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https://www.readbyqxmd.com/read/28090296/endotoxin-and-mechanical-stress-induced-epigenetic-changes-in-the-regulation-of-the-nicotinamide-phosphoribosyltransferase-promoter
#1
Venkateswaran Ramamoorthi Elangovan, Sara M Camp, Gabriel T Kelly, Ankit A Desai, Djanybek Adyshev, Xiaoguang Sun, Stephen M Black, Ting Wang, Joe G N Garcia
Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28035412/nicotinamide-phosphoribosyltransferase-inhibits-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-induced-osteoclast-differentiation-in%C3%A2-vitro
#2
Jong Min Baek, Sung-Jun Ahn, Yoon-Hee Cheon, Myeung Su Lee, Jaemin Oh, Ju-Young Kim
The adipokine nicotinamide phosphoribosyltransferase (Nampt), also known as pre-B-cell colony-enhancing factor or the insulin-mimetic hormone visfatin, has a crucial role in the conversion of nicotinamide to nicotinamide mononucleotide during biosynthesis of the coenzyme nicotinamide adenine dinucleotide. Previous reports have demonstrated the inhibitory effects of Nampt on osteoclast formation from human peripheral blood mononuclear cells and CD14+ monocytes. However, the effects of Nampt on bone marrow macrophage (BMM)‑derived osteoclastogenesis and its precise role in the process remain unclear...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28032230/protective-effect-of-p7c3-on-retinal-ganglion-cells-from-optic-nerve-injury
#3
Hidehiro Oku, Seita Morishita, Taeko Horie, Yuko Nishikawa, Teruyo Kida, Masashi Mimura, Shota Kojima, Tsunehiko Ikeda
PURPOSE: To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing. METHODS: The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7...
December 28, 2016: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/27981536/nicotinamide-phosphoribosyltransferase-enhances-beta-cell-expansion-during-pregnancy
#4
J Feng, H-Y Li, X-L Wang, Y Huo, S-X Liu, L Li
OBJECTIVE: Many factors contribute to the development of gestational diabetes mellitus (GDM). Among these factors, nicotinamide phosphoribosyltransferase (NAMPT) plays a critical role. Previous studies have demonstrated the effects of NAMPT on insulin resistance during GDM, while the effects of NAMPT on beta cells remain unknown. Here we addressed this question. PATIENTS AND METHODS: Mouse islets were isolated and transduced with adeno-associated vectors carrying NAMPT...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27966038/gm-csf-treatment-is-not-effective-in-congenital-neutropenia-patients-due-to-its-inability-to-activate-nampt-signaling
#5
Corinna Koch, Bardia Samareh, Tatsuya Morishima, Perihan Mir, Lothar Kanz, Cornelia Zeidler, Julia Skokowa, Karl Welte
Severe congenital neutropenia (CN) is a bone marrow failure syndrome characterized by an absolute neutrophil count (ANC) below 500 cells/μL and recurrent, life-threatening bacterial infections. Treatment with granulocyte colony-stimulating factor (G-CSF) increases the ANC in the majority of CN patients. In contrary, granulocyte-monocyte colony-stimulating factor (GM-CSF) fails to increase neutrophil numbers in CN patients in vitro and in vivo, suggesting specific defects in signaling pathways downstream of GM-CSF receptor...
December 14, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27930300/an-nad-dependent-transcriptional-program-governs-self-renewal-and-radiation-resistance-in-glioblastoma
#6
Amit D Gujar, Son Le, Diane D Mao, David Y A Dadey, Alice Turski, Yo Sasaki, Diane Aum, Jingqin Luo, Sonika Dahiya, Liya Yuan, Keith M Rich, Jeffrey Milbrandt, Dennis E Hallahan, Hiroko Yano, David D Tran, Albert H Kim
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD(+)). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD(+) synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#7
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek R Clements, Youra Kim, Patrick W K Lee, Shashi A Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27897114/ureas-applications-in-drug-design-and-development
#8
Ajit Dhananjay Jagtap, Nagendra Bharatrao Kondekar, Amit A Sadani, Ji-Wang Chern
The unique hydrogen binding capabilities of ureas make them an important functional group to make drug-target interactions and thus incorporated in small molecules displaying broad range of bioactivities. The related research and numerous excellent achievements of ureas applicability in drug design for the modulation of selectivity, stability, toxicity and pharmacokinetic profile of lead molecules have become active topic. This review aims to provide insights in to the significance of urea in drug design by summarizing successful studies of various urea derivatives as modulators biological targets (viz...
November 29, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27809334/nicotinamide-adenine-dinucleotide-biosynthesis-promotes-liver-regeneration
#9
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
#10
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/27783203/cardiotoxicity-associated-with-nicotinamide-phosphoribosyltransferase-inhibitors-in-rodents-and-in-rat-and-human-derived-cells-lines
#11
D L Misner, M A Kauss, J Singh, H Uppal, A Bruening-Wright, B M Liederer, T Lin, B McCray, N La, T Nguyen, D Sampath, P S Dragovich, T O'Brien, T S Zabka
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein that functions as an enzyme, cytokine, growth factor and hormone. As a target for oncology, NAMPT is particularly attractive, because it catalyzes the rate-limiting step in the salvage pathway to generate nicotinamide adenine dinucleotide (NAD), a universal energy- and signal-carrying molecule involved in cellular energy metabolism and many homeostatic functions. Inhibition of NAMPT generally results in NAD depletion, followed by ATP reduction and loss of cell viability...
October 25, 2016: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/27759041/cytoplasmic-proliferating-cell-nuclear-antigen-connects-glycolysis-and-cell-survival-in-acute-myeloid-leukemia
#12
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/27756900/synchronized-human-skeletal-myotubes-of-lean-obese-and-type-2-diabetic-patients-maintain-circadian-oscillation-of-clock-genes
#13
Jan Hansen, Silvie Timmers, Esther Moonen-Kornips, Helene Duez, Bart Staels, Matthijs K C Hesselink, Patrick Schrauwen
Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (HPM) to investigate if rhythmicity of clock- and metabolic gene expression is altered in donors with obesity or type 2 diabetes compared to metabolically healthy donors...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27754828/small-interfering-rna-mediated-silencing-of-nicotinamide-phosphoribosyltransferase-nampt-and-lysosomal-trafficking-regulator-lyst-induce-growth-inhibition-and-apoptosis-in-human-multiple-myeloma-cells-a-preliminary-study
#14
Ivyna Pau Ni Bong, Ching Ching Ng, Shaik Kamal Fakiruddin, Moon Nian Lim, Zubaidah Zakaria
Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers...
November 10, 2016: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27754252/os-36-03-e-box-cpg-hypomethylation-of-nmn-producing-enzyme-nampt-in-proximal-tubules-enables-constant-supply-of-nmn-from-tubules-to-glomeruli-which-is-disrupted-in-diabetic-nephropathy
#15
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27739514/metabolism-nampt-deletion-blinds-mice
#16
Charlotte Ridler
No abstract text is available yet for this article.
October 14, 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27732642/replicative-senescence-in-human-fibroblasts-is-delayed-by-hydrogen-sulfide-in-a-nampt-sirt1-dependent-manner
#17
Reiko Sanokawa-Akakura, Shin Akakura, Siamak Tabibzadeh
Recent evidence suggests that hydrogen sulfide (H2S) has cytoprotective and anti-aging effects. However, the mechanisms for such properties are not fully understood. Here, we show that the expression of the main H2S producing enzyme, CBS, and production of H2S are coordinately diminished in replicative senescent adult human dermal fibroblasts. The reduced production of H2S falls within the same time-frame that the hallmarks of replicative senescence appear including accumulation of SA-β-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall...
2016: PloS One
https://www.readbyqxmd.com/read/27712122/the-relationship-between-circulating-visfatin-nicotinamide-phosphoribosyltransferase-obesity-inflammation-and-lipids-profile-in-elderly-population-determined-by-structural-equation-modeling
#18
Aleksander J Owczarek, Magdalena Olszanecka-Glinianowicz, Piotr Kocełak, Maria Bożentowicz-Wikarek, Aniceta Brzozowska, Małgorzata Mossakowska, Monika Puzianowska-Kuźnicka, Tomasz Grodzicki, Andrzej Więcek, Jerzy Chudek
BACKGROUND: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. MATERIALS AND METHODS: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR...
December 2016: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/27711204/metabolic-response-to-nad-depletion-across-cell-lines-is-highly-variable
#19
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/27688470/nampt-inhibitor-gmx1778-enhances-the-efficacy-of-177lu-dotatate-treatment-of-neuroendocrine-tumors
#20
Anna-Karin Elf, Peter Bernhardt, Tobias Hofving, Yvonne Arvidsson, Eva Forssell-Aronsson, Bo Wängberg, Ola Nilsson, Viktor Johanson
: Neuroendocrine tumors (NETs) can be treated by peptide receptor radionuclide therapy using radiolabeled somatostatin analogs. However, the efficacy of such treatment is low and needs to be optimized. AIMS: To evaluate the potential radiosensitizing effects of NAMPT inhibition on (177)Lu-DOTATATE treatment in a NET model. METHODS: Nude mice xenografted with the human NET cell line GOT1 were treated with semi-efficient doses of (177)Lu-DOTATATE (7,5 MBq, i...
September 29, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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