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NAD+ increase AND Nicotinamide

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https://www.readbyqxmd.com/read/29320743/a-p300-and-sirt1-regulated-acetylation-switch-of-c-ebp%C3%AE-controls-mitochondrial-function
#1
Mohamad A Zaini, Christine Müller, Tristan V de Jong, Tobias Ackermann, Götz Hartleben, Gertrud Kortman, Karl-Heinz Gührs, Fabrizia Fusetti, Oliver H Krämer, Victor Guryev, Cornelis F Calkhoven
Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29317496/a-functional-link-between-nad-homeostasis-and-n-terminal-protein-acetylation-in-saccharomyces-cerevisiae
#2
Trevor Croft, Christol James Theoga Raj, Michelle Salemi, Brett S Phinney, Su-Ju Lin
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite participating in cellular redox chemistry and signaling, and the complex regulation of NAD+ metabolism is not yet fully understood. To investigate this, we established a NAD+-intermediate specific reporter system to identify factors required for salvage of metabolically-linked nicotinamide (NAM) and nicotinic acid (NA). Mutants lacking components of the NatB complex, NAT3 and MDM20, appeared as hits in this screen. NatB is an Nα-terminal-acetyltransferase responsible for acetylation of the amino terminus of specific Met-retained peptides...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29295624/nad-deficiency-is-a-common-central-pathological-factor-of-a-number-of-diseases-and-aging-mechanisms-and-therapeutic-implications
#3
Mingchao Zhang, Weihai Ying
Increasing evidence has indicated critical roles of NAD+ in various biological functions. NAD+ deficiency has been found in models of a number of diseases such as cerebral ischemia, myocardial ischemia and diabetes, and in models of aging. Application of NAD+ or other approaches that can restore NAD+ levels are highly protective in these models of diseases and aging. NAD+ produces its beneficial effects by targeting at multiple pathological pathways, including attenuating mitochondrial alterations, DNA damage and oxidative stress by modulating such enzymes as sirtuins, glyceraldehyde-3-phosphate dehydrogenase and AP endonuclease...
January 2, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29275540/synthesis-of-%C3%AE-nicotinamide-riboside-using-an-efficient-two-step-methodology
#4
Ning Zhang, Anthony A Sauve
A two-step chemical method for the synthesis of β-nicotinamide riboside (NR) is described. NR has achieved wide use as an NAD+ precursor (vitamin B3) and can significantly increase central metabolite NAD+ concentrations in mammalian cells. β-NR can be prepared with an efficient two-step procedure. The synthesis is initiated via coupling of commercially available 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose with ethyl nicotinate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). 1 H NMR showed that the product was formed with complete stereoselectivity to produce only the β-isomer in high yield (>90% versus starting sugar)...
December 24, 2017: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/29261224/mitochondrial-sirtuins-in-the-rat-adrenal-gland-location-within-the-glands-of-males-and-females-hormonal-and-developmental-regulation-of-gene-expressions
#5
Piotr Celichowski, Karol Jopek, Marta Szyszka, Marianna Tyczewska, Ludwik K Malendowicz, Marcin Rucinski
INTRODUCTION: Sirtuins are NAD dependent class III histone deacetylases. In adrenal cortex mitochondria are able to transform - via nicotinamide nucleotide transhydrogenase (NNT) - NAD into NADPH, which is required for steroidogenesis. These findings suggest that sirtuins expressed in mitochondria, Sirt3, Sirt4 and Sirt5, may be associated with adrenal steroidogenesis. Therefore, the purpose of this study was to characterize the expression of mitochondrial sirtuins (Sirt3-5) in individual compartments of rat adrenal cortex, their developmental regulation and to demonstrate whether their expression is dependent on adrenocorticotrophic hormone (ACTH) and Nampt (nicotinamide phosphoribosyltransferase also known as visfatin/PBEF), the rate-limiting enzyme in the regulation of mammalian NAD synthesis...
December 20, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29245920/nampt-overexpression-induces-cancer-stemness-and-defines-a-novel-tumor-signature-for-glioma-prognosis
#6
Antonio Lucena-Cacace, Daniel Otero-Albiol, Manuel P Jiménez-García, Javier Peinado-Serrano, Amancio Carnero
Gliomas are the most prevalent primary malignant brain tumors associated with poor prognosis. NAMPT, a rate-limiting enzyme that boosts the nicotinamide adenine dinucleotide (NAD) regeneration in the salvage pathway, is commonly expressed in these tumors. NAD metabolism is required to maintain tissue homeostasis. To maintain metabolism, cancer cells require a stable NAD regeneration circuit. However, high levels of NAD confer resistance to therapy to these tumors, usually treated with Temozolomide (TMZ). We report that NAMPT overexpression in glioma cell lines increases tumorigenic properties controlling stem cell pathways and enriching the cancer-initiating cell (CIC) population...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29232252/nicotinamide-adenine-dinucleotide-and-its-related-precursors-for-the-treatment-of-alzheimer-s-disease
#7
Nady Braidy, Ross Grant, Perminder S Sachdev
PURPOSE OF REVIEW: The current review discusses the biology and metabolism of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+) in the central nervous system. We also review recent work suggesting important neuroprotective effects that may be associated with the promotion of NAD+ levels through NAD+ precursors against Alzheimer's disease. RECENT FINDINGS: Perturbations in the physiological homoeostatic state of the brain during the ageing process can lead to impaired cellular function, and ultimately leads to loss of brain integrity and accelerates cognitive and memory decline...
December 9, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29229552/caspase-6-is-a-dispensable-enabler-of-adult-mammalian-axonal-degeneration
#8
V Woo, C Cheng, A Duraikannu, A Chandrasekhar, K Purdy, J A Martinez, D W Zochodne
The progress of axonal degeneration (AxD) following injury or insult impacts both recovery from axonal transection and protection of axons from diverse insults, or axonopathy. Here we provide evidence that increases in capase-6 (Casp6) expression and action contribute to the progression of AxD. The expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing AxD was confirmed. We developed and utilized a new model of axonopathy in live mice by serially visualizing the viability of cutaneous axons in the ear pinna that expressed an axonal YFP transgene, in response to capasaicin-induced AxD...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29217642/nicotinamide-riboside-preserves-cardiac-function-in-a-mouse-model-of-dilated-cardiomyopathy
#9
Nicolas Diguet, Samuel A J Trammell, Cynthia Tannous, Robin Deloux, Jérôme Piquereau, Nathalie Mougenot, Anne Gouge, Mélanie Gressette, Boris Manoury, Jocelyne Blanc, Marie Breton, Jean-François Decaux, Gareth Lavery, István Baczkó, Joffrey Zoll, Anne Garnier, Zhenlin Li, Charles Brenner, Mathias Mericskay
Background -Myocardial metabolic impairment is a major feature in chronic heart failure (HF). As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, NAD+ is emerging as a metabolic target in a number of diseases including HF. Little is known on mechanisms regulating homeostasis of NAD+ in the failing heart. Methods -To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified expression of NAD+ biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRFHKO) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC)...
December 7, 2017: Circulation
https://www.readbyqxmd.com/read/29211728/an-open-label-non-randomized-study-of-the-pharmacokinetics-of-the-nutritional-supplement-nicotinamide-riboside-nr-and-its-effects-on-blood-nad-levels-in-healthy-volunteers
#10
Sophia E Airhart, Laura M Shireman, Linda J Risler, Gail D Anderson, G A Nagana Gowda, Daniel Raftery, Rong Tian, Danny D Shen, Kevin D O'Brien
OBJECTIVES: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium...
2017: PloS One
https://www.readbyqxmd.com/read/29208611/perturbations-of-nad-salvage-systems-impact-mitochondrial-function-and-energy-homeostasis-in-mouse-myoblasts-and-intact-skeletal-muscle
#11
Marianne Agerholm, Morten Dall, Benjamin A H Jensen, Clara Prats, Søren Madsen, Astrid L Basse, Anne-Sofie Graae, Steve Risis, Julie Goldenbaum, Bjørn Quistorff, Steen Larsen, Sara G Vienberg, Jonas T Treebak
Nicotinamide adenine dinucleotide (NAD+) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT for maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (shNampt KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer to express cre recombinase in tibialis anterior muscle of floxed Nampt mice. In shNampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by 70% and 50%, respectively, and maximal respiratory capacity was reduced by 25%...
December 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29203587/nampt-is-a-potent-oncogene-in-colon-cancer-progression-that-modulates-cancer-stem-cell-properties-and-resistance-to-therapy-through-sirt1-and-parp
#12
Amancio Carnero, Antonio Lucena-Cacace, Daniel Otero-Albiol, Manuel P Jimenez-Garcia, Sandra Muñoz-Galvan
PURPOSE: Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men worldwide. However, despite current progress, many patients with advanced and metastatic tumors still die from the malignancy. Refractory disease often relies on nicotinamide adenine dinucleotide(NAD)-dependent mechanisms. NAD metabolism and a stable NAD regeneration circuit are required to maintain tissue homeostasis and metabolism. However, high levels of NAD confer therapy resistance to tumors...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29185343/pyrroloquinoline-quinone-a-redox-active-o-quinone-stimulates-mitochondrial-biogenesis-by-activating-sirt1-pgc-1%C3%AE-signaling-pathway
#13
Kazuhiro Saihara, Ryosuke Kamikubo, Kazuto Ikemoto, Koji Uchida, Mitsugu Akagawa
Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in various foods and mammalian tissues, has received increasing attention in a number of health benefits due to its ability to enhance mitochondrial biogenesis. However, its underlying molecular mechanism remains incompletely understood. We have now established that the exposure of mouse NIH/3T3 fibroblasts to a physiologically relevant concentration of PQQ significantly stimulates the mitochondrial biogenesis. The exposure of NIH/3T3 cells to 10-100 nM PQQ for 48 h resulted in increased Mitotracker staining, the mitochondrial DNA content, and the mitochondrially-encoded cytochrome c oxidase subunit 1 (MTCO1) protein...
November 29, 2017: Biochemistry
https://www.readbyqxmd.com/read/29184669/repeat-dose-nrpt-nicotinamide-riboside-and-pterostilbene-increases-nad-levels-in-humans-safely-and-sustainably-a-randomized-double-blind-placebo-controlled-study
#14
Ryan W Dellinger, Santiago Roel Santos, Mark Morris, Mal Evans, Dan Alminana, Leonard Guarente, Eric Marcotulli
NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X)...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29184484/ketone-based-metabolic-therapy-is-increased-nad-a-primary-mechanism
#15
Marwa Elamin, David N Ruskin, Susan A Masino, Paola Sacchetti
The ketogenic diet's (KD) anticonvulsant effects have been well-documented for nearly a century, including in randomized controlled trials. Some patients become seizure-free and some remain so after diet cessation. Many recent studies have explored its expanded therapeutic potential in diverse neurological disorders, yet no mechanism(s) of action have been established. The diet's high fat, low carbohydrate composition reduces glucose utilization and promotes the production of ketone bodies. Ketone bodies are a more efficient energy source than glucose and improve mitochondrial function and biogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29178516/nicotinamide-phosphoribosyltransferase-delays-cellular-senescence-by-upregulating-sirt1-activity-and-antioxidant-gene-expression-in-mouse-cells
#16
Fiqri D Khaidizar, Yasukazu Nakahata, Akira Kume, Kyosuke Sumizawa, Kenji Kohno, Takaaki Matsui, Yasumasa Bessho
Senescent cells accumulate in tissues of aged animals and deteriorate tissue functions. The elimination of senescent cells from aged mice not only attenuates progression of already established age-related disorders, but also extends median lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ salvage pathway, has shown a protective effect on cellular senescence of human primary cells. However, it still remains unclear how NAMPT has a protective impact on aging in vitro and in vivo...
November 27, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29175372/nad-biosynthetic-enzyme-nmnat1-reduces-early-behavioral-impairment-in-the-htau-mouse-model-of-tauopathy
#17
Francesca Rossi, Philippine C Geiszler, Weina Meng, Matthew R Barron, Malcolm Prior, Anna Herd-Smith, Andrea Loreto, Maria Yanez Lopez, Henryk Faas, Marie-Christine Pardon, Laura Conforti
NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in tauopathies, including Alzheimer's disease. Here, we investigated whether modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important for neuronal maintenance, influences the development of behavioral and neuropathological abnormalities in htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer's disease...
November 23, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29164394/combination-of-nad-and-nadph-offers-greater-neuroprotection-in-ischemic-stroke-models-by-relieving-metabolic-stress
#18
Qiao Huang, Meiling Sun, Mei Li, Dingmei Zhang, Feng Han, Jun Chao Wu, Kohji Fukunaga, Zhong Chen, Zheng-Hong Qin
Both reduced nicotinamide adenine dinucleotide phosphate (NADPH) and β-nicotinamide adenine dinucleotide hydrate (NAD(+)) have been reported to have potent neuroprotective effects against ischemic neuronal injury. Both NADPH and NAD(+) are essential cofactors for anti-oxidation and cellular energy metabolism. We investigated if combined NADPH and NAD(+) could offer better neuroprotective effects on cellular and animal models of ischemic stroke. In vitro studies with primary cultured neurons demonstrated that NAD(+) was effective in protecting neurons against oxygen-glucose deprivation/reoxygenation (OGD/R) injury when given during the early time period of reoxygenation...
November 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29155147/selective-and-membrane-permeable-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase-reverse-high-fat-diet-induced-obesity-in-mice
#19
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29146412/skeletal-muscle-overexpression-of-nicotinamide-phosphoribosyl-transferase-in-mice-coupled-with-voluntary-exercise-augments-exercise-endurance
#20
Sheila R Costford, Bram Brouwers, Meghan E Hopf, Lauren M Sparks, Mauro Dispagna, Ana P Gomes, Heather H Cornnell, Chris Petucci, Peter Phelan, Hui Xie, Fanchao Yi, Glenn A Walter, Timothy F Osborne, David A Sinclair, Randall L Mynatt, Julio E Ayala, Stephen J Gardell, Steven R Smith
OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD(+)), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding...
November 6, 2017: Molecular Metabolism
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