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https://www.readbyqxmd.com/read/29651704/hdac9-polymorphism-alters-blood-gene-expression-in-patients-with-large-vessel-atherosclerotic-stroke
#1
Natasha Shroff, Bradley P Ander, Xinhua Zhan, Boryana Stamova, DaZhi Liu, Heather Hull, Farah R Hamade, Cheryl Dykstra-Aiello, Kwan Ng, Frank R Sharp, Glen C Jickling
The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism's contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls)...
April 13, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/29520069/an-hdac9-malat1-brg1-complex-mediates-smooth-muscle-dysfunction-in-thoracic-aortic-aneurysm
#2
Christian L Lino Cardenas, Chase W Kessinger, Yisha Cheng, Carolyn MacDonald, Thomas MacGillivray, Brian Ghoshhajra, Luai Huleihel, Saifar Nuri, Ashish S Yeri, Farouc A Jaffer, Naftali Kaminski, Patrick Ellinor, Neal L Weintraub, Rajeev Malhotra, Eric M Isselbacher, Mark E Lindsay
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1...
March 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29486577/proteomic-analysis-identifies-nptx1-and-hip1r-as-potential-targets-of-histone-deacetylase-3-mediated-neurodegeneration
#3
Zhe Qu, Santosh R D'Mello
A defining feature of neurodegenerative diseases is the abnormal and excessive loss of neurons. One molecule that is particularly important in promoting neuronal death in a variety of cell culture and in vivo models of neurodegeneration is histone deacetylase-3 (HDAC3), a member of the histone deacetylase family of proteins. As a step towards understanding how HDAC3 promotes neuronal death, we conducted a proteomic screen aimed at identifying proteins that were regulated by HDAC3. HDAC3 was overexpressed in cultured rat cerebellar granule neurons (CGNs) and protein lysates were analyzed by mass spectrometry...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29471042/aspirin-induced-attenuation-of-adipogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-is-accompanied-by-the-disturbed-epigenetic-modification
#4
Yuanbo Zhan, Zhiwei He, Xinpeng Liu, Nan Miao, Feng Lin, Sen Mu, Haibin Mu, Mengtong Yuan, Xiaofang Cao, Han Jin, Zhongshuang Liu, Ying Li, Bin Zhang
Aspirin has positive effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. However, researchers did not give much thought to its effect on BMSCs adipogenic differentiation. Here, we analyzed the effect of aspirin on the BMSCs adipogenic differentiation. To detect whether the effect of aspirin on the adipogenic differentiation of BMSCs is associated with the disturbed epigenetic modification, the expression of histone deacetylases (HDACs), activity of HDACs and HAT, global histone H3 acetylation and H3k9 acetylation alterations were investigated...
February 19, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29463953/autosomal-dominant-retinitis-pigmentosa-rhodopsin-mutant-q344x-drives-specific-alterations-in-chromatin-complex-gene-transcription
#5
Katie L Bales, Lara Ianov, Andrew J Kennedy, J David Sweatt, Alecia K Gross
Purpose: Epigenetic and transcriptional mechanisms have been shown to contribute to long-lasting functional changes in adult neurons. The purpose of this study was to identify any such modifications in diseased retinal tissues from a mouse model of rhodopsin mutation-associated autosomal dominant retinitis pigmentosa (ADRP), Q344X, relative to age-matched wild-type (WT) controls. Methods: We performed RNA sequencing (RNA-seq) at poly(A) selected RNA to profile the transcriptional patterns in 3-week-old ADRP mouse model rhodopsin Q344X compared to WT controls...
2018: Molecular Vision
https://www.readbyqxmd.com/read/29458411/genome-wide-pleiotropy-analysis-of-neuropathological-traits-related-to-alzheimer-s-disease
#6
Jaeyoon Chung, Xiaoling Zhang, Mariet Allen, Xue Wang, Yiyi Ma, Gary Beecham, Thomas J Montine, Steven G Younkin, Dennis W Dickson, Todd E Golde, Nathan D Price, Nilüfer Ertekin-Taner, Kathryn L Lunetta, Jesse Mez, Richard Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Gerard Schellenberg, Gyungah R Jun, Lindsay A Farrer
BACKGROUND: Simultaneous consideration of two neuropathological traits related to Alzheimer's disease (AD) has not been attempted in a genome-wide association study. METHODS: We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs...
February 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29273593/novel-susceptibility-loci-for-moyamoya-disease-revealed-by-a-genome-wide-association-study
#7
MULTICENTER STUDY
Lian Duan, Ling Wei, Yanghua Tian, Zhengshan Zhang, Panpan Hu, Qiang Wei, Sugang Liu, Jun Zhang, Yuyang Wang, Desheng Li, Weizhong Yang, Rui Zong, Peng Xian, Cong Han, Xiangyang Bao, Feng Zhao, Jie Feng, Wei Liu, Wuchun Cao, Guoping Zhou, Chunyan Zhu, Fengqiong Yu, Weimin Yang, Yu Meng, Jingye Wang, Xianwen Chen, Yu Wang, Bing Shen, Bing Zhao, Jinghai Wan, Fengyu Zhang, Gang Zhao, Aimin Xu, Xuejun Zhang, Jianjun Liu, Xianbo Zuo, Kai Wang
BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by bilateral internal carotid artery stenosis and often leads to stroke in children or young adults. Although familial inheritance is well recognized, the genetic basis of MMD remains poorly understood. METHODS: A 2-stage genome-wide association study was conducted involving 1492 cases and 5084 controls. In the discovery stage, logistic regression was used to test associations, and imputation was conducted based on genotyped single-nucleotide polymorphisms (SNPs)...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29247141/sodium-valproate-a-histone-deacetylase-inhibitor-is-associated-with-reduced-stroke-risk-after-previous-ischemic-stroke-or-transient-ischemic-attack
#8
RANDOMIZED CONTROLLED TRIAL
Rebecca L Brookes, Siobhan Crichton, Charles D A Wolfe, Qilong Yi, Linxin Li, Graeme J Hankey, Peter M Rothwell, Hugh S Markus
BACKGROUND AND PURPOSE: A variant in the histone deacetylase 9 ( HDAC9 ) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. METHODS: Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29074567/image-based-drug-screen-identifies-hdac-inhibitors-as-novel-golgi-disruptors-synergizing-with-jq1
#9
Mathieu Gendarme, Jan Baumann, Tatiana I Ignashkova, Ralph K Lindemann, Jan H Reiling
The Golgi apparatus is increasingly recognized as a major hub for cellular signaling and is involved in numerous pathologies, including neurodegenerative diseases and cancer. The study of Golgi stress-induced signaling pathways relies on the selectivity of the available tool compounds of which currently only a few are known. To discover novel Golgi-fragmenting agents, transcriptomic profiles of cells treated with brefeldin A, golgicide A or monensin were generated and compared to a database of gene expression profiles from cells treated with other bioactive small molecules...
October 26, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28975602/apol1-cdkn2a-cdkn2b-and-hdac9-polymorphisms-and-small-vessel-ischemic-stroke
#10
R Akinyemi, H K Tiwari, D K Arnett, B Ovbiagele, M R Irvin, K Wahab, F Sarfo, V Srinivasasainagendra, A Adeoye, R T Perry, A Akpalu, C Jenkins, O Arulogun, M Gebregziabher, L Owolabi, R Obiako, E Sanya, M Komolafe, M Fawale, P Adebayo, G Osaigbovo, T Sunmonu, P Olowoyo, I Chukwuonye, Y Obiabo, A Onoja, J Akinyemi, G Ogbole, S Melikam, R Saulson, M Owolabi
OBJECTIVE: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study...
January 2018: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28855441/microrna-182-promotes-lipoprotein-lipase-expression-and-atherogenesisby-targeting-histone-deacetylase-9-in-apolipoprotein-e-knockout-mice
#11
Hai-Peng Cheng, Duo Gong, Zhen-Wang Zhao, Ping-Ping He, Xiao-Hua Yu, Qiong Ye, Chong Huang, Xin Zhang, Ling-Yan Chen, Wei Xie, Min Zhang, Liang Li, Xiao-Dan Xia, Xin-Ping Ouyang, Yu-Lin Tan, Zong-Bao Wang, Guo-Ping Tian, Xi-Long Zheng, Wei-Dong Yin, Chao-Ke Tang
BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages...
December 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28783689/inhibition-of-hdac8-and-hdac9-by-microbial-short-chain-fatty-acids-breaks-immune-tolerance-of-the-epidermis-to-tlr-ligands
#12
James A Sanford, Ling-Juan Zhang, Michael R Williams, Jon A Gangoiti, Chun-Ming Huang, Richard L Gallo
Epidermal keratinocytes participate in immune defense through their capacity to recognize danger, trigger inflammation, and resist infection. However, normal skin immune function must tolerate contact with an abundant community of commensal microbes without inflammation. We hypothesized that microbial environmental conditions dictate the production of molecules that influence epigenetic events and cause keratinocytes to break innate immune tolerance. Propionibacterium acnes, a commensal skin bacterium, produced the short-chain fatty acids (SCFAs) propionate and valerate when provided a lipid source in hypoxic growth conditions, and these SCFAs inhibited histone deacetylase (HDAC) activity...
October 28, 2016: Science Immunology
https://www.readbyqxmd.com/read/28733598/role-of-hdac9-foxo1-axis-in-the-transcriptional-program-associated-with-hepatic-gluconeogenesis
#13
Jizheng Chen, Zhilei Zhang, Ning Wang, Min Guo, Xiumei Chi, Yu Pan, Jing Jiang, Junqi Niu, Sulaiman Ksimu, John Zhong Li, Xinwen Chen, Qian Wang
Histone deacetylase 9 (HDAC9) regulates hepatic gluconeogenesis by deacetylating Forkhead box O 1 (FoxO1). HDAC9 upregulation is involved in hepatitis C virus (HCV)-associated exaggerated gluconeogenesis. Herein, we found in addition to FoxO1, HDAC9 also regulates other gluconeogenic transcription factors, including peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), cyclic AMP-responsive element-binding protein (CREB), and glucocorticoid receptor (GR). Unlike FoxO1, which is regulated by post-translational modification responses to HDAC9, HDAC9 regulates PGC-1α, CREB and GR by altering gene expression...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729685/nucleocytoplasmic-shuttling-of-histone-deacetylase-9-controls-activity-dependent-thalamocortical-axon-branching
#14
Ricardo Alchini, Haruka Sato, Naoyuki Matsumoto, Tomomi Shimogori, Noriyuki Sugo, Nobuhiko Yamamoto
During development, thalamocortical (TC) axons form branches in an activity-dependent fashion. Here we investigated how neuronal activity is converted to molecular signals, focusing on an epigenetic mechanism involving histone deacetylases (HDACs). Immunohistochemistry demonstrated that HDAC9 was translocated from the nucleus to the cytoplasm of thalamic cells during the first postnatal week in rats. In organotypic co-cultures of the thalamus and cortex, fluorescent protein-tagged HDAC9 also exhibited nuclueocytoplasmic translocation in thalamic cells during culturing, which was reversed by tetrodotoxin treatment...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682229/-epigenetic-mechanisms-and-alcohol-use-disorders-a-potential-therapeutic-target
#15
Rémi Legastelois, Jérôme Jeanblanc, Catherine Vilpoux, Erika Bourguet, Mickael Naassila
Alcohol use disorder is a devastating illness with a profound health impact, and its development is dependent on both genetic and environmental factors. This disease occurs over time and requires changes in brain gene expression. There is converging evidence suggesting that the epigenetic processes may play a role in the alcohol-induced gene regulations and behavior such as the intervention of DNA methylation and histone acetylation. Histone acetylation, like histone methylation, is a highly dynamic process regulated by two classes of enzymes: histone acetyltransferases and histone deacetylases (HDACs)...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28669958/-expression-of-hdac9-in-different-brain-regions-in-mice-with-cerebral-ischemic-stroke
#16
Han-Tao Mai, Tao Jiang, Ai-Wu Zhang, Tian-Ming Lv, Can-Hong Yang, Si-Si Qin
OBJECTIVE: To investigate the expression and the subcellular localization of HDAC9 in different brain regions of mice after cerebral ischemic injury and explore the association between HDAC9 and ischemic stroke. METHODS: Twenty-one male C57BL/6 mice were randomly divided into sham-operated group (n=9) and operated group (n=12). In the latter group, the mice with Zea-Longa neurological deficit scores of 2 or 3 following middle cerebral artery occlusion (MCAO) were assigned into MCAO group (n=9)...
June 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28635037/novel-role-and-regulation-of-hdac4-in-cocaine-related-behaviors
#17
Rachel D Penrod, Maria B Carreira, Makoto Taniguchi, Jaswinder Kumar, Stephanie A Maddox, Christopher W Cowan
Epigenetic mechanisms have been proposed to contribute to persistent aspects of addiction-related behaviors. One family of epigenetic molecules that may regulate maladaptive behavioral changes produced by cocaine use are the histone deacetylases (HDACs)-key regulators of chromatin and gene expression. In particular, the class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) respond to changes in neuronal activity by modulating their distribution between the nucleus and cytoplasm-a process controlled in large part by changes in phosphorylation of conserved residues...
June 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28572913/hdac9-is-an-epigenetic-repressor-of-kidney-angiotensinogen-establishing-a-sex-difference
#18
Camille T Bourgeois, Ryousuke Satou, Minolfa C Prieto
BACKGROUND: Sexual difference has been shown in the pathogenesis of chronic kidney disease induced by hypertension. Females are protected from hypertension and related end-organ damage. Augmentation of renal proximal tubular angiotensinogen (AGT) expression can promote intrarenal angiotensin formation and the development of associated hypertension and kidney injury. Female rodents exhibit lower intrarenal AGT levels than males under normal conditions, suggesting that the suppressed intrarenal AGT production by programmed mechanisms in females may provide protection from these diseases...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28496307/developing-selective-histone-deacetylases-hdacs-inhibitors-through-ebselen-and-analogs
#19
Yuren Wang, Jason Wallach, Stephanie Duane, Yuan Wang, Jianghong Wu, Jeffrey Wang, Adeboye Adejare, Haiching Ma
Histone deacetylases (HDACs) are key regulators of gene expression in cells and have been investigated as important therapeutic targets for cancer and other diseases. Different subtypes of HDACs appear to play disparate roles in the cells and are associated with specific diseases. Therefore, substantial effort has been made to develop subtype-selective HDAC inhibitors. In an effort to discover existing scaffolds with HDAC inhibitory activity, we screened a drug library approved by the US Food and Drug Administration and a National Institutes of Health Clinical Collection compound library in HDAC enzymatic assays...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28436693/expression-of-circulating-mir-17-92-cluster-and-hdac9-gene-in-atherosclerotic-patients-with-unstable-and-stable-carotid-plaques
#20
Silvia Ferronato, Aldo Mombello, Ilaria Posenato, Paola Candiani, Alberto Scuro, Carlo Setacci, Macarena Gomez-Lira
AIMS: The miR-17-92 cluster and the HDAC9 gene are involved in inflammatory, apoptotic, and angiogenic processes that are activated in the vulnerable carotid plaque. The aim of this research was to determine whether expression of one or more of the miRs of the miR-17-92 cluster and/or HDAC9 expression could represent biomarkers for patients with unstable atherosclerotic carotid plaques. MATERIALS AND METHODS: Plasma levels of miRs and HDAC9 expression in peripheral blood were analyzed by real-time PCR in patients with histologically classified stable or unstable plaques...
June 2017: Genetic Testing and Molecular Biomarkers
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