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https://www.readbyqxmd.com/read/28807729/cpg-demethylation-in-the-neurotoxicity-of-1-methyl-4-phenylpyridinium-might-mediate-transcriptional-up-regulation-of-%C3%AE-synuclein-in-sh-sy5y-cells
#1
Jian Yang, Zhaofei Yang, Xuan Wang, Min Sun, Yong Wang, Xiaomin Wang
The accumulation of α-synuclein is the primary pathological hallmark of Parkinson's disease (PD). In PD patients, CpG demethylation of intron-1 has been reported to be associated with α-synuclein up-regulation. Environmental factor, for example neurotoxin, is a major etiological risk factor in PD pathogenesis. However, the role of CpG methylation in neurotoxin-induced PD has not been addressed completely yet. To explore CpG methylation associating with α-synuclein transcription and its underlying mechanisms in the neurotoxin-induced PD pathology, human neuroblastoma SH-SY5Y cells were treated with neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP(+))...
August 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28795598/inhibition-studies-of-dna-methyltransferases-by-maleimide-derivatives-of-rg108-as-non-nucleoside-inhibitors
#2
Grégoire Rondelet, Laurence Fleury, Céline Faux, Véronique Masson, Jean Dubois, Paola B Arimondo, Luc Willems, Johan Wouters
AIM: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. MATERIALS & METHODS: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs...
August 10, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28781955/erbb2-signaling-epigenetically-suppresses-microrna-205-transcription-via-ras-raf-mek-erk-pathway-in-breast-cancer
#3
Takuya Hasegawa, Ryohei Adachi, Hitoshi Iwakata, Takayoshi Takeno, Koji Sato, Toshiyuki Sakamaki
We previously reported that microRNA-205 (miR-205) is downregulated by overexpression of the receptor tyrosine kinase ErbB2 and that ectopic transfection of miR-205 precursor decreases ErbB2 tumorigenicity in soft agar. In this study, we further analyzed the regulatory mechanisms linking ErbB2 overexpression and miR-205 downregulation. In ErbB2-overexpressing breast epithelial cells, miR-205 expression was significantly increased by treatment with MEK inhibitor U0126 or PD98059, Raf-1 inhibitor ZM-336372, and ERK inhibitor SCH772984, but PI3K inhibitor LY294002 and p38 MAPK inhibitor SB203580 had no effect...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28758855/targeting-dna-hypermethylation-computational-modeling-of-dna-demethylation-treatment-of-acute-myeloid-leukemia
#4
Jens Przybilla, Lydia Hopp, Michael Lübbert, Markus Loeffler, Joerg Galle
In acute myeloid leukemia (AML) DNA hypermethylation of gene promoters is frequently observed and often correlates with a block of differentiation. Treatment of AML patients with DNA methyltransferase inhibitors results in global hypomethylation of genes and, thereby, can lead to a reactivation of the differentiation capability. Unfortunately, after termination of treatment both hypermethylation and differentiation block return in most cases. Here, we apply, for the first time, a computational model of epigenetic regulation of transcription in order to: i) provide a mechanistic understanding of the DNA (de-) methylation process in AML and; ii) improve DNA demethylation treatment strategies...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28750405/untargeted-dna-demethylation-therapy-neither-prevents-nor-attenuates-ischemia-reperfusion-induced-renal-fibrosis
#5
Benjamin A Vervaet, Lies Moonen, Lode Godderis, Katrien Poels, Patrick C D'Haese
BACKGROUND: Current treatment options for chronic kidney disease (CKD) are limited and their focus is on slowing its progression by addressing comorbidities. Fibrosis, the common histopathological process in CKD, is a major therapeutic research target. In CKD, fibroblasts are terminally activated due to alterations in their DNA-methylation pattern, particularly hypermethylation. Preventing the copying of pathological DNA-methylation patterns in proliferating fibroblasts could be a new effective therapeutic strategy for treating CKD...
July 28, 2017: Nephron
https://www.readbyqxmd.com/read/28732309/zebularine-induces-replication-dependent-double-strand-breaks-which-are-preferentially-repaired-by-homologous-recombination
#6
Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death...
July 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28720666/inactivation-of-receptor-tyrosine-kinases-reverts-aberrant-dna-methylation-in-acute-myeloid-leukemia
#7
Na Shen, Fei Yan, Jiuxia Pang, Na Zhao, Naseema Gangat, Lai-Chu Wu, Ann M Bode, Aref Al-Kali, Mark R Litzow, Shujun Liu
Purpose: Receptor tyrosine kinases (RTKs) are frequently deregulated in leukemia, yet the biological consequences of this deregulation remain elusive. The mechanisms underlying aberrant methylation, a hallmark of leukemia, are not fully understood. Here we investigated the role of RTKs in methylation abnormalities and characterized the hypomethylating activities of RTK inhibitors.<br />Experimental Design: Whether and how RTKs regulate expression of DNA methyltransferases (DNMTs), tumor suppressor genes (TSGs) as well as global and gene specific DNA methylation were examined...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28716037/phylogeny-expression-patterns-and-regulation-of-dna-methyltransferases-in-early-development-of-the-flatfish-solea-senegalensis
#8
Joana Firmino, Carlos Carballo, Paula Armesto, Marco A Campinho, Deborah M Power, Manuel Manchado
BACKGROUND: The identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2'-deoxycytidine) and temperature was evaluated...
July 17, 2017: BMC Developmental Biology
https://www.readbyqxmd.com/read/28714938/taxifolin-activates-the-nrf2-anti-oxidative-stress-pathway-in-mouse-skin-epidermal-jb6-p-cells-through-epigenetic-modifications
#9
Haixue Kuang, Zhenqiu Tang, Chengyue Zhang, Zhibin Wang, Wenji Li, Chunjuan Yang, Qiuhong Wang, Bingyou Yang, Ah-Ng Kong
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28712054/alcohol-exposure-promotes-dna-methyltransferase-dnmt3a-upregulation-through-reactive-oxygen-species-dependent-mechanisms
#10
Federico Miozzo, Hélène Arnould, Aurélie de Thonel, Anne-Laure Schang, Délara Sabéran-Djoneidi, Anne Baudry, Benoît Schneider, Valérie Mezger
Abundant evidence has accumulated showing that fetal alcohol exposure broadly modifies DNA methylation profiles in the brain. DNA methyltransferases (DNMTs), the enzymes responsible for DNA methylation, are likely implicated in this process. However, their regulation by ethanol exposure has been poorly addressed. Here, we show that alcohol exposure modulates DNMT protein levels through multiple mechanisms. Using a neural precursor cell line and primary mouse embryonic fibroblasts (MEFs), we found that ethanol exposure augments the levels of Dnmt3a, Dnmt3b, and Dnmt3l transcripts...
July 15, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28673584/parp-inhibitors-in-acute-myeloid-leukaemia-therapy-how-a-synthetic-lethality-approach-can-be-a-valid-therapeutic-alternative
#11
Grigore Aristide Gafencu, Ciprian Ionuț Tomuleasa, Gabriel Ghiaur
Acute myeloid leukaemia (AML) is a malignancy in need of new therapeutic options. The current standard of care chemotherapy, leads to complete remission (CR) in the vast majority of adult patients under the age of 60. In contrast, CR rates in patients over the age of 60 reaches only 40-60%. While achievement of a CR is an important stepping stone in the treatment of AML, the majority of these patients experience relapse and die of their disease without adequate consolidation chemotherapy. Blood and marrow transplantation (BMT) can improve outcome in a select patient with AML but unfortunately, it is not a valid treatment option for the majority of older patients...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28669682/differential-expression-pattern-of-key-regulatory-developmental-genes-in-pre-implant-zona-free-cloned-vs-in%C3%A2-vitro-fertilized-goat-embryos
#12
Dharmendra Kumar, Bikash Chandra Sarkhel
The success of Somatic cell nuclear transfer (SCNT) primarily depends on the extent of reprogramming of donor cells genome. The error of reprogramming may lead to inappropriate expression of embryonic genes at any stage of development. Under the present study the relative expression of different genes related to pluripotency (Oct-4 and Nanog), growth factors (IGF-2 and IGF-2R) and DNA methyltransferase gene (Dnmt-1) was evaluated in SCNT embryos at 8-16 cells, morula and blastocyst stages as compared to IVF group...
June 29, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28663119/minimal-traumatic-brain-injury-causes-persistent-changes-in-dna-methylation-at-bdnf-gene-promoters-in-rat-amygdala-a-possible-role-in-anxiety-like-behaviors
#13
Sneha Sagarkar, Tanmayi Bhamburkar, Gajanan Shelkar, Amit Choudhary, Dadasaheb M Kokare, Amul J Sakharkar
Minimal traumatic brain injury (MTBI) often transforms into chronic neuropsychiatric conditions including anxiety, the underlying mechanisms of which are largely unknown. In the present study, we employed the closed-head injury paradigm to induce MTBI in rats and examined whether DNA methylation can explain long-term changes in the expression of the brain-derived neurotrophic factor (BDNF) in the amygdala as well as trauma-induced anxiety-like behaviors. The MTBI caused anxiety-like behaviors and altered the expression of DNA methyltransferase (DNMT) isoforms (DNMT1, DNMT3a, and DNMT3b) and factors involved in DNA demethylation such as the growth arrest and DNA damage 45 (GADD45a and GADD45b)...
June 27, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28652820/a-higher-degree-of-expression-of-dna-methyl-transferase-1-in-cervical-cancer-is-associated-with-poor-survival-outcome
#14
Chandrika J Piyathilake, Suguna Badiga, Samuel G Borak, Janaka Weragoda, Sejong Bae, Roland Matthews, Walter C Bell, Edward E Partridge
BACKGROUND: Even though novel therapies based on aberrant DNA methylation could be of particular importance for the treatment of cervical cancer (CC) because the oncoproteins E6/E7 of high-risk human papillomaviruses, the causative agents for developing CC, have the capacity to bind and upregulate DNA methyltransferases (DNMTs), to our knowledge, no previous studies have evaluated the expression of this enzyme in CC in relation to survival outcomes. The purpose of the study was to evaluate the expression of DNMT1 in CC and its association with survival outcomes...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28645910/epigenetic-drugs-promote-transcription-from-cryptic-start-sites
#15
(no author information available yet)
HDAC and DNMT inhibitors promoted global de novo transcription from nonannotated TSSs (termed TINAT).
June 23, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28642588/epigenetic-targeting-drugs-potentiate-chemotherapeutic-effects-in-solid-tumor-therapy
#16
Jingjing Li, Dapeng Hao, Li Wang, Haitao Wang, Yuan Wang, Zhiqiang Zhao, Peipei Li, Chuxia Deng, Li-Jun Di
Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our meta-analysis. To investigate the synergistic mechanism of ETD and DTD drug combination, the therapeutic effect was studied using both cell lines and mouse engrafted tumors...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629431/microrna-330-3p-promotes-cell-invasion-and-metastasis-in-non-small-cell-lung-cancer-through-gria3-by-activating-mapk-erk-signaling-pathway
#17
Chun-Hua Wei, Gang Wu, Qian Cai, Xi-Can Gao, Fan Tong, Rui Zhou, Rui-Guang Zhang, Ji-Hua Dong, Yu Hu, Xiao-Rong Dong
BACKGROUND: Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28623907/dna-methylation-dysregulations-in-rheumatic-heart-valve-disease
#18
Kangjun Shen, Hui Liu, Ran Jing, Jiangfeng Yi, Xinmin Zhou
BACKGROUND: The epigenetic changes underlying the development of rheumatic heart valve disease (RHVD) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of RHVD. In the present study, we evaluated the DNA methylation dysregulations from myocardial tissue in RHVD patients systematically. METHODS: Right atrial myocardial tissue obtained from rheumatic valvular patients who had undergone valve replacements surgery (n = 73) and were compared to healthy controls (n = 4)...
June 17, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28622390/inhibiting-dna-methylation-activates-cancer-testis-antigens-and-expression-of-the-antigen-processing-and-presentation-machinery-in-colon-and-ovarian-cancer-cells
#19
Cornelia Siebenkäs, Katherine B Chiappinelli, Angela A Guzzetta, Anup Sharma, Jana Jeschke, Rajita Vatapalli, Stephen B Baylin, Nita Ahuja
Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells compared to normal tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28614801/dna-methyltransferase-3b-regulates-articular-cartilage-homeostasis-by-altering-metabolism
#20
Jie Shen, Cuicui Wang, Daofeng Li, Taotao Xu, Jason Myers, John M Ashton, Ting Wang, Michael J Zuscik, Audrey McAlinden, Regis J O'Keefe
Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a complex disease affecting the whole joint but is generally characterized by progressive degradation of articular cartilage. Recent genome-wide association screens have implicated distinct DNA methylation signatures in OA patients. We show that the de novo DNA methyltransferase (Dnmt) 3b, but not Dnmt3a, is present in healthy murine and human articular chondrocytes and its expression decreases in OA mouse models and in chondrocytes from human OA patients...
June 15, 2017: JCI Insight
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