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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/29337590/novel-mechanism-for-nicotinamide-phosphoribosyltransferase-inhibition-of-tnf-%C3%AE-mediated-apoptosis-in-human-lung-endothelial-cells
#1
Radu C Oita, Sara M Camp, Wenli Ma, Ermelinda Ceco, Mark Harbeck, Patrick Singleton, Joe Messana, Xiaoguang Sun, Ting Wang, Joe G N Garcia
Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular (iNAMPT) and extracellular (eNAMPT) proteins. eNAMPT is secreted into the blood and functions as a cytokine/enzyme (cytozyme) that activates NFκB signaling via ligation of the TLR4 receptor, further serving as a biomarker for inflammatory lung disorders such as the acute respiratory distress syndrome (ARDS). In contrast, iNAMPT is involved in nicotinamide mononucleotide (NMN) synthesis and has been implicated in the regulation of cellular apoptosis, although the exact mechanisms for this regulation are poorly understood...
January 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29332790/ultrasensitive-electrochemical-detection-of-poly-adp-ribose-polymerase-1-via-polyaniline-deposition
#2
Yong Liu, Jiahui Fan, Li Shangguan, Yuanjian Liu, Yuanqing Wei, Wei Wei, Songqin Liu
Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target because it is closely related to the development of tumor. So, studies on its detection and inhibitors evaluation have attracted more attention. It is interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the existence of nicotinamide adenine dinucleotide (NAD+), possess twice charge density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and multiple branched strands...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29330025/the-role-of-extracellular-and-intracellular-nicotinamide-phosphoribosyl-transferase-in-cancer-diagnostic-and-therapeutic-perspectives-and-challenges
#3
REVIEW
Maria Dalamaga, Gerasimos Socrates Christodoulatos, Christos S Mantzoros
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties...
January 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29320743/a-p300-and-sirt1-regulated-acetylation-switch-of-c-ebp%C3%AE-controls-mitochondrial-function
#4
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/29318201/protein-engineering-of-oxidoreductases-utilizing-nicotinamide-based-coenzymes-with-applications-in-synthetic-biology
#5
REVIEW
Chun You, Rui Huang, Xinlei Wei, Zhiguang Zhu, Yi-Heng Percival Zhang
Two natural nicotinamide-based coenzymes (NAD and NADP) are indispensably required by the vast majority of oxidoreductases for catabolism and anabolism, respectively. Most NAD(P)-dependent oxidoreductases prefer one coenzyme as an electron acceptor or donor to the other depending on their different metabolic roles. This coenzyme preference associated with coenzyme imbalance presents some challenges for the construction of high-efficiency in vivo and in vitro synthetic biology pathways. Changing the coenzyme preference of NAD(P)-dependent oxidoreductases is an important area of protein engineering, which is closely related to product-oriented synthetic biology projects...
September 2017: Synthetic and Systems Biotechnology
https://www.readbyqxmd.com/read/29317496/a-functional-link-between-nad-homeostasis-and-n-terminal-protein-acetylation-in-saccharomyces-cerevisiae
#6
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/29317476/parp-inhibitor-pj34-attenuated-hepatic-triglyceride-accumulation-in-alcoholic-fatty-liver-disease-in-mice
#7
Shishun Huang, Bing Zhang, Yingli Chen, Huan Liu, Yang Liu, Xin Li, Zhiwei Bao, Zhenyuan Song, Zhigang Wang
Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of alcoholic fatty liver disease (AFLD) is still elusive. In current study, we applied PJ34 to inhibit hepatic PARP activity to examine the corresponding pathological alteration in AFLD in mice and the underlying molecular mechanism. We found that PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD+ level in hepatocyte...
January 9, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29305011/transcriptional-regulation-of-metabolism-by-sirt1-and-sirt7
#8
Kazuya Yamagata, Tatsuya Yoshizawa
Sirtuins are a family of evolutionally conserved nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases/deacylases that regulate metabolism. The mammalian sirtuin family consists of seven sirtuins (SIRT1-7). Recent findings have identified critical roles for SIRT1 and SIRT7 in glucose/lipid metabolism in multiple tissues. This review focuses on the metabolic roles of these two sirtuins and the benefits of modulating the activity of sirtuins for the treatment of metabolic diseases such as type 2 diabetes...
2018: International Review of Cell and Molecular Biology
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
#9
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
#10
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
#11
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/29249689/nad-intermediates-the-biology-and-therapeutic-potential-of-nmn-and-nr
#12
REVIEW
Jun Yoshino, Joseph A Baur, Shin-Ichiro Imai
Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD+ intermediates can exhibit distinct behavior, and their fates appear to depend on the tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and presumptive transporters for each...
December 14, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29247608/a-macrodomain-linked-immunosorbent-assay-mlisa-for-mono-adp-ribosyltransferases
#13
Jingwen Chen, Albert Lam, Yong Zhang
ADP-ribosyltransferases (ARTs) catalyze reversible additions of mono- and poly-ADP-ribose onto diverse types of proteins by using nicotinamide adenine dinucleotide (NAD+) as a cosubstrate. In human ART superfamily, 14 out of 20 members are shown to catalyze endogenous protein mono-ADP-ribosylation and play important roles in regulating various physiological and pathophysiological processes. Identification of new modulators of mono-ARTs can thus potentially lead to discovery of novel therapeutics. In this study, we developed a macrodomain-linked immunosorbent assay (MLISA) for characterizing mono-ARTs...
December 13, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29245920/nampt-overexpression-induces-cancer-stemness-and-defines-a-novel-tumor-signature-for-glioma-prognosis
#14
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/29239724/sirt2-and-lysine-fatty-acylation-regulate-the-transforming-activity-of-k-ras4a
#15
Hui Jing, Xiaoyu Zhang, Stephanie A Wisner, Xiao Chen, Nicole A Spiegelman, Maurine E Linder, Hening Lin
Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#16
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29232252/nicotinamide-adenine-dinucleotide-and-its-related-precursors-for-the-treatment-of-alzheimer-s-disease
#17
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
#18
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/29228460/emissive-synthetic-cofactors-enzymatic-interconversions-of-tza-analogues-of-atp-nad-nadh-nadp-and-nadph
#19
Yitzhak Tor, François Hallé, Andrea Fin, Alexander R Rovira
A series of enzymatic transformations, which generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3-d]pyrimidine analogue of adenosine (tzA), is described. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tzATP to yield NtzAD+, which can be enzymatically phosphorylated by NAD+ kinase and ATP or tzATP to the corresponding NtzADP+. The latter can be engaged in NADP-specific coupled enzymatic transformations involving conversion to NtzADPH by glucose-6-phosphate dehydrogenase and reoxidation to NtzADP+ by glutathione reductase...
December 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#20
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
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