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histone deacetylase metabolic

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https://www.readbyqxmd.com/read/29689264/disruption-of-epithelial-hdac3-in-intestine-prevents-diet-induced-obesity-in-mice
#1
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/29685968/impact-of-dietary-gut-microbial-metabolites-on-the-epigenome
#2
REVIEW
Clarissa Gerhauser
Within the past decade, epigenetic mechanisms and their modulation by natural products have gained increasing interest. Dietary bioactive compounds from various sources, including green tea, soya, fruit and berries, cruciferous vegetables, whole grain foods, fish and others, have been shown to target enzymes involved in epigenetic gene regulation, including DNA methyltransferases, histone acetyltransferases, deacetylases and demethylases in vitro and in cell culture. Also, many dietary agents were shown to alter miRNA expression...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29675169/bioorthogonal-pro-metabolites-for-profiling-short-chain-fatty-acylation
#3
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
#4
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/29667768/quinazoline-based-hydroxamic-acids-design-synthesis-and-evaluation-of-histone-deacetylase-inhibitory-effects-and-cytotoxicity
#5
Doan Thanh Hieu, Duong Tien Anh, Hai Pham-The, Le-Thi-Thu Huong, Eun Jae Park, Jeong Eun Choi, Jong Soon Kang, Sang-Bae Han, Phan Thi Phuong Dung, Nguyen-Hai Nam
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a-i, 6a-i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g. 4g, 4c, 4g-i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat)...
April 18, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29665787/valproic-acid-sensitizes-metformin-resistant-human-renal-cell-carcinoma-cells-by-upregulating-h3-acetylation-and-emt-reversal
#6
Muyun Wei, Shaowei Mao, Guoliang Lu, Liang Li, Xiaopeng Lan, Zhongxian Huang, Yougen Chen, Miaoqing Zhao, Yueran Zhao, Qinghua Xia
BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear...
April 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29648516/the-phosphodiesterase-4-inhibitor-roflumilast-reverts-proteolysis-in-skeletal-muscle-cells-of-patients-with-copd-cachexia
#7
Esther Barreiro, Ester Puig-Vilanova, Anna Salazar-Degracia, Sergi Pascual-Guardia, Carme Casadevall, Joaquim Gea
Peripheral muscle weakness and mass loss are characteristic features in severe COPD. We hypothesized that the phosphodiesterase-4 inhibitor roflumilast-induced cAMP may ameliorate proteolysis and metabolism in skeletal muscles of COPD patients with severe muscle wasting. In myogenic precursor cells (isolated from muscle biopsies and cultured up to obtain differentiated myotubes) from 10 severe COPD patients and 10 healthy controls, which were treated with 1 microM roflumilast N-oxide (RNO) for three time-cohorts (1h, 6h, and 24h), genes of antioxidant defense and oxidative stress marker, myogenesis and muscle metabolism, proteolysis (tyrosine release assay) and ubiquitin-proteasome system markers, autophagy, and myosin isoforms were analyzed using RT-PCR and immunoblotting...
April 12, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29587668/knockdown-delta-5-desaturase-in-breast-cancer-cells-that-overexpress-cox-2-results-in-inhibition-of-growth-migration-and-invasion-via-a-dihomo-%C3%AE-linolenic-acid-peroxidation-dependent-mechanism
#8
Yi Xu, Xiaoyu Yang, Tao Wang, Liu Yang, Yu-Ying He, Keith Miskimins, Steven Y Qian
BACKGROUND: Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional membrane-bound enzyme that typically metabolizes arachidonic acid (downstream ω-6 fatty acid) to form 2-series of prostaglandins known to be involved in cancer development. Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis. Our lab recently demonstrated that COX-2 can also metabolize dihomo-γ-linolenic acid (DGLA, a precursor of ω-6 arachidonic acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that can inhibit growth and migration of colon and pancreatic cancer cells...
March 27, 2018: BMC Cancer
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/29575742/deregulation-of-secondary-metabolism-in-a-histone-deacetylase-mutant-of-penicillium-chrysogenum
#10
Fernando Guzman-Chavez, Oleksandr Salo, Marta Samol, Marco Ries, Jeroen Kuipers, Roel A L Bovenberg, Rob J Vreeken, Arnold J M Driessen
The Pc21 g14570 gene of Penicillium chrysogenum encodes an ortholog of a class 2 histone deacetylase termed HdaA which may play a role in epigenetic regulation of secondary metabolism. Deletion of the hdaA gene induces a significant pleiotropic effect on the expression of a set of polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS)-encoding genes. The deletion mutant exhibits a decreased conidial pigmentation that is related to a reduced expression of the PKS gene Pc21 g16000 (pks17) responsible for the production of the pigment precursor naphtha-γ-pyrone...
March 24, 2018: MicrobiologyOpen
https://www.readbyqxmd.com/read/29575704/essential-role-of-rpd3-dependent-lysine-modification-in-the-growth-development-and-virulence-of-beauveria-bassiana
#11
Qing Cai, Zhi-Kang Wang, Wei Shao, Sheng-Hua Ying, Ming-Guang Feng
Rpd3 is a class I histone deacetylase that reverses lysine acetylation thus influencing cellular processes and functions. However, its role in fungal insect pathogens has not been explored yet. Here we show that Rpd3-dependent lysine modification and gene expression orchestrate growth, conidiation and virulence in Beauveria bassiana. Deletion of Rpd3 resulted in severe growth defects on various carbon/nitrogen sources, 97% reduction in conidiation capacity and drastic attenuation in virulence. These phenotypes concurred with differential expression of 1479 proteins and hyperacetylation or hypoacetylation of 2227 lysine residues on 1134 proteins...
March 24, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29567326/lysine-deacetylases-and-regulated-glycolysis-in-macrophages
#12
REVIEW
Melanie R Shakespear, Abishek Iyer, Catherine Youting Cheng, Kaustav Das Gupta, Amit Singhal, David P Fairlie, Matthew J Sweet
Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes...
March 19, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29535637/the-role-of-sirt6-in-obesity-and-diabetes
#13
REVIEW
Jiangying Kuang, Lei Chen, Qin Tang, Jinhang Zhang, Yanping Li, Jinhan He
Sirt6 is one of the sirtuin family members, a kind of NAD+-dependent histone deacetylase and ADP-ribose transferase enzyme. It has an important role in physiological and pathological processes, regulating aging, cancer, obesity, insulin resistance, inflammation, and energy metabolism. Recent studies have suggested that reduced Sirt6 action is related to obesity and diabetes. Aging and overnutrition, two major risk factors for obesity and diabetes, lead to decreased Sirt6 level and function, which results in abnormal glucose and lipid metabolism...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29520020/rapid-and-transient-oxygen-consumption-increase-following-acute-hdac-kdac-inhibition-in-drosophila-tissue
#14
Lore Becker, Melanie Schmitt Nogueira, Caroline Klima, Martin Hrabe de Angelis, Shahaf Peleg
Epigenetic deregulation, such as the reduction of histone acetylation levels, is thought to be causally linked to various maladies associated with aging. Consequently, histone deacetylase inhibitors are suggested to serve as epigenetic therapy by increasing histone acetylation. However, previous work suggests that many non-histone proteins, including metabolic enzymes, are also acetylated and that post transitional modifications may impact their activity. Furthermore, deacetylase inhibitors were recently shown to impact the acetylation of a variety of proteins...
March 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29515203/natural-polyphenols-as-sirtuin-6-modulators
#15
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
#16
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 Npc1nmf164 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
#17
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...
February 21, 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/29476161/directed-evolution-of-sirt6-for-improved-deacylation-and-glucose-homeostasis-maintenance
#18
Or Gertman, Dotan Omer, Adi Hendler, Daniel Stein, Lior Onn, Yana Khukhin, Miguel Portillo, Raz Zarivach, Haim Y Cohen, Debra Toiber, Amir Aharoni
Mammalian SIRT6 is a well-studied histone deacetylase that was recently shown to exhibit high protein deacylation activity enabling the removal of long chain fatty acyl groups from proteins. SIRT6 was shown to play key roles in cellular homeostasis by regulating a variety of cellular processes including DNA repair and glucose metabolism. However, the link between SIRT6 enzymatic activities and its cellular functions is not clear. Here, we utilized a directed enzyme evolution approach to generate SIRT6 mutants with improved deacylation activity...
February 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#19
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29446717/activators-of-sirtuin-1-and-their-involvement-in-cardioprotection
#20
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
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