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NAD+ increase AND Nicotinamide

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https://www.readbyqxmd.com/read/28336669/a-conserved-nad-binding-pocket-that-regulates-protein-protein-interactions-during-aging
#1
Jun Li, Michael S Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P Hubbard, Alvin J Y Ling, Luis A Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L Aravind, Clemens Steegborn, David A Sinclair
DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD(+) (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD(+) to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate-ribose) polymerase], a critical DNA repair protein...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#2
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28299677/a-reagentless-screen-printed-amperometric-biosensor-for-the-determination-of-glutamate-in-food-and-clinical-applications
#3
G Hughes, R M Pemberton, P R Fielden, J P Hart
A reagentless biosensor has been successfully developed to measure glutamate in food and clinical samples. The enzyme, glutamate dehydrogenase (GLDH) and the cofactor, nicotinamide adenine dinucleotide (NAD(+)) are fully integrated onto the surface of a Meldola's Blue screen-printed carbon electrode (MB-SPCE). The biological components are immobilized by utilizing unpurified multi-walled carbon nanotubes (MWCNT's) mixed with the biopolymer chitosan (CHIT), which are drop-coated onto the surface of the MB-SPCE in a layer-by-layer fashion...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28290889/-platelet-metabolism-in-clopidogrel-resistant-and-sensitive-patients-with-ischemic-heart-disease
#4
I Yu Grinshtein, A A Savchenko, Yu I Grinshtein, I V Filonenko, A A Kosinova
OBJECTIVE: to investigate relationship between activity of platelet nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) dependent dehydrogenases in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) and their sensitivity to clopidogrel. MATERIAL AND METHODS: We studied 51 male patients with chronic IHD before and after CABG. Control group comprised 35 healthy men. In IHD patients spontaneous and induced platelet aggregation was measured by aggregometry before CABG (in 2 weeks after cessation of antiplatelet drugs), after CABG during therapy with clopidogrel (75 mg/day), and in 6 months after surgery...
October 2016: Kardiologiia
https://www.readbyqxmd.com/read/28283058/5-end-nicotinamide-adenine-dinucleotide-cap-in-human-cells-promotes-rna-decay-through-dxo-mediated-denadding
#5
Xinfu Jiao, Selom K Doamekpor, Jeremy G Bird, Bryce E Nickels, Liang Tong, Ronald P Hart, Megerditch Kiledjian
Eukaryotic mRNAs generally possess a 5' end N7 methyl guanosine (m(7)G) cap that promotes their translation and stability. However, mammalian mRNAs can also carry a 5' end nicotinamide adenine dinucleotide (NAD(+)) cap that, in contrast to the m(7)G cap, does not support translation but instead promotes mRNA decay. The mammalian and fungal noncanonical DXO/Rai1 decapping enzymes efficiently remove NAD(+) caps, and cocrystal structures of DXO/Rai1 with 3'-NADP(+) illuminate the molecular mechanism for how the "deNADding" reaction produces NAD(+) and 5' phosphate RNA...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28263025/poly-adp-ribose-polymerases-regulate-cell-division-and-development-in-arabidopsis-roots
#6
Caifeng Liu, Qiao Wu, Weiwei Liu, Zongyin Gu, Wenjing Wang, Ping Xu, Hong Ma, Xiaochun Ge
Root organogenesis involves cell division, differentiation and expansion. The molecular mechanisms regulating root development are not fully understood. In this study, we identified poly (ADP-ribose) polymerases (PARPs) as new players in root development. PARP catalyzes poly (ADP-ribosyl)ation of proteins by repeatedly adding ADP-ribose units onto proteins using nicotinamide adenine dinucleotide (NAD(+) ) as the donor. We found that inhibition of PARP activities by 3-aminobenzomide (3-AB) increased the growth rates of both primary and lateral roots, leading to a more developed root system...
March 6, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28254441/omega-3-polyunsaturated-fatty-acids-suppress-the-inflammatory-responses-of-lipopolysaccharide-stimulated-mouse-microglia-by-activating-sirt1-pathways
#7
Takayuki Inoue, Masashi Tanaka, Shinya Masuda, Ryuji Ohue-Kitano, Hajime Yamakage, Kazuya Muranaka, Hiromichi Wada, Toru Kusakabe, Akira Shimatsu, Koji Hasegawa, Noriko Satoh-Asahara
Obesity and diabetes are known risk factors for dementia, and it is speculated that chronic neuroinflammation contributes to this increased risk. Microglia are brain-resident immune cells modulating the neuroinflammatory state. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major ω-3 polyunsaturated fatty acids (PUFAs) of fish oil, exhibit various effects, which include shifting microglia to the anti-inflammatory phenotype. To identify the molecular mechanisms involved, we examined the impact of EPA, DHA, and EPA+DHA on the lipopolysaccharide (LPS)-induced cytokine profiles and the associated signaling pathways in the mouse microglial line MG6...
February 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28246130/nicotinamide-mononucleotide-an-nad-precursor-rescues-age-associated-susceptibility-to-aki-in-a-sirtuin-1-dependent-manner
#8
Yi Guan, Su-Rong Wang, Xin-Zhong Huang, Qiong-Hong Xie, Yun-Yu Xu, Da Shang, Chuan-Ming Hao
The rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD(+) Supplementation with nicotinamide mononucleotide (NMN), an NAD(+) precursor, restored renal SIRT1 activity and NAD(+) content in 20-month-old mice and further increased both in 3-month-old mice...
February 28, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28228259/sirt1-regulates-dna-methylation-and-differentiation-potential-of-embryonic-stem-cells-by-antagonizing-dnmt3l
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
March 6, 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
#16
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
#17
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...
March 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28131761/sirt3-mediates-decrease-of-oxidative-damage-and-prevention-of-ageing-in-porcine-fetal-fibroblasts
#18
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
#19
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
#20
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
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