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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/28919418/the-nampt-e2f2-sirt1-axis-promotes-proliferation-and-inhibits-p53-dependent-apoptosis-in-human-melanoma-cells
#1
Hailong Zhao, Weiwei Tang, Xiaowen Chen, Siyu Wang, Xianyan Wang, Haiyan Xu, Lijuan Li
Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD(+) biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28916720/glucose-availability-controls-adipogenesis-in-mouse-3t3-l1-adipocytes-via-upregulation-of-nicotinamide-metabolism
#2
Robert M Jackson, Beth A Griesel, Jami M Gurley, Luke I Szweda, Ann Louise Olson
Expansion of adipose tissue in response to a positive energy balance underlies obesity and occurs through both hypertrophy of existing cells and increased differentiation of adipocyte precursors (hyperplasia). To better understand the nutrient signals that promote adipocyte differentiation, we investigated the role of glucose availability in regulating adipocyte differentiation and maturation. 3T3-L1 preadipocytes were grown and differentiated in media containing a standard differentiation hormone cocktail and either 4 or 25mM glucose...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915567/melatonin-inhibits-sirt1-dependent-nampt-and-nfat5-signaling-in-chondrocytes-to-attenuate-osteoarthritis
#3
Jia Yi Guo, Feng Li, Yong Bing Wen, Hong Xun Cui, Ma Long Guo, Lin Zhang, Yun Fei Zhang, Yan Jin Guo, Yan Xing Guo
Osteoarthritis (OA) is a degenerative joint disease mainly characterized by cartilage degradation. Interleukin-1β (IL-1β) contributes to OA pathogenesis by enhancing oxidative stress and inflammation. Melatonin reportedly elicits potent protection against OA. However, the role of melatonin and underlying mechanism in IL-1β-stimulated chondrocytes remain largely unclear. In this study, we found that melatonin inhibited IL-1β-induced toxicity and sirtuin 1 (Sirt1) enhancement in human chondrocytes. Melatonin reduced the IL-1β-increased nicotinamide phosphoribosyltransferase (NAMPT) expression and the NAD(+) level in chondrocytes in a Sirt1-dependent manner...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904384/targeting-the-vulnerability-to-nad-depletion-in-b-cell-acute-lymphoblastic-leukemia
#4
S Takao, W Chien, V Madan, D-C Lin, L-W Ding, Q-Y Sun, A Mayakonda, M Sudo, L Xu, Y Chen, Y-Y Jiang, S Gery, M Lill, E Park, W Senapedis, E Baloglu, M Müschen, H P Koeffler
Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase, which regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD), which plays a vital role in energy metabolism...
September 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28899971/matrix-screen-identifies-synergistic-combination-of-parp-inhibitors-and-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-in-ewing-sarcoma
#5
Christine M Heske, Mindy I Davis, Joshua T Baumgart, Kelli M Wilson, Michael V Gormally, Lu Chen, Xiaohu Zhang, Michele Ceribelli, Damien Duveau, Rajarshi Guha, Marc Ferrer, Fernanda I Arnaldez, Jiuping Jay Ji, Huong-Lan Tran, Yiping Zhang, Arnulfo Mendoza, Lee J Helman, Craig J Thomas
PURPOSE: While many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored the in vitro response of Ewing sarcoma cell lines against a large collection of investigational and approved drugs to identify candidate combinations. EXPERIMENTAL DESIGN: Drugs displaying activity as single agents were evaluated in combinatorial (matrix) format to identify highly active, synergistic drug combinations, and combinations were subsequently validated in multiple cell lines using various agents from each class...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28898552/a-key-tyrosine-substitution-restricts-nucleotide-hydrolysis-by-the-ectoenzyme-npp5
#6
Alexei Gorelik, Antsa Randriamihaja, Katalin Illes, Bhushan Nagar
The ecto-nucleotide pyrophosphatase / phosphodiesterase (NPP) family of proteins mediates purinergic signaling by degrading extracellular nucleotides, and also participates in phospholipid metabolism. NPP5 (ENPP5) is the least characterized member of this group and its specific role is unknown. This enzyme does not display activity on certain nucleotides and on other typical NPP substrates. In order to gain insights into its function, we determined the crystal structure of human and murine NPP5. Structural comparison with close homologs revealed a key phenylalanine to tyrosine substitution that prevents efficient hydrolysis of nucleotide diphosphates and triphosphates; reversal of this mutation enabled degradation of these molecules...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#7
Chandra K Singh, Gagan Chhabra, Mary Ndiaye, Liz Mariely Garcia-Peterson, Nicholas John Mack, Nihal Ahmad
SIGNIFICANCE: Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen or nitrogen species (ROS/RNS) and/or oxidative stress within the cell. Imbalances in these molecules can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS in cells. Recent Advances: Sirtuins (SIRTs 1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with the ability to deacetylate histone and non-histone targets...
September 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28888216/vitamin-b-derivative-nicotinamide-appears-to-reduce-skin-cancer-risk
#8
S Nazarali, P Kuzel
Nicotinamide, an amide form of vitamin B3, has shown the potential to treat a variety of dermatological conditions, including acne, rosacea, and atopic dermatitis. Recent studies have demonstrated the role of nicotinamide, in both topical and oral forms, as a chemopreventive agent against skin cancer. Its anti-carcinogenic role may be due to its ability to enhance DNA repair and prevent ultraviolet (UV)-induced immunosuppression, which is known to contribute to the progression of pre-malignant lesions. Furthermore, nicotinamide is a precursor of essential coenzymes for many important reactions in the body, including the production of nicotinamide adenine dinucleotide (NAD)...
September 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28882480/short-term-administration-of-nicotinamide-mononucleotide-preserves-cardiac-mitochondrial-homeostasis-and-prevents-heart-failure
#9
Rongli Zhang, Yuyan Shen, Lin Zhou, Panjamaporn Sangwung, Hisashi Fujioka, Lilei Zhang, Xudong Liao
Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD(+) levels and NAD(+)-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 deficient mouse line that is sensitive to stress, we found mitochondrial protein hyperacetylation coupled with reduced Sirt3 and NAD(+) levels in the heart before stress, suggesting that the KLF4-deficient heart is predisposed to NAD(+)-associated defects...
September 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28880404/cultivation-and-quantitative-single-cell-analysis-of-saccharomyces-cerevisiae-on-a-multifunctional-microfluidic-device
#10
Simone Stratz, Pascal Emilio Verboket, Karina Hasler, Petra Stephanie Dittrich
Here, we present a multifunctional microfluidic device whose integrative design enables to combine cell culture studies and quantitative single cell biomolecule analysis. The platform consists of 32 analysis units providing two key features; first, a micrometer-sized trap for hydrodynamic capture of a single Saccharomyces cerevisiae (S. cerevisiae) yeast cell; second, a convenient double-valve configuration surrounding the trap. Actuating of the outer valve with integrated opening results in a partial isolation in a volume of 11...
September 7, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28877980/nad-metabolism-fuels-human-and-mouse-intestinal-inflammation
#11
Romana R Gerner, Victoria Klepsch, Sophie Macheiner, Kathrin Arnhard, Timon E Adolph, Christoph Grander, Verena Wieser, Alexandra Pfister, Patrizia Moser, Natascha Hermann-Kleiter, Gottfried Baier, Herbert Oberacher, Herbert Tilg, Alexander R Moschen
OBJECTIVE: Nicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated in inflammation including IBD and counteracts an increased cellular NAD turnover mediated by NAD-depleting enzymes. These constitute an important mechanistic link between inflammatory, metabolic and transcriptional pathways and NAD metabolism...
September 6, 2017: Gut
https://www.readbyqxmd.com/read/28871787/nmr-spectroscopy-based-metabolomics-of-drosophila-model-of-huntington-s-disease-suggests-altered-cell-energetics
#12
Virender Singh, Raj Kumar Sharma, Thamarailingam Athilingam, Pradip Sinha, Neeraj Sinha, Ashwani Kumar Thakur
Huntington's disease (HD) is a neurodegenerative disorder induced by aggregation of the pathological form of Huntingtin protein that has expanded polyglutamine (polyQ) repeats. In the Drosophila model, for instance, expression of transgenes with polyQ repeats induce HD-like pathologies progressively correlating with the increasing lengths of these repeats. Previous studies on both animal models and clinical samples have revealed metabolite imbalances during HD progression. To further explore the physiological processes linked to metabolite imbalances during HD, we have investigated 1D (1)H NMR spectroscopy-based metabolomics profile of Drosophila HD model...
September 5, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28870901/nicotinamide-phosphoribosyl-transferase-a-reliable-marker-of-progression-in-cervical-dysplasia
#13
Moiz Vora, Lubna A Alattia, Junaid Ansari, Menchu Ong, James Cotelingam, Domenico Coppola, Rodney Shackelford
BACKGROUND/AIM: Nicotinamide phosphoribosyl transferase (Nampt) catalyses the rate-limiting step of the mammalian nicotinamide adenine dinucleotide (NAD) salvage pathway. Nampt is highly expressed in several epithelial and mesenchymal neoplasms, where is promotes cell-cycle progression ans chemotherapy resistance. To our knowledge, alterations in Nampt expression have not been examined in cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC). MATERIALS AND METHODS: We performed immunohistochemical analysis for Nampt using tissue microarrays on 14 samples of benign cervical squamous epithelium and 15 CIN I, 15 CIN II, and 13 samples of CIN III...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28870631/the-sirtuin-family-members-sirt1-sirt3-and-sirt6-their-role-in-vascular-biology-and-atherogenesis
#14
REVIEW
Bożena Sosnowska, Mohsen Mazidi, Peter Penson, Anna Gluba-Brzózka, Jacek Rysz, Maciej Banach
The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis...
August 26, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28866798/development-of-an-amperometric-biosensor-platform-for-the-combined-determination-of-l-malic-fumaric-and-l-aspartic-acid
#15
Désirée L Röhlen, Johanna Pilas, Michael J Schöning, Thorsten Selmer
Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD(+)) and the redox mediator hexacyanoferrate (III) (HCFIII)...
September 2, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28863411/sirtuin-1-levels-in-recurrent-implantation-failure
#16
Yaprak Engin-Ustun, A Seval Ozgu-Erdinc, Emel Kiyak Caglayan, Cavidan Gulerman, Esma Sarikaya, Ayla Aktulay, Canan Demirtas, Salim Erkaya, Nafiye Yilmaz
Sirtuin 1 has an important role in cellular processes, including apoptosis and cellular stress. The purpose of this study was to assess serum sirtuin 1 levels in women with recurrent implantation failure (RIF). In this cross-sectional study, we included 28 women with RIF, 29 healthy women who had conceived by in vitro fertilization (IVF), and 30 women with a 1-cycle failure of IVF as controls. Human serum nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin-1 (SIRT1/SIRT2L1) levels were detected using a commercial colorimetric kit...
September 1, 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28860386/structural-basis-of-the-redox-switches-in-the-nad-reducing-soluble-nife-hydrogenase
#17
Y Shomura, M Taketa, H Nakashima, H Tai, H Nakagawa, Y Ikeda, M Ishii, Y Igarashi, H Nishihara, K-S Yoon, S Ogo, S Hirota, Y Higuchi
NAD(+) (oxidized form of NAD:nicotinamide adenine dinucleotide)-reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD(+)):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe-S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules...
September 1, 2017: Science
https://www.readbyqxmd.com/read/28860121/nad-synthesis-pathway-interference-is-a-viable-therapeutic-strategy-for-chondrosarcoma
#18
Elisabeth Fp Peterse, Brendy van den Akker, Bertine Niessen, Jan Oosting, Johnny Suijker, Yvonne de Jong, Erik H Danen, Anne-Marie Cleton-Jansen, Judith V M G Bovee
Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT) are rate-limiting enzymes in the nicotinamide adenine dinucleotide (NAD+) synthesis pathway. Chondrosarcoma is a malignant cartilage forming bone tumor, in which mutations altering isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) activity have been identified as potential driver mutations. Vulnerability for NAD+ depletion has been reported for IDH1/2 mutant cells. Here, the potency of NAMPT inhibitors as a treatment of chondrosarcoma was explored...
August 31, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28858708/the-time-dependent-stimulation-of-sodium-halide-salts-on-redox-reactants-energy-supply-and-luminescence-in-vibrio-fischeri
#19
Zhenyang Yu, Jing Zhang, Meifang Hou
The excess of halide ions (F(-), Cl(-), Br(-), I(-)) can cause adverse effects. Earlier studies demonstrated time-dependent stimulations of organic salts with halide ions on photobacteria. Therefore, inorganic ones with halide ions (e.g., NaX, X=F(-), Cl(-), Br(-), I(-)) were assumed to cause similar effects. In the present study, Vibrio fischeri was exposed to NaX. Results showed that the contents of favin mono-nucleotide (FMN), nicotinamide adenine dinucleotide (NADH), and nicotinamide adenine dinucleotide phosphate (NADPH) were stimulated by NaX with a time-dependent fashion...
August 28, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28858158/glaucoma-as-a-metabolic-optic-neuropathy-making-the-case-for-nicotinamide-treatment-in-glaucoma
#20
Pete A Williams, Jeffrey M Harder, Simon W M John
Mitochondrial dysfunction may be an important, if not essential, component of human glaucoma. Using transcriptomics followed by molecular and neurobiological techniques, we have recently demonstrated that mitochondrial dysfunction within retinal ganglion cells is an early feature in the DBA/2J mouse model of inherited glaucoma. Guided by these findings, we discovered that the retinal level of nicotinamide adenine dinucleotide (NAD, a key molecule for mitochondrial health) declines in an age-dependent manner...
August 28, 2017: Journal of Glaucoma
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