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histone deacetylase metabolic

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https://www.readbyqxmd.com/read/29227474/a-proteolytic-fragment-of-histone-deacetylase-4-protects-the-heart-from-failure-by-regulating-the-hexosamine-biosynthetic-pathway
#1
Lorenz H Lehmann, Zegeye H Jebessa, Michael M Kreusser, Axel Horsch, Tao He, Mariya Kronlage, Matthias Dewenter, Viviana Sramek, Ulrike Oehl, Jutta Krebs-Haupenthal, Albert H von der Lieth, Andrea Schmidt, Qiang Sun, Julia Ritterhoff, Daniel Finke, Mirko Völkers, Andreas Jungmann, Sven W Sauer, Christian Thiel, Alexander Nickel, Michael Kohlhaas, Michaela Schäfer, Carsten Sticht, Christoph Maack, Norbert Gretz, Michael Wagner, Ali El-Armouche, Lars S Maier, Juan E Camacho Londoño, Benjamin Meder, Marc Freichel, Hermann-Josef Gröne, Patrick Most, Oliver J Müller, Stephan Herzig, Eileen E M Furlong, Hugo A Katus, Johannes Backs
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP)...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29224834/hdac1-localizes-to-the-mitochondria-of-cardiac-myocytes-and-contributes-to-early-cardiac-reperfusion-injury
#2
Daniel J Herr, Mauhamad Baarine, Sverre E Aune, Xiaoyang Li, Lauren E Ball, John J Lemasters, Craig C Beeson, James C Chou, Donald R Menick
RATIONALE: Recent evidence indicates that histone deacetylase enzymes (HDACs) contribute to ischemia reperfusion (I/R) injury, and pan-HDAC inhibitors have been shown to be cardioprotective when administered either before an ischemic insult or during reperfusion. We have shown previously that selective inhibition of class I HDACs provides superior cardioprotection when compared to pan-HDAC inhibition in a pretreatment model, but selective class I HDAC inhibition has not been tested during reperfusion, and specific targets of class I HDACs in I/R injury have not been identified...
December 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29223340/silencing-of-histone-deacetylase-slhdt3-delays-fruit-ripening-and-suppresses-carotenoid-accumulation-in-tomato
#3
Jun-E Guo, Zongli Hu, Fenfen Li, Lincheng Zhang, Xiaohui Yu, Boyan Tang, Guoping Chen
The acetylation levels of histones on lysine residues are regulated by histone acetyltransferases and histone deacetylases, which play an important but understudied role in the control of gene expression in plants. There is an increasing research focus on histone deacetylation in crops, but to date, there is little information regarding tomato. With the aim of characterizing the tomato HD2 family of histone deacetylases, an RNA interference (RNAi) expression vector of SlHDT3 was constructed and transformed into tomato plants...
December 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29212069/cellular-effects-of-the-antiepileptic-drug-valproic-acid-in-glioblastoma
#4
Marita Eckert, Lukas Klumpp, Stephan Huber
BACKGROUND/AIMS: Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug is used to treat epileptic seizure of glioblastoma patients. Besides its antiepileptic activity, VPA has been attributed further functions that improve the clinical outcome of glioblastoma patients. Those comprise the inhibition of some histone deacetylase (HDAC) isoforms which reportedly may result in radiosensitization. Retrospective analysis of patient data, however, could not unequivocally confirm a prolonged survival of glioblastoma patients receiving VPA...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29189132/polyphenols-novel-signaling-pathways
#5
Marie-Louise Ricketts, Bradley S Ferguson
BACKGROUND: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance...
November 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29179491/sirt1-promotes-tumor-like-invasion-of-fibroblast-like-synoviocytes-in-rheumatoid-arthritis-via-targeting-timp1
#6
Jiangtao Guo, Wei Zhao, Xuqing Cao, Huiying Yang, Juan Ding, Jingbin Ding, Zifang Tan, Xiaoli Ma, Chunfang Hao, Lili Wu, Zhengjuan Ma, Jianjun Xie, Zhijun Wang
Suppression of tissue inhibitor of matrix metalloproteinase (TIMP) is associated with the tumor-like invasion of fibroblast-like synoviocytes (FLSs) that occurs during rheumatoid arthritis-related cartilage destruction. Silent information regulator 2 homolog1 (SIRT1), a histone deacetylase, is widely involved in transcriptional regulation, genomic stability, metabolism and DNA repair. Recent studies suggest that SIRT1 may also impact inflammatory response and the proliferation of FLSs in rheumatoid arthritis (RA)...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29175209/the-protective-role-of-low-concentration-alcohol-in-high-fructose-induced-adverse-cardiovascular-events-in-mice
#7
Xiaoqi Wu, Bo Pan, Ying Wang, Lingjuan Liu, Xupei Huang, Jie Tian
Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice...
November 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29163504/butyrate-conditions-human-dendritic-cells-to-prime-type-1-regulatory-t-cells-via-both-histone-deacetylase-inhibition-and-g-protein-coupled-receptor-109a-signaling
#8
Maria M M Kaisar, Leonard R Pelgrom, Alwin J van der Ham, Maria Yazdanbakhsh, Bart Everts
Recently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs and how they affect their capacity to prime and polarize T-cell responses have not been addressed. Here, we report that butyrate suppresses LPS-induced maturation and metabolic reprogramming of human monocyte-derived DCs (moDCs) and conditions them to polarize naive CD4+ T cells toward IL-10-producing type 1 regulatory T cells (Tr1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29155817/analysis-of-the-interactome-of-schistosoma-mansoni-histone-deacetylase-8
#9
Stéphanie Caby, Lucile Pagliazzo, Julien Lancelot, Jean-Michel Saliou, Nicolas Bertheaume, Raymond J Pierce, Emmanuel Roger
BACKGROUND: Histone deacetylase 8 from Schistosoma mansoni (SmHDAC8) is essential to parasite growth and development within the mammalian host and is under investigation as a target for the development of selective inhibitors as novel schistosomicidal drugs. Although some protein substrates and protein partners of human HDAC8 have been characterized, notably indicating a role in the function of the cohesin complex, nothing is known of the partners and biological function of SmHDAC8. METHODOLOGY/PRINCIPAL FINDINGS: We therefore employed two strategies to characterize the SmHDAC8 interactome...
November 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29142427/cinnamaldehyde-cinnamic-acid-and-cinnamyl-alcohol-the-bioactives-of-cinnamomum-cassia-exhibit-hdac8-inhibitory-activity-an-in-vitro-and-in-silico-study
#10
Mangesh Patil, Amit S Choudhari, Savita Pandita, Md Ataul Islam, Prerna Raina, Ruchika Kaul-Ghanekar
Background: The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. Objective: In the present work, we have evaluated the potential of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29136592/human-sirtuin-3-sirt3-deacetylates-histone-h3-lysine-56-to-promote-nonhomologous-end-joining-repair
#11
Amrita Sengupta, Devyani Haldar
Human sirtuin 3 (SIRT3) is a conserved NAD(+) dependent deacetylase, which functions in important cellular processes including transcription, metabolism, oxidative stress response. It is a robust mitochondrial deacetylase; however, few studies have indicated its nuclear functions. Here we report interaction of SIRT3 with core histones and identified acetylated histone H3 lysine 56 (H3K56ac) as its novel substrate, in addition to known substrates acetylated H4K16 and H3K9. Further, we showed in response to DNA damage SIRT3 localizes to the repair foci colocalizing with γH2AX and nonhomologous end joining (NHEJ) marker p53-binding protein 1 (53BP1)...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29135083/comparison-of-the-anticancer-properties-of-a-novel-valproic-acid-prodrug-to-leading-histone-deacetylase-inhibitors
#12
Nataly Tarasenko, Hanna Chekroun-Setti, Abraham Nudelman, Ada Rephaeli
The HDAC inhibitory activity of valproic acid (VPA) has led to on-going evaluation of it as an anticancer agent. The histone deacetylase (HDAC) inhibitor AN446, a prodrug of VPA, releases the acid upon metabolic degradation. AN446 is >60 fold more potent than VPA in killing cancer cells in vitro. Herein, we compare the activities of AN446, as an anticancer agent, to those of representative types from each of the four major classes of HDAC inhibitors (HDACIs): vorinostat, romidepsin, entinostat and VPA. AN446 exhibited the greatest selectivity and HDAC inhibitory activity against cancer cells...
November 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29132743/nuclear-sirtuins-and-inflammatory-signaling-pathways
#13
REVIEW
Keila Lopes Mendes, Deborah de Farias Lelis, Sérgio Henrique Sousa Santos
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms...
November 7, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29129787/cd38-nad-axis-regulates-immunotherapeutic-anti-tumor-t-cell-response
#14
Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Megan W Wyatt, Payal Dhar, Shanmugam Paneer Selvam, Jianing Fu, Jinyu Zhang, Hung Nguyen, Inhong Kang, Kyle Toth, Mazen Al-Homrani, Mahvash Husain, Gyda Beeson, Lauren Ball, Kristi Helke, Shahid Husain, Elizabeth Garrett-Mayer, Gary Hardiman, Meenal Mehrotra, Michael I Nishimura, Craig C Beeson, Melanie Gubbels Bupp, Jennifer Wu, Besim Ogretmen, Chrystal M Paulos, Jeffery Rathmell, Xue-Zhong Yu, Shikhar Mehrotra
Heightened effector function and prolonged persistence, the key attributes of Th1 and Th17 cells, respectively, are key features of potent anti-tumor T cells. Here, we established ex vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in vivo while maintaining their effector function. Using transcriptomics and metabolic profiling approaches, we showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD(+)-dependent activity of the histone deacetylase Sirt1...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29129747/mitochondrial-sirt3-and-neurodegenerative-brain-disorders
#15
REVIEW
Anamika, Archita Khanna, Papia Acharjee, Arup Acharjee, Surendra Kumar Trigun
Sirtuins are highly conserved NAD(+) dependent class III histone deacetylases and catalyze deacetylation and ADP ribosylation of a number of non-histone proteins. Since, they require NAD(+) for their activity, the cellular level of Sirtuins represents redox status of the cells and thereby serves as bona fide metabolic stress sensors. Out of seven homologues of Sirtuins identified in mammals, SIRT3, 4 & 5 have been found to be localized and active in mitochondria. During recent past, clusters of protein substrates for SIRT3 have been identified in mitochondria and thereby advocating SIRT3 as the main mitochondrial Sirtuin which could be involved in protecting stress induced mitochondrial integrity and energy metabolism...
November 9, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29129519/sirt6-protects-against-hepatic-ischemia-reperfusion-injury-by-inhibiting-apoptosis-and-autophagy-related-cell-death
#16
Song Zhang, Shuai Jiang, Haiping Wang, Wencheng Di, Chao Deng, Zhenxiao Jin, Wei Yi, Xiao Xiao, Yongzhan Nie, Yang Yang
Silent information regulator 6 (SIRT6), a class III histone deacetylase, has been revealed to participate in multiple metabolic processes in the liver, and it plays important roles in protecting against ischemia/reperfusion (I/R) injury in multiple organs. In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice...
November 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29123941/bile-acids-as-global-regulators-of-hepatic-nutrient-metabolism
#17
Phillip B Hylemon, Kazuaki Takabe, Mikhail Dozmorov, Masayuki Nagahashi, Huiping Zhou
Bile acids (BA) are synthesized from cholesterol in the liver. They are essential for promotion of the absorption of lipids, cholesterol, and lipid-soluble vitamins from the intestines. BAs are hormones that regulate nutrient metabolism by activating nuclear receptors (farnesoid X receptor (FXR), pregnane X receptor, vitamin D) and G protein-coupled receptors (e.g., TGR5, sphingosine-1-phosphate receptor 2 (S1PR2)) in the liver and intestines. In the liver, S1PR2 activation by conjugated BAs activates the extracellular signal-regulated kinase 1/2 and AKT signaling pathways, and nuclear sphingosine kinase 2...
June 2017: Liver Research
https://www.readbyqxmd.com/read/29107034/histone-deacetylase-atsrt1-rregulates-metabolic-flux-and-stress-response-in-arabidopsis
#18
Xiaoyun Liu, Wei Wei, Wenjun Zhu, Lufang Su, Zeyang Xiong, Man Zhou, Yu Zheng, Dao-Xiu Zhou
How plant metabolic flux alters gene expression to optimize plant growth and response to stress remains largely unclear. Here, we report that Arabidopsis thaliana NAD(+)-dependent histone deacetylase AtSRT1 negatively regulates plant tolerance to stress and glycolysis but stimulates mitochondrial respiration. We found that AtSRT1 interacts with Arabidopsis cMyc-Binding Protein-1 (AtMBP-1), a transcriptional repressor produced by alternative translation of the cytosolic glycolytic enolase gene LOS2/ENO2. We demonstrated that AtSRT1 could associate with the chromatin of AtMBP-1 targets LOS2/ENO2 and STZ/ZAT10, both of which encode key stress regulators, and reduce the H3K9ac levels at these genes to repress their transcription...
October 26, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29104258/epigenetic-regulatory-mechanisms-induced-by-resveratrol
#19
REVIEW
Guilherme Felipe Santos Fernandes, Gabriel Dalio Bernardes Silva, Aline Renata Pavan, Diego Eidy Chiba, Chung Man Chin, Jean Leandro Dos Santos
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1)...
November 1, 2017: Nutrients
https://www.readbyqxmd.com/read/29095525/trichostatin-a-alters-cytoskeleton-and-energy-metabolism-of-pancreatic-adenocarcinoma-cells-an-in-depth-proteomic-study
#20
Elisa Dalla Pozza, Marcello Manfredi, Jessica Brandi, Arianna Buzzi, Eleonora Conte, Raffaella Pacchiana, Daniela Cecconi, Emilio Marengo, Massimo Donadelli
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of all human cancers with a high mortality rate. Resistance to conventional treatments and chemotherapeutics is a typical feature of PDAC. To investigate the causes of drug resistance it is essential to deeply investigate the mechanism of action of chemotherapeutics. In this study, we performed an in depth shotgun proteomic approach using the label-free proteomic SWATH-MS analysis to investigate novel insights of the mechanism of action of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) in PDAC cells...
November 2, 2017: Journal of Cellular Biochemistry
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