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histone deacetylase metabolic disease

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https://www.readbyqxmd.com/read/28123081/histone-deacetylase-inhibitors-protect-against-pyruvate-dehydrogenase-dysfunction-in-huntington-s-disease
#1
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/28109165/melatonin-and-sirtuins-a-not-so-unexpected-relationship
#2
REVIEW
Juan C Mayo, Rosa M Sainz, Pedro González Menéndez, Vanesa Cepas, Dun-Xian Tan, Russel J Reiter
Epigenetic modifications, including methylation or acetylation as well as post-transcriptional modifications, are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes, are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival, and apoptosis, thus having important roles in normal and cancer cells. Sirtuins can also regulate metabolic pathways by changing preference for glycolysis under aerobic conditions as well as glutaminolysis...
January 21, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28094444/the-current-state-of-nad-dependent-histone-deacetylases-sirtuins-as-novel-therapeutic-targets
#3
REVIEW
Matthias Schiedel, Dina Robaa, Tobias Rumpf, Wolfgang Sippl, Manfred Jung
Sirtuins are NAD(+) -dependent protein deacylases that cleave off acetyl, as well as other acyl groups, from the ε-amino group of lysines in histones and other substrate proteins. Seven sirtuin isotypes (Sirt1-7) have been identified in mammalian cells. As sirtuins are involved in the regulation of various physiological processes such as cell survival, cell cycle progression, apoptosis, DNA repair, cell metabolism, and caloric restriction, a dysregulation of their enzymatic activity has been associated with the pathogenesis of neoplastic, metabolic, infectious, and neurodegenerative diseases...
January 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28031458/normalization-of-hepatic-homeostasis-in-the-npc1nmf164-mouse-model-of-niemann-pick-type-c-disease-treated-with-the-histone-deacetylase-inhibitor-vorinostat
#4
Andrew B Munkacsi, Natalie Hammond, Remy T Schneider, Dinindu S Senanayake, Katsumi Higaki, Kirill Lagutin, Stephen J Bloor, Daniel S Ory, Robert A Maue, Fannie W Chen, Antonio Hernandez-Ono, Nicole Dahlson, Joyce J Repa, Henry N Ginsberg, Yiannis A Ioannou, Stephen L Sturley
Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no FDA-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1nmf164 mice, which express a missense mutation in the NPC1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of Vorinostat (150 mg/kg, 5 days per week)...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28028356/sirtuins-and-nonalcoholic-fatty-liver-disease
#5
REVIEW
Fatiha Nassir, Jamal A Ibdah
Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class III histone/protein deacetylases. Sirtuins (SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27982123/unraveling-gene-expression-profiles-in-peripheral-motor-nerve-from-amyotrophic-lateral-sclerosis-patients-insights-into-pathogenesis
#6
Nilo Riva, Ferdinando Clarelli, Teuta Domi, Federica Cerri, Francesca Gallia, Amelia Trimarco, Paola Brambilla, Christian Lunetta, Alberto Lazzerini, Giuseppe Lauria, Carla Taveggia, Sandro Iannaccone, Eduardo Nobile-Orazio, Giancarlo Comi, Maurizio D'Antonio, Filippo Martinelli-Boneschi, Angelo Quattrini
The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach was employed. We identified alterations in the expression of 815 genes, with 529 up-regulated and 286 down-regulated in ALS patients...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919737/histone-deacetylases-3-deletion-restrains-pm2-5-induced-mice-lung-injury-by-regulating-nf-%C3%AE%C2%BAb-and-tgf-%C3%AE-smad2-3-signaling-pathways
#7
Li-Zhi Gu, Hong Sun, Jian-Hui Chen
Acute lung injury (ALI) as a serious disease with high mortality has been emphasized as a threat to human health and life. Accumulating studies demonstrated that PM2.5 plays a significant role in metabolic and lung diseases. Histone deacetylases 3 (HDAC3) is an important regulator in control of gene transcription, required in up-regulation of inflammation-related signaling, and has been known as a key hotpot in treating a lot of chronic inflammatory diseases. TGF-β/Smad signaling pathway has been proven to be of significance in fibrosis development...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#8
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
November 24, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27866836/physiological-suppression-of-lipotoxic-liver-damage%C3%A2-by-complementary-actions-of-hdac3-and%C3%A2-scap-srebp
#9
Romeo Papazyan, Zheng Sun, Yong Hoon Kim, Paul M Titchenell, David A Hill, Wenyun Lu, Manashree Damle, Min Wan, Yuxiang Zhang, Erika R Briggs, Joshua D Rabinowitz, Mitchell A Lazar
Liver fat accumulation precedes non-alcoholic steatohepatitis, an increasing cause of end-stage liver disease. Histone deacetylase 3 (HDAC3) is required for hepatic triglyceride homeostasis, and sterol regulatory element binding protein (SREBP) regulates the lipogenic response to feeding, but the crosstalk between these pathways is unknown. Here we show that inactivation of SREBP by hepatic deletion of SREBP cleavage activating protein (SCAP) abrogates the increase in lipogenesis caused by loss of HDAC3, but fatty acid oxidation remains defective...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27764514/sirtuins-and-their-interactions-with-transcription-factors-and-poly-adp-ribose-polymerases
#10
H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27697049/macrolide-hybrid-compounds-drug-discovery-opportunities-in-anti-infective-and-anti-inflammatory-area
#11
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perić
Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model...
27, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27686535/function-of-the-sirt3-mitochondrial-deacetylase-in-cellular-physiology-cancer-and-neurodegenerative-disease
#12
REVIEW
Aneesa Ansari, Md Shahedur Rahman, Subbroto K Saha, Forhad K Saikot, Akash Deep, Ki-Hyun Kim
In mammals, seven members of the sirtuin protein family known as class III histone deacetylase have been identified for their characteristic features. These distinguished characteristics include the tissues where they are distributed or located, enzymatic activities, molecular functions, and involvement in diseases. Among the sirtuin members, SIRT3 has received much attention for its role in cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3 controls energy demand during stress conditions such as fasting and exercise as well as metabolism through the deacetylation and acetylation of mitochondrial enzymes...
February 2017: Aging Cell
https://www.readbyqxmd.com/read/27633396/silencing-of-histone-deacetylase-9-expression-in-podocytes-attenuates-kidney-injury-in-diabetic-nephropathy
#13
Feng Liu, Ming Zong, Xiaofei Wen, Xuezhu Li, Jun Wang, Yi Wang, Wei Jiang, Xiaojun Li, Zhongliang Guo, Hualin Qi
Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN...
September 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27626651/disruption-of-the-class-iia-hdac-corepressor-complex-increases-energy-expenditure-and-lipid-oxidation
#14
Vidhi Gaur, Timothy Connor, Andrew Sanigorski, Sheree D Martin, Clinton R Bruce, Darren C Henstridge, Simon T Bond, Kevin A McEwen, Lyndal Kerr-Bayles, Trent D Ashton, Cassandra Fleming, Min Wu, Lisa S Pike Winer, Denise Chen, Gregg M Hudson, John W R Schwabe, Keith Baar, Mark A Febbraio, Paul Gregorevic, Frederick M Pfeffer, Ken R Walder, Mark Hargreaves, Sean L McGee
Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation...
September 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27604094/regulation-of-platelet-function-by-acetylation-deacetylation-mechanisms
#15
REVIEW
Ana Latorre, Antonio Moscardó
Reversible acetylation of histones is a well-known mechanism of epigenetic regulation of gene expression. More recently, studies have demonstrated that acetylation/deacetylation in several proteins regulate multiple aspects of cellular activity, especially those associated with energetic metabolism. Platelets are key participants in haemostasis and cardiovascular diseases. Although metabolic changes such as diabetes or lipidemia are well recognized risk factors for cardiovascular diseases, there is very little information about the relationship between metabolism and platelet reactivity...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27556491/epigenetic-activation-of-wnt-%C3%AE-catenin-signaling-in-nafld-associated-hepatocarcinogenesis
#16
REVIEW
Yuan Tian, Myth T S Mok, Pengyuan Yang, Alfred S L Cheng
Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC). The Wnt/β-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/β-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding β-catenin protein) or other antagonists targeting Wnt/β-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal β-catenin activities in HCC...
2016: Cancers
https://www.readbyqxmd.com/read/27542094/fluorescence-probe-for-imaging-sirtuin-activity-in-living-cells-based-on-one-step-cleavage-of-dabcyl-quencher
#17
Mitsuyasu Kawaguchi, Shohei Ikegawa, Naoya Ieda, Hidehiko Nakagawa
Sirtuins (SIRTs) are a family of NAD+-dependent histone deacetylases. In mammals, dysfunction of SIRTs is associated with age-related metabolic diseases and cancers, so SIRT modulators are considered attractive therapeutic targets. However, current screening methodologies are problematic, and no tools are available for imaging endogenous SIRT activity in living cells. In this work, we present a series of simple and highly sensitive novel SIRT activity probes. Fluorescence of these probes is activated by SIRT-mediated hydrolytic release of a 4-(4-dimethylaminophenylazo)benzoyl (Dabcyl)-based FRET quencher moiety from the -amino group of lysine in a histone H3K9-derived nonapeptide bearing a C-terminal fluorophore...
August 19, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27536685/sirt1-and-kidney-function
#18
REVIEW
Yi Guan, Chuan-Ming Hao
BACKGROUND: SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology. SUMMARY: SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity...
March 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27534902/sirtuin-6-suppresses-hypoxia-induced-inflammatory-response-in-human-osteoblasts-via-inhibition-of-reactive-oxygen-species-production-and-glycolysis-a-therapeutic-implication-in-inflammatory-bone-resorption
#19
Kuo-Liang Hou, Sze-Kwan Lin, Ling-Hsiu Chao, Eddie Hsiang-Hua Lai, Cheng-Chi Chang, Chia-Tung Shun, Wan-Yu Lu, Jyh-Horng Wang, Michael Hsiao, Chi-Yuan Hong, Sang-Heng Kok
Elevated glycolytic activity and redox imbalance induced by tissue hypoxia are common phenomena of chronic inflammation, including inflammatory bone diseases such as arthritis. However, relation between glycolysis and redox signaling in the inflammatory milieu is unclear. The histone deacetylase sirtuin 6 (SIRT6) is a crucial modulator of inflammation and glucose metabolism, and it is also involved in cellular protection against oxidative injury. The aims of the study were to examine the connection between glycolysis and reactive oxygen species (ROS) production in human osteoblastic cells (HOB) and whether SIRT6 modulates inflammatory response via regulation of glycolytic activity and ROS generation...
August 18, 2016: BioFactors
https://www.readbyqxmd.com/read/27529237/epigenetic-mechanisms-in-bone-biology-and-osteoporosis-can-they-drive-therapeutic-choices
#20
REVIEW
Francesca Marini, Luisella Cianferotti, Maria Luisa Brandi
Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis...
August 12, 2016: International Journal of Molecular Sciences
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