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https://www.readbyqxmd.com/read/27935866/hic1-hypermethylated-in-cancer-1-sumoylation-is-dispensable-for-dna-repair-but-is-essential-for-the-apoptotic-dna-damage-response-ddr-to-irreparable-dna-double-strand-breaks-dsbs
#1
Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince
The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935857/potentiation-of-the-anticancer-effects-of-everolimus-using-a-dual-mtorc1-2-inhibitor-in-hepatocellular-carcinoma-cells
#2
Jong-Ok Kim, Kee-Hwan Kim, In Sang Song, Kwang-Sik Cheon, Ok-Hee Kim, Sang Chul Lee, Sang Kuon Lee, Say-June Kim
There is lots of evidence to support the critical involvement of mTOR signaling in the carcinogenesis of hepatocellular carcinoma (HCC). However, it has not been determined how the roles of individual mTORC1 and mTORC2 inhibitors played in the HCC therapeutics. We thus compared the effects of everolimus, Ku0063794, and a combination of the two therapies on HCC cells, using various in vitro studies (HepG2, Hep3B, and Huh7 cells), ex vivo culturing of HCC tissues obtained from patients, and the in vivo mouse xenograft model of HCC cells...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27930969/rhapontin-ameliorates-colonic-epithelial-dysfunction-in-experimental-colitis-through-sirt1-signaling
#3
Wencheng Wei, Lei Wang, Kai Zhou, Haifeng Xie, Mian Zhang, Chaofeng Zhang
Rhapontin (3, 3', 5-trihydroxy-4'-methoxystilbene-3-O-glucoside) has anti-thrombotic, anti-allergic and anti-diabetic activities. This study aimed to assess the protective effects of rhapontin on intestinal damage in vivo and in vitro. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of rhapontin (100mg/kg) significantly attenuated colonic pathological damage and remarkably inhibited infiltration by inflammatory cells, myeloperoxidase (MPO) activity, NLRP3 inflammasome activation and SIRT1 expression in the colon...
December 5, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27925207/acetate-metabolism-does-not-reflect-astrocytic-activity-contributes-directly-to-gaba-synthesis-and-is-increased-by-silent-information-regulator-1-activation
#4
Benjamin D Rowlands, Matthias Klugmann, Caroline D Rae
[(13) C]acetate is known to label metabolites preferentially in astrocytes rather than neurons and it has consequently been used as a marker for astrocytic activity. Recent discoveries suggest that control of acetate metabolism and its contributions to the synthesis of metabolites in brain is not as simple as first thought. Here, using a Guinea pig brain cortical tissue slice model metabolizing [1-(13) C]D-glucose and [1,2-(13) C]acetate, we investigated control of acetate metabolism and the degree to which it reflects astrocytic activity...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27925196/sirt1-sirt3-axis-regulates-cellular-response-to-oxidative-stress-and-etoposide
#5
Ilaria Carnevale, Laura Pellegrini, Patrizia D'Aquila, Serena Saladini, Emanuela Lococo, Lucia Polletta, Enza Vernucci, Eleonora Foglio, Stefano Coppola, Luigi Sansone, Giuseppe Passarino, Dina Bellizzi, Matteo A Russo, Massimo Fini, Marco Tafani
Sirtuins are conserved NAD+-dependent deacylases. SIRT1 is a nuclear and cytoplasmic sirtuin involved in the control of histones a transcription factors function. SIRT3 is a mitochondrial protein, which regulates mitochondrial function. Although both SIRT1 and SIRT3 have been implicated in resistance to cellular stress, the link between these two sirtuins has not been studied so far. Here we aimed to unravel: i) the role of SIRT1-SIRT3 axis for cellular response to oxidative stress and DNA damage; ii) how mammalian cells modulate such SIRT1-SIRT3 axis and which mechanisms are involved...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924068/protein-inhibitor-of-activated-stat-4-pias4-regulates-liver-fibrosis-through-modulating-smad3-activity
#6
Huihui Xu, Zhiwen Fan, Wenfang Tian, Yong Xu
Excessive fibrogenesis disrupts normal liver structure, impairs liver function, and precipitates the development of cirrhosis, an irreversible end-stage liver disease. A host of factors including nutrition surplus contribute to liver fibrosis but the underlying mechanism is not fully understood. In the present study, we investigated the involvement of protein inhibitor for activated stat 4 (PIAS4) in liver fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH). We report that PIAS4 silencing using short hairpin RNA (shRNA) attenuated high-fat high-carbohydrate (HFHC) diet induced liver fibrosis in mice...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27923775/the-plasticizer-bbp-selectively-inhibits-epigenetic-regulator-sirtuin-during-differentiation-of-c3h10t1-2-stem-cell-line
#7
Jian Zhang, Mahua Choudhury
Exposure to environmental chemicals can perturb an individual's metabolic set point, especially during critical periods of development, and as a result increase his or her propensity towards obesity that is manifested later in life and possibly in successive generations. We hypothesized that benzyl butyl phthalate (BBP), a widespread endocrine disruptor, may impair one important epigenetic regulator, sirtuin, in mesenchymal stem cells and induce adipogenesis. Our results showed that gene expression of two well-known adipogenic markers, aP2 and PPARγ, were significantly increased from day 2 to day 8 under 50μM BBP exposure when compared to control in C3H10T1/2 stem cells (p<0...
December 3, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27917437/nicotine-plus-a-high-fat-diet-triggers-cardiomyocyte-apoptosis
#8
Indrani Sinha-Hikim, Theodore C Friedman, Mark Falz, Victor Chalfant, Mohammad Kamrul Hasan, Jorge Espinoza-Derout, Desean L Lee, Carl Sims, Peter Tran, Sushil K Mahata, Amiya P Sinha-Hikim
Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0...
December 5, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27916733/sirt1-regulates-lipopolysaccharide-induced-cd40-expression-in-renal-medullary-collecting-duct-cells-by-suppressing-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#9
Qin-Qin Lin, Yuan-Wen Geng, Zhong-Wei Jiang, Zhen-Jun Tian
AIMS: Recent evidence indicates that sirtuin1 (SIRT1), a NAD(+)-dependent deacetylase, exerts a protective effect against inflammatory kidney injury by suppressing pro-inflammatory cytokines production. The co-stimulatory molecule, CD40, is expressed in a variety of inflammatory diseases in the kidney. Here, we aimed to investigate the potential effect of SIRT1 on CD40 expression induced by lipopolysaccharide (LPS) and to disclose the underlying mechanisms in renal inner medullary collecting duct (IMCD) cells...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27916687/a-unique-combination-of-micronutrients-rejuvenates-cognitive-performance-in-aged-mice
#10
Sam D Perez, Kristy Du, Catarina Rendeiro, Lin Wang, Qian Wu, Stanislav S Rubakhin, Rema Vazhappilly, Jeffrey H Baxter, Jonathan V Sweedler, Justin S Rhodes
It is widely believed that diet can influence the onset and severity of cognitive aging, but the optimal combination of micronutrients and molecular and cellular mechanisms remain elusive. The purpose of this study was to compare the effects of eight distinct diets, consisting of various concentrations of selected micronutrients, on learning and memory as well as markers of neuronal plasticity, and metabolic and neuro-immune status of the aged hippocampus. Eighteen-month-old male and female C57BL/6J mice were fed the diets for 16 weeks, followed by learning and memory trials on the active avoidance task...
December 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27916095/-decreased-sirt1-expression-is-related-to-bronchopulmonary-dysplasia-in-premature-infants-after-oxygen-exposure
#11
Fengmei Tan, Wenbin Dong, Xiaoping Lei, Xingling Liu, Qingping Li, Lan Kang, Shuai Zhao, Chan Zhang
Objective To observe silent information regulator 1 (SIRT1) expression in the peripheral blood mononuclear cells (PBMCs), and explore the relationship between SIRT1 expression and bronchopulmonary dysplasia (BPD) in premature infants after oxygen exposure. Methods Premature infants with 28 to 30 weeks' gestation were divided into three groups according to the fraction of inspiration O2 (FiO2): low-oxygen group with FiO2<30%, medium-oxygen group with FiO2 being 30%~40%, and high-oxygen group with FiO2≥40%; other premature infants with 28 to 30 weeks' gestation and without inspiration O2 served as a control group...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27914941/therapeutic-role-of-sirtuins-in-neurodegenerative-disease-and-their-modulation-by-polyphenols
#12
REVIEW
Marjan Ajami, Hamidreza Pazoki-Toroudi, Hamed Amani, Seyed Fazel Nabavi, Nady Braidy, Rosa Anna Vacca, Atanas Georgiev Atanasov, Andrei Mocan, Seyed Mohammad Nabavi
Searching for effective therapeutic agents‏‎ to ‎‏prevent‏ ‏neurodegeneration ‎is a challenging task due ‎to ‎the growing list of neurodegenerative disorders associated with a multitude of inter-related pathways.‎ The induction and inhibition of several different signaling pathways has been shown to slow down and/or attenuate ‎neurodegeneration and decline in cognition and locomotor function. Among these signaling pathways, a new class of enzymes known as sirtuins or silent information regulators of gene transcription has been shown to play important regulatory roles in the ageing process...
November 30, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27911441/sirt1-protects-the-heart-from-er-stress-induced-cell-death-through-eif2%C3%AE-deacetylation
#13
Alexandre Prola, Julie Pires Da Silva, Arnaud Guilbert, Lola Lecru, Jérôme Piquereau, Maxance Ribeiro, Philippe Mateo, Mélanie Gressette, Dominique Fortin, Céline Boursier, Cindy Gallerne, Anaïs Caillard, Jane-Lise Samuel, Hélène François, David A Sinclair, Pierre Eid, Renée Ventura-Clapier, Anne Garnier, Christophe Lemaire
Over the past decade, endoplasmic reticulum (ER) stress has emerged as an important mechanism involved in the pathogenesis of cardiovascular diseases including heart failure. Cardiac therapy based on ER stress modulation is viewed as a promising avenue toward effective therapies for the diseased heart. Here, we tested whether sirtuin-1 (SIRT1), a NAD(+)-dependent deacetylase, participates in modulating ER stress response in the heart. Using cardiomyocytes and adult-inducible SIRT1 knockout mice, we demonstrate that SIRT1 inhibition or deficiency increases ER stress-induced cardiac injury, whereas activation of SIRT1 by the SIRT1-activating compound STAC-3 is protective...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27910878/lipids-celastrol-protects-against-fatty-liver-through-sirt1
#14
Charlotte Ridler
No abstract text is available yet for this article.
December 2, 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27909699/aav-mediated-sirt1-overexpression-in-skeletal-muscle-activates-oxidative-capacity-but-does-not-prevent-insulin-resistance
#15
Laia Vilà, Carles Roca, Ivet Elias, Alba Casellas, Ricardo Lage, Sylvie Franckhauser, Fatima Bosch
Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1) specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27908642/negative-regulation-of-nlrp3-inflammasome-by-sirt1-in-vascular-endothelial-cells
#16
Yanxiang Li, Xiaofeng Yang, Yanhao He, Weirong Wang, Jiye Zhang, Wei Zhang, Ting Jing, Bo Wang, Rong Lin
NLRP3 inflammasome not only functions as a critical effector in innate immunity, but also triggers the production of proinflammatory cytokines involved in inflammation-associated diseases. Sirtuin 1 (SIRT1) plays an important role in the regulation of cellular inflammation. However, whether the activation of NLRP3 inflammasome is regulated by SIRT1 remains unknown. In this study, we investigated the regulatory effect of SIRT1 on NLRP3 inflammasome and the underlying mechanisms. We found that lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced the activation of NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs)...
November 4, 2016: Immunobiology
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
#17
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/27901083/resveratrol-serves-as-a-protein-substrate-interaction-stabilizer-in-human-sirt1-activation
#18
Xuben Hou, David Rooklin, Hao Fang, Yingkai Zhang
Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD(+)-dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27898652/natural-mineral-rich-water-ingestion-by-ovariectomized-fructose-fed-sprague-dawley-rats-effects-on-sirtuin-1-and-glucocorticoid-signaling-pathways
#19
Jugal Kishore Das, Milton Severo, Cidália Dionísio Pereira, Emília Patrício, José Magalhães, Rosário Monteiro, Delminda Neves, Maria João Martins
OBJECTIVE: Prevention or induction of metabolic disorders and obesity depend on estrogen signaling and/or exogenous factors, such as mineral content in diet. The protective effects of a Portuguese natural mineral-rich water against the induction of metabolic syndrome in fructose-fed male Sprague-Dawley rats have been reported. The present study was designed to assess the impact of this mineral-rich water on fructose-fed estrogen-deficient female Sprague-Dawley rats. METHODS: Ovariectomized rats had access to tap (TWO) or mineral-rich (MWO) waters, with and without 10% fructose (10-wk treatment)...
November 28, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27897112/harnessing-the-power-of-sirt1-and-non-coding-rnas-in-vascular-disease
#20
Kenneth Maiese
Noncommunicable diseases (NCDs) contribute to a significant amount of disability and death in the world. Of these disorders, vascular disease is ranked high, falls within the five leading causes of death, and impacts multiple other disease entities such as those of the cardiac system, nervous system, and metabolic disease. Targeting the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) pathway and the modulation of micro ribonucleic acids (miRNAs) may hold great promise for the development of novel strategies for the treatment of vascular disease since each of these pathways are highly relevant to cardiac and nervous system disorders as well as to metabolic dysfunction...
November 29, 2016: Current Neurovascular Research
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