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NAD+ increase AND Nicotinamide

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https://www.readbyqxmd.com/read/28548540/nicotinamide-adenine-dinucleotide-nad-sup-sup-metabolism-and-neurodegeneration
#1
Mariana Pehar, Benjamin A Harlan, Kelby M Killoy, Marcelo R Vargas
SIGNIFICANCE: Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) participates in redox reactions and NAD<sup>+</sup>-dependent signaling processes, which involve the cleavage of NAD<sup>+</sup> coupled to post-translational modifications of proteins or the production of second messengers. Either as a primary cause or as a secondary component of the pathogenic process, mitochondrial dysfunction and oxidative stress are prominent features of several neurodegenerative diseases...
May 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28546856/epigenetic-regulation-of-runx2-transcription-and-osteoblast-differentiation-by-nicotinamide-phosphoribosyltransferase
#2
Min Ling, Peixin Huang, Shamima Islam, Daniel P Heruth, Xuanan Li, Li Qin Zhang, Ding-You Li, Zhaohui Hu, Shui Qing Ye
BACKGROUND: Bone degenerative disorders like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Although there are studies suggesting that metabolic changes occur with stem cell differentiation, the molecular mechanisms governing energy metabolism and epigenetic modification are not understood fully. Here we reported the key role of nicotinamide phosphoribosyltransferase (Nampt), which is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide, in the osteogenic differentiation of bone marrow stromal cells...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28543772/parp-inhibitor-rucaparib-induces-changes-in-nad-levels-in-cells-and-liver-tissues-as-assessed-by-mrs
#3
Gilberto S Almeida, Carlo M Bawn, Martin Galler, Ian Wilson, Huw D Thomas, Suzanne Kyle, Nicola J Curtin, David R Newell, Ross J Maxwell
Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ((1) H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD(+) ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28536482/nad-loss-a-new-player-in-ahr-biology-prevention-of-thymus-atrophy-and-hepatosteatosis-by-nad-repletion
#4
Silvia Diani-Moore, Jenny Shoots, Rubi Singh, Joshua B Zuk, Arleen B Rifkind
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a carcinogenic and highly toxic industrial byproduct that persists in the environment and produces a pleiotropic toxicity syndrome across vertebrate species that includes wasting, hepatosteatosis, and thymus atrophy. Dioxin toxicities require binding and activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. However, after nearly 50 years of study, it remains unknown how AhR activation by dioxin produces toxic effects...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#5
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#6
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28507103/nicotinic-acid-phosphoribosyltransferase-regulates-cancer-cell-metabolism-susceptibility-to-nampt-inhibitors-and-dna-repair
#7
Francesco Piacente, Irene Caffa, Silvia Ravera, Giovanna Sociali, Mario Passalacqua, Valerio G Vellone, Pamela Becherini, Daniele Reverberi, Fiammetta Monacelli, Alberto Ballestrero, Patrizio Odetti, Antonia Cagnetta, Michele Cea, Aimable Nahimana, Michel A Duchosal, Santina Bruzzone, Alessio Nencioni
In the last decade, substantial efforts have been made to identify NAD+ biosynthesis inhibitors, specifically against nicotinamide phosphoribosyltransferase (NAMPT), as preclinical studies indicate their potential efficacy as cancer drugs. However, the clinical activity of NAMPT inhibitors has proven limited, suggesting that alternative NAD+ production routes exploited by tumors confer resistance. Here we show the gene encoding nicotinic acid phosphoribosyltransferase (NAPRT), a second NAD+ producing enzyme, is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature...
May 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28495827/hyperbaric-oxygen-reduces-infarction-volume-and-hemorrhagic-transformation-through-atp-nad-sirt1-pathway-in-hyperglycemic-middle-cerebral-artery-occlusion-rats
#8
Qin Hu, Anatol Manaenko, Hetao Bian, Zongduo Guo, Jun-Long Huang, Zhen-Ni Guo, Peng Yang, Jiping Tang, John H Zhang
BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion...
May 11, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28487632/nicotinamide-and-wld-s-act-together-to-prevent-neurodegeneration-in-glaucoma
#9
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Brynn H Cardozo, Kelly E Cochran, Simon W M John
Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with a critical insult damaging their axons in the optic nerve head. This insult is typically secondary to harmfully high levels of intraocular pressure (IOP). We have previously determined that early mitochondrial abnormalities within retinal ganglion cells lead to neuronal dysfunction, with age-related declines in NAD (NAD(+) and NADH) rendering retinal ganglion cell mitochondria vulnerable to IOP-dependent stresses...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28477081/exogenous-nicotinamide-supplementation-and-moderate-physical-exercise-can-attenuate-the-aging-process-in-skeletal-muscle-of-rats
#10
Melitta Pajk, Alexandra Cselko, Csaba Varga, Aniko Posa, Margareta Tokodi, Istvan Boldogh, Sataro Goto, Zsolt Radak
Nicotinamide (NAM) could enhance the availability of NAD(+) and be beneficial to cell function. However, NAM can inhibit the activities of SIRT1 and PARP. The effect of NAM supplementation on the aging process is not well known. In the present study exogenous NAM (1-0.5% in drinking water) was supplemented for 5 weeks and in the last 4 weeks moderate treadmill running was given to 5 mo and 28 mo old rats. The content of SIRT1 was not effected by NAM treatment alone. However, the activity of SIRT1, judged from the acetylated p53/p53 ratio, increased in both NAM treated age groups, suggesting beneficial effects of exogenous NAM...
May 5, 2017: Biogerontology
https://www.readbyqxmd.com/read/28468736/prevention-of-non-melanoma-skin-cancers-with-nicotinamide-in-transplant-recipients-a-case-control-study
#11
Francesco Drago, Giulia Ciccarese, Ludovica Cogorno, Camillo Calvi, Luigina A Marsano, Aurora Parodi
Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for adenosine triphosphate (ATP) production. It has recently been reported to be effective in reducing the rates of new non-melanoma skin cancers (NMSCs) and actinic keratosis (AKs). We studied the efficacy of oral nicotinamide as treatment for AKs in transplant recipients. We recruited 38 transplant (eight liver and 30 kidney) patients with single or multiple AKs. Nineteen patients were randomly assigned to Group 1 and took nicotinamide 500 mg/daily (cases); the other 19 patients were randomly assigned to Group 2 without nicotinamide (controls)...
May 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28449683/inhibition-of-nampt-aggravates-high-fat-diet-induced-hepatic-steatosis-in-mice-through-regulating-sirt1-ampk%C3%AE-srebp1-signaling-pathway
#12
Ling-Fang Wang, Xiao-Nv Wang, Cong-Cong Huang, Long Hu, Yun-Fei Xiao, Xiao-Hui Guan, Yi-Song Qian, Ke-Yu Deng, Hong-Bo Xin
BACKGROUND: Nonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD(+)) biosynthesis and plays an important role in cellular metabolism in variety of organs in mammals. The aim of this study was to investigate the effects of NAMPT on high fat diet-induced hepatic steatosis...
April 27, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28435063/regulation-of-nampt-expression-by-transcriptional-coactivator-ncoa6-in-pancreatic-%C3%AE-cells
#13
Jin Yoon, Kyung Jin Lee, Gyun-Sik Oh, Geun Hyang Kim, Seung-Whan Kim
Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator and crucial for insulin secretion and glucose metabolism in pancreatic β-cells. However, the regulatory mechanism of β-cell function by NCOA6 is largely unknown. In this study, we found that the transcript levels of nicotinamide phosphoribosyltransferase (Nampt) were decreased in islets of NCOA6(+/-) mice compared with NCOA6(+/+) mice. Moreover, NCOA6 overexpression increased the levels of Nampt transcripts in the mouse pancreatic β-cell line NIT-1...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432298/endogenous-two-photon-excited-fluorescence-imaging-characterizes-neuron-and-astrocyte-metabolic-responses-to-manganese-toxicity
#14
Emily Stuntz, Yusi Gong, Disha Sood, Volha Liaudanskaya, Dimitra Pouli, Kyle P Quinn, Carlo Alonzo, Zhiyi Liu, David L Kaplan, Irene Georgakoudi
As neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424540/mc-ppea-as-a-new-and-more-potent-inhibitor-of-clp-induced-sepsis-and-pulmonary-inflammation-than-fk866
#15
Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P Heruth, Li Q Zhang, Dev Maulik, Shui Qing Ye
Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28420001/nicotinamide-n-methyltransferase-suppression-participates-in-nickel-induced-histone-h3-lysine9-dimethylation-in-beas-2b-cells
#16
Qian Li, Min-Di He, Lin Mao, Xue Wang, Yu-Lin Jiang, Min Li, Yong-Hui Lu, Zheng-Ping Yu, Zhou Zhou
BACKGROUND: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 μM NiCl2 for different time periods...
April 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28417163/nicotinamide-is-an-inhibitor-of-sirt1-in-vitro-but-can-be-a-stimulator-in-cells
#17
REVIEW
Eun Seong Hwang, Seon Beom Song
Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell physiology through facilitating NAD(+) redox homeostasis and providing NAD(+) as a substrate to a class of enzymes that catalyze non-redox reactions. These non-redox enzymes include the sirtuin family proteins which deacetylate target proteins while cleaving NAD(+) to yield NAM. Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology...
April 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28416276/synthesis-and-degradation-of-adenosine-5-tetraphosphate-by-nicotinamide-and-nicotinate-phosphoribosyltransferases
#18
Adolfo Amici, Ambra A Grolla, Erika Del Grosso, Roberta Bellini, Michele Bianchi, Cristina Travelli, Silvia Garavaglia, Leonardo Sorci, Nadia Raffaelli, Silverio Ruggieri, Armando A Genazzani, Giuseppe Orsomando
Adenosine 5'-tetraphosphate (Ap4) is a ubiquitous metabolite involved in cell signaling in mammals. Its full physiological significance remains unknown. Here we show that two enzymes committed to NAD biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPT), can both catalyze the synthesis and degradation of Ap4 through their facultative ATPase activity. We propose a mechanism for this unforeseen additional reaction, and demonstrate its evolutionary conservation in bacterial orthologs of mammalian NAMPT and NAPT...
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28413646/role-of-malate-dehydrogenase-in-facilitating-lactate-dehydrogenase-to-support-the-glycolysis-pathway-in-tumors
#19
Siavash Mansouri, Ali Shahriari, Hadi Kalantar, Taraneh Moini Zanjani, Mojtaba Haghi Karamallah
High aerobic glycolysis, as one of the hallmarks of cancer cells, requires nicotinamide adenine dinucleotide (NAD(+)) as a vital co-factor, to guarantee the flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer metabolism, is a source of NAD(+) additional to lactate dehydrogenase (LDH). The current study aimed to elucidate the kinetic parameters of MDH in human breast cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis-Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the crude extracts of human breast tumors and healthy tissue samples, which were obtained directly from the operating theatre...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28408371/leukocyte-overexpression-of-intracellular-nampt-attenuates-atherosclerosis-by-regulating-ppar%C3%AE-dependent-monocyte-differentiation-and-function
#20
Beatriz Bermudez, Tuva B Dahl, Indira Medina, Mathijs Groeneweg, Sverre Holm, Sergio Montserrat-de la Paz, Mat Rousch, Jeroen J T Otten, Veronica Herias, Lourdes M Varela, Trine Ranheim, Arne Yndestad, Almudena Ortega-Gomez, Rocio Abia, Laszlo Nagy, Pal Aukrust, Francisco J G Muriana, Bente Halvorsen, Erik A L Biessen
OBJECTIVE: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD)(+) generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis. APPROACH AND RESULTS: Low-density lipoprotein receptor-deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPT(hi)), on a western type diet, showed attenuated plaque burden with features of lesion stabilization...
April 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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