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HDAC1 HDAC2

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https://www.readbyqxmd.com/read/28107582/immunoexpression-of-hdac1-hdac2-and-hat1-in-actinic-cheilitis-and-lip-squamous-cell-carcinoma
#1
Emanuely da Silva Chrun, Filipe Modolo, Daniella Serafim Couto Vieira, Álvaro Luiz Socorro Borges, Renata Goulart Castro, Filipe Ivan Daniel
BACKGROUND: Acetylation/deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers...
January 20, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28078999/hdacs-and-hdac-inhibitors-in-urothelial-carcinoma-perspectives-for-an-antineoplastic-treatment
#2
Maria Pinkerneil, Michèle J Hoffmann, Wolfgang A Schulz, Günter Niegisch
Histone deacetylases (HDACs) influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms. Class I HDACs are often overexpressed in cancers contributing to a genome-wide epigenetic state permitting increased proliferation, and diminished apoptosis and cell differentiation. Class IIA and IIB isoenzymes may likewise contribute to tumorigenesis as components of specific intranuclear repressor complexes or regulators of posttranslational protein modifications...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28060870/selective-inhibitors-of-histone-deacetylases-1-and-2-synergize-with-azacitidine-in-acute-myeloid-leukemia
#3
Chengyin Min, Nathan Moore, Jeffrey R Shearstone, Steven N Quayle, Pengyu Huang, John H van Duzer, Matthew B Jarpe, Simon S Jones, Min Yang
Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the pathogenesis of AML, and inhibitors of DNA methyltransferase or histone deacetylase (HDAC) enzymes have exhibited activity in preclinical AML models...
2017: PloS One
https://www.readbyqxmd.com/read/28046085/differential-hdac1-and-2-recruitment-by-members-of-the-mier-family
#4
Roya Derwish, Gary D Paterno, Laura L Gillespie
The mier family consists of three related genes encoding ELM2-SANT containing proteins. MIER1 has been well characterized and is known to function in transcriptional repression through its ability to recruit HDAC1 and 2. Little is known about MIER2 or MIER3 function and no study characterizing these two proteins has been published. In this report, we investigate MIER2 and MIER3 localization and function. Confocal analysis revealed that, while MIER2 and MIER3 are mainly nuclear proteins, a substantial proportion (32%) of MIER2 is localized in the cytoplasm...
2017: PloS One
https://www.readbyqxmd.com/read/28038324/ring-opened-tetrahydro-%C3%AE-carbolines-display-cytotoxicity-and-selectivity-with-histone-deacetylase-isoforms
#5
Kunal Nepali, Hsueh-Yun Lee, Mei-Jung Lai, Ritu Ojha, Tung-Yun Wu, Gu-Xian Wu, Mei-Chuan Chen, Jing-Ping Liou
This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5-18) were synthesized and structure-activity relationship studies indicated that the change of the tetrahydro-γ-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials...
December 21, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28030834/histone-deacetylases-1-and-2-cooperate-in-regulating-brca1-chk1-and-rad51-expression-in-acute-myeloid-leukemia-cells
#6
Jianyun Zhao, Chengzhi Xie, Holly Edwards, Guan Wang, Jeffrey W Taub, Yubin Ge
Resistance to chemotherapy and a high relapse rate highlight the importance of finding new therapeutic options for the treatment of acute myeloid leukemia (AML). Histone deacetylase (HDAC) inhibitors (HDACIs) are a promising class of drugs for the treatment of AML. HDACIs have limited single-agent clinical activities, but when combined with conventional or investigational drugs they have demonstrated favorable outcomes. Previous studies have shown that decreasing expression of important DNA damage repair proteins enhances standard chemotherapy drugs...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017732/photoperiodic-and-ovarian-steroid-regulation-of-histone-deacetylase-1-2-and-3-in-siberian-hamster-phodopus-sungorus-reproductive-tissues
#7
Eloise W J Lynch, Christopher S Coyle, Tyler J Stevenson
Epigenetic modifications in reproductive tissues have predominantly focused on pathological conditions, such as ovarian and uterine cancers. The contribution of DNA methylation and histone acetylation to the timing and control of fertility is not well described. Siberian hamsters provide an important model to investigate the relatively short-term regulation of fertility (e.g. estrous) as well as long-term timing of breeding (e.g. seasonal). Recent work has shown that DNA methyltransferase 3a (dnmt3a) expression is associated with reproductive involution...
December 22, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27959513/expression-of-hdac2-but-not-hdac1-transcript-is-reduced-in-dorsolateral-prefrontal-cortex-of-patients-with-schizophrenia
#8
Frederick A Schroeder, Tonya M Gilbert, Ningping Feng, Brendan D Taillon, Nora D Volkow, Robert B Innis, Jacob M Hooker, Barbara K Lipska
Postmortem brain studies support dysregulated expression of the histone deacetylase enzymes, HDAC1 and HDAC2, as a central feature in diseases including schizophrenia, bipolar disorder, and depression. Our objective was to investigate HDAC expression in a large postmortem sample set representing healthy and disease brains. We used >700 well-characterized samples from patients diagnosed with schizophrenia (n = 175), major depressive disorder (n = 135), and bipolar disorder (n = 61) to measure HDAC1 and HDAC2 transcript levels by quantitative real-time PCR in dorsolateral prefrontal cortex (DLPFC) and caudate compared to control samples...
December 13, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27903278/an-overview-on-the-role-of-dietary-phenolics-for-the-treatment-of-cancers
#9
REVIEW
Preethi G Anantharaju, Prathima C Gowda, Manjunatha G Vimalambike, SubbaRao V Madhunapantula
Plant derived phenolic compounds have been shown to inhibit the initiation and progression of cancers by modulating genes regulating key processes such as: (a) oncogenic transformation of normal cells; (b) growth and development of tumors; and (c) angiogenesis and metastasis. Recent studies focusing on identifying the molecular basis of plant phenolics-induced cancer cell death have demonstrated down-regulation of: (a) oncogenic survival kinases such as PI3K and Akt; (b) cell proliferation regulators that include Erk1/2, D-type Cyclins, and Cyclin Dependent Kinases (CDKs); (c) transcription factors such as NF-kβ, NRF2 and STATs; (d) histone deacetylases HDAC1 and HDAC2; and (e) angiogenic factors VEGF, FGFR1 and MIC-1...
December 1, 2016: Nutrition Journal
https://www.readbyqxmd.com/read/27886239/histone-deacetylase-1-plays-a-predominant-pro-oncogenic-role-in-e%C3%AE-myc-driven-b-cell-lymphoma
#10
Vincent Pillonel, Nina Reichert, Chun Cao, Marinus R Heideman, Teppei Yamaguchi, Gabriele Matthias, Alexandar Tzankov, Patrick Matthias
The two histone deacetylases (Hdacs), Hdac1 and Hdac2, are erasers of acetylation marks on histone tails, and are important regulators of gene expression that were shown to play important roles in hematological malignancies. However, several recent studies reported opposing tumor-suppressive or tumor-promoting roles for Hdac1 and Hdac2. Here, we investigated the functional role of Hdac1 and Hdac2 using the Eμ-myc mouse model of B cell lymphoma. We demonstrate that Hdac1 and Hdac2 have a pro-oncogenic role in both Eμ-myc tumorigenesis and tumor maintenance...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27868267/reduced-microrna-188-3p-expression-contributes-to-apoptosis-of-spermatogenic-cells-in-patients-with-azoospermia
#11
Wen-Yan Song, Hui Meng, Xue-Gai Wang, Hai-Xia Jin, Gui-Dong Yao, Sen-Lin Shi, Liang Wu, Xiang-Yang Zhang, Ying-Pu Sun
BACKGROUND AND AIMS: Human mutL homologl (MLH1) works coordinately in sequential steps to initiate repair of DNA mismatches, and aberrant MLH1 expression is related to spermatogenetic malfunction. In the present study, MLH1 expression in patients with azoospermia was investigated, and moderating effects of miR-188-3p on MLH1 expression and spermatogenesis were identified. METHODS: Testicular tissues from 16 patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), and tissues of eight healthy patients were collected...
November 21, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27832326/silencing-of-histone-deacetylase-2-suppresses-malignancy-for-proliferation-migration-and-invasion-of-glioblastoma-cells-and-enhances-temozolomide-sensitivity
#12
Zhiqiang Zhang, Yunmin Wang, Jiehan Chen, Qijia Tan, Caijun Xie, Cong Li, Wengang Zhan, Mei Wang
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27818691/osteogenic-differentiation-of-human-amniotic-fluid-mesenchymal-stem-cells-is-determined-by-epigenetic-changes
#13
Monika Glemžaitė, Rūta Navakauskienė
Osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells (AF-MSCs) has been widely studied in vitro and in vivo as a potential tool for regenerative medicine and tissue engineering. While most of the studies analyze changes in transcriptional profile during differentiation to date there is not much information regarding epigenetic changes in AF-MSCs during differentiation. The aim of our study was to evaluate epigenetic changes during osteogenic differentiation of AF-MS cells. Isolated AF-MSCs were characterized morphologically and osteogenic differentiation was confirmed by cell staining and determining expression of alkaline phosphatase and osteopontin by RT-qPCR...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#14
Christian Griñan-Ferré, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, David Pérez-Cáceres, Júlia Companys-Alemany, Antonio Camins, Daniel Ortuño-Sahagún, M Teresa Rodrigo, Mercè Pallàs
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27781405/valproic-acid-enhances-the-neural-differentiation-of-human-placenta-derived-mesenchymal-stem-cells-in-vitro
#15
Manasi Talwadekar, Sophia Fernandes, Vaijayanti Kale, Lalita Limaye
Mesenchymal stem cells (MSCs) are known to express a wide range of markers belonging to all the three lineages: mesodermal, ectodermal and endodermal. Therefore, the possibility of their transdifferentiation towards a neural lineage has been an aspect of active research. In the present study, MSCs were isolated from human placental tissue (P-MSC) and subjected them to neural differentiation. It was found that the P-MSCs differentiated towards neural lineage in appropriate differentiation conditions. However, when a histone deacetylase (HDAC) inhibitor - valproic acid (VPA) - was incorporated in the medium, there was a further increase in their neural differentiation potential...
October 25, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27761828/modulation-of-stat1-driven-transcriptional-activity-by-histone-deacetylases
#16
Benjamin Y Owusu, Lidija Klampfer
The luciferase (LUC) reporter assay is commonly used to study gene expression at the transcriptional level. It is convenient, fast, sensitive, inexpensive, and provides quantitative data about small changes in transcription. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that plays a crucial role in signaling by interferons (IFNs). Here, we describe LUC reporter studies that address the role of histone deacetylase (HDAC) activity in STAT1-dependent gene activation. These experiments include overexpression of HDAC1, HDAC2, HDAC3, and HDAC4 as well as silencing of HDAC1, HDAC2, and HDAC3 through RNA interference in mammalian cancer cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27729849/hdac3-but-not-hdac2-mediates-visual-experience-dependent-radial-glia-proliferation-in-the-developing-xenopus-tectum
#17
Juanmei Gao, Hangze Ruan, Xianjie Qi, Yi Tao, Xia Guo, Wanhua Shen
Radial glial cells (RGs) are one of the important progenitor cells that can differentiate into neurons or glia to form functional neural circuits in the developing central nervous system (CNS). Histone deacetylases (HDACs) has been associated with visual activity dependent changes in BrdU-positive progenitor cells in the developing brain. We previously have shown that HDAC1 is involved in the experience-dependent proliferation of RGs. However, it is less clear whether two other members of class I HDACs, HDAC2 and HDAC3, are involved in the regulation of radial glia proliferation...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27721407/hdac1-and-hdac2-integrate-the-expression-of-p53-mutants-in-pancreatic-cancer
#18
N Stojanovic, Z Hassan, M Wirth, P Wenzel, M Beyer, C Schäfer, P Brand, A Kroemer, R H Stauber, R M Schmid, A Arlt, A Sellmer, S Mahboobi, R Rad, M Reichert, D Saur, O H Krämer, G Schneider
Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27714131/c60-oh-22-a-potential-histone-deacetylase-inhibitor-with-anti-angiogenic-activity
#19
Chengdu Sun, Liming Wang, Dan Gao, Yuanming Pan, Yuliang Zhao, Chunying Chen, Mingzhou Guo
C60(OH)22 has been reported to suppress human cancer by inhibiting angiogenesis. However, its mechanism of action remains unclear. To explore the role and mechanism of C60(OH)22 in human pancreatic cancer, siRNA knockdown, immunofluorescence and a matrigel plug mouse model were employed. The results demonstrated that C60(OH)22 suppresses endothelial cell invasion and tube formation in vitro. C60(OH)22 suppresses angiogenesis in human umbilical vein endothelial cell (HUVEC) xenograft mice. The enzymatic activities of MMP2 and MMP9, as well as the expression levels of HDAC1, HDAC2, HIF-1α and VEGF, were inhibited by C60(OH)22...
September 15, 2016: Nanoscale
https://www.readbyqxmd.com/read/27672210/class-i-histone-deacetylase-hdac1-and-wrn-recq-helicase-contribute-additively-to-protect-replication-forks-upon-hydroxyurea-induced-arrest
#20
Keffy Kehrli, Michael Phelps, Pavlo Lazarchuk, Eleanor Chen, Ray Monnat, Julia M Sidorova
The WRN helicase/exonuclease is mutated in Werner syndrome of genomic instability and premature aging. WRN-depleted fibroblasts, although remaining largely viable, have a reduced capacity to maintain replication forks active during a transient hydroxyurea-induced arrest. A strand exchange protein, RAD51, is also required for replication fork maintenance, and here we show that recruitment of RAD51 to stalled forks is reduced in the absence of WRN. We performed a siRNA screen for genes that are required for viability of WRN-depleted cells after hydroxyurea treatment, and identified HDAC1, a member of the class I histone deacetylase family...
November 18, 2016: Journal of Biological Chemistry
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