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histone deacetylase metabolic

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https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#1
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29446717/activators-of-sirtuin-1-and-their-involvement-in-cardioprotection
#2
Carlotta Granchi, Filippo Minutolo
SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, which removes acetyl groups from many target proteins, such as histone proteins, transcription factors and cofactors. SIRT1-catalyzed deacetylation of these factors modulates the activity of downstream proteins, thus influencing many biological processes. SIRT1 is involved in the regulation of metabolism, inflammation, and tumor growth. The activity of this enzyme is related to the beneficial health effects of calorie restriction, such as lifespan extension and, in particular, the activation of SIRT1 has a positive impact on the cardiovascular system...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29438462/butyrate-a-double-edged-sword-for-health
#3
Hu Liu, Ji Wang, Ting He, Sage Becker, Guolong Zhang, Defa Li, Xi Ma
Butyrate, a four-carbon short-chain fatty acid, is produced through microbial fermentation of dietary fibers in the lower intestinal tract. Endogenous butyrate production, delivery, and absorption by colonocytes have been well documented. Butyrate exerts its functions by acting as a histone deacetylase (HDAC) inhibitor or signaling through several G protein-coupled receptors (GPCRs). Recently, butyrate has received particular attention for its beneficial effects on intestinal homeostasis and energy metabolism...
January 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29413177/targeting-sirtuins-substrate-specificity-and-inhibitor-design
#4
Nima Rajabi, Iacopo Galleano, Andreas S Madsen, Christian A Olsen
Lysine residues across the proteome are modified by posttranslational modifications (PTMs) that significantly enhance the structural and functional diversity of proteins. For lysine, the most abundant PTM is ɛ-N-acetyllysine (Kac), which plays numerous roles in regulation of important cellular functions, such as gene expression (epigenetic effects) and metabolism. A family of enzymes, namely histone deacetylases (HDACs), removes these PTMs. A subset of these enzymes, the sirtuins (SIRTs), represent class III HDAC and, unlike the rest of the family, these hydrolases are NAD+-dependent...
2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29396295/metabolomic-profiling-reveals-cellular-reprogramming-of-b-cell-lymphoma-by-a-lysine-deacetylase-inhibitor-through-the-choline-pathway
#5
Benet Pera, Jan Krumsiek, Sarit E Assouline, Rossella Marullo, Jayeshkumar Patel, Jude M Phillip, Lidia Román, Koren K Mann, Leandro Cerchietti
Despite the proven clinical antineoplastic activity of histone deacetylase inhibitors (HDACI), their effect has been reported to be lower than expected in B-cell lymphomas. Traditionally considered as "epigenetic drugs", HDACI modify the acetylation status of an extensive proteome, acting as general lysine deacetylase inhibitors (KDACI), and thus potentially impacting various branches of cellular metabolism. Here, we demonstrate through metabolomic profiling of patient plasma and cell lines that the KDACI panobinostat alters lipid metabolism and downstream survival signaling in diffuse large B-cell lymphomas (DLBCL)...
January 25, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29387812/crystal-structure-analysis-of-human-serum-albumin-complexed-with-sodium-4-phenylbutyrate
#6
Akito Kawai, Keishi Yamasaki, Taisuke Enokida, Shuichi Miyamoto, Masaki Otagiri
Sodium 4-phenylbutyrate (PB) is an orphan drug for the treatment of urea cycle disorders. It also inhibits the development of endoplasmic reticulum stress, the action of histone deacetylases and as a regulator of the hepatocanalicular transporter. PB is generally considered to have the potential for use in the treatment of the diseases such as cancer, neurodegenerative diseases and metabolic diseases. In a previous study, we reported that PB is primarily bound to human serum albumin (HSA) in plasma and its binding site is drug site 2...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29376497/l-sulforaphane-confers-protection-against-oxidative-stress-in-an-in-vitro-model-of-age-related-macular-degeneration
#7
Nabeela Khadija Dulull, Daniel Anthony Dias, Thilini Rasika Thrimawithana, Faith Ai Ai Kwa
BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression...
January 25, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29373639/a-novel-metabolism-based-phenotypic-drug-discovery-platform-in-zebrafish-uncovers-hdacs-1-and-3-as-a-potential-combined-anti-seizure-drug-target
#8
Kingsley Ibhazehiebo, Cezar Gavrilovici, Cristiane L de la Hoz, Shun-Chieh Ma, Renata Rehak, Gaurav Kaushik, Paola L Meza Santoscoy, Lucas Scott, Nandan Nath, Do-Young Kim, Jong M Rho, Deborah M Kurrasch
Despite the development of newer anti-seizure medications over the past 50 years, 30-40% of patients with epilepsy remain refractory to treatment. One explanation for this lack of progress is that the current screening process is largely biased towards transmembrane channels and receptors, and ignores intracellular proteins and enzymes that might serve as efficacious molecular targets. Here, we report the development of a novel drug screening platform that harnesses the power of zebrafish genetics and combines it with in vivo bioenergetics screening assays to uncover therapeutic agents that improve mitochondrial health in diseased animals...
January 24, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29369849/sirtuin-1-regulates-pulmonary-artery-smooth-muscle-cell-proliferation-role-in-pulmonary-arterial-hypertension
#9
Giada Zurlo, Jérôme Piquereau, Maryline Moulin, Julie Pires Da Silva, Mélanie Gressette, Benoît Ranchoux, Anne Garnier, Renée Ventura-Clapier, Elie Fadel, Marc Humbert, Christophe Lemaire, Frédéric Perros, Vladimir Veksler
OBJECTIVE: Energy metabolism shift from oxidative phosphorylation toward glycolysis in pulmonary artery smooth muscle cells (PASMCs) is suggested to be involved in their hyperproliferation in pulmonary arterial hypertension (PAH). Here, we studied the role of the deacetylase sirtuin1 (SIRT1) in energy metabolism regulation in PASMCs via various pathways including activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), master regulator of mitochondrial biogenesis...
January 24, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29363375/sodium-butyrate-has-anti-proliferative-pro-differentiating-and-immunomodulatory-effects-in-osteosarcoma-cells-and-counteracts-the-tnf%C3%AE-induced-low-grade-inflammation
#10
Silvia Perego, Veronica Sansoni, Giuseppe Banfi, Giovanni Lombardi
Butyrate, an essential factor for colonocytes and regulator in the development of colon cancer, is partially absorbed by the gut. It influences the proliferation and differentiation of several cell types including osteoblasts. We evaluated the effects of different doses of butyrate on differentiation and functionality of osteosarcoma cells in vitro and the expression of a pro-inflammatory phenotype in a normal or inflammatory environment. SaOS-2 osteosarcoma cells were induced to differentiate and contemporarily treated for 24 h, 48 h, or 7 days with sodium butyrate 10-4, 5 × 10-4, or 10-3 M in the presence or absence of tumor necrosis factor alpha (TNFα) 1 ng/mL, a pro-inflammatory stimulus...
January 2018: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29362416/creb-binding-protein-plays-key-roles-in-juvenile-hormone-action-in-the-red-flour-beetle-tribolium-castaneum
#11
Jingjing Xu, Amit Roy, Subba Reddy Palli
Juvenile hormones (JH) and ecdysteroids regulate many biological and metabolic processes. CREB-binding protein (CBP) is a transcriptional co-regulator with histone acetyltransferase (HAT) activity. Therefore, CBP is involved in activation of many transcription factors that regulate expression of genes associated with postembryonic development in insects. However, the function of CBP in JH action in insects is not well understood. Hence, we studied the role of CBP in JH action in the red flour beetle, Tribolium castaneum and the Tribolium cell line...
January 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29360739/peretinoin-an-acyclic-retinoid-inhibits-hepatitis-b-virus-replication-by-suppressing-sphingosine-metabolic-pathway-in-vitro
#12
Kazuhisa Murai, Takayoshi Shirasaki, Masao Honda, Ryogo Shimizu, Tetsuro Shimakami, Saki Nakasho, Natsumi Shirasaki, Hikari Okada, Yoshio Sakai, Taro Yamashita, Shuichi Kaneko
Hepatocellular carcinoma (HCC) frequently develops from hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. We previously reported that peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA) were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity...
January 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29348808/dual-nampt-hdac-inhibitors-as-a-new-strategy-for-multitargeting-antitumor-drug-discovery
#13
Wei Chen, Guoqiang Dong, Ying Wu, Wannian Zhang, Chaoyu Miao, Chunquan Sheng
Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) inhibitors were designed by a pharmacophore fusion approach. The thiazolocarboxamide inhibitors were highly active for both targets. In particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new strategy for multitarget antitumor drug discovery by simultaneously acting on cancer metabolism and epigenetics.
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29339464/propionate-enters-gabaergic-neurons-inhibits-gaba-transaminase-causes-gaba-accumulation-and-lethargy-in-a-model-of-propionic-acidemia
#14
Cecilie Morland, Anne-Sofie Frøland, Mi Nyguyen Pettersen, Jon Storm-Mathisen, Vidar Gundersen, Frode Rise, Bjørnar Hassel
Propionic acidemia is the accumulation of propionate in blood due to dysfunction of propionyl-CoA carboxylase. The condition causes lethargy and striatal degeneration with motor impairment in humans. How propionate exerts its toxic effect is unclear. Here we show that intravenous administration of propionate causes dose-dependent propionate accumulation in the brain and transient lethargy in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic neurons, as could be seen from increased neuronal histone H4 acetylation in striatum and neocortex...
January 16, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29336543/histone-deacetylase-11-is-a-fatty-acid-deacylase
#15
Zsofia Kutil, Zora Novakova, Marat Meleshin, Jana Mikesova, Mike Schutkowski, Cyril Barinka
Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity. Here we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate. Additionally, N-linked lipoic acid and biotin are removed by the enzyme, although with lower efficacy. Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77,700 M-1s-1 and 149,000 M-1s-1, respectively, making HDAC11 the most proficient fatty acid deacylase of the HDAC family...
January 16, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29325899/do-ketone-bodies-mediate-the-anti-seizure-effects-of-the-ketogenic-diet
#16
REVIEW
Timothy A Simeone, Kristina A Simeone, Carl E Stafstrom, Jong M Rho
Although the mechanisms underlying the anti-seizure effects of the high-fat ketogenic diet (KD) remain unclear, a long-standing question has been whether ketone bodies (i.e., beta-hydroxybutyrate [BHB], acetoacetate [ACA] and acetone), either alone or in combination, contribute mechanistically. The traditional belief has been that while ketone bodies reflect enhanced fatty acid oxidation and a general shift toward intermediary metabolism, they are not likely to be the key mediators of the KD's clinical effects, as blood levels of BHB do not correlate consistently with improved seizure control...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29317660/microbiota-derived-short-chain-fatty-acids-promote-histone-crotonylation-in-the-colon-through-histone-deacetylases
#17
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/29317652/sirt6-dependent-cysteine-monoubiquitination-in-the-pre-set-domain-of-suv39h1-regulates-the-nf-%C3%AE%C2%BAb-pathway
#18
Irene Santos-Barriopedro, Laia Bosch-Presegué, Anna Marazuela-Duque, Carolina de la Torre, Carlota Colomer, Berta N Vazquez, Thomas Fuhrmann, Bárbara Martínez-Pastor, Wenfu Lu, Thomas Braun, Eva Bober, Thomas Jenuwein, Lourdes Serrano, Manel Esteller, Zhenbang Chen, Silvia Barceló-Batllori, Raúl Mostoslavsky, Lluis Espinosa, Alejandro Vaquero
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29302794/evaluation-of-the-neuroprotective-effect-of-sirt3-in-experimental-stroke
#19
Rajkumar Verma, Rodney M Ritzel, Joshua Crapser, Brett D Friedler, Louise D McCullough
Sirtuins (Sirt) are a family of NAD+ dependent histone deacetylase (HDAC) proteins implicated in aging, cell cycle regulation, and metabolism. These proteins are involved in the epigenetic modification of neuromodulatory proteins after strokevia acetylation/deacetylation. The specific role of Sirt3, a mitochondrial sirtuin, in post-stroke injury has been relatively unexplored. Using male Sirt3 knockout (KO) mice and wild-type littermates (WT), we show that Sirt3 KO mice show significant neuroprotection at 3 days after ischemia/reperfusion (I/R) or stroke injury...
January 4, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/29298809/sucrose-non-fermenting-related-kinase-regulates-both-adipose-inflammation-and-energy-homeostasis-in-mice-and-humans
#20
Jie Li, Bin Feng, Yaohui Nie, Ping Jiao, Xiaochen Lin, Mengna Huang, Ran An, Qin He, Huilin Emily Zhou, Arthur Salomon, Kirsten S Sigrist, Zhidan Wu, Simin Liu, Haiyan Xu
Sucrose non-fermenting related kinase (SNRK) is a member of AMPK-related kinase family and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white (WAT) and brown adipose tissue (BAT) but adipose SNRK expression level diminishes in obesity. In the current study, we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival since SNRK global deficient pups die within 24 hours after birth...
January 3, 2018: Diabetes
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