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NAD+ increase 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/28217084/nad-attenuates-bilirubin-induced-hyperexcitation-in-the-ventral-cochlear-nucleus-by-inhibiting-excitatory-neurotransmission-and-neuronal-excitability
#3
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
#4
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/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#5
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/28192231/hypotensive-and-vasorelaxant-effect-of-diapocynin-in-normotensive-rats
#6
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
#7
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/28161061/protective-proteins-and-telomere-length-in-placentas-from-patients-with-pre-eclampsia-in-the-last-trimester-of-gestation
#8
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/28159473/nicotinamide-phosphoribosyltransferase-nampt-may-serve-as-the-marker-for-osteoblast-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells
#9
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/28131761/sirt3-mediates-decrease-of-oxidative-damage-and-prevention-of-ageing-in-porcine-fetal-fibroblasts
#10
Xiaoxian Xie, Liangliang Wang, Binggong Zhao, Yangyang Chen, Jiaqi Li
AIMS: Sirtuin 3 (SIRT3) is a mitochondria-specific protein required for the deacetylation of metabolic enzymes and the action of oxidative phosphorylation by acting as a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase. SIRT3 increases oxidative stress resistance and prevents mitochondrial decay associated with ageing in response to caloric restriction. However, the effects of SIRT3 on oxidative damage and ageing are not well understood. We investigated the physiological functions of porcine SIRT3 on the damage and ageing in porcine fetal fibroblasts (PFFs)...
January 25, 2017: Life Sciences
https://www.readbyqxmd.com/read/28106753/naphthalimides-selectively-inhibit-the-activity-of-bacterial-replicative-dna-ligases-and-display-bactericidal-effects-against-tubercle-bacilli
#11
Malgorzata Korycka-Machala, Marcin Nowosielski, Aneta Kuron, Sebastian Rykowski, Agnieszka Olejniczak, Marcin Hoffmann, Jaroslaw Dziadek
The DNA ligases, enzymes that seal breaks in the backbones of DNA, are essential for all organisms, however bacterial ligases essential for DNA replication use β-nicotinamide adenine dinucleotide as their co-factor, whereas those that are essential in eukaryotes and viruses use adenosine-5'-triphosphate. This fact leads to the conclusion that NAD⁺-dependent DNA ligases in bacteria could be targeted by their co-factor specific inhibitors. The development of novel alternative medical strategies, including new drugs, are a top priority focus areas for tuberculosis research due to an increase in the number of multi-drug resistant as well as totally drug resistant tubercle bacilli strains...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28077334/the-neuroprotective-compound-p7c3-a20-promotes-neurogenesis-and-improves-cognitive-function-after-ischemic-stroke
#12
Zachary B Loris, Andrew A Pieper, W Dalton Dietrich
Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established...
April 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28000862/sirt1%C3%A2-mediated-regulation-of-oxidative-stress-induced-by-pseudomonas-aeruginosa-lipopolysaccharides-in-human-alveolar-epithelial-cells
#13
Xiaoli Liu, Tuo Yang, Tieying Sun, Kuiqing Shao
Sirtuin1 (SIRT1) is an NAD+‑dependent deacetylase that exhibits multiple biological functions, including cell differentiation inhibition, transcription regulation, cell cycle regulation and anti‑apoptosis. Lipopolysaccharides (LPS) are crucial virulence factors produced by Pseudomonas aeruginosa and serve an important role in adjusting the interactions between the host and the pathogen. However, the effect of SIRT1 in the regulation of LPS‑induced A459 human alveolar epithelial cells (AECs) oxidative stress remains unclear...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27994519/anticancer-effects-of-a-new-sirt-inhibitor-mhy2256-against-human-breast-cancer-mcf-7-cells-via-regulation-of-mdm2-p53-binding
#14
Eun Young Park, Youngwoo Woo, Seong Jin Kim, Do Hyun Kim, Eui Kyung Lee, Umasankar De, Kyeong Seok Kim, Jaewon Lee, Jee H Jung, Ki-Tae Ha, Wahn Soo Choi, In Su Kim, Byung Mu Lee, Sungpil Yoon, Hyung Ryong Moon, Hyung Sik Kim
The sirtuins (SIRTs), a family of NAD(+)-dependent class III histone deacetylase, are involved in various biological processes including cell survival, division, senescence, and metabolism via activation of the stress-response pathway. Recently, inhibition of SIRTs has been considered a promising anticancer strategy, but their precise mechanisms of action are not well understood. In particular, the relevance of p53 to SIRT-induced effects has not been fully elucidated. We investigated the anticancer effects of a novel SIRT inhibitor, MHY2256, and its efficacy was compared to that of salermide in MCF-7 (wild-type p53) and SKOV-3 (null-type p53) cells...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27973747/quinolinic-acid-induces-neuritogenesis-in-sh-sy5y-neuroblastoma-cells-independently-of-nmda-receptor-activation
#15
Juan-Manuel Hernandez-Martinez, Caroline M Forrest, L Gail Darlington, Robert A Smith, Trevor W Stone
Glutamate and nicotinamide adenine dinucleotide (NAD(+) ) have been implicated in neuronal development and several types of cancer. The kynurenine pathway of tryptophan metabolism includes quinolinic acid (QA) which is both a selective agonist at N-methyl-D-aspartate (NMDA) receptors and also a precursor for the formation of NAD(+) . The effect of QA on cell survival and differentiation has therefore been examined on SH-SY5Y human neuroblastoma cells. Retinoic acid (RA, 10 μm) induced differentiation of SH-SY5Y cells into a neuronal phenotype showing neurite growth...
December 14, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#16
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek R Clements, Youra Kim, Patrick W K Lee, Shashi A Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27924925/replicatively-senescent-human-fibroblasts-reveal-a-distinct-intracellular-metabolic-profile-with-alterations-in-nad-and-nicotinamide-metabolism
#17
Emma L James, James A E Lane, Ryan D Michalek, Edward D Karoly, E Kenneth Parkinson
Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919636/adrenomedullin-and-angiotensin-ii-signaling-pathways-involved-in-the-effects-on-cerebellar-antioxidant-enzymes-activity
#18
Figueira Leticia, Israel Anita
Human adrenomedullin (AM) is a 52-amino acid peptide involved in cardiovascular control. AM has two specific receptors formed by the calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP) 2 or 3, known as AM1 and AM2 receptors, respectively. In addition, AM has appreciable affinity for the calcitonin gene-1 related peptide receptor (CGRP1), composed of CRLR/RAMP1. In brain, AM and their receptors are expressed in several localized areas, including the cerebellum. AM has been reported as an antioxidant...
January 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#19
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27906624/influence-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-4pyr-on-activities-of-extracellular-enzymes-in-endothelial-human-cells
#20
I Pelikant-Małecka, A Sielicka, E Kaniewska, R T Smoleński, E M Słomińska
Previous studies demonstrated that human endothelial cells were capable to phosphorylate 4-pyridone-3-carboxamide-1β-D-ribonucleoside (4PYR) to monophosphate (4PYMP) and formed another metabolite-an analog of NAD (4PYRAD). Elevated levels of 4PYMP and 4PYRAD had an adverse effect on energy balance-depressed adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD) concentration in human endothelial cells. Ecto-enzymes such as ecto-nucleoside triphosphate diphosphohydrolase (eNTPD); ecto-5'-nucleotidase (e5'NT); and ecto-adenosine deaminase (eADA) are involved in controlling of inflammation and platelet aggregation...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
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