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NR AND nicotinamide

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https://www.readbyqxmd.com/read/28346814/nicotinamide-riboside-a-form-of-vitamin-b3-and-nad-precursor-relieves-the-nociceptive-and-aversive-dimensions-of-paclitaxel-induced-peripheral-neuropathy-in-female-rats
#1
Marta V Hamity, Stephanie R White, Roxanne Y Walder, Mark S Schmidt, Charles Brenner, Donna L Hammond
Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6...
May 2017: Pain
https://www.readbyqxmd.com/read/28211258/effects-of-a-wide-range-of-dietary-nicotinamide-riboside-nr-concentrations-on-metabolic-flexibility-and-white-adipose-tissue-wat-of-mice-fed-a-mildly-obesogenic-diet
#2
Wenbiao Shi, Maria A Hegeman, Dorien A M van Dartel, Jing Tang, Manuel Suarez, Hans Swarts, Bart van der Hee, Lluis Arola, Jaap Keijer
SCOPE: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR. DESIGN AND METHODS: Nine-week-old male C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat) diet containing 0.14% L-tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks...
February 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28062235/new-approach-to-biosensing-of-co-enzyme-nicotinamide-adenine-dinucleotide-nadh-by-incorporation-of-neutral-red-in-aluminum-doped-nanostructured-zno-thin-films
#3
Fidal V T, Chandra T S
Biosensing of NADH on bare electrodes has drawbacks such as high over-potential and poisoning during the oxidation reaction. To overcome this challenge a different approach has been undertaken by incorporating neutral red (NR) in Al doped ZnO (AZO) thin films using one-pot chemical bath deposition (CBD). The surface morphology of the films was hexagonal nanorods along the c-axis, perpendicular to the substrate. The thickness of the thin films were ranging from 400 to 3000nm varying dependent on time of deposition (30 to 150min)...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27924925/replicatively-senescent-human-fibroblasts-reveal-a-distinct-intracellular-metabolic-profile-with-alterations-in-nad-and-nicotinamide-metabolism
#4
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/27809334/nicotinamide-adenine-dinucleotide-biosynthesis-promotes-liver-regeneration
#5
Sarmistha Mukherjee, Karthikeyani Chellappa, Andrea Moffitt, Joan Ndungu, Ryan W Dellinger, James G Davis, Beamon Agarwal, Joseph A Baur
The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27725675/nrk1-controls-nicotinamide-mononucleotide-and-nicotinamide-riboside-metabolism-in-mammalian-cells
#6
Joanna Ratajczak, Magali Joffraud, Samuel A J Trammell, Rosa Ras, Núria Canela, Marie Boutant, Sameer S Kulkarni, Marcelo Rodrigues, Philip Redpath, Marie E Migaud, Johan Auwerx, Oscar Yanes, Charles Brenner, Carles Cantó
NAD(+) is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD(+) precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD(+) synthesis...
October 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27721479/nicotinamide-riboside-is-uniquely-and-orally-bioavailable-in-mice-and-humans
#7
Samuel A J Trammell, Mark S Schmidt, Benjamin J Weidemann, Philip Redpath, Frank Jaksch, Ryan W Dellinger, Zhonggang Li, E Dale Abel, Marie E Migaud, Charles Brenner
Nicotinamide riboside (NR) is in wide use as an NAD(+) precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD(+) metabolism in humans. We report that human blood NAD(+) can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD(+) with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD(+) metabolome in the first clinical trial of NR pharmacokinetics in humans...
October 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27490188/improved-sugar-puckering-profiles-for-nicotinamide-ribonucleoside-for-hybrid-qm-mm-simulations
#8
Yaron Pshetitsky, Reuven Eitan, Gilit Verner, Amnon Kohen, Dan Thomas Major
The coenzyme nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) play ubiquitous roles as oxidizing and reducing agents in nature. The binding, and possibly the chemical redox step, of NAD(+)/NADH may be influenced by the cofactor conformational distribution and, in particular, by the ribose puckering of its nicotinamide-ribonucleoside (NR) moiety. In many hybrid quantum mechanics-molecular mechanics (QM/MM) studies of NAD(+)/NADH dependent enzymes, the QM region is treated by semiempirical (SE) methods...
October 11, 2016: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/27349384/auxotrophic-actinobacillus-pleurpneumoniae-grows-in-multispecies-biofilms-without-the-need-for-nicotinamide-adenine-dinucleotide-nad-supplementation
#9
Abraham Loera-Muro, Mario Jacques, Francisco J Avelar-González, Josée Labrie, Yannick D N Tremblay, Ricardo Oropeza-Navarro, Alma L Guerrero-Barrera
BACKGROUND: Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, which causes important worldwide economic losses in the swine industry. Several respiratory tract infections are associated with biofilm formation, and A. pleuropneumoniae has the ability to form biofilms in vitro. Biofilms are structured communities of bacterial cells enclosed in a self-produced polymer matrix that are attached to an abiotic or biotic surface. Virtually all bacteria can grow as a biofilm, and multi-species biofilms are the most common form of microbial growth in nature...
2016: BMC Microbiology
https://www.readbyqxmd.com/read/27230286/nicotinamide-riboside-opposes-type-2-diabetes-and-neuropathy-in-mice
#10
Samuel A J Trammell, Benjamin J Weidemann, Ankita Chadda, Matthew S Yorek, Amey Holmes, Lawrence J Coppey, Alexander Obrosov, Randy H Kardon, Mark A Yorek, Charles Brenner
Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD...
May 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27127236/nad%C3%A2-%C2%BA-repletion-improves-mitochondrial-and-stem-cell-function-and-enhances-life-span-in-mice
#11
Hongbo Zhang, Dongryeol Ryu, Yibo Wu, Karim Gariani, Xu Wang, Peiling Luan, Davide D'Amico, Eduardo R Ropelle, Matthias P Lutolf, Ruedi Aebersold, Kristina Schoonjans, Keir J Menzies, Johan Auwerx
Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice...
June 17, 2016: Science
https://www.readbyqxmd.com/read/27052539/nicotinamide-riboside-is-a-major-nad-precursor-vitamin-in-cow-milk
#12
Samuel Aj Trammell, Liping Yu, Philip Redpath, Marie E Migaud, Charles Brenner
BACKGROUND: Nicotinamide riboside (NR) is a recently discovered NAD(+) precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+) precursors was unknown. OBJECTIVE: We aimed to determine NAD(+) precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. METHODS: LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+) precursor vitamin concentration and to measure NR stability in raw and commercial milk...
May 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/26791540/safety-assessment-of-nicotinamide-riboside-a-form-of-vitamin-b3
#13
D B Conze, J Crespo-Barreto, C L Kruger
Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg...
January 20, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/26658104/antitumor-effect-of-combined-nampt-and-cd73-inhibition-in-an-ovarian-cancer-model
#14
Giovanna Sociali, Lizzia Raffaghello, Mirko Magnone, Federica Zamporlini, Laura Emionite, Laura Sturla, Giovanna Bianchi, Tiziana Vigliarolo, Aimable Nahimana, Alessio Nencioni, Nadia Raffaelli, Santina Bruzzone
Nicotinamide phosphoribosyltransferase (NAMPT) is a crucial enzyme in the biosynthesis of intracellular NAD+. NAMPT inhibitors have potent anticancer activity in several preclinical models by depleting NAD+ and ATP levels. Recently, we demonstrated that CD73 enables the utilization of extracellular NAD+/nicotinamide mononucleotide (NMN) by converting them to Nicotinamide riboside (NR), which can cross the plasmamembrane and fuel intracellular NAD+ biosynthesis in human cells. These processes are herein confirmed to also occur in a human ovarian carcinoma cell line (OVCAR-3), by means of CD73 or NRK1 specific silencing...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26404765/eliciting-the-mitochondrial-unfolded-protein-response-by-nicotinamide-adenine-dinucleotide-repletion-reverses-fatty-liver-disease-in-mice
#15
Karim Gariani, Keir J Menzies, Dongryeol Ryu, Casey J Wegner, Xu Wang, Eduardo R Ropelle, Norman Moullan, Hongbo Zhang, Alessia Perino, Vera Lemos, Bohkyung Kim, Young-Ki Park, Alessandra Piersigilli, Tho X Pham, Yue Yang, Chai Siah Ku, Sung I Koo, Anna Fomitchova, Carlos Cantó, Kristina Schoonjans, Anthony A Sauve, Ji-Young Lee, Johan Auwerx
UNLABELLED: With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD(+) ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice...
April 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26385918/generation-release-and-uptake-of-the-nad-precursor-nicotinic-acid-riboside-by-human-cells
#16
Veronika Kulikova, Konstantin Shabalin, Kirill Nerinovski, Christian Dölle, Marc Niere, Alexander Yakimov, Philip Redpath, Mikhail Khodorkovskiy, Marie E Migaud, Mathias Ziegler, Andrey Nikiforov
NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro...
November 6, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25974041/nicotinamide-riboside-ameliorates-hepatic-metaflammation-by-modulating-nlrp3-inflammasome-in-a-rodent-model-of-type-2-diabetes
#17
Hee Jae Lee, Young-Shick Hong, Woojin Jun, Soo Jin Yang
Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome...
November 2015: Journal of Medicinal Food
https://www.readbyqxmd.com/read/25825491/reduced-ssy1-ptr3-ssy5-sps-signaling-extends-replicative-life-span-by-enhancing-nad-homeostasis-in-saccharomyces-cerevisiae
#18
Felicia Tsang, Christol James, Michiko Kato, Victoria Myers, Irtqa Ilyas, Matthew Tsang, Su-Ju Lin
Attenuated nutrient signaling extends the life span in yeast and higher eukaryotes; however, the mechanisms are not completely understood. Here we identify the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing pathway as a novel longevity factor. A null mutation of SSY5 (ssy5Δ) increases replicative life span (RLS) by ∼50%. Our results demonstrate that several NAD(+) homeostasis factors play key roles in this life span extension. First, expression of the putative malate-pyruvate NADH shuttle increases in ssy5Δ cells, and deleting components of this shuttle, MAE1 and OAC1, largely abolishes RLS extension...
May 15, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25788480/pharmacological-nad-boosting-strategies-improve-mitochondrial-homeostasis-in-human-complex-i-mutant-fibroblasts
#19
Roberta Felici, Andrea Lapucci, Leonardo Cavone, Sara Pratesi, Rolando Berlinguer-Palmini, Alberto Chiarugi
Mitochondrial disorders are devastating genetic diseases for which efficacious therapies are still an unmet need. Recent studies report that increased availability of intracellular NAD obtained by inhibition of the NAD-consuming enzyme poly(ADP-ribose) polymerase (PARP)-1 or supplementation with the NAD-precursor nicotinamide riboside (NR) ameliorates energetic derangement and symptoms in mouse models of mitochondrial disorders. Whether these pharmacological approaches also improve bioenergetics of human cells harboring mitochondrial defects is unknown...
June 2015: Molecular Pharmacology
https://www.readbyqxmd.com/read/25633578/calorie-restriction-mediated-replicative-lifespan-extension-in-yeast-is-non-cell-autonomous
#20
Szu-Chieh Mei, Charles Brenner
In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media...
January 2015: PLoS Biology
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