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histone deacetylase metabolic

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https://www.readbyqxmd.com/read/28192414/selective-in-vivo-metabolic-cell-labeling-mediated-cancer-targeting
#1
Hua Wang, Ruibo Wang, Kaimin Cai, Hua He, Yang Liu, Jonathan Yen, Zhiyu Wang, Ming Xu, Yiwen Sun, Xin Zhou, Qian Yin, Li Tang, Iwona T Dobrucki, Lawrence W Dobrucki, Eric J Chaney, Stephen A Boppart, Timothy M Fan, Stéphane Lezmi, Xuesi Chen, Lichen Yin, Jianjun Cheng
Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells...
February 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28183450/the-role-of-short-chain-fatty-acids-in-kidney-injury-induced-by-gut-derived-inflammatory-response
#2
REVIEW
Wei Huang, Luping Zhou, Hengli Guo, Youhua Xu, Yong Xu
It has been found that several circulating metabolites derived from gut microbiota fermentation associate with a systemic immuno-inflammatory response and kidney injury, which has been coined the gut-kidney axis. Recent evidence has suggested that short-chain fatty acids (SCFAs), which are primarily originated from fermentation of dietary fiber in the gut, play an important role in regulation of immunity, blood pressure, glucose and lipid metabolism, and seem to be the link between microbiota and host homeostasis...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28123935/deletion-of-histone-deacetylase-3-in-adult-beta-cells-improves-glucose-tolerance-via-increased-insulin-secretion
#3
Jarrett R Remsberg, Benjamin N Ediger, Wesley Y Ho, Manashree Damle, Zhenghui Li, Christopher Teng, Cristina Lanzillotta, Doris A Stoffers, Mitchell A Lazar
OBJECTIVE: Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic β-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in β-cells of adult mice. METHODS: An HDAC3 β-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123081/histone-deacetylase-inhibitors-protect-against-pyruvate-dehydrogenase-dysfunction-in-huntington-s-disease
#4
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/28119491/reactive-oxygen-species-mediated-synergism-of-fenretinide-and-romidepsin-in-preclinical-models-of-t-cell-lymphoid-malignancies
#5
Monish R Makena, Balakrishna Koneru, Thinh H Nguyen, Min H Kang, C Patrick Reynolds
T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitor romidepsin and the synthetic cytotoxic retinoid fenretinide both have achieved durable clinical responses in T-cell lymphomas as single agents. We investigated the potential for using these two agents in combination in TCLMs. We demonstrated cytotoxic synergy between romidepsin and fenretinide in fifteen TCLM cell lines at clinically-achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells)...
January 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28109165/melatonin-and-sirtuins-a-not-so-unexpected-relationship
#6
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/28109123/sodium-butyrate-protects-against-high-fat-diet-induced-cardiac-dysfunction-and-metabolic-disorders-in-type-ii-diabetic-mice
#7
Ling Zhang, Jianfeng Du, Naohiro Yano, Hao Wang, Yu Tina Zhao, Dubielecka-Szczerba Patricia, Shougang Zhuang, Eugene Y Chin, Gangjian Qin, Ting C Zhao
Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in type II diabetes and obesity remains unknown. Here we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28094444/the-current-state-of-nad-dependent-histone-deacetylases-sirtuins-as-novel-therapeutic-targets
#8
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/28092678/6-phosphofructo-2-kinase-fructose-2-6-biphosphatase-4-is-essential-for-p53-null-cancer-cells
#9
S Ros, J Flöter, I Kaymak, C Da Costa, A Houddane, S Dubuis, B Griffiths, R Mitter, S Walz, S Blake, A Behrens, K M Brindle, N Zamboni, M H Rider, A Schulze
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28070968/bacterial-short-chain-fatty-acid-metabolites-modulate-the-inflammatory-response-against-infectious-bacteria
#10
R O Corrêa, A Vieira, E M Sernaglia, M Lancellotti, A T Vieira, M J Avila-Campos, H G Rodrigues, M A R Vinolo
Short-chain fatty acids (SCFAs), predominantly acetic, propionic, and butyric acids, are bacterial metabolites with an important role in the maintenance of homeostasis due to their metabolic and immunomodulatory actions. Some evidence suggests that they may also be relevant during infections. Therefore, we aimed to investigate the effects of SCFAs in the effector functions of neutrophils to an opportunistic pathogenic bacterium, Aggregatibacter actinomycetemcomitans. Using a subcutaneous model to generate a mono, isolated infection of A...
January 9, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28035339/emerging-roles-for-histone-deacetylases-in-age-related-muscle-atrophy
#11
REVIEW
Michael E Walsh, Holly Van Remmen
BACKGROUND: Skeletal muscle atrophy during aging, a process known as sarcopenia, is associated with muscle weakness, frailty, and the loss of independence in older adults. The mechanisms contributing to sarcopenia are not totally understood, but muscle fiber loss due to apoptosis, reduced stimulation of anabolic pathways, activation of catabolic pathways, denervation, and altered metabolism have been observed in muscle from old rodents and humans. OBJECTIVE: Recently, histone deacetylases (HDACs) have been implicated in muscle atrophy and dysfunction due to denervation, muscular dystrophy, and disuse, and HDACs play key roles in regulating metabolism in skeletal muscle...
October 27, 2016: Nutr Healthy Aging
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
#12
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
#13
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/28028175/the-transcriptional-corepressor-sin3-directly-regulates-genes-involved-in-methionine-catabolism-and-affects-histone-methylation-linking-epigenetics-and-metabolism
#14
Mengying Liu, Lori A Pile
Chromatin modification and cellular metabolism are tightly connected. Chromatin modifiers regulate the expression of genes involved in metabolism and, in turn, the levels of metabolites. The generated metabolites are utilized by chromatin modifiers to affect epigenetic modification. The mechanism for this cross-talk, however, remains incompletely understood. The corepressor SIN3 controls histone acetylation through association with the histone deacetylase RPD3. The SIN3 complex is known to regulate genes involved in a number of metabolic processes...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28011426/improving-potency-and-metabolic-stability-by-introducing-an-alkenyl-linker-to-pyridine-based-histone-deacetylase-inhibitors-for-orally-available-runx3-modulators
#15
Doona Song, Chulho Lee, Yoon Jeong Kook, Soo Jin Oh, Jong Soon Kang, Hyun-Jung Kim, Gyoonhee Han
RUNX3, a tumor suppressor, is suppressed in various cancers by abnormal epigenetic changes. Histone deacetylases (HDACs) can deacetylate the lysine residues of RUNX3, followed by degradation via a ubiquitin-mediated pathway. Inhibition of HDAC leads to functional restoration of the RUNX3 protein by epigenetic expression and RUNX3 protein stabilization. We previously reported a series of HDAC inhibitors that restored RUNX3 function. In the present study, we introduced an alkenyl linker group to pyridine-based HDAC inhibitors to improve their potencies and chemical properties...
December 1, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28010116/chrono-integrates-behavioral-stress-and-epigenetic-control-of-metabolism
#16
Fumiyuki Hatanaka, Toru Takumi
Circadian rhythms are a critical part of the body's homeostatic mechanisms. These rhythms repeat with a cycle-length of approximately 24 h and are generated by a transcriptional-translational feedback loop. These rhythms are critical for proper behavioral, physiological, and molecular functions. CHRONO, a novel circadian clock gene, forms a complex with other clock proteins and modulates the circadian machinery. CHRONO also interacts with histone deacetylase (HDAC) to modulate the epigenetic status of the transcriptional regulation...
January 19, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/27997009/-genomics-of-lung-adenocarcinoma-pathogenetic-significance-and-clinical-applications
#17
Raffaele Palmirotta, Silvana Acquafredda, Antonella Argentiero, Claudia Carella, Laura Lanotte, Nicla Pappagallo, Davide Quaresmini, Franco Silvestris
Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27994519/anticancer-effects-of-a-new-sirt-inhibitor-mhy2256-against-human-breast-cancer-mcf-7-cells-via-regulation-of-mdm2-p53-binding
#18
Eun Young Park, Youngwoo Woo, Seong Jin Kim, Do Hyun Kim, Eui Kyung Lee, Umasankar De, Kyeong Seok Kim, Jaewon Lee, Jee H Jung, Ki-Tae Ha, Wahn Soo Choi, In Su Kim, Byung Mu Lee, Sungpil Yoon, Hyung Ryong Moon, Hyung Sik Kim
The sirtuins (SIRTs), a family of NAD(+)-dependent class III histone deacetylase, are involved in various biological processes including cell survival, division, senescence, and metabolism via activation of the stress-response pathway. Recently, inhibition of SIRTs has been considered a promising anticancer strategy, but their precise mechanisms of action are not well understood. In particular, the relevance of p53 to SIRT-induced effects has not been fully elucidated. We investigated the anticancer effects of a novel SIRT inhibitor, MHY2256, and its efficacy was compared to that of salermide in MCF-7 (wild-type p53) and SKOV-3 (null-type p53) cells...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27991918/dissociation-of-muscle-insulin-sensitivity-from-exercise-endurance-in-mice-by-hdac3-depletion
#19
Sungguan Hong, Wenjun Zhou, Bin Fang, Wenyun Lu, Emanuele Loro, Manashree Damle, Guolian Ding, Jennifer Jager, Sisi Zhang, Yuxiang Zhang, Dan Feng, Qingwei Chu, Brian D Dill, Henrik Molina, Tejvir S Khurana, Joshua D Rabinowitz, Mitchell A Lazar, Zheng Sun
Type 2 diabetes and insulin resistance are associated with reduced glucose utilization in the muscle and poor exercise performance. Here we find that depletion of the epigenome modifier histone deacetylase 3 (HDAC3) specifically in skeletal muscle causes severe systemic insulin resistance in mice but markedly enhances endurance and resistance to muscle fatigue, despite reducing muscle force. This seemingly paradoxical phenotype is due to lower glucose utilization and greater lipid oxidation in HDAC3-depleted muscles, a fuel switch caused by the activation of anaplerotic reactions driven by AMP deaminase 3 (Ampd3) and catabolism of branched-chain amino acids...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/27988168/dna-methylation-and-histone-deacetylation-regulating-insulin-sensitivity-due-to-chronic-cold-exposure
#20
Xiaoqing Wang, Lai Wang, Yizheng Sun, Ruiping Li, Jinbo Deng, Jiexin Deng
In this study, we investigated the causal relationship between chronic cold exposure and insulin resistance and the mechanisms of how DNA methylation and histone deacetylation regulate cold-reduced insulin resistance. 46 adult male mice from postnatal day 90-180 were randomly assigned to control group and cold-exposure group. Mice in cold-exposure group were placed at temperature from -1 to 4 °C for 30 days to mimic chronic cold environment. Then, fasting blood glucose, blood insulin level and insulin resistance index were measured with enzymatic methods...
December 14, 2016: Cryobiology
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