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SIRT1,HDAC

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https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#1
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#2
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
November 24, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27875274/sirt1-inhibits-ev71-genome-replication-and-rna-translation-by-interfering-viral-polymerase-and-5-utr-rna
#3
Yang Han, Lvyin Wang, Jin Cui, Yu Song, Zhen Luo, Junbo Chen, Ying Xiong, Qi Zhang, Fang Liu, Wenzhe Ho, Yingle Liu, Kailang Wu, Jianguo Wu
Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5'untranslated region (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from nuclear to cytoplasm. More interestingly, activated SIRT1 subsequently binds with EV71 3D protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D, resulting in the attenuation of viral genome replication...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27764514/sirtuins-and-their-interactions-with-transcription-factors-and-poly-adp-ribose-polymerases
#4
H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27725455/identification-of-a-selective-sirt2-inhibitor-and-its-anti-breast-cancer-activity
#5
Asad Ali Shah, Akihiro Ito, Akiko Nakata, Minoru Yoshida
SIRT2 is a member of the human sirtuin family of proteins and possesses nicotinamide adenine dinucleotide (NAD)-dependent lysine deacetylase activity. SIRT2 has been involved in various cellular processes including gene transcription, genome constancy, and the cell cycle. In addition, SIRT2 is deeply implicated in diverse diseases including cancer. In this study, we identified a small molecule inhibitor of SIRT2 with a structure different from known SIRT2 inhibitors by screening from a chemical library. The hit compound showed a high selectivity toward SIRT2 as it only inhibited SIRT2, and not other sirtuins including SIRT1 and SIRT3 or zinc-dependent histone deacetylases (HDACs) including HDAC1 and HDAC6, in vitro...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27714819/short-and-long-term-hindlimb-immobilization-and-reloading-profile-of-epigenetic-events-in-gastrocnemius
#6
Alba Chacon-Cabrera, Joaquim Gea, Esther Barreiro
Skeletal muscle dysfunction and atrophy are characteristic features accompanying chronic conditions. Epigenetic events regulate muscle mass and function maintenance. We hypothesized that the pattern of epigenetic events (muscle-enriched microRNAs and histone acetylation) and acetylation of transcription factors known to signal muscle wasting may differ between early- and late-time points in skeletal muscles of mice exposed to hindlimb immobilization (I) and recovery following I. Body and muscle weights, grip strength, muscle-enriched microRNAs, histone deacetylases (HDACs), acetylation of proteins, histones, and transcription factors (TF), myogenic TF factors, and muscle phenotype were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days, I groups) of hindlimb immobilization, and in those exposed to reloading for different periods of time (1, 3, 7, 15, and 30 days, R groups) following 7-day immobilization...
October 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27535045/high-glucose-induces-reactivation-of-latent-kaposi-s-sarcoma-associated-herpesvirus
#7
Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao
: High prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi's sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno-grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice...
August 17, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27245255/association-between-functional-sirt1-polymorphisms-and-the-clinical-characteristics-of-patients-with-autoimmune-thyroid-disease
#8
Mika Sarumaru, Mikio Watanabe, Naoya Inoue, Yuko Hisamoto, Emi Morita, Yuya Arakawa, Yoh Hidaka, Yoshinori Iwatani
Sirtuin1 (SIRT1) is a Class 3 nicotinamide adenine dinucleotide-dependent histone deacetylase (HDAC) that is thought to be implicated in the protection against autoimmune diseases. However, an association between SIRT1 and autoimmune thyroid disease (AITD) has not been reported. In this study, we selected four single nucleotide polymorphisms (SNPs) in the SIRT1 gene, rs12049646 T/C (termed SNP1), rs12778366 T/C (termed SNP2), rs3758391 T/C (termed SNP3), and rs4746720 T/C (termed SNP4). We genotyped each of these polymorphic sites in 185 patients with Graves' disease (GD), including 76 patients with intractable GD and 57 patients with GD in remission; 151 patients with Hashimoto's disease (HD), including 68 patients with severe HD and 54 patients with mild HD; and 96 healthy volunteers...
August 2016: Autoimmunity
https://www.readbyqxmd.com/read/27124741/expression-of-the-significance-of-silent-information-regulator-type-1-in-angioimmunoblastic-t-cell-lymphoma-is-greater-association-with-tumorigenesis-and-has-strong-implications-for-adverse-prognosis
#9
Yuyue Ren, Yunhe Gu, Wei Wang, Jinghua Wang, Xiaoyun Li, Ying Wang, Haiyan Gao, Xiushuai Dong, Yaoyao Tian
Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2 mm core from 45 AITL patients...
June 17, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27086164/sirt1-is-a-critical-regulator-of-k562-cell-growth-survival-and-differentiation
#10
Mark T Duncan, Teresa A DeLuca, Hsin-Yu Kuo, Minchang Yi, Milan Mrksich, William M Miller
Inhibition of histone deacetylases (HDACi) has emerged as a promising approach in the treatment of many types of cancer, including leukemias. Among the HDACs, Class III HDACs, also known as sirtuins (SIRTs), are unique in that their function is directly related to the cell's metabolic state through their dependency on the co-factor NAD(+). In this study, we examined the relation between SIRTs and the growth, survival, and differentiation of K562 erythroleukemia cells. Using a mass spectrometry approach we previously developed, we show that SIRT expression and deacetylase activity in these cells changes greatly with differentiation state (undifferentiated vs...
May 15, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27010499/ampk-snf1-signaling-regulates-histone-acetylation-impact-on-gene-expression-and-epigenetic-functions
#11
REVIEW
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
AMP-activated protein kinase (AMPK) and its yeast homolog, Snf1, are critical regulators in the maintenance of energy metabolic balance not only stimulating energy production but also inhibiting energy-consuming processes. The AMPK/Snf1 signaling controls energy metabolism by specific phosphorylation of many metabolic enzymes and transcription factors, enhancing or suppressing their functions. The AMPK/Snf1 complexes can be translocated from cytoplasm into nuclei where they are involved in the regulation of transcription...
August 2016: Cellular Signalling
https://www.readbyqxmd.com/read/26940009/class-iii-specific-hdac-inhibitor-tenovin-6-induces-apoptosis-suppresses-migration-and-eliminates-cancer-stem-cells-in-uveal-melanoma
#12
Wei Dai, Jingfeng Zhou, Bei Jin, Jingxuan Pan
Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSCs) of UM. We testified this hypothesis in four lines of UM cells (92.1, Mel 270, Omm 1 and Omm 2.3). Our results showed that inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26918332/solar-simulated-ultraviolet-radiation-induces-global-histone-hypoacetylation-in-human-keratinocytes
#13
Xiaoru Zhang, Thomas Kluz, Lisa Gesumaria, Mary S Matsui, Max Costa, Hong Sun
Ultraviolet radiation (UVR) from sunlight is the primary effector of skin DNA damage. Chromatin remodeling and histone post-translational modification (PTM) are critical factors in repairing DNA damage and maintaining genomic integrity, however, the dynamic changes of histone marks in response to solar UVR are not well characterized. Here we report global changes in histone PTMs induced by solar simulated UVR (ssUVR). A decrease in lysine acetylation of histones H3 and H4, particularly at positions of H3 lysine 9, lysine 56, H4 lysine 5, and lysine 16, was found in human keratinocytes exposed to ssUVR...
2016: PloS One
https://www.readbyqxmd.com/read/26740209/identification-of-new-inhibitors-for-human-sirt1-an-in-silico-approach
#14
Balasundaram Padmanabhan, Manjula Ramu, Shruti Mathur, Sruthi Unni, Saravanamuthu Thiyagarajan
BACKGROUND: Human SIRT1 is a class III histone deacetylase (HDAC) family protein. As the overexpression of hSIRT1 leads to cancer, inhibiting its HDAC function may be a better strategy for the treatment of cancer. Till now, only a few reported inhibitor compounds have reached the stage of animal studies; hence, identifying high efficacy inhibitors of hSIRT1 is essential. OBJECTIVE: The main objective of the study is to obtain a new class of inhibitor compounds of hSIRT1 by the rational structure-based method...
2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/26657080/the-proteomic-profile-of-deleted-in-breast-cancer-1-dbc1-interactions-points-to-a-multifaceted-regulation-of-gene-expression
#15
Sophie S B Giguère, Amanda J Guise, Pierre M Jean Beltran, Preeti M Joshi, Todd M Greco, Olivia L Quach, Jeffery Kong, Ileana M Cristea
Deleted in breast cancer 1 (DBC1) has emerged as an important regulator of multiple cellular processes, ranging from gene expression to cell cycle progression. DBC1 has been linked to tumorigenesis both as an inhibitor of histone deacetylases, HDAC3 and sirtuin 1, and as a transcriptional cofactor for nuclear hormone receptors. However, despite mounting interest in DBC1, relatively little is known about the range of its interacting partners and the scope of its functions. Here, we carried out a functional proteomics-based investigation of DBC1 interactions in two relevant cell types, T cells and kidney cells...
March 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/26530275/sirtuin-inhibitors-ex527-and-agk2-suppress-cell-migration-by-inhibiting-hsf1-protein-stability
#16
Hyun-Woo Kim, Soo-A Kim, Sang-Gun Ahn
The histone deacetylases (HDACs), Sirtuin 1 (Sirt1) and Sirt2, play crucial roles in many biological processes, including cell proliferation, differentiation and apoptosis. HDAC inhibitors have been considered as a potential therapeutic approach for various types of cancers. Here, we demonstrated that the Sirt1 and Sirt2 inhibitors EX527 and AGK2 suppressed cell growth and caused G1 phase arrest by inhibiting the expression of Cdk6 and/or Cdk4. An agar colony formation assay revealed that EX527 and AGK2 decreased colony formation in soft agar...
January 2016: Oncology Reports
https://www.readbyqxmd.com/read/26462881/growth-attenuation-is-associated-with-histone-deacetylase-10-induced-autophagy-in-the-liver
#17
Galit Pinto, Biana Shtaif, Moshe Phillip, Galia Gat-Yablonski
Our previous data suggested that the histone deacetylase (HDAC) SIRT1 is involved in mediating the effect of nutrition on growth. The aim of the present research was to study the mechanism by which additional HDACs may be involved in nutrition-induced linear growth. The in vivo studies were performed in young male Sprague-Dawley rats that were either fed ad libitum (AL) or subjected to 10days of 40% food restriction (RES) and then refed (CU). For in vitro studies, Huh7 hepatoma cells were used. Food restriction led to significant reduction in liver weight, concomitant with increased autophagy (i...
January 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/26459286/epigenetic-based-combinatorial-resveratrol-and-pterostilbene-alters-dna-damage-response-by-affecting-sirt1-and-dnmt-enzyme-expression-including-sirt1-dependent-%C3%AE-h2ax-and-telomerase-regulation-in-triple-negative-breast-cancer
#18
Rishabh Kala, Harsh N Shah, Samantha L Martin, Trygve O Tollefsbol
BACKGROUND: Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses...
October 12, 2015: BMC Cancer
https://www.readbyqxmd.com/read/26405459/post-transcriptional-control-of-the-epigenetic-stem-cell-regulator-plzf-by-sirtuin-and-hdac-deacetylases
#19
Melanie J McConnell, Laetitia Durand, Emma Langley, Lise Coste-Sarguet, Arthur Zelent, Christine Chomienne, Tony Kouzarides, Jonathan D Licht, Fabien Guidez
BACKGROUND: The transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) is critical for the regulation of normal stem cells maintenance by establishing specific epigenetic landscape. We have previously shown that CBP/p300 acetyltransferase induces PLZF acetylation in order to increase its deoxynucleotidic acid (DNA) binding activity and to enhance its epigenetic function (repression of PLZF target genes). However, how PLZF is inactivated is not yet understood. RESULTS: In this study, we demonstrate that PLZF is deacetylated by both histone deacetylase 3 and the NAD+ dependent deacetylase silent mating type information regulation 2 homolog 1 (SIRT1)...
2015: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/26372908/differential-expression-of-hdac-and-hat-genes-in-atrophying-skeletal-muscle
#20
Adam W Beharry, Andrew R Judge
INTRODUCTION: Histone deacetylase (HDAC) proteins, which counter the activity of histone acetyltransferases (HATs), are necessary for normal muscle atrophy in response to several pathophysiological conditions. Despite this, it remains unknown whether a common or unique transcriptional profile of HDAC and HAT genes exist during the progression of muscle atrophy. METHODS: Muscles were harvested from cast immobilized, denervated, or nutrient deprived animals for quantitative reverse transcriptase-polymerase chain reaction analysis of HDAC and HAT gene expression...
December 2015: Muscle & Nerve
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