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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/29146412/skeletal-muscle-overexpression-of-nicotinamide-phosphoribosyl-transferase-in-mice-coupled-with-voluntary-exercise-augments-exercise-endurance
#1
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
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#2
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142413/antiurolithiatic-potential-of-neeri-against-calcium-oxalate-stones-by-crystallization-inhibition-free-radicals-scavenging-and-nrk-52e-cell-protection-from-oxalate-injury
#3
Parveen Kumar Goyal, Santosh Kumar Verma, Anil Kumar Sharma
Background: Neeri is a well-established polyherbal formulation prescribed for renal stones by the physicians but has not been experimentally evaluated for its antiurolithiatic potential using cell-lines. Objective: This study is aimed to scientifically substantiate the antiurolithiatic effect of Neeri extract (NRE) through calcium oxalate (CaOx) crystallization inhibition, scavenging of free radicals, and protection of renal tubular epithelial NRK-52E cells from oxalate-induced injury...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29129662/review-of-nad-p-h-dependent-oxidoreductases-properties-engineering-and-application
#4
REVIEW
Lara Sellés Vidal, Ciarán L Kelly, Paweł M Mordaka, John T Heap
NAD(P)H-dependent oxidoreductases catalyze the reduction or oxidation of a substrate coupled to the oxidation or reduction, respectively, of a nicotinamide adenine dinucleotide cofactor NAD(P)H or NAD(P)(+). NAD(P)H-dependent oxidoreductases catalyze a large variety of reactions and play a pivotal role in many central metabolic pathways. Due to the high activity, regiospecificity and stereospecificity with which they catalyze redox reactions, they have been used as key components in a wide range of applications, including substrate utilisation, the synthesis of chemicals, biodegradation and detoxification...
November 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29128917/heterologous-expression-of-mitochondrial-nicotinamide-adenine-dinucleotide-transporter-ndt1-from-aspergillus-fumigatus-rescues-impaired-growth-in-%C3%AE-ndt1%C3%AE-ndt2-saccharomyces-cerevisiae-strain
#5
Laís de Lourdes de Lima Balico, Emerson de Souza Santos, Silveli Suzuki-Hatano, Lucas Oliveira Sousa, Ana Elisa Caleiro Seixas Azzolini, Yara Maria Lucisano-Valim, Taisa Magnani Dinamarco, Vinicius Kannen, Sérgio Akira Uyemura
Our understanding of nicotinamide adenine dinucleotide mitochondrial transporter 1 (Ndt1A) in Aspergillus fumigatus remains poor. Thus, we investigated whether Ndt1A could alter fungi survival. To this end, we engineered the expression of an Ndt1A-encoding region in a Δndt1Δndt2 yeast strain. The resulting cloned Ndt1A protein promoted the mitochondrial uptake of nicotinamide adenine dinucleotide (NAD(+)), generating a large mitochondrial membrane potential. The NAD(+) carrier utilized the electrochemical proton gradient to drive NAD(+) entrance into mitochondria when the mitochondrial membrane potential was sustained by succinate...
November 11, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#6
Peter M LoCoco, April L Risinger, Hudson R Smith, Teresa S Chavera, Kelly A Berg, William P Clarke
Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX...
November 10, 2017: ELife
https://www.readbyqxmd.com/read/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#7
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120675/utility-of-adenosine-monophosphate-detection-system-for-monitoring-the-activities-of-diverse-enzyme-reactions
#8
Subhanjan Mondal, Kevin Hsiao, Said A Goueli
Adenosine monophosphate (AMP) is a key cellular metabolite regulating energy homeostasis and signal transduction. AMP is also a product of various enzymatic reactions, many of which are dysregulated during disease conditions. Thus, monitoring the activities of these enzymes is a primary goal for developing modulators for these enzymes. In this study, we demonstrate the versatility of an enzyme-coupled assay that quantifies the amount of AMP produced by any enzymatic reaction regardless of its substrates. We successfully implemented it to enzyme reactions that use adenosine triphosphate (ATP) as a substrate (aminoacyl tRNA synthetase and DNA ligase) by an elaborate strategy of removing residual ATP and converting AMP produced into ATP; so it can be detected using luciferase/luciferin and generating light...
October 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29120608/biochemical-gas-sensors-biosniffers-using-forward-and-reverse-reactions-of-secondary-alcohol-dehydrogenase-for-breath-isopropanol-and-acetone-as-potential-volatile-biomarkers-of-diabetes-mellitus
#9
Po-Jen Chien, Takuma Suzuki, Masato Tsujii, Ming Ye, Isao Minami, Kanako Toda, Hiromi Otsuka, Koji Toma, Takahiro Arakawa, Kouji Araki, Yasuhiko Iwasaki, Kayoko Shinada, Yoshihiro Ogawa, Kohji Mitsubayashi
This study describes two biosniffers to determine breath acetone and isopropanol (IPA) levels and applies them for breath measurement in healthy subjects and diabetic patients. Secondary alcohol dehydrogenase (S-ADH) can reduce acetone and oxidize nicotinamide adenine dinucleotide (NADH to NAD(+)) in a weak acid environment. NADH can be excited by 340 nm excitation lights and subsequently emit 490 nm fluorescence. Therefore, acetone can be measured by the decrease in NADH fluorescence intensity. S-ADH can also oxidize IPA and reduce NAD(+) to NADH when it is in an alkaline environment...
November 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29118980/sirt1-dependent-modulation-of-methylation-and-acetylation-of-histone-h3-on-lysine-9-h3k9-in-the-zygotic-pronuclei-improves-porcine-embryo-development
#10
Katerina Adamkova, Young-Joo Yi, Jaroslav Petr, Tereza Zalmanova, Kristyna Hoskova, Pavla Jelinkova, Jiri Moravec, Milena Kralickova, Miriam Sutovsky, Peter Sutovsky, Jan Nevoral
Background: The histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD(+)-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29118320/nicotinamide-mononucleotide-nmn-supplementation-ameliorates-the-impact-of-maternal-obesity-in-mice-comparison-with-exercise
#11
Golam Mezbah Uddin, Neil A Youngson, Bronte M Doyle, David A Sinclair, Margaret J Morris
Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD(+)). We have shown that the NAD(+) precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29108235/regulation-of-sirt3-signal-related-metabolic-reprogramming-in-gastric-cancer-by-helicobacter-pylori-oncoprotein-caga
#12
Do Yeon Lee, Dawoon E Jung, Sung Sook Yu, Yeo Song Lee, Beom Ku Choi, Yong Chan Lee
Injection of the Helicobacter pylori cytotoxin-associated gene A (CagA) is closely associated with the development of chronic gastritis and gastric cancer. Individuals infected with H. pylori possessing the CagA protein produce more reactive oxygen species (ROS) and show an increased risk of developing gastric cancer. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases and mitochondrial SIRT3 is known to be a tumor suppressor via its ability to suppress ROS and hypoxia inducible factor 1α (HIF-1α)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104634/endogenous-nampt-upregulation-is-associated-with-diabetic-nephropathy-inflammatory-fibrosis-through-the-nf-%C3%AE%C2%BAb-p65-and-sirt1-pathway-nmn-alleviates-diabetic-nephropathy-inflammatory-fibrosis-by-inhibiting-endogenous-nampt
#13
Ye Chen, Yuzhen Liang, Tingting Hu, Riming Wei, Congjie Cai, Ping Wang, Lingyu Wang, Wei Qiao, Leping Feng
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD(+)) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29100430/novel-naprt-specific-antibody-identifies-small-cell-lung-cancer-and-neuronal-cancers-as-promising-clinical-indications-for-a-nampt-inhibitor-niacin-co-administration-strategy
#14
Jonathan Cole, Marie-Christine Guiot, Michel Gravel, Cynthia Bernier, Gordon C Shore, Anne Roulston
Tumor cells are particularly dependent on NAD(+) due to higher rates of metabolism, DNA synthesis and repair. Nicotinamide phosphoribosyltransferase inhibitors (NAMPTis) inhibit NAD(+) biosynthesis and represent promising new anti-cancer agents. However, clinical efficacy has been limited by toxicities demonstrating the need for drug combinations to broaden the therapeutic index. One potential combination involves niacin/NAMPTi co-administration. Niacin can rescue NAD(+) biosynthesis through a parallel pathway that depends on nicotinic acid phosphoribosyltransferase (NAPRT) expression...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29091865/the-role-of-sirt1-in-diabetic-retinopathy
#15
REVIEW
Hedyieh Karbasforooshan, Gholamreza Karimi
The prevalence of diabetes mellitus (DM), has been increasing worldwide. Diabetic retinopathy (DR) is the most common microvascular complication in diabetes. It is a multifactorial disease that occurs primarily through the long-term detrimental effects of hyperglycemia. The pathogenesis of DR is complex, including inflammation, oxidative stress and advanced glycation end products (AGES). SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DR...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29088980/spectrophotometric-assays-for-measuring-redox-biomarkers-in-blood-and-tissues-the-nadph-network
#16
Aristidis S Veskoukis, Nikos V Margaritelis, Antonios Kyparos, Vassilis Paschalis, Michalis G Nikolaidis
Nicotinamide adenine dinucleotide (NAD(+)/NADH) along with its phosphorylated form (NADP(+)/NADPH) are two molecules ubiquitously present in all organisms, and they play key roles as cofactors in fundamental catabolic and anabolic processes, respectively. The oxidation of NADPH to NADP(+) initiates a cascade of reactions, where a network of molecules is implicated. The molecules of this cascade form a network with eminent translational potential in redox metabolism. A special point of interest is that spectrophotometric assays have been developed both for NADH/NADPH and the molecules directly regulated by them...
October 31, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29074724/conversion-of-prps-hexamer-to-monomer-by-ampk-mediated-phosphorylation-inhibits-nucleotide-synthesis-in-response-to-energy-stress
#17
Xu Qian, Xinjian Li, Lin Tan, Jong-Ho Lee, Yan Xia, Qingsong Cai, Yanhua Zheng, Hongxia Wang, Philip L Lorenzi, Zhimin Lu
Tumors override energy stress to grow. However, how nucleotide synthesis is regulated under energy stress is unclear. We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS) 1 S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. Knock-in of non-phosphorylatable PRPS1/2 mutants, which have uninhibited activity, in brain tumor cells under energy stress exhausts cellular ATP and NADPH and increases ROS levels, thereby promoting cell apoptosis...
October 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29072717/stable-isotope-labeling-by-essential-nutrients-in-cell-culture-silec-for-accurate-measurement-of-nicotinamide-adenine-dinucleotide-metabolism
#18
David W Frederick, Sophie Trefely, Alexia Buas, Jason Goodspeed, Jay Singh, Clementina Mesaros, Joseph A Baur, Nathaniel W Snyder
Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are conserved metabolic cofactors that mediate reduction-oxidation (redox) reactions throughout all domains of life. The diversity of synthetic routes and cellular processes involving the transfer of reducing equivalents to and from these cofactors makes the accurate quantitation and metabolic tracing of NAD(H) and NADP(H) of broad interest. However, current analytical techniques typically rely on standard curves that do not incorporate confounding effects of the sample matrix...
October 26, 2017: Analyst
https://www.readbyqxmd.com/read/29069580/nicotinamide-prevents-sweet-beverage-induced-hepatic-steatosis-in-rats-by-regulating-the-g6pd-nadph-nadp-and-gsh-gssg-ratios-and-reducing-oxidative-and-inflammatory-stress
#19
Selene Ángeles Mejía, Luis Arturo Baiza Gutman, Clara Ortega Camarillo, Rafael Medina Navarro, Martha Catalina Sánchez Becerra, Leticia Damasio Santana, Miguel Cruz, Elizabeth Hernández Pérez, Margarita Díaz Flores
The disruption of redox state homeostasis, the overexpression of lipogenic transcription factors and enzymes, and the increase in lipogenic precursors induced by sweetened beverages are determinants of the development of nonalcoholic fatty liver disease. This study evaluated the action of nicotinamide (NAM) on the expression of glucose-6-phosphate dehydrogenase (G6PD) and redox, oxidative, and inflammatory states in a model of nonalcoholic hepatic steatosis induced by high and chronic consumption of carbohydrates...
October 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29054583/dietary-resveratrol-increases-mid-life-fecundity-of-female-nothobranchius-guentheri
#20
Youngjoo Lee, Andrew C Drake, Nicholas O Thomas, Lindsey G Ferguson, Patrick E Chappell, Kate Petersen Shay
The decline of female reproductive function is an early phenotype of aging in humans, occurring only midway through the lifespan. Yet the number of women delaying pregnancy continues to rise in industrialized societies due to personal or socioeconomic circumstances, often resulting in subfertility or difficulty conceiving. There are few defined mechanisms associated with this etiology, and equally few effective therapies. To combat this problem, we used a novel emerging model, Nothobranchius guentheri, that recapitulates the age-associated spectrum of changes that adversely affect human fertility...
October 17, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
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