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https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#1
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333140/metabolic-and-molecular-insights-into-an-essential-role-of-nicotinamide-phosphoribosyltransferase
#2
Li Q Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P Heruth, Charlie Bi, Roger Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt(-/-)) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28330719/nicotinamide-mononucleotide-inhibits-jnk-activation-to-reverse-alzheimer-disease
#3
Zhiwen Yao, Wenhao Yang, Zhiqiang Gao, Peng Jia
Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice...
March 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28322315/quantitative-proteomic-analysis-on-activated-hepatic-stellate-cells-reversion-reveal-stat1-as-a-key-regulator-between-liver-fibrosis-and-recovery
#4
Hongyu Zhang, Fangyan Chen, Xu Fan, Cong Lin, Yunwei Hao, Handong Wei, Weiran Lin, Ying Jiang, Fuchu He
Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295415/adipose-tissue-nad-biology-in-obesity-and-insulin-resistance-from-mechanism-to-therapy
#5
REVIEW
Shintaro Yamaguchi, Jun Yoshino
Nicotinamide adenine dinucleotide (NAD(+) ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD(+) biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD(+) biosynthesis, together with its key downstream mediator, namely the NAD(+) -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner...
March 15, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28293019/novel-adipokines-methodological-utility-in-human-obesity-research
#6
F Eichelmann, N Rudovich, A F Pfeiffer, M B Schulze, R di Giuseppe, H Boeing, K Aleksandrova
BACKGROUND: Adipokines could pose a link between adiposity, systemic inflammation and metabolic disease risk. However, it is unclear whether representative biomarkers are methodologically suitable for use in human obesity research. METHODS: We assessed the intra-individual reproducibility of selected adipokines in a sample of 207 apparently healthy participants with available biosample collections over 4 month period. Concentrations of the following adipokines were measured at each sampling time point: fatty-acid binding protein-4 (FABP-4), lipocalin-2, monocyte chemoattractant protein 1 (MCP-1), procalcitonin, progranulin, vaspin and visfatin/Nampt...
March 15, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28276108/circrna-hsa_circ_0005105-up-regulates-nampt-expression-and-promotes-chondrocyte-extracellular-matrix-degradation-by-sponging-mir-26a
#7
You Wu, Ying Zhang, Yu Zhang, Jia-Jia Wang
Osteoarthritis (OA) is a chronic disease pathologically characterized by articular cartilage degeneration and damage. Currently, studies have found that circular RNA (circRNA) is involved in intracellular RNA regulating network and is closely related to the occurrence and development of diseases, therefore it may become a new biological marker and therapeutic target. After stimulating chondrocytes with interleukin-1 beta (IL-1β), hsa_circ_0005105 expression was significantly upregulated, while miR-26a expression was significantly inhibited...
March 8, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28271737/could-nampt-inhibition-become-a-potential-treatment-option-in-hepatocellular-carcinoma
#8
Antje Garten, Susanne Schuster, Melanie Penke
No abstract text is available yet for this article.
March 8, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28254441/omega-3-polyunsaturated-fatty-acids-suppress-the-inflammatory-responses-of-lipopolysaccharide-stimulated-mouse-microglia-by-activating-sirt1-pathways
#9
Takayuki Inoue, Masashi Tanaka, Shinya Masuda, Ryuji Ohue-Kitano, Hajime Yamakage, Kazuya Muranaka, Hiromichi Wada, Toru Kusakabe, Akira Shimatsu, Koji Hasegawa, Noriko Satoh-Asahara
Obesity and diabetes are known risk factors for dementia, and it is speculated that chronic neuroinflammation contributes to this increased risk. Microglia are brain-resident immune cells modulating the neuroinflammatory state. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major ω-3 polyunsaturated fatty acids (PUFAs) of fish oil, exhibit various effects, which include shifting microglia to the anti-inflammatory phenotype. To identify the molecular mechanisms involved, we examined the impact of EPA, DHA, and EPA+DHA on the lipopolysaccharide (LPS)-induced cytokine profiles and the associated signaling pathways in the mouse microglial line MG6...
February 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28251652/sirt1-may-play-a-crucial-role-in-overload-induced-hypertrophy-of-skeletal-muscle
#10
Erika Koltai, Zoltán Bori, Clovis Chabert, Hervé Dubouchaud, Hisashi Naito, Shuichi Machida, Kelvin Ja Davies, Zsolt Murlasits, Andrew C Fry, Istvan Boldogh, Zsolt Radak
Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well-studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus, and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in SIRT1 content and activity (P < 0...
March 2, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28251397/effect-of-lifelong-football-training-on-the-expression-of-muscle-molecular-markers-involved-in-healthy-longevity
#11
A Mancini, D Vitucci, G Labruna, E Imperlini, M B Randers, J F Schmidt, M Hagman, T R Andersen, R Russo, S Orrù, P Krustrup, F Salvatore, P Buono
PURPOSE: We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. METHODS: Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively...
March 1, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28224719/cardiomyocyte-differentiation-promotes-cell-survival-during-nicotinamide-phosphoribosyltransferase-inhibition-through-increased-maintenance-of-cellular-energy-stores
#12
Erin M Kropp, Katarzyna A Broniowska, Matthew Waas, Alyssa Nycz, John A Corbett, Rebekah L Gundry
To address concerns regarding the tumorigenic potential of undifferentiated human pluripotent stem cells (hPSC) that may remain after in vitro differentiation and ultimately limit the broad use of hPSC-derivatives for therapeutics, we recently described a method to selectively eliminate tumorigenic hPSC from their progeny by inhibiting nicotinamide phosphoribosyltransferase (NAMPT). Limited exposure to NAMPT inhibitors selectively removes hPSC from hPSC-derived cardiomyocytes (hPSC-CM) and spares a wide range of differentiated cell types; yet, it remains unclear when and how cells acquire resistance to NAMPT inhibition during differentiation...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205648/identification-of-a-novel-nampt-inhibitor-by-crispr-cas9-chemogenomic-profiling-in-mammalian-cells
#13
David Estoppey, Jeffrey W Hewett, Chantale T Guy, Edmund Harrington, Jason R Thomas, Markus Schirle, Rachel Cuttat, Annick Waldt, Bertran Gerrits, Zinger Yang, Sven Schuierer, Xuewen Pan, Kevin Xie, Walter Carbone, Judith Knehr, Alicia Lindeman, Carsten Russ, Elizabeth Frias, Gregory R Hoffman, Malini Varadarajan, Nadire Ramadan, John S Reece-Hoyes, Qiong Wang, Xin Chen, Gregory McAllister, Guglielmo Roma, Tewis Bouwmeester, Dominic Hoepfner
Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets and the mechanism of bioactive compounds. Until recently, genome-wide, high-resolution experiments of this nature have been limited to fungal systems due to lack of mammalian genome-wide deletion collections. With the example of a novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, we demonstrate that the CRISPR/Cas9 system enables the generation of transient homo- and heterozygous deletion libraries and allows for the identification of efficacy targets and pathways mediating hypersensitivity and resistance relevant to the compound mechanism of action...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#14
Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M Camp, Haiyang Tang, Shui Quing Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F Machado
Background -Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT), is a cytozyme which regulates intracellular NAD levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling, and that inhibition of NAMPT could attenuate pulmonary hypertension. Methods -Plasma and mRNA and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells (PAECs) from PAH patients, as well as in lungs of rodent models of pulmonary hypertension (PH)...
February 15, 2017: Circulation
https://www.readbyqxmd.com/read/28198380/a-novel-orally-bioavailable-compound-kpt-9274-inhibits-pak4-and-blocks-triple-negative-breast-cancer-tumor-growth
#15
Chetan Rane, William Senapedis, Erkan Baloglu, Yosef Landesman, Marsha Crochiere, Soumyasri Das-Gupta, Audrey Minden
Breast cancer is a heterogeneous disease consisting of several subtypes. Among these subtypes, triple negative breast cancer is particularly difficult to treat. This is due to a lack of understanding of the mechanisms behind the disease, and consequently a lack of druggable targets. PAK4 plays critical roles in cell survival, proliferation, and morphology. PAK4 protein levels are high in breast cancer cells and breast tumors, and the gene is often amplified in basal like breast cancers, which are frequently triple negative...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28177124/acute-exercise-elicits-differential-expression-of-insulin-resistance-genes-in-the-skeletal-muscle-of-patients-with-polycystic-ovary-syndrome
#16
Wagner Silva Dantas, Igor Hisashi Murai, Luiz Augusto Perandini, Hatylas Azevedo, Carlos Alberto Moreira-Filho, Niels Olsen Saraiva Camara, Hamilton Roschel, Bruno Gualano
OBJECTIVE: This study aimed to explore the role of acute exercise on skeletal muscle gene expression related to insulin resistance in patients with polycystic ovary syndrome (PCOS) and controls. METHODS: Four obese women with PCOS and 4 body controls subjects (CTRL) participated in this study. After an overnight fast, the subjects underwent a single 40-minute bout of aerobic exercise. Muscle samples were obtained from vastus lateralis at baseline and 60 minutes after exercise...
February 8, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28168205/role-of-nampt-and-visceral-adiposity-in-esophagogastric-junction-adenocarcinoma
#17
Haijun Li, E Bai, Yong Zhang, Zhuoqi Jia, Shicai He, Junke Fu
Nampt including eNampt and iNampt may contribute to mediating obesity-associated cancers. This study investigated the role of Nampt in esophagogastric junction adenocarcinoma (EGA), a cancer strongly correlated with obesity. Visceral adiposity was defined by waist circumference or VFA. eNampt in sera were measured by enzyme-linked immunosorbent assay. iNampt expression in EGA was determined by PCR, western blot, and immunohistochemistry. Sera eNampt were significantly elevated in these overweight and obese patients, especially for viscerally obese patients, and positively correlated with BMI, waist circumference, VFA, and also primary tumor, regional lymph nodes, and TNM stage (P < 0...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28165872/nampt-is-an-essential-regulator-of-ra-mediated-periodontal-inflammation
#18
D Kim, G Lee, Y H Huh, S Y Lee, K H Park, S Kim, J Kim, J Koh, J Ryu
Recent studies have indicated a potential correlation between rheumatoid arthritis (RA) and periodontal inflammation. We undertook this study to verify whether RA mediates periodontitis-like phenotypes in experimental mouse models of RA and to explore the role of nicotinamide phosphoribosyltransferase (NAMPT) in periodontal inflammation during RA pathogenesis. Periodontal inflammation and alveolar bone loss have been reported in mice with collagen-induced arthritis (CIA) and in genetically modified tumor necrosis factor-α (TNF-α) transgenic (TG) mouse models...
February 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28165742/identification-of-novel-triazole-based-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-endowed-with-antiproliferative-and-antiinflammatory-activity
#19
Cristina Travelli, Silvio Aprile, Reza Rahimian, Ambra A Grolla, Federica Rogati, Mattia Bertolotti, Floriana Malagnino, Rosanna di Paola, Daniela Impellizzeri, Roberta Fusco, Valentina Mercalli, Alberto Massarotti, Giorgio Stortini, Salvatore Terrazzino, Erika Del Grosso, Gohar Fakhfouri, Maria Pia Troiani, Maria Alessandra Alisi, Giorgio Grosa, Giovanni Sorba, Pier Luigi Canonico, Giuseppe Orsomando, Salvatore Cuzzocrea, Armando A Genazzani, Ubaldina Galli, Gian Cesare Tron
Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme involved in the recycling of nicotinamide to maintain adequate NAD levels inside the cells. It has been postulated to be a pharmacological target, as it is overexpressed in cancer cells as well as in inflammatory diseases. We describe the synthesis and characterization of a novel class of one-digit nanomolar NAMPT inhibitors based on in vitro characterization. The most active compound tested, 30c, displayed activity in xenograft and allograft models, strengthening the potential of NAMPT inhibitors as antitumoral drugs...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28163205/localization-pattern-of-visfatin-nampt-in-d-galactose-induced-aged-rat-testis
#20
Malsawmhriatzuala Jeremy, Guruswami Gurusubramanian, Vikas Kumar Roy
Aging is a complex irreversible process which leads to decline in body physiology including reproductive activity. Neurological and brain functions defects have been studied in the d-gal induced aging rodent model. However, there is dearth of literature on reproductive aging induced by d-gal treatment. Visfatin is an adipokine which regulates testicular steroidogenesis and its level increases under stress conditions to cope and extend longevity. To the best of our knowledge the expression and localization pattern of visfatin and histological evaluation of d-gal induced aged testis have not been investigated...
February 3, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
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