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histone deacetylase metabolic disease

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https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#1
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
#2
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...
November 10, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27764514/sirtuins-and-their-interactions-with-transcription-factors-and-poly-adp-ribose-polymerases
#3
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
#4
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perića
5-LOX - 5-lipoxygenase; ACT - artemisinin-based combination therapies; ADME - absorption, distribution, metabolism and excretion; BAL - broncho alveolar lavage; CABP - community acquired bacterial pneumonia; cAMP - cyclic adenosine monophosphate; CAP - community-acquired pneumonia; CF - cystic fibrosis, BOS bronchiolitis obliterans syndrome; cGMP - cyclic guanosine monophosphate; COPD - chronic obstructive pulmonary disease; COX - cyclooxygenase; DPB - diffuse panbronchiolitis; HDACs - histone deacetylases; IBD - inflammatory bowel disease; IL-1p - interleukin 1p; IL-6 - interleukin 6; MIC - minimal inhibitory concentrations; MLSB - macrolide, lincosamide, streptogramin B; NSAIDs - non-steroidal anti-inflammatory drugs; OVA - ovalbumin; PDE4 - phosphodiesterase 4; PMA - phorbol 12-myristate 13-acetate; RA - rheumatoid arthritis; RTI - respiratory tract infections; SAHA - suberoylanilide hydroxamic acid; SAR - structure-activity-relationship; Th1 - type 1 helper T-cell; TNBS - trinitrobenzene sulfonic acid; TNF-α - tumour necrosis factor α; UN - United Nations, WHO - World Health Organisation...
September 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
#5
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...
September 29, 2016: Aging Cell
https://www.readbyqxmd.com/read/27633396/silencing-of-histone-deacetylase-9-expression-in-podocytes-attenuates-kidney-injury-in-diabetic-nephropathy
#6
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...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27626651/disruption-of-the-class-iia-hdac-corepressor-complex-increases-energy-expenditure-and-lipid-oxidation
#7
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
#8
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...
September 7, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27556491/epigenetic-activation-of-wnt-%C3%AE-catenin-signaling-in-nafld-associated-hepatocarcinogenesis
#9
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
#10
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
#11
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
#12
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
#13
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...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27528044/dictyostelium-discoideum-sir2d-protein-an-ortholog-of-human-1-sirt1-modulates-cell-type-specific-gene-expression-and-is-involved-in-autophagy
#14
Rakhee Lohia, Punita Jain, Mukul Jain, Pradeep Kumar Burma, Anju Shrivastava, Shweta Saran
Sirtuins belong to class III histone deacetylases and require NAD (+)for its activity. They relate to nutritional state of the cell and directly link cellular metabolic signalling to the state of protein post-translational modifications. Sirtuins play an important role in healthy aging, longevity, age-related diseases as well as the cell survival mechanism like autophagy. Here, we investigate the functions of Dictyostelium discoideum Sir2D that show similarity to human SIRT1. This gene is expressed throughout growth and development...
August 16, 2016: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/27479696/acetylation-control-of-cardiac-fatty-acid-%C3%AE-oxidation-and-energy-metabolism-in-obesity-diabetes-and-heart-failure
#15
Arata Fukushima, Gary D Lopaschuk
Alterations in cardiac energy metabolism are an important contributor to the cardiac pathology associated with obesity, diabetes, and heart failure. High rates of fatty acid β-oxidation with cardiac insulin resistance represent a cardiac metabolic hallmark of diabetes and obesity, while a marginal decrease in fatty acid oxidation and a prominent decrease in insulin-stimulated glucose oxidation are commonly seen in the early stages of heart failure. Alterations in post-translational control of energy metabolic processes have recently been identified as an important contributor to these metabolic changes...
July 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27453763/combinatorial-epigenetic-therapy-in-diffuse-large-b-cell-lymphoma-pre-clinical-models-and-patients
#16
Benet Pera, Tiffany Tang, Rossella Marullo, Shao-Ning Yang, Haelee Ahn, Jayeshkumar Patel, Rebecca Elstrom, Jia Ruan, Richard Furman, John Leonard, Leandro Cerchietti, Peter Martin
BACKGROUND: Refractory and/or relapsed diffuse large B cell lymphoma (RR-DLBCL) patients are incurable with conventional chemotherapy due to the aggressiveness and the chemorefractory state of these tumors. DNA hypermethylation and histone deacetylation are two major epigenetic modifications by which aggressive DLBCL maintain their oncogenic state. We have previously reported that DNA methyltransferase inhibitors (DNMTI) affect RR-DLBCL growth and improve chemosensitivity. Here, we hypothesized that the combination of DNMTI with histone deacetylase inhibitor (HDI) would be an active and feasible therapeutic strategy in RR-DLBCL...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27448578/microbiota-metabolite-short-chain-fatty-acids-gpcr-and-inflammatory-bowel-diseases
#17
Mingming Sun, Wei Wu, Zhanju Liu, Yingzi Cong
Gut microbiota has been well recognized in regulation of intestinal homeostasis and pathogenesis of inflammatory bowel diseases. However, the mechanisms involved are still not completely understood. Further, the components of the microbiota which are critically responsible for such effects are also largely unknown. Accumulating evidence suggests that, in addition to pathogen-associated molecular patterns, nutrition and bacterial metabolites might greatly impact the immune response in the gut and beyond. Short chain fatty acids (SCFA), which are metabolized by gut bacteria from otherwise indigestible fiber-rich diets, have been shown to ameliorate diseases in animal models of inflammatory bowel diseases (IBD) and allergic asthma...
July 23, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27443303/virtual-screening-and-experimental-validation-of-novel-histone-deacetylase-inhibitors
#18
Yan-Xin Huang, Jian Zhao, Qiu-Hang Song, Li-Hua Zheng, Cong Fan, Ting-Ting Liu, Yong-Li Bao, Lu-Guo Sun, Li-Biao Zhang, Yu-Xin Li
BACKGROUND: Histone deacetylases (HDACs) are promising therapeutic targets for the treatment of cancer, diabetes and other human diseases. HDAC inhibitors, as a new class of potential therapeutic agents, have attracted a great deal of interest for both research and clinical applications. Increasing efforts have been focused on the discovery of HDAC inhibitors and some HDAC inhibitors have been approved for use in cancer therapy. However, most HDAC inhibitors, including the clinically approved agents, do not selectively inhibit the deacetylase activity of class I and II HDAC isforms, and many suffer from metabolic instability...
2016: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27433579/improved-in-vitro-antileukemic-activity-of-all-trans-retinoic-acid-loaded-in-cholesteryl-butyrate-solid-lipid-nanoparticles
#19
Elton Luiz Silva, Flávia Alves Lima, Guilherme Carneiro, Ramos Jonas Periera, Dawidson Assis Gomes, Elaine Maria de Souza-Fagundes, Lucas Antônio Miranda Ferreira
All-trans retinoic acid, a hydrophobic drug, has become one of the most successful examples of differentiation agents used for treatment of acute promyelocytic leukemia. On the other hand, histone deacetylase inhibitors, such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid. Solid lipid nanoparticles represent a promising alternative for administration of hydrophobic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of all-trans retinoic acid-loaded solid lipid nanoparticles for leukemia treatment...
February 2016: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/27423863/biology-chemistry-and-pharmacology-of-sirtuins
#20
A Bedalov, S Chowdhury, J A Simon
Sirtuins are a family of protein deacylases related by amino acid sequence and cellular function to the yeast Saccharomyces cerevisiae protein Sir2 (Silent Information Regulator-2), the first of this class of enzymes to be identified and studied in detail. Based on its initially discovered activity, Sir2 was classified as a histone deacetylase that removes acetyl groups from histones H3 and H4. The acetylation/deacetylation of these particular substrates leads to changes in transcriptional silencing at specific loci in the yeast genome, hence its name...
2016: Methods in Enzymology
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