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HDAC1 HDAC2

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https://www.readbyqxmd.com/read/29317660/microbiota-derived-short-chain-fatty-acids-promote-histone-crotonylation-in-the-colon-through-histone-deacetylases
#1
Rachel Fellows, Jérémy Denizot, Claudia Stellato, Alessandro Cuomo, Payal Jain, Elena Stoyanova, Szabina Balázsi, Zoltán Hajnády, Anke Liebert, Juri Kazakevych, Hector Blackburn, Renan Oliveira Corrêa, José Luís Fachi, Fabio Takeo Sato, Willian R Ribeiro, Caroline Marcantonio Ferreira, Hélène Perée, Mariangela Spagnuolo, Raphaël Mattiuz, Csaba Matolcsi, Joana Guedes, Jonathan Clark, Marc Veldhoen, Tiziana Bonaldi, Marco Aurélio Ramirez Vinolo, Patrick Varga-Weisz
The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29301062/regulatory-roles-of-histone-deacetylases-1-and-2-in-pb-induced-neurotoxicity
#2
Yulan Wu, Yi Xu, Xiyao Huang, Danlei Ye, Miaomiao Han, Hui-Li Wang
Lead (Pb) prevails among the environmental hazards against human health. Although increasing evidence highlights the epigenetic roles underlying the Pb-induced neurotoxicity, the exact mechanisms concerning histone acetylation and its causative agents are still at its infancy. In the present study, the roles of histone deacetylases 1 and 2 (HDAC1/2), as well as histone H3 Lys9 acetylation (Ac-H3K9), in Pb-induced neurotoxicity were investigated. Pb was administered to PC12 cells at 10 μM for 24 hours. And Sprague- Dawley rats were chronically exposed to Pb through drinking water containing 250 ppm Pb for 2 months...
January 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29218547/expression-of-class-i%C3%A2-histone-deacetylases-in-ipsilateral-and-contralateral-hemispheres-after-the-focal-photothrombotic-infarction-in-the-mouse-brain
#3
Svetlana Demyanenko, Maria Neginskaya, Elena Berezhnaya
Histone acetylation and deacetylation are among the most important epigenetic processes that regulate gene expression. Nonselective inhibitors of histone deacetylases (HDAC) can protect brain cells during ischemia and stroke. However, which HDAC isoform is involved in this effect is unknown. Some isoforms of histone deacetylases (HDACs) protect brain cells after ischemia, whereas others can promote their death. Most studies consider early periods (1-24 h) after stroke, whereas little is known on the involvement of HDACs during recovery after stroke...
December 7, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29202397/design-synthesis-and-biological-evaluation-of-novel-2-aminobenzamides-containing-dithiocarbamate-moiety-as-histone-deacetylase-inhibitors-and-potent-antitumor-agents
#4
Rui Xie, Yan Li, Pingwah Tang, Qipeng Yuan
A novel series of 2-aminobenzamides with dithiocarbamate as cap group were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most newly synthesized compounds displayed potent antiproliferative activity against diverse human tumor cell lines. The most potent compounds, M101, M122 and M133 exhibited remarkably enhanced anticancer potency against 6 kinds of cancer cell lines with IC50 values of as low as 0.54-2.49 μM compared with CS055 (2.28∼ >26 μM) and MS275 (0.47-6.74 μM). HDAC isoform selectivity assay indicated that M101, M122 and M133 are HDAC1 and HDAC2 selective inhibitors...
August 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29184483/h3k9ac-and-hdac2-activity-are-involved-in-the-expression-of-monocarboxylate-transporter-1-in-oligodendrocyte
#5
Qingwei Lai, Wantong Du, Jian Wu, Xiao Wang, Xinyu Li, Xuebin Qu, Xiuxiang Wu, Fuxing Dong, Ruiqin Yao, Hongbin Fan
Recently, it is reported that monocarboxylate transporter 1 (MCT1) plays crucial role in oligodendrocyte differentiation and myelination. We found that MCT1 is strongly expressed in oligodendrocyte but weakly expressed in oligodendrocyte precursors (OPCs), and the underlying mechanisms remain elusive. Histone deacetylases (HDACs) activity is required for induction of oligodendrocyte differentiation and maturation. We asked whether HDACs are involved in the regulation of MCT1 expression. This work revealed that the acetylation level of histone H3K9 (H3K9ac) was much higher in mct1 gene (Slc16a1) promoter in OPCs than that in oligodendrocyte...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29174530/increased-cortical-neuronal-responses-to-nmda-and-improved-attentional-set-shifting-performance-in-rats-following-prebiotic-b-gos%C3%A2-ingestion
#6
Benjamin Gronier, Helene M Savignac, Mathieu Di Miceli, Sherif M Idriss, George Tzortzis, Daniel Anthony, Philip W J Burnet
We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno™ galacto-oligosaccharides (B-GOS®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing...
November 21, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29170627/combinatorial-in-silico-strategy-towards-identifying-potential-hotspots-during-inhibition-of-structurally-identical-hdac1-and-hdac2-enzymes-for-effective-chemotherapy-against-neurological-disorders
#7
Shabir Ahmad Ganai, Ehsaan Abdullah, Romana Rashid, Mohammad Altaf
Histone deacetylases (HDACs) regulate epigenetic gene expression programs by modulating chromatin architecture and are required for neuronal development. Dysregulation of HDACs and aberrant chromatin acetylation homeostasis have been implicated in various diseases ranging from cancer to neurodegenerative disorders. Histone deacetylase inhibitors (HDACi), the small molecules interfering HDACs have shown enhanced acetylation of the genome and are gaining great attention as potent drugs for treating cancer and neurodegeneration...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29159826/pharmacological-and-molecular-approaches-for-the-treatment-of-%C3%AE-hemoglobin-disorders
#8
REVIEW
Neelam Lohani, Nupur Bhargava, Anjana Munshi, Sivaprakash Ramalingam
β-hemoglobin disorders, such as β-thalassemia and sickle cell anemia are among the most prevalent inherited genetic disorders worldwide. These disorders are caused by mutations in the gene encoding hemoglobin-β (HBB), a vital protein found in red blood cells (RBCs) that carries oxygen from lungs to all parts of the human body. As a consequence, there has been an enduring interest in this field in formulating therapeutic strategies for the treatment of these diseases. Currently, there is no cure available for hemoglobin disorders, although, some patients have been treated with bone marrow transplantation, whose scope is limited because of the difficulty in finding a histocompatible donor and also due to transplant-associated clinical complications that can arise during the treatment...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29156785/in-silico-and-in-vitro-identification-of-inhibitory-activities-of-sorafenib-on-histone-deacetylases-in-hepatocellular-carcinoma-cells
#9
Tsang-Pai Liu, Yi-Han Hong, Pei-Ming Yang
Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#10
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29096654/the-analgesic-effects-of-triptolide-in-the-bone-cancer-pain-rats-via-inhibiting-the-upregulation-of-hdacs-in-spinal-glial-cells
#11
Xiao-Fan Hu, Xiao-Tao He, Kai-Xiang Zhou, Chen Zhang, Wen-Jun Zhao, Ting Zhang, Jin-Lian Li, Jian-Ping Deng, Yu-Lin Dong
BACKGROUND: Bone cancer pain (BCP) severely compromises the quality of life, while current treatments are still unsatisfactory. Here, we tested the antinociceptive effects of triptolide (T10), a substance with considerable anti-tumor efficacies on BCP, and investigated the underlying mechanisms targeting the spinal dorsal horn (SDH). METHODS: Intratibial inoculation of Walker 256 mammary gland carcinoma cells was used to establish a BCP model in rats. T10 was intrathecally injected, and mechanical allodynia was tested by measuring the paw withdrawal thresholds (PWTs)...
November 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29080240/design-synthesis-molecular-modeling-and-biological-evaluation-of-novel-amine-based-histone-deacetylase-inhibitors
#12
Pavel A Petukhov, Hazem Abdelkarim, Raghupathi Neelarapu, Antonett Madriaga, Irida Kastrati, Yue-Ting Wang, Aditya S Vaidya, Taha Y Taha, Gregory R J Thatcher, Jonna Frasor
Histone deacetylases (HDACs) are promising drug targets for a variety of therapeutic applications. Here we describe the design, synthesis, biological evaluation in cellular models of cancer, and preliminary drug metabolism and pharmacokinetic studies (DMPK) of a series of secondary and tertiary amine-based HDAC inhibitors. Introduction of an amino group with one or two surface binding groups (SBGs) yielded a successful strategy to develop novel and potent HDAC inhibitors. Secondary amines 2 were found to be generally more potent than the corresponding tertiary amines 3...
October 27, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29050320/epigenetic-regulation-of-interleukin-8-expression-by-class-i-hdac-and-cbp-in-ovarian-cancer-cells
#13
Himavanth R Gatla, Yue Zou, Mohammad M Uddin, Ivana Vancurova
Although inhibitors of epigenetic regulators have been effective in the treatment of cutaneous T cell lymphoma (CTCL) and other hematopoietic malignancies, they have been less effective in solid tumors, including ovarian cancer (OC). We have previously shown that inhibition of histone deacetylase (HDAC) activity induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (CXCL8, IL-8) in OC cells, resulting in their increased survival and proliferation. Here, we show that in addition to ovarian cancer SKOV3, OVCAR3, and CAOV3 cells, HDAC inhibition induces the CXCL8 expression in HeLa cells, but not in CTCL Hut-78 cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045501/scaffold-dependent-histone-deacetylase-hdac-inhibitor-induced-re-equilibration-of-the-subcellular-localization-and-post-translational-modification-state-of-class-i-hdacs
#14
Thomas W Hanigan, Taha Y Taha, Shaimaa M Aboukhatwa, Jonna Frasor, Pavel A Petukhov
The mechanism of action of histone deacetylase inhibitors (HDACi) is mainly attributed to the inhibition of the deacetylase catalytic activity for their histone substrates. In this study, we analyzed the abundance of class I HDACs in the cytosolic, nuclear soluble and chromatin bound cellular fractions in breast cancer cells after HDACi treatment. We found that potent N-hydroxy propenamide-based HDACi induced a concentration dependent decrease in the HDAC1 associated with chromatin and a lasting concomitant increase in cytoplasmic HDAC1 while maintaining total protein expression...
2017: PloS One
https://www.readbyqxmd.com/read/28987602/design-and-synthesis-of-tranylcypromine-derivatives-as-novel-lsd1-hdacs-dual-inhibitors-for-cancer-treatment
#15
Ying-Chao Duan, Yong-Cheng Ma, Wen-Ping Qin, Li-Na Ding, Yi-Chao Zheng, Ying-Li Zhu, Xiao-Yu Zhai, Jing Yang, Chao-Ya Ma, Yuan-Yuan Guan
Lysine specific demethylase 1 (LSD1) and Histone deacetylases (HDACs) are promising drug targets for cancers. Recent studies reveal an important functional interplay between LSD1 and HDACs, and there is evidence for the synergistic effect of combined LSD1 and HDAC inhibitors on cancers. Therefore, development of inhibitors targeting both LSD1 and HDACs might be a promising strategy for epigenetic therapy of cancers. We report herein the synthesis of a series of tranylcypromine derivatives as LSD1/HDACs dual inhibitors...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28982677/inhibiting-histone-deacetylase-2-hdac2-promotes-functional-recovery-from-stroke
#16
Ying Tang, Yu-Hui Lin, Huan-Yu Ni, Jian Dong, Hong-Jin Yuan, Yu Zhang, Hai-Ying Liang, Meng-Cheng Yao, Qi-Gang Zhou, Hai-Yin Wu, Lei Chang, Chun-Xia Luo, Dong-Ya Zhu
BACKGROUND: Stroke is a leading cause of long-term disability worldwide. However, current therapies that promote functional recovery from stroke are limited to physical rehabilitation. No pharmacological therapy is available. Thus, understanding the role of histone deacetylase 2 (HDAC2) in the pathophysiological process of stroke-induced functional loss may provide a novel strategy for stroke recovery. METHODS AND RESULTS: Focal stroke was induced by photothrombosis...
October 5, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28982113/crispr-mediated-hdac2-disruption-identifies-two-distinct-classes-of-target-genes-in-human-cells
#17
Priyanka Somanath, Rachel Herndon Klein, Paul S Knoepfler
The transcriptional functions of the class I histone deacetylases (HDACs) HDAC1 and HDAC2 are mainly viewed as both repressive and redundant based on murine knockout studies, but they may have additional independent roles and their physiological functions in human cells are not as clearly defined. To address the individual epigenomic functions of HDAC2, here we utilized CRISPR-Cas9 to disrupt HDAC2 in human cells. We find that while HDAC2 null cells exhibited signs of cross-regulation between HDAC1 and HDAC2, specific epigenomic phenotypes were still apparent using RNA-seq and ChIP assays...
2017: PloS One
https://www.readbyqxmd.com/read/28962688/hdac2-was-involved-in-placental-p-glycoprotein-regulation-both-in%C3%A2-vitro-and-vivo
#18
Hongyu Duan, Kaiyu Zhou, Yi Zhang, Peng Yue, Tao Wang, Yifei Li, Dajian Qiu, Jinlin Wu, Yimin Hua, Chuan Wang
INTRODUCTION: Placental P-glycoprotein (P-gp) 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 regulation of placental P-gp is rare. Our previous study has demonstrated that HDACs inhibition could up-regulate placental P-gp and HDAC1/2/3 might be involved in this process. The present study was carried out to further explore whether HDAC1/2/3 were indeed involved in the regulation of placental P-gp or not and screen out the subtype engaged in this process...
October 2017: Placenta
https://www.readbyqxmd.com/read/28959017/the-whhere-coactivator-complex-is-required-for-retinoic-acid-dependent-regulation-of-embryonic-symmetry
#19
Gonçalo C Vilhais-Neto, Marjorie Fournier, Jean-Luc Plassat, Mihaela E Sardiu, Anita Saraf, Jean-Marie Garnier, Mitsuji Maruhashi, Laurence Florens, Michael P Washburn, Olivier Pourquié
Bilateral symmetry is a striking feature of the vertebrate body plan organization. Vertebral precursors, called somites, provide one of the best illustrations of embryonic symmetry. Maintenance of somitogenesis symmetry requires retinoic acid (RA) and its coactivator Rere/Atrophin2. Here, using a proteomic approach we identify a protein complex, containing Wdr5, Hdac1, Hdac2 and Rere (named WHHERE), which regulates RA signaling and controls embryonic symmetry. We demonstrate that Wdr5, Hdac1, and Hdac2 are required for RA signaling in vitro and in vivo...
September 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28892521/a-systems-medicine-approach-for-finding-target-proteins-affecting-treatment-outcomes-in-patients-with-non-hodgkin-lymphoma
#20
Faezeh Ajorloo, Mohammad Vaezi, Alireza Saadat, Seyed Reza Safaee, Behrouz Gharib, Mostafa Ghanei, Seyed Davar Siadat, Farzam Vaziri, Abolfazl Fateh, Mehrdad Pazhouhandeh, Behrouz Vaziri, Reza Moazemi, Fereidoun Mahboudi, Fatemeh Rahimi Jamnani
Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively...
2017: PloS One
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