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https://www.readbyqxmd.com/read/27905989/the-histone-deacetylase-inhibitor-sodium-butyrate-exhibits-neuroprotective-effects-for-ischemic-stroke-in-middle-aged-female-rats
#1
Min Jung Park, Farida Sohrabji
BACKGROUND: Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of stroke as well as a myocardial ischemia model. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals. METHODS: To determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (9-11 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27902771/piceatannol-attenuates-renal-fibrosis-induced-by-unilateral-ureteral-obstruction-via-downregulation-of-histone-deacetylase-4-5-or-p38-mapk-signaling
#2
Sin Young Choi, Zhe Hao Piao, Li Jin, Jung Ha Kim, Gwi Ran Kim, Yuhee Ryu, Ming Quan Lin, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong
Piceatannol, a resveratrol metabolite, is a phenolic compound found in red wine and grapes. We investigated the effect of piceatannol on renal fibrosis and histone deacetylase (HDAC) expression in a mouse model of unilateral ureteral obstruction (UUO). Fibrosis was established by UUO and piceatannol was intraperitoneally injected for 2 weeks. Piceatannol suppressed extracellular matrix (ECM) protein deposition including collagen type I and fibronectin as well as connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in UUO kidneys...
2016: PloS One
https://www.readbyqxmd.com/read/27900262/impaired-histone-deacetylases-5-and-6-expression-mimics-the-effects-of-obesity-and-hypoxia-on-adipocyte-function
#3
Julien Bricambert, Dimitri Favre, Saška Brajkovic, Amélie Bonnefond, Raphael Boutry, Roberto Salvi, Valérie Plaisance, Mohamed Chikri, Giulia Chinetti-Gbaguidi, Bart Staels, Vittorio Giusti, Robert Caiazzo, François Pattou, Gérard Waeber, Philippe Froguel, Amar Abderrahmani
OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adipose tissue (WAT) of C57Bl6-Rj mice fed a normal or high fat diet (HFD) for 16 weeks. HDAC activity was measured by colorimetric assay whereas the gene and protein expression were monitored by real-time PCR and by western blotting, respectively...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27884140/phase-ii-clinical-study-of-valproic-acid-plus-cisplatin-and-cetuximab-in-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-head-and-neck-v-chance-trial
#4
Francesco Caponigro, Elena Di Gennaro, Franco Ionna, Francesco Longo, Corrado Aversa, Ettore Pavone, Maria Grazia Maglione, Massimiliano Di Marzo, Paolo Muto, Ernesta Cavalcanti, Antonella Petrillo, Fabio Sandomenico, Piera Maiolino, Roberta D'Aniello, Gerardo Botti, Rossella De Cecio, Nunzia Simona Losito, Stefania Scala, Annamaria Trotta, Andrea Ilaria Zotti, Francesca Bruzzese, Antonio Daponte, Ester Calogero, Massimo Montano, Monica Pontone, Gianfranco De Feo, Francesco Perri, Alfredo Budillon
BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds...
November 25, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27883221/alcohol-exposure-causes-overexpression-of-heart-development-related-genes-by-affecting-the-histone-h3-acetylation-via-bmp-signaling-pathway-in-cardiomyoblast-cells
#5
Jin Shi, Weian Zhao, Bo Pan, Min Zheng, Lina Si, Jing Zhu, Lingjuan Liu, Jie Tian
BACKGROUND: Abusive alcohol utilization of pregnant woman may cause congenital heart disease (CHD) of fetus, where alcohol ignites histone H3 hyperacetylation leading to abnormal development of heart morphogenesis and associated genes. Knowledge about the regularized upstream genes is little, but bone morphogenetic protein (BMP) signaling may actively and prominently take part in alteration in acetylation of histone H3. The supreme objective of this study was to unearth the involvement of BMP signaling pathway in alcohol-driven hyperacetylation of histone H3 in cardiomyoblast cells...
November 24, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#6
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
November 24, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27877082/histone-deacetylase-inhibitor-trichostatin-a-promotes-the-apoptosis-of-osteosarcoma-cells-through-p53-signaling-pathway-activation
#7
Zhantao Deng, Xiaozhou Liu, Jiewen Jin, Haidong Xu, Qian Gao, Yong Wang, Jianning Zhao
Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6 patients with primary osteosarcoma...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27863490/suberoylanilide-hydroxamic-acid-represses-glioma-stem-like-cells
#8
Che-Chia Hsu, Wen-Chang Chang, Tsung-I Hsu, Jr-Jiun Liu, Shiu-Hwa Yeh, Jia-Yi Wang, Jing-Ping Liou, Chiung-Yuan Ko, Kwang-Yu Chang, Jian-Ying Chuang
BACKGROUND: Glioma stem-like cells (GSCs) are proposed to be responsible for high resistance in glioblastoma multiforme (GBM) treatment. In order to find new strategies aimed at reducing GSC stemness and improving GBM patient survival, we investigated the effects and mechanism of a histone deacetylases (HDACs) inhibitor, suberoylanilide hydroxamic acid (SAHA), since HDAC activity has been linked to cancer stem-like cell (CSC) abundance and properties. METHODS: Human GBM cell lines were plated in serum-free suspension cultures allowed for sphere forming and CSC enrichment...
November 18, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27821078/vorinostat-enhances-the-cisplatin-mediated-anticancer-effects-in-small-cell-lung-cancer-cells
#9
Chun-Hao Pan, Ying-Fang Chang, Ming-Shuo Lee, B-Chen Wen, Jen-Chung Ko, Sheng-Kai Liang, Mei-Chih Liang
BACKGROUND: Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). METHODS: We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines...
November 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27818231/epigenetic-reactivation-of-rassf1a-by-phenethyl-isothiocyanate-peitc-and-promotion-of-apoptosis-in-lncap-cells
#10
Sarandeep S S Boyanapalli, Wenji Li, Francisco Fuentes, Yue Guo, Christina N Ramirez, Ximena-Parades Gonzalez, Douglas Pung, Ah-Ng Tony Kong
Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive...
November 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27809464/hat-inhibitors-antagonize-ampk-in-postmortem-glycolysis
#11
Qiong Li, Zhongwen Li, Aihua Lou, Zhenyu Wang, Dequan Zhang, Qingwu Shen
Objective: The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK) activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. Methods: A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR, a specific activator of AMPK), AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II) and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases)...
October 28, 2016: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/27798112/leucine-rich-repeat-kinase-2-exacerbates-neuronal-cytotoxicity-through-phosphorylation-of-histone-deacetylase3-and-histone-deacetylation
#12
Kyung Ah Han, Wongi Seol, Hyemyung Seo, CheMyong Ko, Kwang Chul Chung
Parkinson's disease (PD) is characterized by slow, progressive degeneration of dopaminergic neurons in the substantia nigra. The cause of neuronal death in PD is largely unknown, but several genetic loci, including leucine-rich repeat kinase 2 (LRRK2), have been identified. LRRK2 has guanosine triphosphatase (GTPase) and kinase activities, and mutations in LRRK2 are the major cause of autosomal-dominant familial PD. Histone deacetylases (HDACs) remove acetyl groups from lysine residues on histone tails, promoting transcriptional repression via condensation of chromatin...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27789688/epigenetic-changes-in-histone-acetylation-underpin-resistance-to-the-topoisomerase-i-inhibitor-irinotecan
#13
Cornelia Meisenberg, Mohamed E Ashour, Lamia El-Shafie, Chunyan Liao, Adam Hodgson, Alice Pilborough, Syed A Khurram, Jessica A Downs, Simon E Ward, Sherif F El-Khamisy
The topoisomerase I (TOP1) inhibitor irinotecan triggers cell death by trapping TOP1 on DNA, generating cytotoxic protein-linked DNA breaks (PDBs). Despite its wide application in a variety of solid tumors, the mechanisms of cancer cell resistance to irinotecan remains poorly understood. Here, we generated colorectal cancer (CRC) cell models for irinotecan resistance and report that resistance is neither due to downregulation of the main cellular target of irinotecan TOP1 nor upregulation of the key TOP1 PDB repair factor TDP1...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27761827/assessing-hdac-function-in-the-regulation-of-signal-transducer-and-activator-of-transcription-5-stat5-activity-using-chromatin-immunoprecipitation-chip
#14
Sophia Pinz, Anne Rascle
Transcriptional activation by STAT5 is repressed by deacetylase inhibitors. Investigating the role of deacetylases (HDACs) in STAT5-mediated transcription implies the analysis of molecular events taking place at the chromatin level. We describe here two alternative methods of chromatin immunoprecipitation that allow the characterization of chromatin modifications ensuing STAT5 activation and its inhibition by deacetylase inhibitors, in particular changes in histone acetylation, in histone occupancy, and in the association/dissociation of transcription factors and other chromatin-associated factors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27761816/dna-fiber-spreading-assay-to-test-hdaci-effects-on-dna-and-its-replication
#15
Teodora Nikolova, Anja Göder, Ann Parplys, Kerstin Borgmann
DNA fiber spreading assay is an invaluable technique to visualize and follow the spatial and temporal progress of individual DNA replication forks. It provides information on the DNA replication progress and its regulation under normal conditions as well as on replication stress induced by environmental genotoxic agents or cancer drugs. The method relies on the detection of incorporated thymidine analogues during DNA synthesis in the S phase of the cell cycle by indirect immunofluorescence. Here, we describe the procedure established in our laboratories for sequential pulse labeling of human cells with 5-chloro-2'-deoxyuridine (CldU) and 5-iodo-2'-deoxyuridine (IdU), cell lysis, and DNA fiber spreading on slides and sequential immunodetection of the incorporated thymidine analogues by primary antibodies recognizing specifically CldU or IdU alone...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27742468/effects-of-histone-deacetylase-inhibitor-sodium-butyrate-on-heroin-seeking-behavior-in-the-nucleus-accumbens-in-rats
#16
Wei-Sheng Chen, Wen-Jin Xu, Hua-Qiang Zhu, Lei Gao, Miao-Jun Lai, Fu-Qiang Zhang, Wen-Hua Zhou, Hui-Fen Liu
Histone acetylation and other modifications of the chromatin are important regulators of gene expression and may contribute to drug-induced behaviors and neuroplasticity. Inhibition of histone deacetylases (HDAC) activity results in the change of some drug-induced behaviors,however, relatively little is known about the effects of HDAC inhibitors on heroin-seeking behavior. In the present study, male rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, followed by 14 daily 2hours extinction session in the operant chamber...
October 11, 2016: Brain Research
https://www.readbyqxmd.com/read/27739328/mc1568-inhibits-hdac6-8-activity-and-influenza-a-virus-replication-in-lung-epithelial-cells-role-of-hsp90-acetylation
#17
Simona Panella, Maria Elena Marcocci, Ignacio Celestino, Sergio Valente, Clemens Zwergel, Domenica Donatella Li Puma, Lucia Nencioni, Antonello Mai, Anna Teresa Palamara, Giovanna Simonetti
AIM: Histone deacetylases (HDACs) regulate the life-cycle of several viruses. We investigated the ability of different HDAC-inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. RESULTS: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs...
October 14, 2016: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/27717044/synthesis-of-potent-and-selective-hdac6-inhibitors-bearing-a-cyclohexane-or-cycloheptane-annulated-1-5-benzothiazepine-scaffold
#18
Rob De Vreese, Lisa Galle, Yves Depetter, Jorick Franceus, Tom Desmet, Kristof Van Hecke, Veronick Benoy, Ludo Van Den Bosch, Matthias D'hooghe
Selective inhibitors of histone deacetylase 6 (HDAC6) are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Herein, the synthesis of ten new benzohydroxamic acids, constructed by employing the tetrahydrobenzothiazepine core as a privileged pharmacophoric unit, is described. This is the first report on the synthesis and isolation of octahydrodibenzothiazepines and octahydro-6H-benzocycloheptathiazepines, which were then used to develop a new class of HDAC6 inhibitors...
October 7, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27706906/valproic-acid-selectively-increases-vascular-endothelial-tissue-type-plasminogen-activator-production-and-reduces-thrombus-formation-in-the-mouse
#19
P Larsson, I Alwis, B Niego, M Sashindranath, P Fogelstrand, M C L Wu, L Glise, M Magnusson, M Daglas, N Bergh, S P Jackson, R L Medcalf, S Jern
BACKGROUND: The endogenous fibrinolytic system has rarely been considered as a target to prevent thrombotic disease. Tissue plasminogen activator (t-PA) is potently increased by histone deacetylase (HDAC) inhibitors in endothelial cells in vitro, but whether this translates into increased vascular t-PA production and an enhanced fibrinolytic capacity in vivo is unknown. OBJECTIVES: The aim of this study was to determine if the HDAC inhibitor valproic acid (VPA) stimulates production of t-PA in the vasculature of mice, and further, if VPA pre-treatment affects fibrin deposition and clot formation after mechanical vessel injury...
October 5, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27697049/macrolide-hybrid-compounds-drug-discovery-opportunities-in-anti-infective-and-anti-inflammatory-area
#20
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perića
5-LOX - 5-lipoxygenase; ACT - artemisinin-based combination therapies; ADME - absorption, distribution, metabolism and excretion; BAL - broncho alveolar lavage; CABP - community acquired bacterial pneumonia; cAMP - cyclic adenosine monophosphate; CAP - community-acquired pneumonia; CF - cystic fibrosis, BOS bronchiolitis obliterans syndrome; cGMP - cyclic guanosine monophosphate; COPD - chronic obstructive pulmonary disease; COX - cyclooxygenase; DPB - diffuse panbronchiolitis; HDACs - histone deacetylases; IBD - inflammatory bowel disease; IL-1p - interleukin 1p; IL-6 - interleukin 6; MIC - minimal inhibitory concentrations; MLSB - macrolide, lincosamide, streptogramin B; NSAIDs - non-steroidal anti-inflammatory drugs; OVA - ovalbumin; PDE4 - phosphodiesterase 4; PMA - phorbol 12-myristate 13-acetate; RA - rheumatoid arthritis; RTI - respiratory tract infections; SAHA - suberoylanilide hydroxamic acid; SAR - structure-activity-relationship; Th1 - type 1 helper T-cell; TNBS - trinitrobenzene sulfonic acid; TNF-α - tumour necrosis factor α; UN - United Nations, WHO - World Health Organisation...
September 27, 2016: Current Topics in Medicinal Chemistry
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