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histone deacetylase metabolic disease

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https://www.readbyqxmd.com/read/29446717/activators-of-sirtuin-1-and-their-involvement-in-cardioprotection
#1
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/29413177/targeting-sirtuins-substrate-specificity-and-inhibitor-design
#2
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/29387812/crystal-structure-analysis-of-human-serum-albumin-complexed-with-sodium-4-phenylbutyrate
#3
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
#4
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
#5
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/29249955/expression-of-sirtuins-in-the-retinal-neurons-of-mice-rats-and-humans
#6
Hongdou Luo, Min Zhou, Kaibao Ji, Jiejie Zhuang, Wenjie Dang, Shiya Fu, Tao Sun, Xu Zhang
Sirtuins are a class of histone deacetylases (HDACs) that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7) that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29233643/trichostatin-a-inhibits-deacetylation-of-histone-h3-and-p53-by-sirt6
#7
Marci Wood, Stacia Rymarchyk, Song Zheng, Yana Cen
SIRT6 is an epigenetic modification enzyme that regulates gene transcription through its deacetylase activity. In addition to histone protein, SIRT6 also modify other proteins and enzymes, some of which are central players in metabolic reprogramming and aging process. Therefore, SIRT6 has emerged as a therapeutic target for the treatment of metabolic disorder and age-related diseases. Here, we report that SIRT6 deacetylates lysine 382 of p53 in short synthetic peptide sequence and in full length p53. Further studies showed that the deacetylation of H3K9Ac and p53K382Ac are insensitive to nicotinamide inhibition, but are sensitive to trichostatin A (TSA) inhibition...
December 9, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29233468/butyrate-suppresses-motility-of-colorectal-cancer-cells-via-deactivating-akt-erk-signaling-in-histone-deacetylase-dependent-manner
#8
Qingran Li, Chujie Ding, Tuo Meng, Wenjie Lu, Wenyue Liu, Haiping Hao, Lijuan Cao
Butyrate is a typical short chain fatty acid produced by gut microbiota of which the dysmetabolism has been consistently associated with colorectal diseases. However, whether butyrate affects metastatic colorectal cancer is not clear. In this study we investigated in vitro the effect of butyrate on motility, a significant metastatic factor of colorectal cancer cells and explored the potential mechanism. By using wound healing and transwell-based invasion models, we demonstrated that pretreatment of butyrate significantly inhibited motility of HCT116, HT29, LOVO and HCT8 cells, this activity was further attributed to deactivation of Akt1 and ERK1/2...
December 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29189132/polyphenols-novel-signaling-pathways
#9
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/29175209/the-protective-role-of-low-concentration-alcohol-in-high-fructose-induced-adverse-cardiovascular-events-in-mice
#10
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/29132743/nuclear-sirtuins-and-inflammatory-signaling-pathways
#11
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/29129747/mitochondrial-sirt3-and-neurodegenerative-brain-disorders
#12
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/29104258/epigenetic-regulatory-mechanisms-induced-by-resveratrol
#13
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/29091298/the-mechanism-and-potential-targets-of-class-ii-hdacs-in-angiogenesis
#14
Fei Hou, Dandan Li, Honglian Yu, Qingsheng Kong
Angiogenesis refers to the new blood vessels deriving from the existing blood vessels, and it's a complex regulatory process. Angiogenesis is associated with the normal development of the body and tumor growth and migration. The imbalance of histone deacetylase, as an epigenetic modification, could induce the production of diseases, such as cancer, metabolic diseases, etc., and it also plays an important role in angiogenesis. Many researches indicate that class II HDACs nuclear shuttle and its phosphorylation are necessary for the diseases and the protection of the collective itself...
November 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29049850/-epigenetic-control-of-early-neurodegenerative-events-in-diabetic-retinopathy-by-the-histone-deacetylase-sirt6
#15
María A Zorrilla-Zubilete, Ada Yeste, Francisco J Quintana, Debra Toiber, Raul Mostoslavsky, Dafne M Silberman
Diabetic retinopathy (DR) is one of the common complications associated with diabetes mellitus (DM) and the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Moreover, glucose-induced neuron and glial cell damage may occur shortly after the onset of diabetes which makes the disease hard to diagnose at early stages. SIRT6, a NAD-dependent sirtuin deacylase, modulates aging, energy metabolism and neurodegeneration...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29030662/oral-histone-deacetylase-inhibitor-synergises-with-t-cell-targeted-immunotherapy-to-preserve-beta-cell-metabolic-function-and-induce-stable-remission-of-new-onset-autoimmune-diabetes-in-nod-mice
#16
Alix Besançon, Tania Goncalves, Fabrice Valette, Mattias S Dahllöf, Thomas Mandrup-Poulsen, Lucienne Chatenoud, Sylvaine You
AIM/HYPOTHESIS: Combination therapy targeting the major actors involved in the immune-mediated destruction of pancreatic beta cells appears to be an indispensable approach to treat type 1 diabetes effectively. We hypothesised that the combination of an orally active pan-histone deacetylase inhibitor (HDACi: givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy to treat ongoing autoimmunity. METHODS: NOD mice transgenic for the human CD3ε (also known as CD3E) chain (NOD-huCD3ε) were treated for recent-onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3 antibodies (otelixizumab, 50 μg/day, 5 days, i...
October 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/28984064/loss-of-sirt2-leads-to-axonal-degeneration-and-locomotor-disability-associated-with-redox-and-energy-imbalance
#17
Stéphane Fourcade, Laia Morató, Janani Parameswaran, Montserrat Ruiz, Tatiana Ruiz-Cortés, Mariona Jové, Alba Naudí, Paloma Martínez-Redondo, Mara Dierssen, Isidre Ferrer, Francesc Villarroya, Reinald Pamplona, Alejandro Vaquero, Manel Portero-Otín, Aurora Pujol
Sirtuin 2 (SIRT2) is a member of a family of NAD(+) -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice...
December 2017: Aging Cell
https://www.readbyqxmd.com/read/28972001/the-metabolic-and-proliferative-state-of-vascular-adventitial-fibroblasts-in-pulmonary-hypertension-is-regulated-through-a-mir-124-ptbp1-pkm-axis
#18
Hui Zhang, Daren Wang, Min Li, Lydie Plecitá-Hlavatá, Angelo D'Alessandro, Jan Tauber, Suzette Riddle, Sushil Kumar, Amanda R Flockton, B Alexandre McKeon, Maria G Frid, Julie A Reisz, Paola Caruso, Karim C El Kasmi, Petr Ježek, Nicholas W Morrell, Cheng-Jun Hu, Kurt R Stenmark
Background -An emerging "metabolic theory" of pulmonary hypertension (PH) suggests that cellular and mitochondrial metabolic dysfunction underlies the pathology of this disease. We and others have previously demonstrated the existence of hyper-proliferative, apoptosis-resistant, pro-inflammatory adventitial fibroblasts from human and bovine hypertensive pulmonary arterial walls (PH-Fibs) exhibit constitutive reprogramming of glycolytic and mitochondrial metabolism, accompanied by an increased ratio of glucose catabolism through glycolysis versus the TCA cycle...
September 26, 2017: Circulation
https://www.readbyqxmd.com/read/28971711/epigenetic-regulation-in-bacterial-infections-targeting-histone-deacetylases
#19
Aleksander M Grabiec, Jan Potempa
Pathogens have developed sophisticated strategies to evade the immune response, among which manipulation of host cellular epigenetic mechanisms plays a prominent role. In the last decade, modulation of histone acetylation in host cells has emerged as an efficient strategy of bacterial immune evasion. Virulence factors and metabolic products of pathogenic microorganisms alter expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to suppress transcription of host defense genes through epigenetic changes in histone acetylation marks...
October 3, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28966044/hdac6-suppresses-age-dependent-ectopic-fat-accumulation-by-maintaining-the-proteostasis-of-plin2-in-drosophila
#20
Yan Yan, Hao Wang, Minling Hu, Lifen Jiang, Yang Wang, Pingsheng Liu, Xuehong Liang, Jiyong Liu, Changqing Li, Anya Lindström-Battle, Sin Man Lam, Guanghou Shui, Wu-Min Deng, Renjie Jiao
Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2...
October 9, 2017: Developmental Cell
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