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histone deacetylase metabolic

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https://www.readbyqxmd.com/read/28621016/acute-effects-of-phenylbutyrate-on-glutamine-branched-chain-amino-acid-and-protein-metabolism-in-skeletal-muscles-of-rats
#1
Milan Holecek, Melita Vodenicarovova, Pavel Siman
Phenylbutyrate (PB) acts as chemical chaperone and histone deacetylase inhibitor, which is used to decrease ammonia in urea cycle disorders and has been investigated for use in the treatment of a number of lethal illnesses. We performed in vivo and in vitro experiments to examine the effects of PB on glutamine (GLN), branched-chain amino acid (BCAA; valine, leucine and isoleucine) and protein metabolism in rats. In the first study, animals were sacrificed one hour after three injections of PB (300mg/kg b...
June 16, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28614293/histone-deacetylase-3-prepares-brown-adipose-tissue-for-acute-thermogenic-challenge
#2
Matthew J Emmett, Hee-Woong Lim, Jennifer Jager, Hannah J Richter, Marine Adlanmerini, Lindsey C Peed, Erika R Briggs, David J Steger, Tao Ma, Carrie A Sims, Joseph A Baur, Liming Pei, Kyoung-Jae Won, Patrick Seale, Zachary Gerhart-Hines, Mitchell A Lazar
Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28579897/tsa-protects-h9c2-cells-against-thapsigargin-induced-apoptosis-related-to-endoplasmic-reticulum-stress-mediated-mitochondrial-injury
#3
Zhiping Li, Yan Liu, Xinlun Dai, Qiangqiang Zhou, Xueli Liu, Zeyu Li, Xia Chen
Endoplasmic reticulum stress (ERS) activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. Recently, TSA has shown protective effects on ERS and its mechanisms related to ER pathway has been previously characterized. However, whether TSA exerts its protective role via metabolic events remain largely undefined. Objectives: To explore the possible involvement of the metabolic changes during ERS and to better understand how TSA influence mitochondrial function to facilitate cellular adaptation...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28556401/quantitative-proteome-based-systematic-identification-of-sirt7-substrates
#4
Chaohua Zhang, Zichao Zhai, Ming Tang, Zhongyi Cheng, Tingting Li, Haiying Wang, Wei-Guo Zhu
SIRT7 is a class III histone deacetylase that is involved in numerous cellular processes. Only six substrates of SIRT7 have been reported thus far, so we aimed to systematically identify SIRT7 substrates using stable-isotope labeling with amino acids in cell culture (SILAC) coupled with quantitative mass spectrometry (MS). Using SIRT7(+/+) and SIRT7(-/-) mouse embryonic fibroblasts as our model system, we identified and quantified 1,493 acetylation sites in 789 proteins, of which 261 acetylation sites in 176 proteins showed ≥2-fold change in acetylation state between SIRT7(-/-) and SIRT7(+/+) cells...
May 27, 2017: Proteomics
https://www.readbyqxmd.com/read/28554803/integrated-omics-approaches-to-characterize-a-nuclear-receptor-corepressor-associated-histone-deacetylase-in-mouse-skeletal-muscle
#5
REVIEW
Yingyun Gong, Rui Cao, Guolian Ding, Sungguan Hong, Wenjun Zhou, Wenyun Lu, Manashree Damle, Bin Fang, Chuhan C Wang, Justin Qian, Natasha Lie, Cristina Lanzillotta, Joshua D Rabinowitz, Zheng Sun
Nuclear receptors regulate gene expression by differentially binding to coactivators or corepressors in a ligand-dependent manner, which further recruits a set of epigenome-modifying enzymes that remodel chromatin conformation. Histone acetylation is a major epigenomic change controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC3 is the only HDAC that confers the enzymatic activity to the complexes nucleated by nuclear receptor corepressors NCoR and SMRT. To address the metabolic function of HDAC3, we have deleted it specifically in mouse skeletal muscles...
May 26, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28553227/srt1720-alleviates-anit-induced-cholestasis-in-a-mouse-model
#6
Linxi Yu, Xiaoxin Liu, Zihang Yuan, Xiaojiaoyang Li, Hang Yang, Ziqiao Yuan, Lixin Sun, Luyong Zhang, Zhengzhou Jiang
Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and oxidative stress. SIRT1 is regarded as a class III histone deacetylase (HDAC). According to a set of researches, SIRT1 is one of the most important factors which can regulate the hepatic bile acid metabolism. SRT1720 is a kind of activator of SIRT1 which is 1000 times more potent than resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28539829/multifaceted-regulation-of-gene-expression-by-the-apoptosis-and-splicing-associated-protein-complex-and-its-components
#7
REVIEW
Bhagyashree Deka, Kusum Kumari Singh
The differential deposition of RNA-binding proteins (RBPs) on pre-mRNA mediates the processes of gene expression. One of the complexes containing RBPs that play a crucial part in RNA metabolism is the apoptosis-and splicing-associated protein (ASAP) complex. In this review, we present a summary of the structure of ASAP complex and its localization. Also, we discuss the findings by different groups on various functions of the subunits of the ASAP complex in RNA metabolism. The subunits of the ASAP complex are RNPS1, Acinus and SAP18...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28533489/sirtuin-6-inhibits-epithelial-to-mesenchymal-transition-during-idiopathic-pulmonary-fibrosis-via-inactivating-tgf-%C3%AE-1-smad3-signaling
#8
Kunming Tian, Panpan Chen, Zhiping Liu, Shutian Si, Qian Zhang, Yong Mou, Lianyong Han, Qin Wang, Xue Zhou
Sirt6 which is implicated in the control of aging, cancer, and metabolism, has been shown to have anti-fibrosis function in heart and liver. However, whether Sirt6 inhibits idiopathic pulmonary fibrosis remains elusive. Epithelial to mesenchymal transition has been found to be involved in the pathogenesis of idiopathic pulmonary fibrosis. In the present study, forced expression of Sirt6 significantly abrogated TGF-β1-induced epithelial to mesenchymal transition-like phenotype and cell behaviors in A549 cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28527050/interplay-between-sirt-3-metabolism-and-its-tumor-suppressor-role-in-hepatocellular-carcinoma
#9
REVIEW
Serena De Matteis, Anna Maria Granato, Roberta Napolitano, Chiara Molinari, Martina Valgiusti, Daniele Santini, Francesco Giuseppe Foschi, Giorgio Ercolani, Umberto Vespasiani Gentilucci, Luca Faloppi, Mario Scartozzi, Giovanni Luca Frassineti, Andrea Casadei Gardini
Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD(+))-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC)...
May 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28516954/histone-deacetylase-10-structure-and-molecular-function-as-a-polyamine-deacetylase
#10
Yang Hai, Stephen A Shinsky, Nicholas J Porter, David W Christianson
Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish)...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28496053/chemical-and-structural-biology-of-protein-lysine-deacetylases
#11
REVIEW
Minoru Yoshida, Norio Kudo, Saori Kosono, Akihiro Ito
Histone acetylation is a reversible posttranslational modification that plays a fundamental role in regulating eukaryotic gene expression and chromatin structure/function. Key enzymes for removing acetyl groups from histones are metal (zinc)-dependent and NAD(+)-dependent histone deacetylases (HDACs). The molecular function of HDACs have been extensively characterized by various approaches including chemical, molecular, and structural biology, which demonstrated that HDACs regulate cell proliferation, differentiation, and metabolic homeostasis, and that their alterations are deeply involved in various human disorders including cancer...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28485501/mir-34a-targets-hdac1-regulated-h3k9-acetylation-on-lipid-accumulation-induced-by-homocysteine-in-foam-cells
#12
Qingguo Zhao, Shuqiang Li, Nan Li, Xiaoling Yang, Shengchao Ma, Anning Yang, Hui Zhang, Songhao Yang, Caiyan Mao, Lingbo Xu, Tingting Gao, Xiaoming Yang, Huiping Zhang, Yideng Jiang
Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR-34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE(-/-) mice fed with high methionine diet, whereas miR-34a expression was inhibited...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28474205/chaperone-co-inducer-bgp-15-inhibits-histone-deacetylases-and-enhances-the-heat-shock-response-through-increased-chromatin-accessibility
#13
Marek A Budzyński, Tim Crul, Samu V Himanen, Noemi Toth, Ferenc Otvos, Lea Sistonen, Laszlo Vigh
Defects in cellular protein homeostasis are associated with many severe and prevalent pathological conditions such as neurodegenerative diseases, muscle dystrophies, and metabolic disorders. One way to counteract these defects is to improve the protein homeostasis capacity through induction of the heat shock response. Despite numerous attempts to develop strategies for chemical activation of the heat shock response by heat shock transcription factor 1 (HSF1), the underlying mechanisms of drug candidates' mode of action are poorly understood...
May 4, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28465348/sirtuin-e-is-a-fungal-global-transcriptional-regulator-that-determines-the-transition-from-the-primary-growth-to-the-stationary-phase
#14
Eriko Itoh, Rika Odakura, Ken-Ichi Oinuma, Motoyuki Shimizu, Shunsuke Masuo, Naoki Takaya
In response to limited nutrients, fungal cells exit the primary growth phase, enter the stationary phase, and cease proliferation. Although fundamental to microbial physiology in many environments, the regulation of this transition is poorly understood, but likely involves many transcriptional regulators. These may include the sirtuins, which deacetylate acetyllysine residues of histones, and epigenetically regulate global transcription. Therefore, we investigated the role of a nuclear sirtuin, sirtuin E (SirE), from the ascomycete fungus, Aspergillus nidulans...
May 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28450154/phenyl-butyrate-inhibits-pyruvate-dehydrogenase-kinase-1-and-contributes-to-its-anti-cancer-effect
#15
Wen Zhang, Shao-Lin Zhang, Xiaohui Hu, Kin Yip Tam
Phenyl butyrate (PB) has been proved to decrease pyruvate dehydrogenase (PDH) phosphorylation level and increase PDH activity by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) in fibroblast cells, PDH deficiency zebrafish and wild type mice. PB has also shown efficacy in many cancers and so far, all of its anti-tumor activity has been attributed to the histone deacetylase (HDAC) inhibition. As PDK1/PDH controls the critical switch between oxidative phosphorylation and glycolysis in cancer cells, PDK1 is a key target in tumor metabolism for anti-cancer treatment...
April 25, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28447074/chidamide-tablets-hdac-inhibition-to-treat-lymphoma
#16
REVIEW
Y Xu, P Zhang, Y Liu
Chidamide is the first oral subtype-selective histone deacetylase inhibitor (HDACI) approved in China as well as the first HDACI of the benzamide class approved for the treatment of relapsed and refractory peripheral T-cell lymphoma (PTCL). This review addresses detailed information regarding chidamide, including the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, clinical studies and application, safety, drug interactions and ongoing clinical trials. Although twice-weekly chidamide monotherapy has been recommended based on the evidence from preclinical and clinical studies with tolerable toxicities, its clinical efficacy could be further increased by combination with multidrug chemotherapy or chemo-free regimens...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28446321/-drug-resistant-mechanism-of-multiple-myeloma-and-its-therapy-combined-with-hdaci-review
#17
Liu-Fang Gu, Xiao-Guang Cui, Xing-Mei Cao, She-Ping Chen
Drug resistance of multiple myeloma(MM) has become more and more common, and greatly decreased the survival rate of these patients. The occurence of drug-resistance involves in many factors such as bone marrow microenveronment, tumor cell self-metabolism, cytokines, specific targets and so on. In this review, the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism, including the changes of heat slock protein expression, mRNA expression, related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28444216/dietary-metabolites-derived-from-gut-microbiota-critical-modulators-of-epigenetic-changes-in-mammals
#18
Mohd Iqbal Bhat, Rajeev Kapila
The mammalian gastrointestinal tract harbors trillions of commensal microorganisms, collectively known as the microbiota. The microbiota is a critical source of environmental stimuli and, thus, has a tremendous impact on the health of the host. The microbes within the microbiota regulate homeostasis within the gut, and any alteration in their composition can lead to disorders that include inflammatory bowel disease, allergy, autoimmune disease, diabetes, mental disorders, and cancer. Hence, restoration of the gut flora following changes or imbalance is imperative for the host...
May 1, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#19
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28437180/a-drug-induced-hybrid-electrospun-poly-capro-lactone-cell-derived-extracellular-matrix-scaffold-for-liver-tissue-engineering
#20
Rhiannon Grant, David C Hay, Anthony Callanan
Liver transplant is the only treatment option for patients with end-stage liver failure, however, there are too few donor livers available for transplant. Whole organ tissue engineering presents a potential solution to the problem of rapidly escalating donor liver shortages worldwide. A major challenge for liver tissue engineers is the creation of a hepatocyte microenvironment; a niche in which liver cells can survive and function optimally. While polymers and decellularized tissues pose an attractive option for scaffold manufacturing, neither alone has thus far proved sufficient...
May 3, 2017: Tissue Engineering. Part A
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