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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/28228259/sirt1-regulates-dna-methylation-and-differentiation-potential-of-embryonic-stem-cells-by-antagonizing-dnmt3l
#1
Jinbeom Heo, Jisun Lim, Seungun Lee, Jaeho Jeong, Hyunsook Kang, YongHwan Kim, Jeong Wook Kang, Hwan Yeul Yu, Eui Man Jeong, Kyunggon Kim, Magda Kucia, Sabine J Waigel, Wolfgang Zacharias, Yinlu Chen, In-Gyu Kim, Mariusz Z Ratajczak, Dong-Myung Shin
Embryonic stem cell (ESC) abnormalities in genome methylation hamper the utility of their therapeutic derivatives; however, the underlying mechanisms are unknown. Here, we show that the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, Sirt1, selectively prevents abnormal DNA methylation of some developmental genes in murine ESCs by antagonizing Dnmt3l. Transcriptome and DNA methylome analyses demonstrated that Sirt1-null (Sirt1(-/-)) ESCs repress expression of a subset of imprinted and germline genes concomitant with increased DNA methylation of regulatory elements...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28224719/cardiomyocyte-differentiation-promotes-cell-survival-during-nicotinamide-phosphoribosyltransferase-inhibition-through-increased-maintenance-of-cellular-energy-stores
#2
Erin M Kropp, Katarzyna A Broniowska, Matthew Waas, Alyssa Nycz, John A Corbett, Rebekah L Gundry
To address concerns regarding the tumorigenic potential of undifferentiated human pluripotent stem cells (hPSC) that may remain after in vitro differentiation and ultimately limit the broad use of hPSC-derivatives for therapeutics, we recently described a method to selectively eliminate tumorigenic hPSC from their progeny by inhibiting nicotinamide phosphoribosyltransferase (NAMPT). Limited exposure to NAMPT inhibitors selectively removes hPSC from hPSC-derived cardiomyocytes (hPSC-CM) and spares a wide range of differentiated cell types; yet, it remains unclear when and how cells acquire resistance to NAMPT inhibition during differentiation...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28223499/two-metal-versus-one-metal-mechanisms-of-lysine-adenylylation-by-atp-dependent-and-nad-dependent-polynucleotide-ligases
#3
Mihaela-Carmen Unciuleac, Yehuda Goldgur, Stewart Shuman
Polynucleotide ligases comprise a ubiquitous superfamily of nucleic acid repair enzymes that join 3'-OH and 5'-PO4 DNA or RNA ends. Ligases react with ATP or NAD(+) and a divalent cation cofactor to form a covalent enzyme-(lysine-Nζ)-adenylate intermediate. Here, we report crystal structures of the founding members of the ATP-dependent RNA ligase family (T4 RNA ligase 1; Rnl1) and the NAD(+)-dependent DNA ligase family (Escherichia coli LigA), captured as their respective Michaelis complexes, which illuminate distinctive catalytic mechanisms of the lysine adenylylation reaction...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28217084/nad-attenuates-bilirubin-induced-hyperexcitation-in-the-ventral-cochlear-nucleus-by-inhibiting-excitatory-neurotransmission-and-neuronal-excitability
#4
Min Liang, Xin-Lu Yin, Lu-Yang Wang, Wei-Hai Yin, Ning-Ying Song, Hai-Bo Shi, Chun-Yan Li, Shan-Kai Yin
Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#5
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28209901/vitamin-b3-modulates-mitochondrial-vulnerability-and-prevents-glaucoma-in-aged-mice
#6
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Kelly E Cochran, Vivek M Philip, Vittorio Porciatti, Oliver Smithies, Simon W M John
Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD(+), a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#7
Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M Camp, Haiyang Tang, Shui Quing Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F Machado
Background -Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT), is a cytozyme which regulates intracellular NAD levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling, and that inhibition of NAMPT could attenuate pulmonary hypertension. Methods -Plasma and mRNA and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells (PAECs) from PAH patients, as well as in lungs of rodent models of pulmonary hypertension (PH)...
February 15, 2017: Circulation
https://www.readbyqxmd.com/read/28198851/interrogation-of-metabolic-and-oxygen-states-of-tumors-with-fiber-based-luminescence-lifetime-spectroscopy
#8
Maria Lukina, Anna Orlova, Marina Shirmanova, Daniil Shirokov, Anton Pavlikov, Antje Neubauer, Hauke Studier, Wolfgang Becker, Elena Zagaynova, Toshitada Yoshihara, Seiji Tobita, Vladislav Shcheslavskiy
The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optic probe provides a promising tool for optical interrogation of metabolic and oxygen states of a tumor in vivo. In our experiments, the excitation light from a ps diode laser source is delivered to the sample through an exchangeable tip via a multimode fiber, and the emission light is transferred to the detector by another multimode fiber...
February 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28197299/sirtuins-expression-and-their-role-in-retinal-diseases
#9
REVIEW
Sankarathi Balaiya, Khaled K Abu-Amero, Altaf A Kondkar, Kakarla V Chalam
Sirtuins have received considerable attention since the discovery that silent information regulator 2 (Sir2) extends the lifespan of yeast. Sir2, a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase, serves as both a transcriptional effector and energy sensor. Oxidative stress and apoptosis are implicated in the pathogenesis of neurodegenerative eye diseases. Sirtuins confer protection against oxidative stress and retinal degeneration. In mammals, the sirtuin (SIRT) family consists of seven proteins (SIRT1-SIRT7)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28192231/hypotensive-and-vasorelaxant-effect-of-diapocynin-in-normotensive-rats
#10
Simone R Potje, Jéssica A Troiano, Murilo E Graton, Valdecir F Ximenes, Ana Claúdia M S Nakamune, Cristina Antoniali
Nicotinamide adenine dinucleotide phosphate oxidase (NAD(P)H-oxidase) is a multicomponent enzyme system that generates superoxide anion by one-electron reduction of molecular oxygen and represents the major source of reactive oxygen species (ROS) in the vascular cells. Apocynin has been extensively used as an inhibitor of NADPH oxidase (NOX) in phagocytic cells and as an antioxidant in non-phagocytic cells. In phagocytes cells, due to the presence of myeloperoxidase, apocynin can be the converted to diapocynin, which is supposed to be the active form of this phytochemical...
February 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28183717/the-transcriptional-regulator-of-the-chaperone-response-hsf1-controls-hepatic-bioenergetics-and-protein-homeostasis
#11
Aijun Qiao, Xiongjie Jin, Junfeng Pang, Demetrius Moskophidis, Nahid F Mivechi
Metabolic energy reprogramming facilitates adaptations to a variety of stress conditions and cellular dysfunction, but how the energetic demands are monitored and met in response to physiological stimuli remains elusive. Our data support a model demonstrating that heat shock factor 1 (HSF1), a master transcriptional regulator of the chaperone response, has been coopted from its role as a critical protein quality-control regulator to having a central role in systemic energy sensing and for metabolic adaptation to nutrient availability...
February 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28169272/a-substrate-bound-structure-of-cyanobacterial-biliverdin-reductase-identifies-stacked-substrates-as-critical-for-activity
#12
Haruna Takao, Kei Hirabayashi, Yuki Nishigaya, Haruna Kouriki, Tetsuko Nakaniwa, Yoshinori Hagiwara, Jiro Harada, Hideaki Sato, Toshimasa Yamazaki, Yoichi Sakakibara, Masahito Suiko, Yujiro Asada, Yasuhiro Takahashi, Ken Yamamoto, Keiichi Fukuyama, Masakazu Sugishima, Kei Wada
Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it catalyses remain unknown. Here we present the crystal structure of biliverdin reductase in complex with biliverdin and NADP(+). Unexpectedly, two biliverdin molecules, which we designated the proximal and distal biliverdins, bind with stacked geometry in the active site...
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28167526/vibrio-phage-kvp40-encodes-a-functional-nad-salvage-pathway
#13
Jae Yun Lee, Zhiqun Li, Eric S Miller
: The genome of T4-type Vibrio bacteriophage KVP40 has five genes predicted to encode proteins of pyridine nucleotide metabolism, of which two, nadV and natV, would suffice for an NAD(+) salvage pathway. NadV is an apparent nicotinamide phosphoribosyltransferase (NAmPRTase) and NatV is an apparent bifunctional nicotinamide mononucleotide adenylyltransferase (NMNATase) and nicotinamide-adenine dinucleotide pyrophosphatase (Nudix hydrolase). Genes encoding the predicted salvage pathway were cloned, expressed in E...
February 6, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28165742/identification-of-novel-triazole-based-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-endowed-with-antiproliferative-and-antiinflammatory-activity
#14
Cristina Travelli, Silvio Aprile, Reza Rahimian, Ambra A Grolla, Federica Rogati, Mattia Bertolotti, Floriana Malagnino, Rosanna di Paola, Daniela Impellizzeri, Roberta Fusco, Valentina Mercalli, Alberto Massarotti, Giorgio Stortini, Salvatore Terrazzino, Erika Del Grosso, Gohar Fakhfouri, Maria Pia Troiani, Maria Alessandra Alisi, Giorgio Grosa, Giovanni Sorba, Pier Luigi Canonico, Giuseppe Orsomando, Salvatore Cuzzocrea, Armando A Genazzani, Ubaldina Galli, Gian Cesare Tron
Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme involved in the recycling of nicotinamide to maintain adequate NAD levels inside the cells. It has been postulated to be a pharmacological target, as it is overexpressed in cancer cells as well as in inflammatory diseases. We describe the synthesis and characterization of a novel class of one-digit nanomolar NAMPT inhibitors based on in vitro characterization. The most active compound tested, 30c, displayed activity in xenograft and allograft models, strengthening the potential of NAMPT inhibitors as antitumoral drugs...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28164517/prognostic-and-predictive-role-of-sirtuin1-expression-in-lung-adenocarcinoma
#15
Jun Wang, Changli Wang
BACKGROUND: SIRT1 is the homologue of sir2 in mammals, which is a nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylase. Several studies have reported that the overexpression of Sirtuin1 (SIRT1) was associated with poor prognosis in various human cancers. However, little is known regarding the prognostic value of SIRT1 in lung adenocarcinoma. METHODS: SIRT 1 expression in tissues of 60 lung adenocarcinoma (LAC) patients was evaluated using immunohistochemistry...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28163307/role-of-nad-and-mitochondrial-sirtuins-in-cardiac-and-renal-diseases
#16
REVIEW
Kathleen A Hershberger, Angelical S Martin, Matthew D Hirschey
The coenzyme nicotinamide adenine dinucleotide (NAD(+)) has key roles in the regulation of redox status and energy metabolism. NAD(+) depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD(+) repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD(+) enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD(+) functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes...
February 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28161061/protective-proteins-and-telomere-length-in-placentas-from-patients-with-pre-eclampsia-in-the-last-trimester-of-gestation
#17
Autumn J Broady, Matthew H Loichinger, Hyeong Jun Ahn, Philip M C Davy, Richard C Allsopp, Gillian D Bryant-Greenwood
INTRODUCTION: Visfatin/nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in energy metabolism and sirtuins, SIRT1 and SIRT3, which are NAD-dependent deacetylases, are critical for cellular function. All three either regulate or are regulated by intracellular NAD+ levels and therefore available cellular energy, important for placental cell survival and successful pregnancy. This study investigates whether these protective proteins are involved in the placental pathophysiology of pre-eclampsia (PE) and if they are associated with 8-oxo-deoxyguanosine (8OHdG), a marker of oxidative damage or with placental telomere length...
February 2017: Placenta
https://www.readbyqxmd.com/read/28160567/ews-fli1-confers-exquisite-sensitivity-to-nampt-inhibition-in-ewing-sarcoma-cells
#18
Cornelia N Mutz, Raphaela Schwentner, Dave N T Aryee, Eric D J Bouchard, Edgard M Mejia, Grant M Hatch, Maximilian O Kauer, Anna M Katschnig, Jozef Ban, Antje Garten, Javier Alonso, Versha Banerji, Heinrich Kovar
Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159473/nicotinamide-phosphoribosyltransferase-nampt-may-serve-as-the-marker-for-osteoblast-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells
#19
Xu He, Jiaxue He, Yingai Shi, Chenchen Pi, Yue Yang, Yanan Sun, Cao Ma, Lin Lin, Lihong Zhang, Yulin Li, Yan Li
Decreased bone volume and strength with aging and enhanced risk of fractures are in part due to reduced number of bone-forming mesenchymal stem cells (MSCs) and cellular dysfunction. In a previous study, we found that osteogenic differentiation of the multipotent and omnipotent preosteoblasts are accompanied by the alterations of intracellular NAD metabolism in which nicotinamide phosphoribosyltransferase (Nampt) plays a regulatory role. The increased Nampt during osteoblast differentiation, the enzyme catalyzing NAD resynthesis from nicotinamide was noted...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28152599/discovery-of-nicotinamide-adenine-dinucleotide-binding-proteins-in-the-escherichia-coli-proteome-using-a-combined-energetic-and-structural-bioinformatics-based-approach
#20
Lingfei Zeng, Woong-Hee Shin, Xiaolei Zhu, Sung Hoon Park, Chiwook Park, W Andy Tao, Daisuke Kihara
Protein-ligand interaction plays a critical role in regulating the biochemical functions of proteins. Discovering protein targets for ligands is vital to new drug development. Here, we present a strategy that combines experimental and computational approaches to identify ligand-binding proteins in a proteomic scale. For the experimental part, we coupled pulse proteolysis with filter-assisted sample preparation (FASP) and quantitative mass spectrometry. Under denaturing conditions, ligand binding affected protein stability, which resulted in altered protein abundance after pulse proteolysis...
February 3, 2017: Journal of Proteome Research
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