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https://www.readbyqxmd.com/read/28191472/suppression-of-excessive-histone-deacetylases-activity-in-diabetic-hearts-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondria-apoptosis-pathway
#1
Yang Wu, Yan Leng, Qingtao Meng, Rui Xue, Bo Zhao, Liying Zhan, Zhongyuan Xia
Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28174211/overlapping-and-divergent-actions-of-structurally-distinct-hdac-inhibitors-in-cardiac-fibroblasts
#2
Katherine B Schuetze, Matthew S Stratton, Weston W Blakeslee, Michael F Wempe, Florence F Wagner, Edward B Holson, Yin-Ming Kuo, Andrew J Andrews, Tonya M Gilbert, Jacob M Hooker, Timothy A McKinsey
Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly impact cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiological and pathophysiological processes...
February 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28160167/histone-deacetylase-inhibitors-vpa-and-tsa-induce-apoptosis-and-autophagy-in-pancreatic-cancer-cells
#3
Maria Saveria Gilardini Montani, Marisa Granato, Claudio Santoni, Paola Del Porto, Nicolò Merendino, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
PURPOSE: Histone deacetylase inhibitors (HDACi) are anti-neoplastic agents that are known to affect the growth of different cancer types, but their underlying mechanisms are still incompletely understood. Here, we compared the effects of two HDACi, i.e., Trichostatin A (TSA) and Valproic Acid (VPA), on the induction of cell death and autophagy in pancreatic cancer-derived cells that exhibit a high metastatic capacity and carry KRAS/p53 double mutations. METHODS: Cell viability and proliferation tests were carried out using Trypan blue dye exclusion, MTT and BrdU assays...
February 3, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28129645/epigenetic-alterations-of-gastrokine-1-gene-expression-in-gastric-cancer
#4
Filomena Altieri, Chiara Stella Di Stadio, Antonella Federico, Giuseppina Miselli, Maurizio De Palma, Emilia Rippa, Paolo Arcari
The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown. Here, we investigated the causes of GKN1 silencing to determine if epigenetic mechanisms such as histonic modification could contribute to its down-regulation...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28123081/histone-deacetylase-inhibitors-protect-against-pyruvate-dehydrogenase-dysfunction-in-huntington-s-disease
#5
Luana Naia, Teresa Cunha-Oliveira, Joana Rodrigues, Tatiana R Rosenstock, Ana Oliveira, Márcio Ribeiro, Catarina Carmo, Sofia I Oliveira-Sousa, Ana I Duarte, Michael R Hayden, A Cristina Rego
: Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We previously showed that histone deacetylase inhibitors (HDACi), trichostatin A and sodium butyrate (SB), ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work we investigated the effect of HDACi on regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28114389/tsa-and-bix-01294-induced-normal-dna-and-histone-methylation-and-increased-protein-expression-in-porcine-somatic-cell-nuclear-transfer-embryos
#6
Zubing Cao, Renyun Hong, Biao Ding, Xiaoyuan Zuo, Hui Li, Jianping Ding, Yunsheng Li, Weiping Huang, Yunhai Zhang
The poor efficiency of animal cloning is mainly attributed to the defects in epigenetic reprogramming of donor cells' chromatins during early embryonic development. Previous studies indicated that inhibition of histone deacetylases or methyltransferase, such as G9A, using Trichostatin A (TSA) or BIX-01294 significantly enhanced the developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. However, potential mechanisms underlying the improved early developmental competence of SCNT embryos exposed to TSA and BIX-01294 are largely unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28112984/effects-of-trichostatin-a-and-pxd101-on-the-in-vitro-development-of-mouse-somatic-cell-nuclear-transfer-embryos
#7
Xiaoyan Qiu, Haihong You, Xiong Xiao, Nan Li, Yuemin Li
The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) is believed to be associated with aberrant epigenetic nuclear reprogramming. It has been demonstrated that treatment with histone deacetylase inhibitors (HDACis) enhances developmental potential of SCNT embryos. Previous studies in many species revealed that treatment of SCNT embryos with trichostatin A (TSA)-an HDACi-significantly enhances the in vitro development of SCNT embryos. In this study, we compared two different SCNT protocols with TSA and investigate, for the first time, the effect of another new HDACi, PXD101 (belinostat), on in vitro development of mouse SCNT embryo...
February 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28110187/insecticidal-activities-of-histone-deacetylase-inhibitors-against-a-dipteran-parasite-of-sheep-lucilia-cuprina
#8
Neil H Bagnall, Barney M Hines, Andrew J Lucke, Praveer K Gupta, Robert C Reid, David P Fairlie, Andrew C Kotze
Histone deacetylase inhibitors (HDACi) are being investigated for the control of various human parasites. Here we investigate their potential as insecticides for the control of a major ecto-parasite of sheep, the Australian sheep blowfly, Lucilia cuprina. We assessed the ability of HDACi from various chemical classes to inhibit the development of blowfly larvae in vitro, and to inhibit HDAC activity in nuclear protein extracts prepared from blowfly eggs. The HDACi prodrug romidepsin, a cyclic depsipeptide that forms a thiolate, was the most potent inhibitor of larval growth, with equivalent or greater potency than three commercial blowfly insecticides...
January 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28109017/clostridium-butyricum-b1-alleviates-high-fat-diet-induced-steatohepatitis-in-mice-via-enterohepatic-immunoregulation
#9
Da Zhou, Qin Pan, Xiao-Lin Liu, Rui-Xu Yang, Yuan-Wen Chen, Chang Liu, Jian-Gao Fan
BACKGROUND AND AIM: Enterohepatic immunologic derangement is associated with nonalcoholic steatohepatitis (NASH). Here, we investigated whether Clostridium butyricum B1 (CB) would be an effective immune-targeted substance to attenuate steatohepatitis in mice. METHODS: Thirty mice were randomized into a control group fed with common forage, a high-fat diet (HFD) group fed a HFD for 16 weeks, and a HFD + CB group treated with CB for the latter 8 weeks. Inflammation- or metabolism-associated genes in the liver or epididymal fat tissue were quantified, intrahepatic and intestinal immune factors were detected...
January 20, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#10
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue, and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue. Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous white adipose tissues, but not in epididymal visceral white adipose tissue, in vivo...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28090296/endotoxin-and-mechanical-stress-induced-epigenetic-changes-in-the-regulation-of-the-nicotinamide-phosphoribosyltransferase-promoter
#11
Venkateswaran Ramamoorthi Elangovan, Sara M Camp, Gabriel T Kelly, Ankit A Desai, Djanybek Adyshev, Xiaoguang Sun, Stephen M Black, Ting Wang, Joe G N Garcia
Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28086911/enhanced-neuroinflammation-mediated-by-dna-methylation-of-the-glucocorticoid-receptor-triggers-cognitive-dysfunction-after-sevoflurane-anesthesia-in-adult-rats-subjected-to-maternal-separation-during-the-neonatal-period
#12
Yangzi Zhu, Yu Wang, Rui Yao, Ting Hao, Junli Cao, He Huang, Liwei Wang, Yuqing Wu
BACKGROUND: Mounting evidence indicates that children who experience abuse and neglect are prone to chronic diseases and premature mortality later in life. One mechanistic hypothesis for this phenomenon is that early life adversity alters the expression or functioning of the glucocorticoid receptor (GR) throughout the course of life and thereby increases sensitivity to inflammatory stimulation. An exaggerated pro-inflammatory response is generally considered to be a key cause of postoperative cognitive dysfunction (POCD)...
January 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28067448/oled-loki-as-a-catalyst-for-tertiary-amine-and-hydroxamate-glycosylation
#13
Ryan R Hughes, Khaled A Shaaban, Jianjun Zhang, Hongnan Cao, George N Phillips, Jon S Thorson
We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N-glycosylation of tertiary-amine-containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary-amine N-glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases...
January 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28060760/pi3k-mtor-dual-inhibitor-bez235-and-histone-deacetylase-inhibitor-trichostatin-a-synergistically-exert-anti-tumor-activity-in-breast-cancer
#14
Liyan Chen, Tiefeng Jin, Kun Zhu, Yingshi Piao, Taihao Quan, Chunji Quan, Zhenhua Lin
Molecule-targeted therapy has achieved great progress in cancer therapy. Effective drug combinations are one way to enhance the therapeutic efficacy and combat resistance. Here, we determined the effect of the PI3K/mTOR dual inhibitor BEZ235 and the histone deacetylase inhibitor Trichostatin A (TSA) on human breast cancer. We demonstrated that the combination of BEZ235 and TSA results in significant synergistic growth inhibition of multiple breast cancer cell lines. Mechanistic studies revealed that the combined therapy induced apoptosis in a caspase-dependent manner, which might be related to the further depression of the PI3K/Akt/mTOR signalling pathway...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057758/down-regulation-of-claudin-2-expression-and-proliferation-by-epigenetic-inhibitors-in-human-lung-adenocarcinoma-a549-cells
#15
Asami Hichino, Miki Okamoto, Saeko Taga, Risa Akizuki, Satoshi Endo, Toshiyuki Matsunaga, Akira Ikari
Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases proliferation in adenocarcinoma cells. The chemicals that reduce claudin-2 expression may have anti-cancer effects, but such therapeutic medicines have not been developed. We found that azacitidine (AZA), a DNA methylation inhibitor, and trichostatin A (TSA) and sodium butyrate (NaB), histone deacetylase (HDAC) inhibitors, decrease claudin-2 levels. The effect of AZA was mediated by the inhibition of phosphorylated Akt and NF-κB. LY-294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), and BAY 11-7082, an NF-κB inhibitor, decreased claudin-2 levels...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28054438/epigenetic-regulates-transcription-and-pathogenesis-in-the-parasite-trichomonas-vaginalis
#16
Tomas Pachano, Yesica R Nievas, Ayelen Lizarraga, Patricia J Johnson, Pablo H Strobl-Mazzulla, Natalia de Miguel
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Different T. vaginalis strains vary greatly in their adherence and cytolysis capacities. These phenotypic differences might be attributed to differentially expressed genes as a consequence of extra-genetic variation, such as epigenetic modifications. In this study we explored the role of histone acetylation in regulating gene transcription and pathogenesis in T...
January 5, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28038431/comparative-effects-of-histone-deacetylases-inhibitors-and-resveratrol-on-trypanosoma-cruzi-replication-differentiation-infectivity-and-gene-expression
#17
Vanina A Campo
Histone post-translational modification, mediated by histone acetyltransferases and deacetylases, is one of the most studied factors affecting gene expression. Recent data showing differential histone acetylation states during the Trypanosoma cruzi cell cycle suggest a role for epigenetics in the control of this process. As a starting point to study the role of histone deacetylases in the control of gene expression and the consequences of their inhibition and activation in the biology of T. cruzi, two inhibitors for different histone deacetylases: trichostatin A for class I/II and sirtinol for class III and the activator resveratrol for class III, were tested on proliferative and infective forms of this parasite...
December 21, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28031332/regulator-of-g-protein-signaling-10-rgs10-expression-is-transcriptionally-silenced-in-activated-microglia-by-histone-deacetylase-activity
#18
Mohammed Alqinyah, Nagini Maganti, Mourad W Ali, Ruchi Yadav, Mei Gao, Han-Rong Weng, Susanna F Greer, Shelley B Hooks
RGS10 has emerged as a key regulator of pro-inflammatory cytokine production in microglia, functioning as an important neuroprotective factor. While RGS10 is normally expressed in microglia at high levels, expression is silenced in vitro following activation of TLR4 receptor. Given the ability of RGS10 to regulate inflammatory signaling, dynamic regulation of RGS10 levels in microglia may be an important mechanism to tune inflammatory responses. The goals of the current study were to confirm that RGS10 is suppressed in an in vivo inflammatory model of microglial activation and to determine the mechanism for activation-dependent silencing of Rgs10 expression in microglia...
December 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/28031235/htp-nutraceutical-screening-for-histone-deacetylase-inhibitors-and-effects-of-hdacis-on-tumor-suppressing-mirnas-by-trichostatin-a-and-grapeseed-vitis-vinifera-in-hela-cells
#19
Elizabeth A Mazzio, Karam F A Soliman
BACKGROUND/AIM: Aggressive tumor malignancies are a consequence of delayed diagnosis, epigenetic/phenotype changes and chemo-radiation resistance. Histone deacetylases (HDACs) are a major epigenetic regulator of transcriptional repression, which are highly overexpressed in advanced malignancy. While original chemotherapy drugs were modeled after phytochemicals elucidated by botanical screenings, HDAC inhibitors (HDACi) such as apicidin, trichostatin A (TSA) and butyrate were discovered as products of fungus and microbes, in particular, gut microbiota...
2, 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28012453/the-effect-of-histone-deacetylase-inhibition-on-the-expression-of-p-glycoprotein-in-human-placental-trophoblast-cell-lines
#20
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
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