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histone deacetylase metabolic disease

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https://www.readbyqxmd.com/read/29896416/sirt3-protects-rotenone-induced-injury-in-sh-sy5y-cells-by-promoting-autophagy-through-the-lkb1-ampk-mtor-pathway
#1
Meng Zhang, Yong-Ning Deng, Jing-Yi Zhang, Jie Liu, Yan-Bo Li, Hua Su, Qiu-Min Qu
SIRT3 is a class III histone deacetylase that modulates energy metabolism, genomic stability and stress resistance. It has been implicated as a potential therapeutic target in a variety of neurodegenerative diseases, including Parkinson's disease (PD). Our previous study demonstrates that SIRT3 had a neuroprotective effect on a rotenone-induced PD cell model, however, the exact mechanism is unknown. In this study, we investigated the underlying mechanism. We established a SIRT3 stable overexpression cell line using lentivirus infection in SH-SY5Y cells...
April 2018: Aging and Disease
https://www.readbyqxmd.com/read/29847446/nutriepigenetics-and-cardiovascular-disease
#2
Anastasia Z Kalea, Konstantinos Drosatos, Jessica L Buxton
PURPOSE OF REVIEW: We present a current perspective of epigenetic alterations that can lead to cardiovascular disease (CVD) and the potential of dietary factors to counteract their actions. In addition, we discuss the challenges and opportunities of dietary treatments as epigenetic modifiers for disease prevention and therapy. RECENT FINDINGS: Recent epigenome-wide association studies along with candidate gene approaches and functional studies in cell culture and animal models have delineated mechanisms through which nutrients, food compounds and dietary patterns may affect the epigenome...
July 2018: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29802856/evidence-supporting-a-mechanistic-role-of-sirtuins-in-mood-and-metabolic-disorders
#3
REVIEW
Asem Alageel, Julia Tomasi, Claudia Tersigni, Elisa Brietzke, Hannah Zuckerman, Mehala Subramaniapillai, Yena Lee, Michelle Iacobucci, Joshua D Rosenblat, Rodrigo B Mansur, Roger S McIntyre
Sirtuins are NAD+ -dependent histone deacetylases that play essential roles in cell survival, energy metabolism, inflammation, and aging; therefore, sirtuins are potential therapeutic targets in the treatment of type 2 diabetes, cancer, inflammatory and metabolic disorders, and neurodegenerative diseases. Available evidence provides the basis for hypothesizing that sirtuins 1, 2, and 3 (SIRT1, SIRT2, and SIRT3) may have a mechanistic role subserving mood disorders (i.e. downregulation) and associated co-morbidity (e...
May 23, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29792136/zinc-dependent-histone-deacetylase-inhibitors-in-cancer-therapeutics-recent-update
#4
Panagiotis I Georgianos, Maria Divani, Theodoros Eleftheriadis, Peter R Mertens, Vassilios Liakopoulos
BACKGROUND: Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD...
May 23, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29708970/histone-acetyltransferase-tgf-1-regulates-trichoderma-atroviride-secondary-metabolism-and-mycoparasitism
#5
Elida Yazmín Gómez-Rodríguez, Edith Elena Uresti-Rivera, Olga Araceli Patrón-Soberano, María Auxiliadora Islas-Osuna, Alberto Flores-Martínez, Lina Riego-Ruiz, María Teresa Rosales-Saavedra, Sergio Casas-Flores
Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1), a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani...
2018: PloS One
https://www.readbyqxmd.com/read/29689264/disruption-of-epithelial-hdac3-in-intestine-prevents-diet-induced-obesity-in-mice
#6
Jordan Whitt, Vivienne Woo, Patrick Lee, Jessica Moncivaiz, Yael Haberman, Lee Denson, Patrick Tso, Theresa Alenghat
BACKGROUND & AIMS: Intestinal microbiota modulate metabolism and associate closely with epithelial cells in the intestine. In intestinal epithelial cells (IECs), histone deacetylase 3 (HDAC3) integrates microbiota-derived signals to control intestinal homeostasis. We investigated whether HDAC3 in IECs regulates metabolism and the development of obesity in mice. METHODS: Adult C57BL/6 (control) mice and mice with constitutive or inducible IEC-specific disruption of Hdac3 (HDAC3ΔIEC mice) were placed on a standard chow or high-fat diet (HFD, 60% kcal from fat)...
April 21, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29675169/bioorthogonal-pro-metabolites-for-profiling-short-chain-fatty-acylation
#7
Wilson R Sinclair, Jonathan H Shrimp, Thomas T Zengeya, Rhushikesh A Kulkarni, Julie M Garlick, Hans Luecke, Andrew J Worth, Ian A Blair, Nathaniel W Snyder, Jordan L Meier
Short chain fatty acids (SCFAs) play a central role in health and disease. One function of these signaling molecules is to serve as precursors for short chain fatty acylation, a class of metabolically-derived posttranslational modifications (PTMs) that are established by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Via this mechanism, short chain fatty acylation serves as an integrated reporter of metabolism as well as KAT and KDAC activity, and has the potential to illuminate the role of these processes in disease...
February 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29671355/hdac-inhibitors-a-2013-2017-patent-survey
#8
Micaela Faria Freitas, Muriel Cuendet, Philippe Bertrand
Zinc-dependent histone deacetylases (HDAC) inhibitors represent an important class of biologically active compounds with four of them approved by the FDA. A wide range of molecules has been reported for applications in several human diseases.Area covered: This review covers recent efforts in the synthesis and applications of HDAC inhibitors from 2013-2017.Expert opinion: HDAC inhibitors represent an important class of biologically active compounds for single or combination therapies. The current synthetic methodologies are oriented towards selective HDAC isoforms to achieve better therapeutic effects...
April 19, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29579087/class-i-hdac-inhibition-is-a-novel-pathway-for-regulating-astrocytic-apoe-secretion
#9
Erica Dresselhaus, James M Duerr, Fabien Vincent, Emily K Sylvain, Mercedes Beyna, Lorraine F Lanyon, Erik LaChapelle, Martin Pettersson, Kelly R Bales, Gayathri Ramaswamy
Despite the important role of apolipoprotein E (apoE) secretion from astrocytes in brain lipid metabolism and the strong association of apoE4, one of the human apoE isoforms, with sporadic and late onset forms of Alzheimer's disease (AD) little is known about the regulation of astrocytic apoE. Utilizing annotated chemical libraries and a phenotypic screening strategy that measured apoE secretion from a human astrocytoma cell line, inhibition of pan class I histone deacetylases (HDACs) was identified as a mechanism to increase apoE secretion...
2018: PloS One
https://www.readbyqxmd.com/read/29515203/natural-polyphenols-as-sirtuin-6-modulators
#10
Minna Rahnasto-Rilla, Jonna Tyni, Marjo Huovinen, Elina Jarho, Tomasz Kulikowicz, Sarangan Ravichandran, Vilhelm A Bohr, Luigi Ferrucci, Maija Lahtela-Kakkonen, Ruin Moaddel
Flavonoids are polyphenolic secondary metabolites synthesized by plants and fungus with various pharmacological effects. Due to their plethora of biological activities, they have been studied extensively in drug development. They have been shown to modulate the activity of a NAD+ -dependent histone deacetylase, SIRT6. Because SIRT6 has been implicated in longevity, metabolism, DNA-repair, and inflammatory response reduction, it is an interesting target in inflammatory and metabolic diseases as well as in cancer...
March 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29497113/tolerance-of-chronic-hdaci-treatment-for-neurological-visceral-and-lung-niemann-pick-type-c-disease-in-mice
#11
Md Suhail Alam, Bruce Cooper, Joseph D Farris, Kasturi Haldar
Histone deacetylase (HDAC) inhibitors are of significant interest as drugs. However, their use to treat neurological disorders has raised concern because HDACs are required for brain function. We have previously shown that a triple combination formulation (TCF) of the pan HDACi vorinostat (Vo), 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and polyethylene glycol (PEG) 400 improves pharmacokinetic exposure and entry of Vo into the brain. TCF treatment significantly delayed both neurodegeneration and death in the Npc1 nmf164 murine model of Niemann-Pick Type C (NPC) disease...
March 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29476819/role-of-sirtuin1-p53-regulatory-axis-in-aging-cancer-and-cellular-reprogramming
#12
REVIEW
Agnes L C Ong, Thamil Selvee Ramasamy
Regulatory role of Sirtuin 1 (SIRT1), one of the most extensively studied members of its kind in histone deacetylase family in governing multiple cellular fates, is predominantly linked to p53 activity. SIRT1 deacetylates p53 in a NAD+-dependent manner to inhibit transcription activity of p53, in turn modulate pathways that are implicated in regulation of tissue homoeostasis and many disease states. In this review, we discuss the role of SIRT1-p53 pathway and its regulatory axis in the cellular events which are implicated in cellular aging, cancer and reprogramming...
May 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/29446717/activators-of-sirtuin-1-and-their-involvement-in-cardioprotection
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
January 15, 2018: 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
#20
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
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