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NAD+ increase AND Nicotinamide

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https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#1
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...
November 29, 2016: 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
#2
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
https://www.readbyqxmd.com/read/27902689/using-intrinsic-flavoprotein-and-nad-p-h-imaging-to-map-functional-circuitry-in-the-main-olfactory-bulb
#3
Cedric R Uytingco, Adam C Puche, Steven D Munger
Neurons exhibit strong coupling of electrochemical and metabolic activity. Increases in intrinsic fluorescence from either oxidized flavoproteins or reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] in the mitochondria have been used as an indicator of neuronal activity for the functional mapping of neural circuits. However, this technique has not been used to investigate the flow of olfactory information within the circuitry of the main olfactory bulb (MOB). We found that intrinsic flavoprotein fluorescence signals induced by electrical stimulation of single glomeruli displayed biphasic responses within both the glomerular (GL) and external plexiform layers (EPL) of the MOB...
2016: PloS One
https://www.readbyqxmd.com/read/27892943/temperature-responses-of-rubisco-from-paniceae-grasses-provide-opportunities-for-improving-c3-photosynthesis
#4
Robert E Sharwood, Oula Ghannoum, Maxim V Kapralov, Laura H Gunn, Spencer M Whitney
Enhancing the catalytic properties of the CO2-fixing enzyme Rubisco is a target for improving agricultural crop productivity. Here, we reveal extensive diversity in the kinetic response between 10 and 37 °C by Rubisco from C3 and C4 species within the grass tribe Paniceae. The CO2 fixation rate (kcatc) for Rubisco from the C4 grasses with nicotinamide adenine dinucleotide (NAD) phosphate malic enzyme (NADP-ME) and phosphoenolpyruvate carboxykinase (PCK) photosynthetic pathways was twofold greater than the kcatc of Rubisco from NAD-ME species across all temperatures...
November 28, 2016: Nature Plants
https://www.readbyqxmd.com/read/27889611/anti-apoptotic-quinolinate-phosphoribosyltransferase-qprt-is-a-target-gene-of-wilms-tumor-gene-1-wt1-protein-in-leukemic-cells
#5
Tove Ullmark, Giorgia Montano, Linnea Järvstråt, Helena Jernmark Nilsson, Erik Håkansson, Kristina Drott, Björn Nilsson, Karina Vidovic, Urban Gullberg
Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between WT1 and QPRT, we overexpressed WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of QPRT expression...
November 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27819129/roles-of-sirt3-in-heart-failure-from-bench-to-bedside
#6
De-Xing Hu, Xian-Bao Liu, Wen-Chao Song, Jian-An Wang
Heart failure (HF) represents the most common endpoint of most cardiovascular diseases (CVDs) which are the leading causes of death around the world. Despite the advances in treating CVDs, the prevalence of HF continues to increase. It is believed that better results of prognosis are obtained from prevention rather than additional treatment for HF. Therefore, it is reasonable to prevent the development of CVDs or other complications to HF. Most types of HF are attributed to contractile dysfunction, cardiac hypertrophy or remodeling, and ischemic injuries...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27809334/nicotinamide-adenine-dinucleotide-biosynthesis-promotes-liver-regeneration
#7
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...
November 3, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27798264/nad-repletion-improves-muscle-function-in-muscular-dystrophy-and-counters-global-parylation
#8
Dongryeol Ryu, Hongbo Zhang, Eduardo R Ropelle, Vincenzo Sorrentino, Davi A G Mázala, Laurent Mouchiroud, Philip L Marshall, Matthew D Campbell, Amir Safi Ali, Gary M Knowels, Stéphanie Bellemin, Shama R Iyer, Xu Wang, Karim Gariani, Anthony A Sauve, Carles Cantó, Kevin E Conley, Ludivine Walter, Richard M Lovering, Eva R Chin, Bernard J Jasmin, David J Marcinek, Keir J Menzies, Johan Auwerx
Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD(+)) synthesis, consistent with a potential role for the essential cofactor NAD(+) in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD(+) and are involved in pleiotropic events, including inflammation...
October 19, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27783975/8-thioalkyl-adenosine-derivatives-inhibit-listeria-monocytogenes-nad-kinase-through-a-novel-binding-mode
#9
Julie Paoletti, Liliane Assairi, Muriel Gelin, Valérie Huteau, Marie-Anne Nahori, Olivier Dussurget, Gilles Labesse, Sylvie Pochet
Increased resistance of pathogens to existing antibiotics necessitates the search for novel targets to develop potent antimicrobials. Biosynthetic pathways of several cofactors important for bacterial growth, such as nicotinamide adenine dinucleotide phosphate (NADP), have been proposed as a promising source of antibiotic targets. Nicotinamide adenine dinucleotide kinases (NADK; EC 2.7.1.23) are attractive for inhibitor development, since they catalyze the phosphorylation of NAD to NADP, which is an essential step of NADP metabolism...
October 18, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27773814/role-of-sirtuin3-in-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells
#10
Xiaocui Jiao, Ying Li, Tao Zhang, Maodong Liu, Yanqing Chi
The apoptosis of renal tubular epithelial cells contributes to the pathogenesis of diabetic nephropathy. High glucose-induced mitochondrial oxidative stress is considered to be an important mediator for renal tubular cell apoptosis. Sirtuin3(Sirt3), a kind of mitochondria-localized nicotinamide adenine dinucleotide(NAD(+))-dependent protein deacetylase, has been reported to regulate the generation of ROS in mitochondria through regulating acetylation level and activity of several key mitochondrial enzymes. In this study, we investigated the role of Sirt3 on high glucose-induced apoptosis in HK-2 cells...
October 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27759041/cytoplasmic-proliferating-cell-nuclear-antigen-connects-glycolysis-and-cell-survival-in-acute-myeloid-leukemia
#11
Delphine Ohayon, Alessia De Chiara, Nicolas Chapuis, Céline Candalh, Julie Mocek, Jean-Antoine Ribeil, Lamya Haddaoui, Norbert Ifrah, Olivier Hermine, Frédéric Bouillaud, Philippe Frachet, Didier Bouscary, Véronique Witko-Sarsat
Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S)...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725455/identification-of-a-selective-sirt2-inhibitor-and-its-anti-breast-cancer-activity
#12
Asad Ali Shah, Akihiro Ito, Akiko Nakata, Minoru Yoshida
SIRT2 is a member of the human sirtuin family of proteins and possesses nicotinamide adenine dinucleotide (NAD)-dependent lysine deacetylase activity. SIRT2 has been involved in various cellular processes including gene transcription, genome constancy, and the cell cycle. In addition, SIRT2 is deeply implicated in diverse diseases including cancer. In this study, we identified a small molecule inhibitor of SIRT2 with a structure different from known SIRT2 inhibitors by screening from a chemical library. The hit compound showed a high selectivity toward SIRT2 as it only inhibited SIRT2, and not other sirtuins including SIRT1 and SIRT3 or zinc-dependent histone deacetylases (HDACs) including HDAC1 and HDAC6, in vitro...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27725413/%C3%AE-nicotinamide-mononucleotide-an-anti-aging-candidate-compound-is-retained-in-the-body-for-longer-than-nicotinamide-in-rats
#13
Tomoyo Kawamura, Noriyuki Mori, Katsumi Shibata
The turnover of the oxidized form of nicotinamide adenine dinucleotide (NAD(+)) has attracted interest in regard to longevity. Thus, compounds that can rapidly increase the cellular NAD(+) concentration have been surveyed by many researchers. Of those, β-nicotinamide mononucleotide (β-NMN) has been focused on. Studies on the biosynthesis of NAD(+) from β-NMN have been reported at the cellular level, but not at the whole animal level. In the present study, we investigated whether β-NMN is superior to nicotinamide (Nam) as a precursor of NAD(+) in whole animal experiments...
2016: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/27721479/nicotinamide-riboside-is-uniquely-and-orally-bioavailable-in-mice-and-humans
#14
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/27711204/metabolic-response-to-nad-depletion-across-cell-lines-is-highly-variable
#15
Yang Xiao, Mandy Kwong, Anneleen Daemen, Marcia Belvin, Xiaorong Liang, Georgia Hatzivassiliou, Thomas O'Brien
Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner...
2016: PloS One
https://www.readbyqxmd.com/read/27683265/spatial-characterization-of-bioenergetics-and-metabolism-of-primordial-to-preovulatory-follicles-in-whole-ex-vivo-murine-ovary
#16
Rachel Cinco, Michelle A Digman, Enrico Gratton, Ulrike Luderer
Previous work characterizing ovarian bioenergetics has defined follicular metabolism by measuring metabolic byproducts in culture media. However, culture conditions perturb the native state of the follicle, and these methods do not distinguish between metabolism occurring within oocytes or granulosa cells. We applied the phasor approach to fluorescent lifetime imaging microscopy (Phasor FLIM) at 740 nm 2-photon excitation to examine the spatial distribution of free and protein-bound nicotinamide adenine dinucleotide hydride (NADH) during primordial through preovulatory stages of follicular development in fresh ex vivo murine neonatal and gonadotropin stimulated pre-pubertal ovaries...
September 28, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27663419/inhibiting-poly-adp-ribosylation-increases-fatty-acid-oxidation-and-protects-against-fatty-liver-disease
#17
Karim Gariani, Dongryeol Ryu, Keir J Menzies, Hyon-Seung Yi, Sokrates Stein, Hongbo Zhang, Alessia Perino, Vera Lemos, Elena Katsyuba, Pooja Jha, Sandrine Vijgen, Laura Rubbia-Brandt, Yong Kyung Kim, Jung Tae Kim, Koon Soon Kim, Minho Shong, Kristina Schoonjans, Johan Auwerx
BACKGROUND & AIMS: To date, no pharmacological therapy has been approved for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the therapeutic potential of poly ADP-ribose polymerase (PARP) inhibitors in mouse models of NAFLD. METHODS: As poly ADP-ribosylation (PARylation) of proteins by PARPs consumes nicotinamide adenine dinucleotide (NAD(+)), we hypothesized that overactivation of PARPs drives NAD(+) depletion in NAFLD. Therefore, we assessed the effectiveness of PARP inhibition to replenish NAD(+) and activate NAD(+)-dependent sirtuins, hence improving hepatic fatty acid oxidation...
September 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27651178/hellp-syndrome-altered-hypoxic-response-of-the-fatty-acid-oxidation-regulator-sirt-4
#18
Mareike Sandvoß, Arne Björn Potthast, Frauke von Versen-Höynck, Anibh Martin Das
The hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is frequently observed in mothers whose offspring have long-chain fatty acid oxidation defects. We previously found that fatty acid oxidation is compromised not only in these inborn errors of metabolism but also in human umbilical vein endothelial cells (HUVECs) from all pregnancies complicated by the HELLP syndrome. Sirtuins are oxidized nicotinamide adenine dinucleotide (NAD(+))dependent deacetylases linked to the metabolic status of the cell...
September 20, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27621425/nad-acts-as-an-integral-regulator-of-multiple-defense-layers
#19
Pierre Pétriacq, Jurriaan Ton, Oriane Patrit, Guillaume G B Tcherkez, Bertrand Gakiere
Pyridine nucleotides, such as nicotinamide adenine dinucleotide (NAD), are crucial redox carriers and have emerged as important signaling molecules in stress responses. Previously, we have demonstrated in Arabidopsis thaliana (Arabidopsis) that the inducible NAD-overproducing nadC lines are more resistant to an avirulent strain of Pseudomonas syringae pv. tomato (Pst-AvrRpm1), which was associated with salicylic acid-dependent defense. Here, we have further characterized the NAD-dependent immune response in Arabidopsis...
September 12, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27621317/3-nadp-and-3-naadp-two-metabolites-formed-by-the-bacterial-type-iii-effector-avrrxo1
#20
Felix Schuebel, Andrea Rocker, Daniel Edelmann, Julia Schessner, Clara Brieke, Anton Meinhart
An arsenal of effector proteins is injected by bacterial pathogens into the host cell or its vicinity to increase virulence. The commonly used top-down approaches inferring the toxic mechanism of individual effector proteins from the host's phenotype are often impeded by multiple targets of different effectors as well as by their pleiotropic effects. Here we describe our bottom-up approach, showing that the bacterial type III effector AvrRxo1 of plant pathogens is an authentic phosphotransferase that produces two novel metabolites by phosphorylating nicotinamide / nicotinic acid adenine dinucleotide at the adenosine 3'-hydroxyl group...
September 12, 2016: Journal of Biological Chemistry
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