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https://www.readbyqxmd.com/read/28102966/histone-deacetylase-2-is-decreased-in-peripheral-blood-pro-inflammatory-cd8-t-and-nkt-like-lymphocytes-following-lung-transplant
#1
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N Reynolds, Mark Holmes
BACKGROUND AND OBJECTIVE: Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown...
February 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28073598/hdac10-as-a-potential-therapeutic-target-in-ovarian-cancer
#2
Muhtadi M Islam, Tapahsama Banerjee, Colin Z Packard, Shweta Kotian, Karuppaiyah Selvendiran, David E Cohn, Jeffrey D Parvin
OBJECTIVE: We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy...
January 7, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28056398/clinical-outcome-of-myeloid-sarcoma-in-adult-patients-and-effect-of-allogeneic-stem-cell-transplantation-results-from-a-multicenter-survey
#3
Davide Lazzarotto, Anna Candoni, Carla Filì, Fabio Forghieri, Livio Pagano, Alessandro Busca, Giuseppina Spinosa, Maria Elena Zannier, Erica Simeone, Miriam Isola, Erika Borlenghi, Lorella Melillo, Federico Mosna, Federica Lessi, Renato Fanin
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease...
December 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28053023/ricolinostat-the-first-selective-histone-deacetylase-6-inhibitor-in-combination-with-bortezomib-and-dexamethasone-for-relapsed-or-refractory-multiple-myeloma
#4
Dan T Vogl, Noopur S Raje, Sundar Jagannath, Paul G Richardson, Parameswaran Hari, Robert Z Orlowski, Jeffrey G Supko, David Tamang, Min Yang, Simon S Jones, Catherine Wheeler, Robert J Markelewicz, Sagar Lonial
PURPOSE: Histone deacetylase (HDAC) inhibition improves the efficacy of proteasome inhibition for multiple myeloma but adds substantial toxicity. Preclinical models suggest that the observed synergy is due to the role of HDAC6 in mediating resistance to proteasome inhibition via the aggresome/autophagy pathway of protein degradation. EXPERIMENTAL DESIGN: We conducted a phase 1/2 trial of the HDAC6-selective inhibitor ricolinostat to define the safety, preliminary efficacy, and recommended phase 2 dose in combination with standard proteasome inhibitor therapy...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28046085/differential-hdac1-and-2-recruitment-by-members-of-the-mier-family
#5
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/28031458/normalization-of-hepatic-homeostasis-in-the-npc1nmf164-mouse-model-of-niemann-pick-type-c-disease-treated-with-the-histone-deacetylase-inhibitor-vorinostat
#6
Andrew B Munkacsi, Natalie Hammond, Remy T Schneider, Dinindu S Senanayake, Katsumi Higaki, Kirill Lagutin, Stephen J Bloor, Daniel S Ory, Robert A Maue, Fannie W Chen, Antonio Hernandez-Ono, Nicole Dahlson, Joyce J Repa, Henry N Ginsberg, Yiannis A Ioannou, Stephen L Sturley
Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no FDA-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1nmf164 mice, which express a missense mutation in the NPC1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of Vorinostat (150 mg/kg, 5 days per week)...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28025089/histone-deacetylase-5-modulates-the-effects-of-social-adversity-in-early-life-on-cocaine-induced-behavior
#7
Alessandro Valzania, Clarissa Catale, Maria Teresa Viscomi, Stefano Puglisi-Allegra, Valeria Carola
Psychostimulants induce stable changes in neural plasticity and behavior in a transcription-dependent manner. Further, stable cellular changes require transcription that is regulated by epigenetic mechanisms that alter chromatin structure, such as histone acetylation. This mechanism is typically catalyzed by enzymes with histone acetyltransferase or histone deacetylase (HDAC) activity. Class IIa HDACs are notable for their high expression in important regions of the brain reward circuitry and their neural activity-dependent shuttling in and out of the cell nucleus...
December 23, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/28012453/the-effect-of-histone-deacetylase-inhibition-on-the-expression-of-p-glycoprotein-in-human-placental-trophoblast-cell-lines
#8
Hongyu Duan, Chuan Wang, Kaiyu Zhou, Tao Wang, Yifei Li, Dajian Qiu, Qiang Li, Yi Zhang, Yimin Hua
INTRODUCTIONS: Placental P-glycoprotein (P-gp), encoded by ABCB1 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic control of placental P-gp is rare. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on P-gp expression in placental trophoblast cell lines and to explore whether HDAC1/2/3 was involved in this process preliminarily...
January 2017: Placenta
https://www.readbyqxmd.com/read/27993690/a-seasonal-switch-in-histone-deacetylase-gene-expression-in-the-hypothalamus-and-their-capacity-to-modulate-nuclear-signaling-pathways
#9
Patrick N Stoney, Diana Rodrigues, Gisela Helfer, Thabat Khatib, Anna Ashton, Elizabeth A Hay, Robert Starr, Dagmara Kociszewska, Peter Morgan, Peter McCaffery
Seasonal animals undergo changes in physiology and behavior between summer and winter conditions. These changes are in part driven by a switch in a series of hypothalamic genes under transcriptional control by hormones and, of recent interest, inflammatory factors. Crucial to the control of transcription are histone deacetylases (HDACs), generally acting to repress transcription by local histone modification. Seasonal changes in hypothalamic HDAC transcripts were investigated in photoperiod-sensitive F344 rats by altering the day-length (photoperiod)...
December 18, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27980017/nitric-oxide-modulates-histone-acetylation-at-stress-genes-by-inhibition-of-histone-deacetylases
#10
Alexander Mengel, Alexandra Ageeva, Elisabeth Georgii, Jörg Bernhardt, Keqiang Wu, Jörg Durner, Christian Lindermayr
Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by nitric oxide (NO), in plants however, it is unknown whether NO affects histone acetylation. We found that treatment with the physiological NO-donor S-nitroso-glutathione (GSNO) increased the abundance of several histone acetylation marks in Arabidopsis, which was strongly diminished in the presence of the NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO)...
December 15, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27956831/a-facile-route-to-form-self-carried-redox-responsive-vorinostat-nanodrug-for-effective-solid-tumor-therapy
#11
Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang
Small molecule-based nanodrugs with nanoparticles (NPs) that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA) is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27943581/reverse-biosynthesis-generating-combinatorial-pools-of-drug-leads-from-enzyme-mediated-fragmentation-of-natural-products
#12
Tomas Richardson-Sanchez, William Tieu, Rachel Codd
A combinatorial pool of hydroxamic acid fragments as potential metalloprotein drug leads was generated from the enzyme-mediated hydrolysis of the natural product desferrioxamine B (DFOB). DFOB is a metabolite produced by Streptomyces pilosus for iron acquisition that can be selectively catabolized by Niveispirillum irakense to access carbon for growth. The supernatant of a DFOB-supplemented culture of N. irakense was analyzed by LC-MS at 7-8 intervals to 168 h and a mixture of endo-hydroxamic acid fragments were identified that contained reactive terminal groups...
December 11, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27939885/tescalcin-is-a-potential-target-of-class-i-histone-deacetylase-inhibitors-in-neurons
#13
Gakuya Takamatsu, Chiaki Katagiri, Tsumuraya Tomoyuki, Chigusa Shimizu-Okabe, Wakako Nakamura, Mariko Nakamura-Higa, Tomoko Hayakawa, Shigeo Wakabayashi, Tsuyoshi Kondo, Chitoshi Takayama, Masayuki Matsushita
Class I histone deacetylase (HDAC) inhibitors are believed to have positive effects on neurite outgrowth, synaptic plasticity, and neurogenesis in adult brain. However, the downstream molecular targets of class I HDAC inhibitors in neurons are not clear. Although class I HDAC inhibitors are thought to broadly promote transcription of many neuronal genes through enhancement of histone acetylation, the affected gene set may include unidentified genes that are essential for neuronal survival and function. To identify novel genes that are targets of class I HDAC inhibitors, we used a microarray to screen transcripts from neuronal cultures and evaluated changes in protein and mRNA expression following treatment with four HDAC inhibitors...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27936591/impact-of-scaffold-exploration-on-novel-dual-acting-histone-deacetylases-and-phosphodiesterase-5-inhibitors-for-the-treatment-of-alzheimer-s-disease
#14
Juan A Sánchez-Arias, Obdulia Rabal, Mar Cuadrado-Tejedor, Irene de Miguel, Marta Pérez-González, Ana Ugarte, Elena Sáez, Maria Espelosin, Susana Ursua, Tan Haizhong, Wu Wei, Xu Musheng, Ana Garcia-Osta, Julen Oyarzabal
A novel systems therapeutics approach, involving simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylase (HDAC), has been validated as a potentially novel therapeutic strategy for the treatment of Alzheimer's disease (AD). First-in-class dual inhibitors bearing a sildenafil core have been very recently reported, and the lead molecule 7 has proven this strategy in AD animal models. Because scaffolds may play a critical role in primary activities and ADME-Tox profiling as well as on intellectual property, we have explored alternative scaffolds (vardenafil- and tadalafil-based cores) and evaluated their impact on critical parameters such as primary activities, permeability, toxicity, and in vivo (pharmacokinetics and functional response in hippocampus) to identify a potential alternative lead molecule bearing a different chemotype for in vivo testing...
December 27, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27928959/potential-application-of-5-aryl-substituted-2-amino-benzamide-type-of-hdac1-2-selective-inhibitors-to-pharmaceuticals
#15
Shinichi Uesato, Yoshiyuki Hirata, Tsutomu Sasaki
Diverse histone deacetylase (HDAC) inhibitors have been developed to date. They control not only histone modification but also gene expression of diverse proteins and thus are expected to provide useful therapeutic effects on various diseases, including cancers, psychiatric and cognitive disorders and neurodegenerative diseases, as well as cardiovascular and diabetic diseases. Some isoform-nonselective HDAC inhibitors have been successfully used for clinical treatments of the haematological malignancies, including advanced forms of cutaneous T-cell lymphoma, refractory peripheral T-cell lymphoma and multiple myeloma...
December 8, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27925271/validation-of-an-lc-ms-ms-method-for-simultaneous-detection-of-four-hdac-inhibitors-belinostat-panobinostat-rocilinostat-and-vorinostat-in-mice-plasma-and-its-application-to-a-mice-pharmacokinetic-study
#16
Kalpesh Kumar Giri, Suresh P S, Syed Mohd Saim, Mohd Zainuddin, Ravi Kanth Bhamidipati, Purushottam Dewang, Mahanandeesha S Hallur, Sridharan Rajagopal, Sriram Rajagopal, Ramesh Mullangi
A sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous quantitation of four HDAC inhibitors namely belinostat (BST), panobinostat (PST), rocilinostat (RST) and vorinostat (VST) in mice plasma as per regulatory guidelines. The analytes and internal standard were extracted from 50 μL mice plasma by protein precipitation, followed by chromatographic separation using an Atlantis C18 column with an isocratic mobile phase comprising 0.1% formic acid: acetonitrile (25:75,, v/v) at a flow rate of 0...
December 7, 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/27922200/a-fluorescence-lifetime-based-binding-assay-for-class-iia-histone-deacetylases
#17
Christian Meyners, Monique Mertens, Pablo Wessig, Franz-Josef Meyer-Almes
Class IIa HDACs show extremely low enzymatic activity and no commonly accepted endogenous substrate is known today. Increasing evidence suggests that these enzymes exert their effect rather through molecular recognition of acetylated proteins and recruiting other proteins like HDAC3 to the desired target location. Accordingly, class IIa HDACs like bromodomains have been suggested to act as "Readers" of acetyl marks, whereas enzymatically active HDACs from class I or IIb are called "Erasers" to highlight their capability to remove acetyl groups from acetylated histones or other proteins...
December 6, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27917100/synthesis-of-st7612aa1-a-novel-oral-hdac-inhibitor-via-radical-%C3%A2-thioacetic-acid-addition
#18
Gianfranco Battistuzzi, Giuseppe Giannini
ABSTRACT BACKGROUND: In the expanding field of anticancer drugs, HDAC inhibitors are playing an increasingly important role. To date, four/five HDAC inhibitors have been approved by FDA. All these compounds fit the widely accepted HDAC inhibitors pharmacophore model characterized by a cap group, a linker chain and a zinc binding group (ZBG), able to bind the Zn(2+) ion in a pocket of the HDAC active site. Romidepsin, a natural compound, is the only thiol derivative. We have selected a new class of synthetic HDAC inhibitors, the thio-ω(lactam-carboxamide) derivatives, with ST7612AA1 as drug candidate, pan-inhibitor active in the range of single- to two-digit nanomolar concentrations...
December 2016: Current Bioactive Compounds
https://www.readbyqxmd.com/read/27916575/circannual-and-circadian-rhythms-of-hypothalamic-dna-methyltransferase-and-histone-deacetylase-expression-in-male-siberian-hamsters-phodopus-sungorus
#19
Tyler J Stevenson
Precise timing of gene transcription is a fundamental component of many biological rhythms. DNA methylation and histone acetylation are two epigenetic modifications that can affect the probability of gene transcription and RNA expression. Enzymes involved in DNA methylation (dnmts) have been shown to exhibit photoperiodic rhythms in expression in the hypothalamus, which coincide with hypothalamic expression of deiodinase type III (dio3), a gene involved in the photoperiodic regulation of reproduction. It is currently unknown whether enzymes involved in histone deacetylation (hdacs) also vary in response to photoperiod, nor have seasonal changes in the circadian waveforms of methylation and/or acetylation enzymes been examined...
December 1, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27914010/recruitment-by-the-repressor-freud-1-of-histone-deacetylase-brg1-chromatin-remodeling-complexes-to-strengthen-htr1a-gene-repression
#20
Tatiana Souslova, Kim Mirédin, Anne M Millar, Paul R Albert
Five-prime repressor element under dual repression binding protein-1 (Freud-1)/CC2D1A is genetically linked to intellectual disability and implicated in neuronal development. Freud-1 represses the serotonin-1A (5-HT1A) receptor gene HTR1A by histone deacetylase (HDAC)-dependent or HDAC-independent mechanisms in 5-HT1A-negative (e.g., HEK-293) or 5-HT1A-expressing cells (SK-N-SH), respectively. To identify the underlying mechanisms, Freud-1-associated proteins were affinity-purified from HEK-293 nuclear extracts and members of the Brg1/SMARCCA chromatin remodeling and Sin3A-HDAC corepressor complexes were identified...
December 2, 2016: Molecular Neurobiology
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