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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/29782205/nad-repletion-produces-no-therapeutic-effect-in-mice-with-respiratory-chain-complex-iii-deficiency-and-chronic-energy-deprivation
#1
Janne Purhonen, Jayasimman Rajendran, Saara Tegelberg, Olli-Pekka Smolander, Eija Pirinen, Jukka Kallijärvi, Vineta Fellman
Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improve mitochondrial function. We found decreased hepatic NAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed these mice nicotinamide riboside (NR), a NAD+ precursor. A targeted metabolomics verified successful administration and suggested enhanced NAD+ biosynthesis in the treated mice, although hepatic NAD+ concentration was unchanged at the end point...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29760313/detection-of-sirtuin-1-protein-expression-in-peripheral-blood-leukocytes-in-dogs
#2
Kuniko Yoshimura, Aya Matsuu, Kai Sasaki, Yasuyuki Momoi
Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylase with a large number of protein substrates. It has attracted a lot of attention in association with extending lifespan. The objective of this study was to enable the evaluation of SIRT1 expression in peripheral blood mononuclear cells (PBMCs) from dogs by flow cytometry. Three transcript variants were amplified from PBMCs by reverse transcription PCR and the nucleotide sequences were analyzed. On the basis deduced amino acid sequence, a monoclonal antibody against human SIRT1, 1F3, was selected to detect canine SIRT1...
May 11, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29757993/profiling-redox-and-energy-coenzymes-in-whole-blood-tissue-and-cells-using-nmr-spectroscopy
#3
REVIEW
G A Nagana Gowda
Coenzymes of cellular redox reactions and cellular energy, as well as antioxidants mediate biochemical reactions fundamental to the functioning of all living cells. Conventional analysis methods lack the opportunity to evaluate these important redox and energy coenzymes and antioxidants in a single step. Major coenzymes include redox coenzymes: NAD⁺ (oxidized nicotinamide adenine dinucleotide), NADH (reduced nicotinamide adenine dinucleotide), NADP⁺ (oxidized nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate); energy coenzymes: ATP (adenosine triphosphate), ADP (adenosine diphosphate) and AMP (adenosine monophosphate); and antioxidants: GSSG (oxidized glutathione) and GSH (reduced glutathione)...
May 14, 2018: Metabolites
https://www.readbyqxmd.com/read/29757967/epigenetics-of-subcellular-structure-functioning-in-the-origin-of-risk-or-resilience-to-comorbidity-of-neuropsychiatric-and-cardiometabolic-disorders
#4
REVIEW
Carlos Manuel Zapata-Martín Del Campo, Martín Martínez-Rosas, Verónica Guarner-Lans
Mechanisms controlling mitochondrial function, protein folding in the endoplasmic reticulum (ER) and nuclear processes such as telomere length and DNA repair may be subject to epigenetic cues that relate the genomic expression and environmental exposures in early stages of life. They may also be involved in the comorbid appearance of cardiometabolic (CMD) and neuropsychiatric disorders (NPD) during adulthood. Mitochondrial function and protein folding in the endoplasmic reticulum are associated with oxidative stress and elevated intracellular calcium levels and may also underlie the vulnerability for comorbid CMD and NPD...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29754052/detection-of-parp-1-activity-based-on-hyperbranched-poly-adp-ribose-polymers-responsive-current-in-artificial-nanochannels
#5
Yong Liu, Jiahui Fan, Haitang Yang, Ensheng Xu, Wei Wei, Yuanjian Zhang, Songqin Liu
The cellular enzyme poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) plays key roles in DNA repair. Its activity is closely related to various cancer developments. Detection of PARP-1 activity is significant, however, it is relatively difficult since it lacks superiority property that can be used to detect conveniently. PARP-1 lead to the synthesis of hyperbranched poly (ADP-ribose) polymers (PAR) using nicotinamide adenine dinucleotide (NAD+ ) as substrate during DNA damage repairing. In this paper, we found that hyper-branched PAR increased the steric hindrance and reduced the flux of probe ions effectively in anodic aluminum oxide (AAO) nanochannels...
May 4, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29753648/nicotinamide-phosphoribosyltransferase-regulates-cocaine-reward-through-sirtuin-1
#6
Jueying Kong, Changman Du, Linhong Jiang, Wei Jiang, Pengchi Deng, Xue Shao, Baolai Zhang, Yan Li, Ruiming Zhu, Qian Zhao, Dengqi Fu, Hui Gu, Li Luo, Hailei Long, Yinglan Zhao, Xiaobo Cen
Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice...
May 10, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29752474/checkpoint-suppressor-1-suppresses-transcriptional-activity-of-er%C3%AE-and-breast-cancer-cell-proliferation-via-deacetylase-sirt1
#7
Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Kangkai Xia, Yuxi Yang, Xiahui Li, Miao Wang, Shujing Li, Huijian Wu
Breast cancer is a highly heterogeneous carcinoma in women worldwide, but the underlying mechanisms that account for breast cancer initiation and development have not been fully established. Mounting evidence indicates that Checkpoint suppressor 1 (CHES1) is tightly associated with tumorigenesis and prognosis in many types of cancer. However, the definitive function of CHES1 in breast cancer remains to be explored. Here we showed that CHES1 had a physical interaction with estrogen receptor-α (ERα) and repressed the transactivation of ERα in breast cancer cells...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29750296/hyperoside-protects-human-kidney%C3%A2-2-cells-against-oxidative-damage-induced-by-oxalic-acid
#8
Yongliang Chen, Lihong Ye, Wangjian Li, Dongzhang Li, Feng Li
The majority of renal calculi (kidney stones) are calcium stones. Oxidative damage to renal tubular epithelial cells induced by reactive oxygen species (ROS) is the predominant cause of calcium oxalate stone formation. Hyperoside (Hyp) is a flavonol glycoside extracted from medicinal plants and appears to exhibit potent antioxidant activity in various cells. The aim of the present study was to investigate the protective effect of Hyp on renal cells exposed to oxidative stress simulated by oxalic acid (OA), and to determine whether the underlying mechanism involves the nuclear factor E2‑related factor2 (Nrf2)‑antioxidative response element signaling pathway...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748257/metabolic-regulation-of-transcription-through-compartmentalized-nad-biosynthesis
#9
Keun Woo Ryu, Tulip Nandu, Jiyeon Kim, Sridevi Challa, Ralph J DeBerardinis, W Lee Kraus
NAD+ (nicotinamide adenine dinucleotide in its oxidized state) is an essential molecule for a variety of physiological processes. It is synthesized in distinct subcellular compartments by three different synthases (NMNAT-1, -2, and -3). We found that compartmentalized NAD+ synthesis by NMNATs integrates glucose metabolism and adipogenic transcription during adipocyte differentiation. Adipogenic signaling rapidly induces cytoplasmic NMNAT-2, which competes with nuclear NMNAT-1 for the common substrate, nicotinamide mononucleotide, leading to a precipitous reduction in nuclear NAD+ levels...
May 11, 2018: Science
https://www.readbyqxmd.com/read/29746531/the-1h-nmr-based-metabolite-profile-of-acute-alcohol-consumption-a-metabolomics-intervention-study
#10
Cindy Irwin, Mari van Reenen, Shayne Mason, Lodewyk J Mienie, Ron A Wevers, Johan A Westerhuis, Carolus J Reinecke
Metabolomics studies of disease conditions related to chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways underlying the pathophysiology of alcoholism. The objective of the present study was to utilize proton nuclear magnetic resonance (1H-NMR) spectroscopy metabolomics to study the holistic metabolic consequences of acute alcohol consumption in humans. The experimental design was a cross-over intervention study which included a number of substances to be consumed-alcohol, a nicotinamide adenine dinucleotide (NAD) supplement, and a benzoic acid-containing flavoured water vehicle...
2018: PloS One
https://www.readbyqxmd.com/read/29744033/nad-biosynthesis-aging-and-disease
#11
REVIEW
Sean Johnson, Shin-Ichiro Imai
Nicotinamide adenine dinucleotide (NAD + ) biosynthesis and its regulation have recently been attracting markedly increasing interest. Aging is marked by a systemic decrease in NAD + across multiple tissues. The dysfunction of NAD + biosynthesis plays a critical role in the pathophysiologies of multiple diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders. As downstream effectors, NAD + -dependent enzymes, such as sirtuins, are involved in the progression of such disorders...
2018: F1000Research
https://www.readbyqxmd.com/read/29721178/extracellular-nicotinamide-phosphoribosyltransferase-enampt-is-a-novel-marker-for-patients-with-braf-mutated-metastatic-melanoma
#12
Valentina Audrito, Antonella Managò, Federica Zamporlini, Eliana Rulli, Federica Gaudino, Gabriele Madonna, Stefania D'Atri, Gian Carlo Antonini Cappellini, Paolo Antonio Ascierto, Daniela Massi, Nadia Raffaelli, Mario Mandalà, Silvia Deaglio
Metastatic melanoma carrying BRAF mutations represent a still unmet medical need as success of BRAF inhibitors is limited by development of resistance. Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in NAD biosynthesis. An extracellular form (eNAMPT) possesses cytokine-like functions and is up-regulated in inflammatory disorders, including cancer. Here we show that eNAMPT is actively released in culture supernatants of melanoma cell lines. Furthermore, cells that become resistant to BRAF inhibitors (BiR) show a significant increase of eNAMPT levels...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719225/a-potent-and-specific-cd38-inhibitor-ameliorates-age-related-metabolic-dysfunction-by-reversing-tissue-nad-decline
#13
Mariana G Tarragó, Claudia C S Chini, Karina S Kanamori, Gina M Warner, Ariel Caride, Guilherme C de Oliveira, Micaela Rud, Adrienne Samani, Kyaw Z Hein, Runqing Huang, Diana Jurk, Dong Seong Cho, James J Boslett, Jordan D Miller, Jay L Zweier, João F Passos, Jason D Doles, David J Becherer, Eduardo N Chini
Aging is characterized by the development of metabolic dysfunction and frailty. Recent studies show that a reduction in nicotinamide adenine dinucleotide (NAD+ ) is a key factor for the development of age-associated metabolic decline. We recently demonstrated that the NADase CD38 has a central role in age-related NAD+ decline. Here we show that a highly potent and specific thiazoloquin(az)olin(on)e CD38 inhibitor, 78c, reverses age-related NAD+ decline and improves several physiological and metabolic parameters of aging, including glucose tolerance, muscle function, exercise capacity, and cardiac function in mouse models of natural and accelerated aging...
May 1, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29718667/transmembrane-nadh-oxidation-with-tetracyanoquinodimethane
#14
MinHui Wang, Christian Wölfer, Lado Otrin, Ivan Ivanov, Tanja Vidaković-Koch, Kai Sundmacher
The design of efficient schemes for nicotinamide adenine dinucleotide (NAD) regeneration is essential for the development of enzymatic biotechnological processes in order to sustain continuous production. In line with our motivation for the encapsulation of redox cascades in liposomes to serve as microbioreactors, we developed a straightforward strategy for the interfacial oxidation of entrapped NADH by ferricyanide as an external electron acceptor. Instead of the commonly applied enzymatic regeneration methods, we employed a hydrophobic redox shuttle embedded in the liposome bilayer...
May 2, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29714801/chemo-enzymatic-synthesis-of-isotopically-labeled-nicotinamide-riboside
#15
Ai Tran, Ryota Yokose, Yana Cen
As a cofactor for numerous reactions, NAD+ is found widely dispersed across many maps of cellular metabolism. This core redox role alone makes the biosynthesis of NAD+ of great interest. Recent studies have revealed new biological roles for NAD+ as a substrate for diverse enzymes that regulate a broad spectrum of key cellular tasks. These NAD+-consuming enzymes further highlight the importance of understanding NAD+ biosynthetic pathways. In this study, we developed a chemo-enzymatic synthesis of isotopically labeled NAD+ precursor, nicotinamide riboside (NR)...
May 1, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29714371/nonconventional-regeneration-of-redox-enzymes-a-practical-approach-for-organic-synthesis
#16
Wuyuan Zhang, Frank Hollmann
Oxidoreductases have become useful tools in the hands of chemists to perform selective and mild oxidation and reduction reactions. Instead of mimicking native catalytic cycles, generally involving costly and unstable nicotinamide cofactors, more direct, NAD(P)-independent methodologies are being developed. The promise of these approaches not only lies with simpler and cheaper reaction schemes but also with higher selectivity as compared to whole cell approaches and their mimics.
May 1, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29710809/anti-oxidant-and-anti-inflammatory-activity-of-ketogenic-diet-new-perspectives-for-neuroprotection-in-alzheimer-s-disease
#17
REVIEW
Alessandro Pinto, Alessio Bonucci, Elisa Maggi, Mariangela Corsi, Rita Businaro
The ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD⁺/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins...
April 28, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29699388/enhancement-of-replication-and-differentiation-potential-of-human-bone-marrow-stem-cells-by-nicotinamide-treatment
#18
Jeong Su Ok, Seon Beom Song, Eun Seong Hwang
Background and Objectives: Therapies using mesenchymal stem cells (MSCs) generally require substantial expansion of cell populations. However, the replicative life span of MSCs is limited and their multipotency declines over continued passages, imposing a limitation on their application especially in aged individuals. In an effort to increase MSC life span, we tested the effects of nicotinamide (NAM), a precursor of NAD+ that has been shown to reduce reactive oxygen species generation and delay the onset of replicative senescence in fibroblasts...
April 30, 2018: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29695187/restoring-nad-levels-with-nad-intermediates-the-second-law-of-thermodynamics-and-aging-delay
#19
Borut Poljsak, Irina Milisav
The hypothesis regarding the role of increased nicotinamide adenine dinucleotide (NAD+) levels with reference to the fundamental concepts of ageing and entropy is presented. Considering the second law of thermodynamics, NAD+ seems the appropriate candidate for reversing many aging-associated pathologies. NAD+ is presented as an essential compound that enables organisms to stay highly organized and well-maintained, with a lower entropy state.
April 26, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29685734/quantitative-analysis-of-nad-synthesis-breakdown-fluxes
#20
Ling Liu, Xiaoyang Su, William J Quinn, Sheng Hui, Kristin Krukenberg, David W Frederick, Philip Redpath, Le Zhan, Karthikeyani Chellappa, Eileen White, Marie Migaud, Timothy J Mitchison, Joseph A Baur, Joshua D Rabinowitz
The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including poly-ADP-ribose-polymerases (PARPs) and sirtuins. NAD concentration falls during aging, which has triggered intense interest in strategies to boost NAD levels. A limitation in understanding NAD metabolism has been reliance on concentration measurements. Here, we present isotope-tracer methods for NAD flux quantitation. In cell lines, NAD was made from nicotinamide and consumed largely by PARPs and sirtuins...
April 20, 2018: Cell Metabolism
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