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https://www.readbyqxmd.com/read/28923781/low-dose-of-alcohol-attenuates-pro-atherosclerotic-activity-of-thrombin
#1
Masaaki Toda, Toshiaki Totoki, Chizu Nakamura, Taro Yasuma, Corina N D' Alessandro-Gabazza, Rumi Mifuji-Moroka, Kota Nishihama, Motoh Iwasa, Noriyuki Horiki, Esteban C Gabazza, Yoshiyuki Takei
BACKGROUND AND AIMS: Thrombin, the active enzyme of the coagulation system, plays a critical role in the pathogenesis of atherosclerosis. Vascular repair promoted by stromal cell-derived factor-1 is a protective process in atherosclerosis. Consumption of low amount of alcohol is believed to reduce the risk of atherosclerotic cardiovascular disease but the mechanism is unclear. This study evaluated whether alcohol can modulate the expression of stromal cell-derived factor-1 and the pro-atherosclerotic activity of thrombin...
September 5, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28916721/loss-of-cardiac-carnitine-palmitoyltransferase-2-results-in-rapamycin-resistant-acetylation-independent-hypertrophy
#2
Andrea S Pereyra, Like Y Hasek, Kate L Harris, Alycia G Berman, Frederick W Damen, Craig J Goergen, Jessica M Ellis
Cardiac hypertrophy is closely linked to impaired fatty acid oxidation, but the molecular basis of this link is unclear. Here, we investigated the loss of an obligate enzyme in mitochondrial long-chain fatty acid oxidation, carnitine palmitoyltransferase 2 (CPT2), on muscle and heart structure, function, and molecular signatures in a muscle- and heart-specific CPT2-deficient mouse (Cpt2M-/-) model. CPT2 loss in heart and muscle reduced complete oxidation of long-chain fatty acids by 87% and 69%, respectively, without altering body weight, energy expenditure, respiratory quotient, or adiposity...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916629/histone-deacetylase-inhibition-induces-odor-preference-memory-extension-and-maintains-enhanced-ampa-receptor-expression-in-the-rat-pup-model
#3
Sriya Bhattacharya, Bandhan Mukherjee, Jules J E Doré, Qi Yuan, Carolyn W Harley, John H McLean
Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in neonate rat pups that normally produces only 24-h memory to test behavior and examine receptor protein expression. Our behavioral studies showed that intrabulbar infusion of TSA, prior to pairing of the conditioned stimulus (peppermint odor) with the unconditioned stimulus (tactile stimulation), prolonged 24-h odor preference memory for at least 9 d...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916365/sodium-phenylbutyrate-abrogates-african-swine-fever-virus-replication-by-disrupting-the-virus-induced-hypoacetylation-status-of-histone-h3k9-k14
#4
Gonçalo Frouco, Ferdinando B Freitas, Carlos Martins, Fernando Ferreira
African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study...
September 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28899682/caveolin-1-controls-hyperresponsiveness-to-mechanical-stimuli-and-fibrogenesis-associated-runx2-activation-in-keloid-fibroblasts
#5
Chao-Kai Hsu, Hsi-Hui Lin, Hans I-Chen Harn, Rei Ogawa, Yang-Kao Wang, Yen-Ting Ho, Wan-Rung Chen, Yi-Chao Lee, Julia Yu-Yun Lee, Shyh-Jou Shieh, Chao-Min Cheng, John A McGrath, Ming-Jer Tang
Keloids are pathological scars characterized by excessive extracellular matrix production that are prone to form in body sites with increased skin tension. Caveolin-1 (CAV1), the principal coat protein of caveolae, has been associated with the regulation of cell mechanics, including cell softening and loss of stiffness sensing ability in NIH3T3 fibroblasts. Although CAV1 is present in low amounts in keloid fibroblasts (KFs), the causal association between CAV1 downregulation and its aberrant responses to mechanical stimuli remain unclear...
September 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28884479/transcriptional-repression-of-aurora-a-gene-by-wild-type-p53-through-directly-binding-to-its-promoter-with-histone-deacetylase-1-and-msin3a
#6
Tsung-Ying Yang, Chieh-Lin Teng, Tsung-Chieh Chester Lin, Kun-Chieh Chen, Shih-Lan Hsu, Chun-Chi Wu
In this study, we firstly showed that p53 transcriptionally represses Aurora-A gene expression through directly binding to its promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay indicated that p53 physically bound to the Aurora-A promoter. Moreover, the in vitro and in vivo assays showed that p53 directly bound to the Aurora-A promoter together with histone deacetylase 1 (HDAC1) and mSin3a as corepressors. Furthermore, we identified that the nucleotides -360 to -354 (CCTGCCC), upstream of the Aurora-A transcriptional start site, was responsible for the p53-mediated repression...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28881218/downregulated-expression-of-mir-223-promotes-toll-like-receptor-activated-inflammatory-responses-in-macrophages-by-targeting-rhob
#7
Ningjie Zhang, Liyao Fu, Yanhong Bu, Yao Yao, Yongjun Wang
Toll-like receptors (TLRs) induced-inflammatory response must be tightly regulated to avoid impairment in host itself. Numerous factors have been identified in regulation of TLR-triggered inflammatory response. Among these, microRNAs (miRNAs) are small non-coding RNA molecules which have got much attention. MiR-223, which highly expresses in myeloid cells of the bone marrow, has reported to participate in kinds of inflammatory responses by targeting inflammasome sensor-NLRP3 to repress production of IL-6 and IL-1β, and thus attenuate inflammatory response...
September 4, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28871002/trichostatin-a-sensitizes-hepatocellular-carcinoma-cells-to-enhanced-nk-cell-mediated-killing-by-regulating-immune-related-genes
#8
Sangsu Shin, Miok Kim, Seon-Jin Lee, Kang-Seo Park, Chang Hoon Lee
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The ability of HCC to avoid immune detection is considered one of the main factors making it difficult to cure. Abnormal histone deacetylation is thought to be one of the mechanisms for HCC immune escape, making histone deacetylases (HDACs) attractive targets for HCC treatment. Here, we investigated the effect of trichostatin A (TSA), a highly potent HDAC inhibitor, on HCC (HepG2) gene expression and function...
September 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28860353/histone-deacetylase-hdac-inhibitors-relax-mouse-aorta-partly-by-their-inhibitory-action-on-l-type-ca2-channels
#9
Changbo Zheng, Mingkui Zhong, Zenghua Qi, Fan Shen, Qiannan Zhao, Lulu Wu, Yu Huang, Suk-Ying Tsang, Xiaoqiang Yao
Histone deacetylase (HDAC) inhibitors modulate acetylation/deacetylation of histone and non-histone proteins. They have been widely used for cancer treatment. However, there are only a few reports investigating the effect of HDAC inhibitors on vascular tone regulation, most of which involves chronic treatment with HDAC inhibitors. In the present study, we found that two hydroxamate-based pan-HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) could partially but acutely relax the high extracellular K+-induced contraction of mouse aortas...
August 31, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28856432/kruppel-like-factor-4-regulates-matrix-metalloproteinase-and-aggrecanase-gene-expression-in-chondrocytes
#10
Junji Fujikawa, Yuto Takeuchi, Satoshi Kanazawa, Ahmed G Nomir, Akiyoshi Kito, Eman Elkhashab, Amr M Ghaleb, Vincent W Yang, Shigehisa Akiyama, Ichijiro Morisaki, Takashi Yamashiro, Satoshi Wakisaka, Makoto Abe
Kruppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays crucial roles during the development and maintenance of multiple organs. We and others have previously shown that KLF4 is involved in bone modeling and remodeling but roles played by KLF4 during skeletogenesis are still not fully understood. Here, we show that KLF4 is expressed in the epiphyseal growth plate and articular chondrocytes. Most articular chondrocytes expressed KLF4 in embryos but it localized only in a subset of superficial zone cells in postnatal mice...
August 31, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28844099/epigenetic-silencing-of-prss3-provides-growth-and-metastasis-advantage-for-human-hepatocellular-carcinoma
#11
Bonan Lin, Xiaomeng Zhou, Shuye Lin, Xiaoyue Wang, Meiying Zhang, Baoping Cao, Yan Dong, Shuai Yang, Ji Ming Wang, Mingzhou Guo, Jiaqiang Huang
Protease, serine, 3 (PRSS3), a member of the trypsin family of serine proteases, has been shown to be aberrantly expressed in several cancer types and to play important roles in tumor progression and metastasis. However, the expression and function of PRSS3 gene in hepatocellular carcinoma (HCC) remain unclear. Here we found that PRSS3 expression was decreased in human HCC cell lines and HCC surgical specimens. This was associated with intragenic methylation of PRSS3 gene. Treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor trichostatin A restored PRSS3 expression in HCC cell lines...
August 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28840784/indirect-regulation-of-cyp2c19-gene-expression-via-dna-methylation
#12
Kathryn Elisa Burns, Phillip Shepherd, Graeme Finlay, Malcolm Drummond Tingle, Nuala Ann Helsby
Despite speculation that the CYP2C19 gene may contain CpG islands, there has been little direct assessment of the role for epigenetics in the regulation of this pharmacogene. The effect of 5-aza-2'-deoxycytidine (5azaDC), a DNA methyltransferase inhibitor, and trichostatin A (TSA), an inhibitor of histone deacetylases, on the expression of CYP2C19 and five of its known transcription factors (TF) has been assessed in cell lines derived from neoplastic liver and intestine. CYP2C19 mRNA was substantially up-regulated (>18-fold) after treatment with 5azaDC despite the fact that the two intronic CpG islands in this gene remained substantially methylated (>50%)...
August 25, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28829415/simultaneous-measurement-of-hdac1-and-hdac6-activity-in-hela-cells-using-uhplc-ms
#13
Claudia A Simões-Pires, Vincent Zwick, Sylvian Cretton, Muriel Cuendet
The search for new histone deacetylase (HDAC) inhibitors is of increasing interest in drug discovery. Isoform selectivity has been in the spotlight since the approval of romidepsin, a class I HDAC inhibitor for cancer therapy, and the clinical investigation of HDAC6-specific inhibitors for multiple myeloma. The present method is used to determine the inhibitory activity of test compounds on HDAC1 and HDAC6 in cells. The isoform activity is measured using the ultra-high-performance liquid chromatography - mass spectrometry (UHPLC-MS) analysis of specific substrates incubated with treated and untreated HeLa cells...
August 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28802016/involvement-of-sperm-acetylated-histones-and-the-nuclear-isoform-of-glutathione-peroxidase-4-in-fertilization
#14
Simona Pipolo, Rossella Puglisi, Valentina Mularoni, Valentina Esposito, Andrea Fuso, Marco Lucarelli, M T Fiorenza, Franco Mangia, Carla Boitani
We previously demonstrated that the nuclear form of Glutathione Peroxidase 4 (nGPx4) has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome and that sperm lacking nGPx4 are more prone to decondensation in vitro. In this study we have hypothesized that sperm retained acetylated histones and nGPx4 are implicated in paternal chromatin decondensation and male pronucleus formation at fertilization. Indeed, significant higher amounts of acetylated histone H4 and acetylated histone H3 were observed by both immunofluorescence and western blotting in nGPx4-KO sperm vs WT ones...
August 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28791254/transcriptional-profiling-defines-histone-acetylation-as-a-regulator-of-gene-expression-during-human-to-mosquito-transmission-of-the-malaria-parasite-plasmodium-falciparum
#15
Che J Ngwa, Meike J Kiesow, Olga Papst, Lindsey M Orchard, Michael Filarsky, Alina N Rosinski, Till S Voss, Manuel Llinás, Gabriele Pradel
Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28791052/inhibition-of-histone-methyltransferase-histone-deacetylase-and-%C3%AE-catenin-synergistically-enhance-the-cardiac-potential-of-bone-marrow-cells
#16
Jinpu Yang, Keerat Kaur, John G Edwards, Carol A Eisenberg, Leonard M Eisenberg
Previously, we reported that treatment with the G9a histone methyltransferase inhibitor BIX01294 causes bone marrow mesenchymal stem cells (MSCs) to exhibit a cardiocompetent phenotype, as indicated by the induction of the precardiac markers Mesp1 and brachyury. Here, we report that combining the histone deacetylase inhibitor trichostatin A (TSA) with BIX01294 synergistically enhances MSC cardiogenesis. Although TSA by itself had no effect on cardiac gene expression, coaddition of TSA to MSC cultures enhanced BIX01294-induced levels of Mesp1 and brachyury expression 5...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28767685/histone-deacetylase-inhibition-prevents-cell-death-induced-by-loss-of-tricellular-tight-junction-proteins-in-temperature-sensitive-mouse-cochlear-cells
#17
Kenichi Takano, Takuya Kakuki, Yakuto Kaneko, Takayuki Kohno, Shin Kikuchi, Tetsuo Himi, Takashi Kojima
Tricellular tight junctions (tTJs) are specialized structures that occur where the corners of three cells meet to seal adjacent intercellular space. The molecular components of tTJs include tricellulin (TRIC) and lipolysis-stimulated lipoprotein receptor (LSR) which recruits TRIC, are required for normal hearing. Although loss of TRIC causes hearing loss with degeneration of cochlear cells, the detailed mechanisms remains unclear. In the present study, by using temperature-sensitive mouse cochlear cells, US/VOT-E36 cell line, we investigated the changes of TRIC and LSR during cochlear cell differentiation and the effects of histone deacetylase (HDAC) inhibitors against cell degeneration induced by loss of TRIC and LSR...
2017: PloS One
https://www.readbyqxmd.com/read/28752355/trichostatin-a-increases-embryo-and-green-plant-regeneration-in-wheat
#18
Fengying Jiang, Daria Ryabova, Jeremie Diedhiou, Pierre Hucl, Harpinder Randhawa, Elizabeth-France Marillia, Nora A Foroud, Francois Eudes, Palak Kathiria
Chemical agents such as trichostatin A (TSA) can assist in optimization of doubled haploidy for rapid improvements in wheat germplasm and addressing recalcitrance issues in cell culture responses. In wheat, plant regeneration through microspore culture is an integral part of doubled haploid (DH) production. However, low response to tissue culture and genotype specificity are two major constraints in the broad deployment of this breeding tool. Recently, the structure of chromatin was shown to be linked with cell transitions during tissue culture...
July 27, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28743636/valproate-increases-dopamine-transporter-expression-through-histone-acetylation-and-enhanced-promoter-binding-of-nurr1
#19
Ashley L Green, Le Zhan, Aseel Eid, Helmut Zarbl, Grace L Guo, Jason R Richardson
The dopamine transporter (DAT) is the key regulator of dopaminergic transmission and is a target of several xenobiotics, including pesticides and pharmacological agents. Previously, we identified a prominent role for histone deacetylases in the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50% increase in protein levels, which were accompanied by increased H3 acetylation levels...
October 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28736194/the-epigenetic-drug-trichostatin-a-ameliorates-experimental-autoimmune-encephalomyelitis-via-t-cell-tolerance-induction-and-impaired-influx-of-t-cells-into-the-spinal-cord
#20
Arathi Jayaraman, Advait Soni, Bellur S Prabhakar, Mark Holterman, Sundararajan Jayaraman
Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization of myelin antigen-specific T lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment of NOD mice with the histone deacetylase inhibitor, Trichostatin A affords robust protection against myelin peptide induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis...
July 20, 2017: Neurobiology of Disease
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