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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/28548540/nicotinamide-adenine-dinucleotide-nad-sup-sup-metabolism-and-neurodegeneration
#1
Mariana Pehar, Benjamin A Harlan, Kelby M Killoy, Marcelo R Vargas
SIGNIFICANCE: Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) participates in redox reactions and NAD<sup>+</sup>-dependent signaling processes, which involve the cleavage of NAD<sup>+</sup> coupled to post-translational modifications of proteins or the production of second messengers. Either as a primary cause or as a secondary component of the pathogenic process, mitochondrial dysfunction and oxidative stress are prominent features of several neurodegenerative diseases...
May 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28546856/epigenetic-regulation-of-runx2-transcription-and-osteoblast-differentiation-by-nicotinamide-phosphoribosyltransferase
#2
Min Ling, Peixin Huang, Shamima Islam, Daniel P Heruth, Xuanan Li, Li Qin Zhang, Ding-You Li, Zhaohui Hu, Shui Qing Ye
BACKGROUND: Bone degenerative disorders like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Although there are studies suggesting that metabolic changes occur with stem cell differentiation, the molecular mechanisms governing energy metabolism and epigenetic modification are not understood fully. Here we reported the key role of nicotinamide phosphoribosyltransferase (Nampt), which is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide, in the osteogenic differentiation of bone marrow stromal cells...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28545736/amino-acid-sensing-and-degrading-pathways-in-immune-regulation
#3
Ursula Grohmann, Giada Mondanelli, Maria L Belladonna, Ciriana Orabona, Maria T Pallotta, Alberta Iacono, Paolo Puccetti, Claudia Volpi
Indoleamine 2,3-dioxygenases (IDOs) - belonging in the heme dioxygenase family and degrading tryptophan - are responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD(+)). As such, they are expressed by a variety of invertebrate and vertebrate species. In mammals, IDO1 has remarkably evolved to expand its functions, so to become a prominent homeostatic regulator, capable of modulating infection and immunity in multiple ways, including local tryptophan deprivation, production of biologically active tryptophan catabolites, and non-enzymatic cell-signaling activity...
May 18, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28545714/anticystogenic-activity-of-a-small-molecule-pak4-inhibitor-may-be-a-novel-treatment-for-autosomal-dominant-polycystic-kidney-disease
#4
Vicki J Hwang, Xia Zhou, Xiaonan Chen, Josephine Trott, Omran Abu Aboud, Kyuhwan Shim, Lai Kuan Dionne, Kenneth J Chmiel, William Senapedis, Erkan Baloglu, Moe R Mahjoub, Xiaogang Li, Robert H Weiss
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary renal disease with no currently available targeted therapies. Based on the established connection between β-catenin signaling and renal ciliopathies, and on data from our and other laboratories showing striking similarities of this disease and cancer, we evaluated the use of an orally bioavailable small molecule, KPT-9274 (a dual inhibitor of the protein kinase PAK4 and nicotinamide phosphoribosyl transferase), for treatment of ADPKD...
May 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28543772/parp-inhibitor-rucaparib-induces-changes-in-nad-levels-in-cells-and-liver-tissues-as-assessed-by-mrs
#5
Gilberto S Almeida, Carlo M Bawn, Martin Galler, Ian Wilson, Huw D Thomas, Suzanne Kyle, Nicola J Curtin, David R Newell, Ross J Maxwell
Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ((1) H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD(+) ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28536482/nad-loss-a-new-player-in-ahr-biology-prevention-of-thymus-atrophy-and-hepatosteatosis-by-nad-repletion
#6
Silvia Diani-Moore, Jenny Shoots, Rubi Singh, Joshua B Zuk, Arleen B Rifkind
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a carcinogenic and highly toxic industrial byproduct that persists in the environment and produces a pleiotropic toxicity syndrome across vertebrate species that includes wasting, hepatosteatosis, and thymus atrophy. Dioxin toxicities require binding and activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. However, after nearly 50 years of study, it remains unknown how AhR activation by dioxin produces toxic effects...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536194/wild-tobacco-genomes-reveal-the-evolution-of-nicotine-biosynthesis
#7
Shuqing Xu, Thomas Brockmöller, Aura Navarro-Quezada, Heiner Kuhl, Klaus Gase, Zhihao Ling, Wenwu Zhou, Christoph Kreitzer, Mario Stanke, Haibao Tang, Eric Lyons, Priyanka Pandey, Shree P Pandey, Bernd Timmermann, Emmanuel Gaquerel, Ian T Baldwin
Nicotine, the signature alkaloid of Nicotiana species responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos, Nicotiana attenuata (2.5 Gb) and Nicotiana obtusifolia (1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole-genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated these Nicotiana genomes, promoted expression divergences among duplicated genes, and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28527050/interplay-between-sirt-3-metabolism-and-its-tumor-suppressor-role-in-hepatocellular-carcinoma
#8
REVIEW
Serena De Matteis, Anna Maria Granato, Roberta Napolitano, Chiara Molinari, Martina Valgiusti, Daniele Santini, Francesco Giuseppe Foschi, Giorgio Ercolani, Umberto Vespasiani Gentilucci, Luca Faloppi, Mario Scartozzi, Giovanni Luca Frassineti, Andrea Casadei Gardini
Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD(+))-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC)...
May 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#9
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516115/a-modified-chromogenic-assay-for-determination-of-the-ratio-of-free-intracellular-nad-nadh-in-streptococcus-mutans
#10
Jonathon L Baker, Roberta C Faustoferri, Robert G Quivey
Nicotinamide adenine dinucleotide is a coenzyme present in all kingdoms of life and exists in two forms: oxidized (NAD(+)) and reduced (NADH). NAD(H) is involved in a multitude of essential metabolic redox reactions, providing oxidizing or reducing equivalents. The ratio of free intracellular NAD(+)/NADH is fundamentally important in the maintenance of cellular redox homeostasis (Ying, 2008). Various chromogenic cycling assays have been used to determine the ratio of NAD(+)/NADH in both bacterial and mammalian cells for more than forty years (Bernofsky and Swan, 1973; Nisselbaum and Green, 1969)...
August 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#11
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514875/identification-of-novel-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-using-computational-approaches
#12
Manish Kesherwani, Sriram Raghavan, Krishnasamy Gunasekaran, Devadasan Velmurugan
Nicotinamide Phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the biosynthesis of NAD. Cancer cells have elevated poly [ADP-Ribose] polymerase 1 (PARP) activity as well as the immense necessity of ATP: thereby consuming NAD at a higher rate than normal tissues. The perturbation of these intracellular processes is more sensitive and highly dependent on NAMPT to maintain the required NAD levels. Functional inhibition of NAMPT is, therefore, a promising drug target in therapeutic oncology. In this study, the importance of intermolecular contacts was realized based on contact occupancy and favorable energetic from molecular dynamic simulation to discern non-critical contacts of four different classes of potential NAMPT inhibitor bound complexes...
May 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28507103/nicotinic-acid-phosphoribosyltransferase-regulates-cancer-cell-metabolism-susceptibility-to-nampt-inhibitors-and-dna-repair
#13
Francesco Piacente, Irene Caffa, Silvia Ravera, Giovanna Sociali, Mario Passalacqua, Valerio G Vellone, Pamela Becherini, Daniele Reverberi, Fiammetta Monacelli, Alberto Ballestrero, Patrizio Odetti, Antonia Cagnetta, Michele Cea, Aimable Nahimana, Michel A Duchosal, Santina Bruzzone, Alessio Nencioni
In the last decade, substantial efforts have been made to identify NAD+ biosynthesis inhibitors, specifically against nicotinamide phosphoribosyltransferase (NAMPT), as preclinical studies indicate their potential efficacy as cancer drugs. However, the clinical activity of NAMPT inhibitors has proven limited, suggesting that alternative NAD+ production routes exploited by tumors confer resistance. Here we show the gene encoding nicotinic acid phosphoribosyltransferase (NAPRT), a second NAD+ producing enzyme, is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature...
May 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28500115/erroneously-elevated-glucose-values-due-to-maltose-interference-in-mutant-glucose-dehydrogenase-pyrroloquinolinequinone-mutant-gdh-pqq-based-glucometer
#14
Partha Pratim Chakraborty, Shinjan Patra, Rana Bhattacharjee, Subhankar Chowdhury
Currently available glucose test strip enzymes include glucose oxidase (GOD) and glucose dehydrogenase (GDH). In GDH-based glucometers, glucose oxidation can be catalysed by different cofactors: nicotinamide adenine dinucleotide (GDH-NAD), flavin adenine dinucleotide (GDH-FAD), pyrroloquinolinequinone (GDH-PQQ) and mutant GDH-PQQ. GOD-based and GDH-NAD-based glucometers are substrate-specific and do not react with sugars other than glucose. GDH-FAD reacts with xylose only in addition to glucose. GDH-PQQ is not glucose-specific; in addition to glucose, it reacts with different other sugars and produces falsely high values of capillary glucose in the presence of such substances...
May 12, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28495827/hyperbaric-oxygen-reduces-infarction-volume-and-hemorrhagic-transformation-through-atp-nad-sirt1-pathway-in-hyperglycemic-middle-cerebral-artery-occlusion-rats
#15
Qin Hu, Anatol Manaenko, Hetao Bian, Zongduo Guo, Jun-Long Huang, Zhen-Ni Guo, Peng Yang, Jiping Tang, John H Zhang
BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion...
May 11, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28487632/nicotinamide-and-wld-s-act-together-to-prevent-neurodegeneration-in-glaucoma
#16
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Brynn H Cardozo, Kelly E Cochran, Simon W M John
Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with a critical insult damaging their axons in the optic nerve head. This insult is typically secondary to harmfully high levels of intraocular pressure (IOP). We have previously determined that early mitochondrial abnormalities within retinal ganglion cells lead to neuronal dysfunction, with age-related declines in NAD (NAD(+) and NADH) rendering retinal ganglion cell mitochondria vulnerable to IOP-dependent stresses...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28477081/exogenous-nicotinamide-supplementation-and-moderate-physical-exercise-can-attenuate-the-aging-process-in-skeletal-muscle-of-rats
#17
Melitta Pajk, Alexandra Cselko, Csaba Varga, Aniko Posa, Margareta Tokodi, Istvan Boldogh, Sataro Goto, Zsolt Radak
Nicotinamide (NAM) could enhance the availability of NAD(+) and be beneficial to cell function. However, NAM can inhibit the activities of SIRT1 and PARP. The effect of NAM supplementation on the aging process is not well known. In the present study exogenous NAM (1-0.5% in drinking water) was supplemented for 5 weeks and in the last 4 weeks moderate treadmill running was given to 5 mo and 28 mo old rats. The content of SIRT1 was not effected by NAM treatment alone. However, the activity of SIRT1, judged from the acetylated p53/p53 ratio, increased in both NAM treated age groups, suggesting beneficial effects of exogenous NAM...
May 5, 2017: Biogerontology
https://www.readbyqxmd.com/read/28468779/discovery-and-characterization-of-novel-non-substrate-and-substrate-nampt-inhibitors
#18
Julie L Wilsbacher, Min Cheng, Dong Cheng, Samuel A J Trammell, Yan Shi, Jun Guo, Stormy L Koeniger, Peter J Kovar, Yupeng He, Sujatha Selvaraju, H Robin Heyman, Bryan K Sorensen, Richard F Clark, T Matthew Hansen, Kenton L Longenecker, Diana Raich, Alla V Korepanova, Steven Cepa, Danli L Towne, Vivek C Abraham, Hua Tang, Paul L Richardson, Shaun M McLoughlin, Ilaria Badagnani, Michael L Curtin, Michael R Michaelides, David Maag, F Greg Buchanan, Gary G Chiang, Wenqing Gao, Saul H Rosenberg, Charles Brenner, Chris Tse
Cancer cells are highly reliant on nicotinamide adenine dinucleotide (NAD(+))-dependent processes including glucose metabolism, calcium signaling, DNA repair, and regulation of gene expression. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD(+) salvage from nicotinamide (NAM), has been investigated as a target for anti-cancer therapy. Known NAMPT inhibitors with potent cell activity are composed of a nitrogen-containing aromatic group, which is phosphoribosylated by the enzyme...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28468736/prevention-of-non-melanoma-skin-cancers-with-nicotinamide-in-transplant-recipients-a-case-control-study
#19
Francesco Drago, Giulia Ciccarese, Ludovica Cogorno, Camillo Calvi, Luigina A Marsano, Aurora Parodi
Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for adenosine triphosphate (ATP) production. It has recently been reported to be effective in reducing the rates of new non-melanoma skin cancers (NMSCs) and actinic keratosis (AKs). We studied the efficacy of oral nicotinamide as treatment for AKs in transplant recipients. We recruited 38 transplant (eight liver and 30 kidney) patients with single or multiple AKs. Nineteen patients were randomly assigned to Group 1 and took nicotinamide 500 mg/daily (cases); the other 19 patients were randomly assigned to Group 2 without nicotinamide (controls)...
May 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28455340/engineering-escherichia-coli-nicotinic-acid-mononucleotide-adenylyltransferase-for-fully-active-amidated-nad-biosynthesis
#20
Xueying Wang, Yongjin J Zhou, Lei Wang, Wujun Liu, Yuxue Liu, Chang Peng, Zongbao K Zhao
Nicotinamide adenine dinucleotide (NAD) and its reduced form NADH function as essential redox cofactors and have major roles in determining cellular metabolic features. NAD can be synthesized through deamidated and amidated pathway, of which the key reaction involves adenylylation of nicotinic acid mononucleotide (NaMN) and nicotinamide mononucleotide (NMN), respectively. In Escherichia coli, NAD de novo biosynthesis depends on the protein NadD-catalyzed adenylylation of NaMN to nicotinic acid adenine dinucleotide (NaAD), followed by NAD synthase-catalyzed amidation...
April 28, 2017: Applied and Environmental Microbiology
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