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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/28718934/nad-a-key-metabolic-regulator-with-great-therapeutic-potential
#1
REVIEW
Ghazal Sultani, Azrah F Samsudeen, Brenna Osborne, Nigel Turner
Nicotinamide adenine dinucleotide (NAD(+) ) is a ubiquitous metabolite that serves an essential role in the catabolism of nutrients. Recently there has been a surge of interest in NAD(+) biology, with the recognition that NAD(+) influences many biological processes beyond metabolism, including transcription, signalling and cell survival. There are a multitude of pathways involved in the synthesis and breakdown of NAD(+) , and alterations in NAD(+) homeostasis have emerged as a common feature of a range of disease states...
July 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28714034/inhibition-of-nampt-decreases-cell-growth-and-enhances-susceptibility-to-oxidative-stress
#2
Renhua Xu, Zhenwei Yuan, Lijuan Yang, Lele Li, Dan Li, Changjun Lv
Nicotinamide adenine dinucleotide (NAD) is an essential molecule for living organisms and plays a vital role in aging and age-associated diseases. In eukaryotic cells, cellular NAD is mainly generated by the scavenge pathway in which nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the formation of nicotinamide mononucleotide. Inhibition of NAMPT is a therapeutic strategy for cancer treatment. To explore the effects of NAMPT inhibition on cellular processes, cells were treated with 10 nM FK866, an NAMPT inhibitor, resulting in a decrease in the cellular NAD level, a lower growth rate, and enhanced susceptivity to oxidative stress as compared to the untreated cells...
July 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28714019/salidroside-protects-pc12-cells-from-a%C3%AE-1%C3%A2-40%C3%A2-induced-cytotoxicity-by-regulating-the-nicotinamide-phosphoribosyltransferase-signaling-pathway
#3
Xujiao Huang, Sanli Xing, Chuan Chen, Zhihua Yu, Jiulin Chen
Alzheimer's disease (AD) is the most common type of senile dementia, which often develops in elderly or presenile individuals. As one of the pathological features of AD, amyloid β‑protein (Aβ) causes energy dysmetabolism, thereby inducing cellular damage and apoptosis. Salidroside is the main active component of the traditional Chinese medicine Rhodiola. Previous studies have demonstrated that salidroside exerts a regulatory role in energy metabolism. However, the role and the mechanism of action of salidroside in AD remain unclear...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28707979/emerging-roles-for-sirt5-in-metabolism-and-cancer
#4
Lauren Rose Bringman-Rodenbarger, Angela H Guo, Costas A Lyssiotis, David B Lombard
SIGNIFICANCE: Developing evidence in the literature suggests that SIRT5 may be involved in metabolic reprogramming, an emerging hallmark of cancer by which neoplastic cells reconfigure their metabolism to support the anabolic demands of rapid cell division. Sirtuin 5 (SIRT5) is one of the seven members of the nicotinamide adenine dinucleotide (NAD+)-dependent sirtuin family of lysine deacylases. It removes succinyl, malonyl, and glutaryl groups from protein targets within the mitochondrial matrix and other subcellular compartments...
July 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28707004/host-sirtuin-1-regulates-mycobacterial-immunopathogenesis-and-represents-a-therapeutic-target-against-tuberculosis
#5
Catherine Y Cheng, Nuria M Gutierrez, Mardiana B Marzuki, Xiaohua Lu, Taylor W Foreman, Bhairav Paleja, Bernett Lee, Akhila Balachander, Jinmiao Chen, Liana Tsenova, Natalia Kurepina, Karen W W Teng, Kim West, Smriti Mehra, Francesca Zolezzi, Michael Poidinger, Barry Kreiswirth, Deepak Kaushal, Hardy Kornfeld, Evan W Newell, Amit Singhal
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. This has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, in monocytes/macrophages, TB animal models, and TB patients with active disease...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28705804/loss-of-nitric-oxide-mediated-inhibition-of-purine-neurotransmitter-release-in-the-colon-in-the-absence-of-interstitial-cells-of-cajal
#6
Leonie Durnin, Andrea Lees, Sheerien Manzoor, Kent C Sasse, Kenton M Sanders, Violeta N Mutafova-Yambolieva
Regulation of colonic motility depends upon the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit(W)/Kit(W-v) (W/W(v) ) mice that display lesions in ICC-IM along the gastrointestinal tract...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28704960/fabrication-of-flexible-arrayed-lactate-biosensor-based-on-immobilizing-ldh-nad%C3%A2-%C2%BA-on-nio-film-modified-by-go-and-mbs
#7
Jung-Chuan Chou, Siao-Jie Yan, Yi-Hung Liao, Chih-Hsien Lai, You-Xiang Wu, Cian-Yi Wu, Hsiang-Yi Chen, Hong-Yu Huang, Tong-Yu Wu
We proposed the flexible arrayed lactate biosensor based on immobilizing l-lactate dehydrogenase (LDH) and nicotinamide adenine dinucleotide ( NAD + ) on nickel oxide (NiO) film, and which the average sensitivity could be enhanced by using graphene oxide (GO) and magnetic beads (MBs). By using GO and MBs, it exhibits excellent sensitivity (45.397 mV/mM) with a linearity of 0.992 in a range of 0.2 mM to 3 mM. According to the results of electrochemical impedance spectroscopy (EIS), the electron transfer resistance of LDH- NAD + -MBs/GPTS/GO/NiO film was smaller than those of LDH-NAD⁺/GPTS/GO/NiO film and LDH- NAD + /GPTS/NiO film, and it presented the outstanding electron transfer ability...
July 12, 2017: Sensors
https://www.readbyqxmd.com/read/28695527/computational-and-experimental-studies-of-adp-ribosylation
#8
Robert G Hammond, Xuan Tan, Matthew Chan, Anupam Goel, Margaret A Johnson
The macrodomains are a multifunctional protein family that function as receptors and enzymes acting on poly(ADP-ribose), ADP-ribosylated proteins, and other metabolites of nicotinamide adenine dinucleotide (NAD(+)). Several new functions for macrodomains, such as nucleic acid binding and protein-protein interaction, have recently been identified in this family. Here, we discuss methods for the identification of new macrodomains in viruses and the prediction of their function. This is followed by the expression and purification of these proteins following overexpression in bacterial cells and confirmation of folding and function using biophysical methods...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695524/studying-catabolism-of-protein-adp-ribosylation
#9
Luca Palazzo, Dominic I James, Ian D Waddell, Ivan Ahel
Protein ADP-ribosylation is a conserved posttranslational modification that regulates many major cellular functions, such as DNA repair, transcription, translation, signal transduction, stress response, cell division, aging, and cell death. Protein ADP-ribosyl transferases catalyze the transfer of an ADP-ribose (ADPr) group from the β-nicotinamide adenine dinucleotide (β-NAD(+)) cofactor onto a specific target protein with the subsequent release of nicotinamide. ADP-ribosylation leads to changes in protein structure, function, stability, and localization, thus defining the appropriate cellular response...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695506/using-clickable-nad-analogs-to-label-substrate-proteins-of-parps
#10
Lu Zhang, Hening Lin
ADP-ribosylation has been well known as an important posttranslational modification, which is catalyzed by a family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARPs transfer of a single or multiple adenine diphosphate ribose (ADP-ribose) units from nicotinamide adenine dinucleotide (NAD(+)) to specific amino acids on substrate proteins. Through mono- or poly-ADP-ribosylation enzymatic activities, PARPs regulate various biological processes, including DNA damage repair, chromatin remodeling, transcriptional regulation, RNA processing and metabolism...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695502/compartment-specific-poly-adp-ribose-formation-as-a-biosensor-for-subcellular-nad-pools
#11
Magali R VanLinden, Marc Niere, Andrey A Nikiforov, Mathias Ziegler, Christian Dölle
Nicotinamide adenine dinucleotide (NAD) is vital to many cellular processes and is distributed between distinct subcellular pools in the compartmentalized eukaryotic cell. The detection and relative quantification of these individual pools is difficult because of the methods usually applied, which require cell disruption and fractionation.Here, we describe an immunochemical method to visualize and relatively quantify subcellular NAD(+) pools, which relies on the NAD(+)-consuming activity of poly-ADP-ribose polymerase 1 (PARP1)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28685427/imaging-redox-state-in-mouse-muscles-of-different-ages
#12
Lily Moon, David W Frederick, Joseph A Baur, Lin Z Li
Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD(+)) and the NAD(+)-coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD(+) falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD(+)/NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28677728/overexpression-of-sirt1-prevents-hypoxia%C3%A2-induced-apoptosis-in-osteoblast-cells
#13
Lu Zhou, Sung Il Wang, Young Jae Moon, Kyoung Min Kim, Kwang Bok Lee, Byung-Hyun Park, Kyu Yun Jang, Jung Ryul Kim
Hypoxic‑ischemic injury of the bone results in osteonecrosis. Nicotinamide adenosine dinucleotide (NAD)‑dependent deacetylase sirtuin‑1 (SIRT1), a type of NAD‑dependent deacetylase, is involved in multiple biological functions, particularly in anti‑apoptosis. However, the effects of SIRT1 in osteoblasts remain unclear and whether SIRT1 protects osteoblasts in hypoxic conditions remains to be elucidated. In the present study, the role of SIRT1 in the osteoblast cells under hypoxia and the underlying mechanism of the anti‑apoptotic activity of SIRT1 were investigated...
July 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28671679/2-deoxyadenosine-5-diphosphoribose-is-an-endogenous-trpm2-superagonist
#14
Ralf Fliegert, Andreas Bauche, Adriana-Michelle Wolf Pérez, Joanna M Watt, Monika D Rozewitz, Riekje Winzer, Mareike Janus, Feng Gu, Annette Rosche, Angelika Harneit, Marianne Flato, Christelle Moreau, Tanja Kirchberger, Valerie Wolters, Barry V L Potter, Andreas H Guse
Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca(2+)-permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca(2+) signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca(2+) entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10...
June 26, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28668830/increased-nicotinamide-phosphoribosyltransferase-and-cystathionine-%C3%AE-synthase-in-renal-oncocytomas-renal-urothelial-carcinoma-and-renal-clear-cell-carcinoma
#15
Rodney E Shackelford, Jehan Abdulsattar, Eric X Wei, James Cotelingam, Domenico Coppola, Guillermo A Herrera
BACKGROUND: Renal oncocytomas (ROs), and clear cell (RCC) and urothelial carcinomas (UC), are common renal neoplasms. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of NAD(+) synthesis and its expression is increased in several tumors. Nampt concomitantly regulates hydrogen sulfide (H2S)-synthesizing enzyme levels, including cystathionine-β-synthase (CBS). MATERIALS AND METHODS: We used tissue microarrays to examine Nampt and the H2S-synthesizing enzyme CBS protein levels in benign kidney, RCC, UC and ROs...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666871/structural-bases-of-the-altered-catalytic-properties-of-a-pathogenic-variant-of-apoptosis-inducing-factor
#16
Luca Sorrentino, Federica Cossu, Mario Milani, Alessandro Aliverti, Eloise Mastrangelo
The apoptosis-inducing factor (AIF) is a FAD-containing protein playing critical roles in caspase-independent apoptosis and mitochondrial respiratory chain biogenesis and maintenance. While its lethal role is well known, the details of its mitochondrial function remain elusive. So far, nineteen allelic variants of AIF have been associated to human diseases, mainly affecting the nervous system. A strict correlation is emerging between the degree of impairment of its ability to stabilize the charge-transfer (CT) complex between FAD and NAD(+) and the severity of the resulting pathology...
June 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28663844/fluorescence-quenching-of-free-and-bound-nadh-in-hela-cells-determined-by-hyperspectral-imaging-and-unmixing-of-cell-autofluorescence
#17
Aziz Ul Rehman, Ayad G Anwer, Martin E Gosnell, Saabah B Mahbub, Guozhen Liu, Ewa M Goldys
Carbonyl cyanide-p-trifluoro methoxyphenylhydrazone (FCCP) is a well-known mitochondrial uncoupling agent. We examined FCCP-induced fluorescence quenching of reduced nicotinamide adenine dinucleotide / nicotinamide adenine dinucleotide phosphate (NAD(P)H) in solution and in cultured HeLa cells in a wide range of FCCP concentrations from 50 to 1000µM. A non-invasive label-free method of hyperspectral imaging of cell autofluorescence combined with unsupervised unmixing was used to separately isolate the emissions of free and bound NAD(P)H from cell autofluorescence...
March 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28661724/sirt1-and-sirt6-signaling-pathways-in-cardiovascular-disease-protection
#18
Nunzia D'Onofrio, Luigi Servillo, Maria Luisa Balestrieri
SIGNIFICANCE: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD(+))-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD...
June 29, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28659716/aspects-of-tryptophan-and-nicotinamide-adenine-dinucleotide-in-immunity-a-new-twist-in-an-old-tale
#19
REVIEW
Hector Rodriguez Cetina Biefer, Anju Vasudevan, Abdallah Elkhal
Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan's involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28656393/emerging-roles-of-sirtuins-in-ischemic-stroke
#20
REVIEW
David T She, Dong-Gyu Jo, Thiruma V Arumugam
Ischemic stroke is one of the leading causes of death worldwide. It is characterized by a sudden disruption of blood flow to the brain causing cell death and damage, which will lead to neurological impairments. In the current state, only one drug is approved to be used in clinical setting and new therapies that confer ischemic neuroprotection are desperately needed. Several targets and pathways have been indicated to be neuroprotective in ischemic stroke, among which the sirtuin family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases has emerged as important modulators of several processes in the normal physiology and pathological conditions such as stroke...
June 27, 2017: Translational Stroke Research
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