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HDAC1 HDAC2

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https://www.readbyqxmd.com/read/28192098/anti-leukemic-effects-of-hdaci-belinostat-and-hmti-3-deazaneplanocin-a-on-human-acute-promyelocytic-leukemia-cells
#1
Giedrė Valiulienė, Ieva Stirblytė, Monika Jasnauskaitė, Veronika Borutinskaitė, Rūta Navakauskienė
Development of acute myeloid leukemia is usually sustained by deregulated epigenome. Alterations in DNA methylation and histone modifications are common manifestations of the disease. Acute promyelocytic leukemia (APL) is not an exception. Therefore, drugs that target epigenetic processes suggest an appealing strategy for APL treatment. In this study we tested the anti-leukemic activity of histone deacetylase inhibitor (HDACi) Belinostat (PXD101, (2E)-N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide), and histone methyltransferase inhibitor (HMTi) 3-Deazaneplanocin A (DZNep, 5R-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)-3-cyclopentene-1S,2R-diol) combined with retinoic acid (RA) in APL cells NB4 and HL-60...
February 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28174211/overlapping-and-divergent-actions-of-structurally-distinct-hdac-inhibitors-in-cardiac-fibroblasts
#2
Katherine B Schuetze, Matthew S Stratton, Weston W Blakeslee, Michael F Wempe, Florence F Wagner, Edward B Holson, Yin-Ming Kuo, Andrew J Andrews, Tonya M Gilbert, Jacob M Hooker, Timothy A McKinsey
Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly impact cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiological and pathophysiological processes...
February 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28139683/delaying-histone-deacetylase-response-to-injury-accelerates-conversion-into-repair-schwann-cells-and-nerve-regeneration
#3
Valérie Brügger, Mert Duman, Maëlle Bochud, Emmanuelle Münger, Manfred Heller, Sophie Ruff, Claire Jacob
The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28125812/investigation-of-new-therapeutic-targets-in-undifferentiated-endometrial-sarcoma
#4
Min-Hyun Baek, Jeong-Yeol Park, Chae Chun Rhim, Jong-Hyeok Kim, Yangsoon Park, Kyu-Rae Kim, Joo-Hyun Nam
BACKGROUND: Undifferentiated endometrial sarcoma (UES) is a very rare subtype of uterine sarcoma, which has no consensus on the treatment. We investigated the expression of potential new therapeutic targets in UES to improve its aggressive clinical course and poor survival outcome. METHODS: The immunohistochemical expressions of vascular endothelial growth factor (VEGF), c-KIT, c-ABL, platelet derived growth factor receptor (PDGFR), protein kinase B (AKT1), mammalian target of rapamycin, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER2), Wilms tumor (WT1), aromatase inhibitor (CYP19A1), and histone deacetylase (HDAC) series in 10 UES patients were assessed using tissue microarrays...
January 27, 2017: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/28107582/immunoexpression-of-hdac1-hdac2-and-hat1-in-actinic-cheilitis-and-lip-squamous-cell-carcinoma
#5
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
#6
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
#7
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
#8
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
#9
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...
February 15, 2017: 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
#10
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...
January 24, 2017: 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
#11
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
#12
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
#13
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
#14
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
#15
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...
February 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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