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histone deacetylase diabetes

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https://www.readbyqxmd.com/read/29142410/methanolic-extract-of-costus-pictus-d-don-induces-cytotoxicity-in-liver-hepatocellular-carcinoma-cells-mediated-by-histone-deacetylase-inhibition
#1
P V Neethu, K Suthindhiran, M A Jayasri
Background: Leaves of Costus pictus D. Don, (insulin plant) are used as dietary supplement for the treatment of diabetes. Objective: The antidiabetic activity of this plant is well documented, but its activity on different cell types and mechanism remains unknown. Thus, the present study evaluates the cytotoxicity of C. pictus methanolic extract (CPME) against various cancer and normal cells. Materials and Methods: Dried leaves of C. pictus were extracted using methanol and were subjected to histone deacetylase (HDAC) inhibition and toxicity studies...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29132743/nuclear-sirtuins-and-inflammatory-signaling-pathways
#2
REVIEW
Keila Lopes Mendes, Deborah de Farias Lelis, Sérgio Henrique Sousa Santos
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms...
November 7, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29115461/histone-deacetylase-inhibition-of-cardiac-autophagy-in-rats-on-a-high%C3%A2-fat-diet-with-low%C3%A2-dose-streptozotocin-induced-type-2-diabetes-mellitus
#3
Ting-I Lee, Kuan-Jen Bai, Yao-Chang Chen, Ting-Wei Lee, Cheng-Chih Chung, Wen-Chih Tsai, Shin-Yi Tsao, Yu-Hsun Kao
Autophagy serves a role in preserving cellular homeostasis. Diabetes mellitus (DM) impairs cardiac autophagy and is associated with an accumulation of cytotoxic proteins that may provoke apoptosis and damage cardiomyocytes. Histone deacetylase (HDAC) inhibitors attenuate cardiac fibrosis and inflammation, and improve cardiomyopathy resulting from DM. However, the effect of HDAC inhibition on autophagy in DM cardiomyopathy has not been investigated. The purpose of the present study was to evaluate whether HDAC inhibition modulates cardiac autophagy and to investigate the potential mechanisms in type 2 DM (T2DM) hearts...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29104258/epigenetic-regulatory-mechanisms-induced-by-resveratrol
#4
REVIEW
Guilherme Felipe Santos Fernandes, Gabriel Dalio Bernardes Silva, Aline Renata Pavan, Diego Eidy Chiba, Chung Man Chin, Jean Leandro Dos Santos
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1)...
November 1, 2017: Nutrients
https://www.readbyqxmd.com/read/29049850/-epigenetic-control-of-early-neurodegenerative-events-in-diabetic-retinopathy-by-the-histone-deacetylase-sirt6
#5
María A Zorrilla-Zubilete, Ada Yeste, Francisco J Quintana, Debra Toiber, Raul Mostoslavsky, Dafne M Silberman
Diabetic retinopathy (DR) is one of the common complications associated with diabetes mellitus (DM) and the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Moreover, glucose-induced neuron and glial cell damage may occur shortly after the onset of diabetes which makes the disease hard to diagnose at early stages. SIRT6, a NAD-dependent sirtuin deacylase, modulates aging, energy metabolism and neurodegeneration...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29042441/transcription-factor-19-interacts-with-histone-3-lysine-4-trimethylation-and-controls-gluconeogenesis-via-the-nucleosome-remodeling-deacetylase-complex
#6
Sabyasachi Sen, Sulagna Sanyal, Dushyant Kumar Srivastava, Dipak Dasgupta, Siddhartha Roy, Chandrima Das
Transcription Factor 19 (TCF19) has been reported as type 1 diabetes associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbours both a plant homeodomain (PHD) and a forkhead-associated domain (FHA) implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation (H3K4Me3) through its PHD finger...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29030662/oral-histone-deacetylase-inhibitor-synergises-with-t-cell-targeted-immunotherapy-to-preserve-beta-cell-metabolic-function-and-induce-stable-remission-of-new-onset-autoimmune-diabetes-in-nod-mice
#7
Alix Besançon, Tania Goncalves, Fabrice Valette, Mattias S Dahllöf, Thomas Mandrup-Poulsen, Lucienne Chatenoud, Sylvaine You
AIM/HYPOTHESIS: Combination therapy targeting the major actors involved in the immune-mediated destruction of pancreatic beta cells appears to be an indispensable approach to treat type 1 diabetes effectively. We hypothesised that the combination of an orally active pan-histone deacetylase inhibitor (HDACi: givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy to treat ongoing autoimmunity. METHODS: NOD mice transgenic for the human CD3ε (also known as CD3E) chain (NOD-huCD3ε) were treated for recent-onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3 antibodies (otelixizumab, 50 μg/day, 5 days, i...
October 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/28966044/hdac6-suppresses-age-dependent-ectopic-fat-accumulation-by-maintaining-the-proteostasis-of-plin2-in-drosophila
#8
Yan Yan, Hao Wang, Minling Hu, Lifen Jiang, Yang Wang, Pingsheng Liu, Xuehong Liang, Jiyong Liu, Changqing Li, Anya Lindström-Battle, Sin Man Lam, Guanghou Shui, Wu-Min Deng, Renjie Jiao
Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28928236/histone-deacetylase-inhibition-ameliorates-hypertension-and-hyperglycemia-in-a-model-of-cushing-s-syndrome
#9
Hae-Ahm Lee, Seol-Hee Kang, Mina Kim, Eunjo Lee, Hyun-Min Cho, Eun-Kyung Moon, Inkyeom Kim
Cushing's syndrome (CS) caused by hypercortisolism is occasionally accompanied by metabolic disorders such as hypertension, diabetes mellitus (DM), dyslipidemia and central obesity. Thus, morbidity and mortality, observed in cardiovascular disease, are elevated in patients with CS. We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS. To establish an animal model of hypercortisolism, Sprague-Dawley rats were infused with adrenocorticotropic hormone (ACTH, 40 ng/day) or dexamethasone (Dex, 10 μg/day) via osmotic minipumps for 4 weeks...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28886276/systems-approach-to-the-pharmacological-actions-of-hdac-inhibitors-reveals-ep300-activities-and-convergent-mechanisms-of-regulation-in-diabetes
#10
Haloom Rafehi, Antony Kaspi, Mark Ziemann, Jun Okabe, Tom C Karagiannis, Assam El-Osta
Given the skyrocketing costs to develop new drugs, repositioning of approved drugs, such as histone deacetylase (HDAC) inhibitors, may be a promising strategy to develop novel therapies. However, a gap exists in the understanding and advancement of these agents to meaningful translation for which new indications may emerge. To address this, we performed systems-level analyses of 33 independent HDAC inhibitor microarray studies. Based on network analysis, we identified enrichment for pathways implicated in metabolic syndrome and diabetes (insulin receptor signaling, lipid metabolism, immunity and trafficking)...
September 8, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28886131/histone-deacetylase-regulates-insulin-signaling-via-two-pathways-in-pancreatic-%C3%AE-cells
#11
Yukina Kawada, Shun-Ichiro Asahara, Yumiko Sugiura, Ayaka Sato, Ayuko Furubayashi, Mao Kawamura, Alberto Bartolome, Emi Terashi-Suzuki, Tomoko Takai, Ayumi Kanno, Maki Koyanagi-Kimura, Tomokazu Matsuda, Naoko Hashimoto, Yoshiaki Kido
Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic β cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic β cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#12
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28860191/isoform-selective-inhibitor-of-histone-deacetylase-3-hdac3-limits-pancreatic-islet-infiltration-and-protects-female-nonobese-diabetic-mice-from-diabetes
#13
Ercument Dirice, Raymond W S Ng, Rachael Martinez, Jiang Hu, Florence F Wagner, Edward B Holson, Bridget K Wagner, Rohit N Kulkarni
Preservation of insulin-secreting β-cells is an important goal for therapies aimed at restoring normoglycemia in patients with diabetes. One approach, the inhibition of histone deacetylases (HDACs), has been reported to suppress pancreatic islet inflammation and β-cell apoptosis in vitro In this report, we demonstrate the efficacy of HDAC inhibitors (HDACi) in vivo We show that daily administration of BRD3308, an isoform-selective HDAC3 inhibitor, for 2 weeks to female nonobese diabetic (NOD) mice, beginning at 3 weeks of age, followed by twice-weekly injections until age 25 weeks, protects the animals from diabetes...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28843433/hdac-inhibitors-a-new-promising-drug-class-in-anti-aging-research
#14
REVIEW
Elena G Pasyukova, Alexander M Vaiserman
In the last years, epigenetic regulation of gene expression is regarded as an important factor involved in a broad spectrum of aging-associated processes including loss of physical activity, frailty and genomic instability, and in development of various pathological conditions such as atherosclerosis, type 2 diabetes, cancer, immune deficits and neurodegenerative diseases. Accordingly, inhibitors of the members of superfamilies of histone deacetylases (HDACs) have been proposed, among other drugs targeting epigenetic pathways, as a promising type of therapeutics that is able to combat aging and its manifestations...
August 24, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28822994/glucagon-like-peptide-1-receptor-agonist-stimulates-mitochondrial-bioenergetics-in-human-adipocytes
#15
Joanna Góralska, Agnieszka Śliwa, Anna Gruca, Urszula Raźny, Monika Chojnacka, Anna Polus, Bogdan Solnica, Małgorzata Malczewska-Malec
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28751803/cape-increases-the-expression-of-sod3-through-epigenetics-in-human-retinal-endothelial-cells
#16
Atsuko Ohashi, Hiroyuki Yasuda, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD or SOD3), which catalyzes the dismutation of superoxide anions into hydrogen peroxide, plays a key role in vascular protection against reactive oxygen species (ROS). The excess generation of ROS is closely involved in the pathogenesis of diabetic retinopathy (DR); therefore, the maintenance of SOD3 expression at high levels is important for the prevention of DR. In the present study, we showed that caffeic acid phenethyl ester (CAPE) increased the expression of SOD3 through the acetylation of histone within the SOD3 promoter region in human retinal endothelial cells (HRECs)...
July 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28733598/role-of-hdac9-foxo1-axis-in-the-transcriptional-program-associated-with-hepatic-gluconeogenesis
#17
Jizheng Chen, Zhilei Zhang, Ning Wang, Min Guo, Xiumei Chi, Yu Pan, Jing Jiang, Junqi Niu, Sulaiman Ksimu, John Zhong Li, Xinwen Chen, Qian Wang
Histone deacetylase 9 (HDAC9) regulates hepatic gluconeogenesis by deacetylating Forkhead box O 1 (FoxO1). HDAC9 upregulation is involved in hepatitis C virus (HCV)-associated exaggerated gluconeogenesis. Herein, we found in addition to FoxO1, HDAC9 also regulates other gluconeogenic transcription factors, including peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), cyclic AMP-responsive element-binding protein (CREB), and glucocorticoid receptor (GR). Unlike FoxO1, which is regulated by post-translational modification responses to HDAC9, HDAC9 regulates PGC-1α, CREB and GR by altering gene expression...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684291/lysine-demethylase-inhibition-protects-pancreatic-%C3%AE-cells-from-apoptosis-and-improves-%C3%AE-cell-function
#18
Marie Balslev Backe, Jan Legaard Andersson, Karl Bacos, Dan Ploug Christensen, Jakob Bondo Hansen, Jerzy Jòzef Dorosz, Michael Gajhede, Tina Dahlby, Madhusudhan Bysani, Line Hyltoft Kristensen, Charlotte Ling, Lars Olsen, Thomas Mandrup-Poulsen
Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress. Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting a possible role in inflammation-induced β-cell destruction...
July 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28679650/effects-of-microrna-211-on-proliferation-and-apoptosis-of-lens-epithelial-cells-by-targeting-sirt1-gene-in-diabetic-cataract-mice
#19
Kun Zeng, Qi-Gao Feng, Bao-Tao Lin, Da-Hui Ma, Chun-Min Liu
Our study aimed at exploring the effects of miR-211 on the proliferation and apoptosis of lens epithelial cells in diabetic cataract mice by targetting NAD(+)-dependent histone deacetylase sirtulin 1 (SIRT1). Healthy male mice were assigned into normal and diabetic cataract groups. Blood glucose, lens turbidity, and apoptosis were measured. Lens epithelial cells were classified into the normal, blank, negative control (NC), miR-211 mimics, miR-211 inhibitors, siRNA-SIRT1, and miR-211 inhibitors + siRNA-SIRT1 groups...
August 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28650731/combination-treatments-with-luteolin-and-fisetin-enhance-anti-inflammatory-effects-in-high-glucose-treated-thp-1-cells-through-histone-acetyltransferase-histone-deacetylase-regulation
#20
Arang Kim, Jung-Mi Yun
Hyperglycemia leads to diabetes and its diabetic complications. In this study, we investigated the synergistic effects of luteolin and fisetin on proinflammatory cytokine secretion and its underlying epigenetic regulation in human monocytes exposed to hyperglycemic (HG) concentrations. Human monocytic cells (THP-1) were cultured under controlled (14.5 mM mannitol), normoglycemic (5.5 mM glucose), or HG (20 mM glucose) conditions in the absence or presence of the two phytochemicals for 48 h. Whereas HG conditions significantly induced histone acetylation, nuclear factor-kappa B (NF-κB) activation, interleukin 6, and tumor necrosis factor-α release from THP-1 cells; combination treatments with the two phytochemicals (500 nM fisetin, and l μM and 500 nM luteolin) suppressed NF-κB activity and inflammatory cytokine release...
August 2017: Journal of Medicinal Food
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