of ATF3-/- mice were all notably reduced relative to the wild-type littermates...
January 26, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29363258/atf3-represses-pink1-gene-transcription-in-lung-epithelial-cells-to-control-mitochondrial-homeostasis
#6
Marta Bueno, Judith Brands, Lauren Voltz, Kaitlin Fiedler, Brenton Mays, Claudette St Croix, John Sembrat, Rama K Mallampalli, Mauricio Rojas, Ana L Mora
PINK1 (PTEN-induced putative kinase 1) is a key regulator of mitochondrial homeostasis that is relatively depleted in aging lungs and in lung epithelial cells from patients with idiopathic pulmonary fibrosis (IPF), a disease linked with aging. Impaired PINK1 expression and accumulation of damaged mitochondria in lung epithelial cells from fibrotic lungs were associated with the presence of ER stress. Here, we show that ATF3 (activating transcription factor 3), a member of the integrated stress response (ISR), negatively regulates transcription of the PINK1 gene...
January 24, 2018: Aging Cell
https://www.readbyqxmd.com/read/29352505/p53-independent-noxa-induction-by-cisplatin-is-regulated-by-atf3-atf4-in-head-and-neck-squamous-cell-carcinoma-cells
#7
Kanika Sharma, Thien-Trang Vu, Wade Cook, Mitra Naseri, Kevin Zhan, Wataru Nakajima, Hisashi Harada
The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family-dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of pro-apoptotic BCL-2 family protein, Noxa, that can bind to the pro-survival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death...
January 19, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29346801/early-gene-expression-profile-in-retinal-ganglion-cell-layer-after-optic-nerve-crush-in-mice
#8
Satoru Ueno, Azusa Yoneshige, Yoshiki Koriyama, Man Hagiyama, Yoshikazu Shimomura, Akihiko Ito
Purpose: Optic nerve crush (ONC) induces retinal ganglion cell (RGC) death, which causes vision loss in glaucoma. To investigate early events leading to apoptosis of RGCs, we performed gene expression analysis of injured retinas in the period before RGC loss. Methods: The temporal changes of gene profiles at 0, 1, and 4 days after ONC were determined by DNA microarray. To verify the gene expression changes in RGCs, we enriched RGCs by laser-captured microdissection and performed real-time RT-PCR of 14 selected genes...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29335507/highly-conserved-molecular-pathways-including-wnt-signaling-promote-functional-recovery-from-spinal-cord-injury-in-lampreys
#9
Paige E Herman, Angelos Papatheodorou, Stephanie A Bryant, Courtney K M Waterbury, Joseph R Herdy, Anthony A Arcese, Joseph D Buxbaum, Jeramiah J Smith, Jennifer R Morgan, Ona Bloom
In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327812/hyper-acetylation-contributes-to-the-sensitivity-of-chemo-resistant-prostate-cancer-cells-to-histone-deacetylase-inhibitor-trichostatin-a
#10
Qingqing Xu, Xiaofei Liu, Shiqin Zhu, Xuelei Hu, Huanmin Niu, Xiulei Zhang, Deyu Zhu, Effat Un Nesa, Keli Tian, Huiqing Yuan
Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29307816/neurotoxic-effect-of-oxaliplatin-comparison-with-its-oxalate-free-analogue-cis-ptii-1r-2r-dach-3-acetoxy-1-1-cyclobutanedicarboxylato-llc-1402-in-mice
#11
Anamaria Falcão Pereira, Francisco Fábio Bezerra de Oliveira, Bruno Wesley de Freitas Alves, Karoline Luanne Santos de Menezes, Aline Kelly Viana de Mesquita, Mario Roberto Pontes Lisboa, Kalina Kelma Oliveira de Sousa, Mariana Lima Vale
Studies suggest that oxalate is involved in the development oxaliplatin-induced peripheral sensory neuropathy (OPSN). This study aimed to compare the neurotoxic effects of oxaliplatin with its oxalate-free cytotoxic analogue cis-[PtII(1R,2R-DACH)(3-acetoxy-1,1-cyclobutanedicarboxylato)] (LLC-1402) in mice. Oxaliplatin and LLC-1402 were intravenously injected in male Swiss mice with a total of nine injections. Oxalate was intraperitoneally injected in other animals. The development of OPSN was evaluated using mechanical and thermal sensitivity tests...
January 4, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29306704/neuroprotective-effect-of-acute-ethanol-intoxication-in-tbi-is-associated-to-the-hierarchical-modulation-of-early-transcriptional-responses
#12
Akila Chandrasekar, Bahar Aksan, Florian Olde Heuvel, Philip Förstner, Daniela Sinske, Rida Rehman, Annette Palmer, Albert Ludolph, Markus Huber-Lang, Tobias Böckers, Daniela Mauceri, Bernd Knöll, Francesco Roselli
Ethanol intoxication is a risk factor for traumatic brain injury (TBI) but clinical evidence suggests that it may actually improve the prognosis of intoxicated TBI patients. We have employed a closed, weight-drop TBI model of different severity (2cm or 3cm falling height), preceded (-30min) or followed (+20min) by ethanol administration (5g/Kg). This protocol allows us to study the interaction of binge ethanol intoxication in TBI, monitoring behavioral changes, histological responses and the transcriptional regulation of a series of activity-regulated genes (immediate early genes, IEGs)...
January 4, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29254483/gene-expression-regulation-of-den-and-hbx-induced-hcc-mice-models-and-comparisons-of-tumor-para-tumor-and-normal-tissues
#13
Qin Tang, Qi Wang, Qiong Zhang, Sheng-Yan Lin, Yanhong Zhu, Xiangliang Yang, An-Yuan Guo
BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality. Chemical and virus induction are two major risk factors, however, the potential molecular mechanisms of their differences remain elusive. In this study, to identify the similarities and differences between chemical and virus induced HCC models, we compared the gene expression profiles between DEN and HBx mice models, as well as the differences among tumor, para-tumor and normal tissues. METHODS: We sequenced both gene and microRNA (miRNA) expression for HCC tumor tissues, para-tumor and normal liver tissues from DEN model mice (30-week-old) and downloaded the corresponding microarray expression data of HBx model from GEO database...
December 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29242753/activating-transcription-factor-3-in-immune-response-and-metabolic-regulation
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
February 2018: 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
#20
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
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