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https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#1
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333140/metabolic-and-molecular-insights-into-an-essential-role-of-nicotinamide-phosphoribosyltransferase
#2
Li Q Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P Heruth, Charlie Bi, Roger Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt(-/-)) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28325093/differences-in-intracellular-mobile-zinc-levels-affect-susceptibility-to-plasma-activated-medium-induced-cytotoxicity
#3
Hirokazu Hara, Sayako Sueyoshi, Miko Taniguchi, Tetsuro Kamiya, Tetsuo Adachi
There is growing evidence that plasma-activated medium (PAM), which is prepared by non-thermal plasma (NTP) irradiation of cell-free medium, is a beneficial tool for cancer therapy. PAM has been reported to preferentially kill cancer cells; however, its mechanism is not fully understood. Since PAM contains reactive oxygen species (ROS) and reactive nitrogen species, the anti-cancer effects of PAM are thought to be attributed to oxidative stress induced by these reactive molecules. Oxidative stress has been shown to release zinc (Zn(2+)) from intracellular Zn(2+) stores and provoke Zn(2+)-dependent cell death...
March 21, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28323211/metabolic-pathway-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-and-its-effects-on-cellular-energetics
#4
Iwona Pelikant-Malecka, Ewa Kaniewska-Bednarczuk, Sylwia Szrok, Alicja Sielicka, Maciej Śledziński, Czesława Orlewska, Ryszard T Smolenski, Ewa M Słomińska
4-Pirydone-3-carboxamide-1β-D-ribonucleoside (4PYR) is an endogenous nucleoside that could be converted to triphosphates, diphosphates, monophosphates and an analogue of NAD - 4PYRAD. Elevated level of these compounds were observed in chronic renal failure, cancer and active HIV infection. However, little is known about the effect on cell functionality and the metabolic pathways. This study tested effects of 4PYR in different cell types on nucleotide and energy metabolism and clarified enzymes that are involved in conversions of 4PYR...
March 17, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28315326/identification-of-parp14-inhibitors-using-novel-methods-for-detecting-auto-ribosylation
#5
Mariko Yoneyama-Hirozane, Shin-Ichi Matsumoto, Yukio Toyoda, Singh Saikatendu Kumar, Yumi Zama, Kazuko Yonemori, Motomi Oonishi, Tsuyoshi Ishii, Tomohiro Kawamoto
Poly(ADP-ribose) polymerases (PARPs) use nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate to transfer ADP-ribose when it releases nicotinamide as the metabolized product. Enzymes of the PARP family play key roles in detecting and repairing DNA, modifying chromatin, regulating transcription, controlling energy metabolism, and inducing cell death. PARP14, the original member of the PARP family, has been reported to be associated with the development of inflammatory diseases and various cancer types, making it a potential therapeutic target...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28301150/discovery-of-new-sirt2-inhibitors-by-utilizing-a-consensus-docking-scoring-strategy-and-structure-activity-relationship-analysis
#6
Shen-Zhen Huang, Chun-Li Song, Xiang Wang, Guo Zhang, Yan-Lin Wang, Xiao-Juan Jiang, Qi-Zheng Sun, Lu-Yi Huang, Rong Xiang, Yi-Guo Hu, Lin-Li Li, Sheng-Yong Yang
SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought as potential interfering agents for relevant diseases. Discovery of SIRT2 inhibitor has attracted much attention recently. In this investigation, we first adopted a consensus docking/scoring strategy to screen for novel SIRT2 inhibitors...
March 16, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28291250/site-to-site-interdomain-communication-may-mediate-different-loss-of-function-mechanisms-in-a-cancer-associated-nqo1-polymorphism
#7
Encarnación Medina-Carmona, Jose L Neira, Eduardo Salido, Julian E Fuchs, Rogelio Palomino-Morales, David J Timson, Angel L Pey
Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73α oncosuppressors...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28287418/dietary-broccoli-alters-rat-cecal-microbiota-to-improve-glucoraphanin-hydrolysis-to-bioactive-isothiocyanates
#8
Xiaoji Liu, Yanling Wang, Jennifer L Hoeflinger, Bárbara P Neme, Elizabeth H Jeffery, Michael J Miller
Broccoli consumption brings many health benefits, including reducing the risk of cancer and inflammatory diseases. The objectives of this study were to identify global alterations in the cecal microbiota composition using 16S rRNA sequencing analysis and glucoraphanin (GRP) hydrolysis to isothiocyanates ex vivo by the cecal microbiota, following different broccoli diets. Rats were randomized to consume AIN93G (control) or different broccoli diets; AIN93G plus cooked broccoli, a GRP-rich powder, raw broccoli, or myrosinase-treated cooked broccoli...
March 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28278478/abnormality-detection-in-correlated-gaussian-molecular-nano-networks-design-and-analysis
#9
Siavash Ghavami, Farshad Lahouti
A nano abnormality detection scheme (NADS) in molecular nano-networks is studied. This is motivated by the fact that early detection of diseases such as cancer play a crucial role in their successful treatment. The proposed NADS is in fact a two-tier network of sensor nano-machines (SNMs) in the first tier and a data-gathering node (DGN) at the sink. The SNMs detect the presence of competitor cells (abnormality) by variations in input and/or parameters of a nano-communications channel (NCC). The noise of SNMs as their nature suggest is considered correlated in time and space and herein assumed additive Gaussian...
March 2, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28272714/role-of-dwi-assessing-nodal-involvement-and-response-to-neoadjuvant-chemotherapy-in-advanced-breast-cancer
#10
P Belli, E Bufi, C Buccheri, P Rinaldi, M Giuliani, M Romani, G Fabrizi, A D'angelo, C Brunelli, A Mule', G Franceschini, C Colosimo
OBJECTIVE: To explore the role of diffusion-weighted imaging (DWI) in the staging of axillary lymph nodes and the restaging after neoadjuvant chemotherapy (NAD) in advanced breast cancer. PATIENTS AND METHODS: MRI examinations of forty-two patients diagnosed with advanced breast cancer addressed to NAD and axillary lymph node dissection (ALND) were reviewed. Apparent diffusion coefficients (ADC) of each visible node in DWI in the pathologic axilla (PA) and healthy axilla (HA) were measured at the time of diagnosis (t0) and after chemotherapy (t1); mean values of the ADC were calculated...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28263975/disruption-of-nad-p-h-quinone-oxidoreductase-1-gene-in-mice-leads-to-20s-proteasomal-degradation-of-p63-resulting-in-thinning-of-epithelium-and-chemical-induced-skin-cancer
#11
https://www.readbyqxmd.com/read/28263970/cytosolic-malate-dehydrogenase-activity-helps-support-glycolysis-in-actively-proliferating-cells-and-cancer
#12
E A Hanse, C Ruan, M Kachman, D Wang, X H Lowman, A Kelekar
Increased glucose consumption is a hallmark of cancer cells. The increased consumption and subsequent metabolism of glucose during proliferation creates the need for a constant supply of NAD, a co-factor in glycolysis. Regeneration of the NAD required to support enhanced glycolysis has been attributed to the terminal glycolytic enzyme, lactate dehydrogenase (LDH). However, loss of glucose carbons to biosynthetic pathways early in glycolysis reduces the carbon supply to LDH. Thus, alternative routes for NAD regeneration must exist to support the increased glycolytic rate while allowing for the diversion of glucose to generate biomass and support proliferation...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28258219/resolving-the-cofactor-binding-site-in-the-proline-biosynthetic-enzyme-human-pyrroline-5-carboxylate-reductase-1
#13
Emily M Christensen, Sagar M Patel, David A Korasick, Ashley C Campbell, Kurt L Krause, Donald F Becker, John J Tanner
Pyrroline-5-carboxylate reductase (PYCR) is the final enzyme in proline biosynthesis, catalyzing the NAD(P)H-dependent reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline. Mutations in the PYCR1 gene alter mitochondrial function and cause the connective tissue disorder cutis laxa. Furthermore, PYCR1 is overexpressed in multiple cancers, and the PYCR1 knockout suppresses tumorigenic growth, suggesting PYCR1 is a potential cancer target. However, inhibitor development has been stymied by limited mechanistic details for the enzyme, particularly in light of a previous crystallographic study that placed the cofactor binding site in the C-terminal domain rather than the anticipated Rossmann fold of the N-terminal domain...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28241112/lysine-deacetylase-inhibitors-in-parasites-past-present-and-future-perspectives
#14
Gebremedhin Solomon Hailu, Dina Robaa, Mariantonietta Forgione, Wolfgang Sippl, Dante Rotili, Antonello Mai
Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their helpfulness is being seriously compromised by the drug resistance problem. Globally, this is pushing discovery research of anti-parasitic drugs towards new agents endowed with new mechanisms of action. By using a "drug repurposing" strategy, histone deacetylase inhibitors (HDACi), which are presently clinically approved for cancer use, are now under investigation for various parasite infections...
February 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28240897/development-of-1-2-4-oxadiazoles-as-potent-and-selective-inhibitors-of-the-human-deacetylase-sirtuin-2-structure-activity-relationship-x-ray-crystal-structure-and-anticancer-activity
#15
Sébastien Moniot, Mariantonietta Forgione, Alessia Lucidi, Gebremedhin S Hailu, Angela Nebbioso, Vincenzo Carafa, Francesca Baratta, Lucia Altucci, Nicola Giacché, Daniela Passeri, Roberto Pellicciari, Antonello Mai, Clemens Steegborn, Dante Rotili
Sirt2 is a target for the treatment of neurological, metabolic, and age-related diseases including cancer. Here we report a series of Sirt2 inhibitors based on the 1,2,4-oxadiazole scaffold. These compounds are potent Sirt2 inhibitors active at single-digit μM level by using the Sirt2 substrate α-tubulin-acetylLys40 peptide and inactive up to 100 μM against Sirt1, -3, and -5 (deacetylase and desuccinylase activities). Their mechanism of inhibition is uncompetitive toward both the peptide substrate and NAD(+), and the crystal structure of a 1,2,4-oxadiazole analog in complex with Sirt2 and ADP-ribose reveals its orientation in a still unexplored subcavity useful for further inhibitor development...
March 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28240865/a-near-infrared-wavelength-shiftable-turn-on-fluorescent-probe-for-the-detection-and-imaging-of-cancer-tumor-cells
#16
Zhenhua Shen, Bijeta Prasai, Yuko Nakamura, Hisataka Kobayashi, Milcah S Jackson, Robin L McCarley
Fast, selective, and noninvasive reporting of intracellular cancer-associated events and species will lead to a better understanding of tumorigenesis at the molecular level and development of precision medicine approaches in oncology. Overexpressed reductase presence in solid tumor cells is key to cancer progression and protection of diseased cells from the oxidative effects of therapeutics meant to kill them. Human NAD(P)H:quinone oxidoreductase isozyme I (hNQO1), a cytoprotective 2-electron-specific reductase found at unusually high activity levels in cancer cells of multiple origins, has attracted significant attention due to its major role in metastatic pathways and its link to low survival rates in patients, as well as its ability to effectively activate quinone-based, anti-cancer drugs...
February 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28238213/extracellular-renalase-protects-cells-and-organs-by-outside-in-signalling
#17
REVIEW
Yang Wang, Robert Safirstein, Heino Velazquez, Xiao-Jia Guo, Lindsay Hollander, John Chang, Tian-Min Chen, Jian-Jun Mu, Gary V Desir
Renalase was discovered as a protein synthesized by the kidney and secreted in blood where it circulates at a concentration of approximately 3-5 μg/ml. Initial reports suggested that it functioned as an NAD(P)H oxidase and could oxidize catecholamines. Administration of renalase lowers blood pressure and heart rate and also protects cells and organs against ischaemic and toxic injury. Although renalase's protective effect was initially ascribed to its oxidase properties, a paradigm shift in our understanding of the cellular actions of renalase is underway...
February 26, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28236663/catalytic-competence-structure-and-stability-of-the-cancer-associated-r139w-variant-of-the-human-nad-p-h-quinone-oxidoreductase-1-nqo1
#18
Wolf-Dieter Lienhart, Emilia Strandback, Venugopal Gudipati, Karin Koch, Alexandra Binter, Michael K Uhl, David M Rantasa, Benjamin Bourgeois, Tobias Madl, Klaus Zangger, Karl Gruber, Peter Macheroux
The human NAD(P)H:quinone oxidoreductase 1 (NQO1; EC 1.6.99.2) is an essential enzyme in the antioxidant defence system. Furthermore, NQO1 protects tumour suppressors like p53, p33(ING)(1b) and p73 from proteasomal degradation. The activity of NQO1 is also exploited in chemotherapy for the activation of quinone-based treatments. Various single nucleotide polymorphisms are known, such as NQO1*2 and NQO1*3 yielding protein variants of NQO1 with single amino acid replacements, i.e. P187S and R139W, respectively...
February 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28223550/nadh-autofluorescence-a-new-metabolic-biomarker-for-cancer-stem-cells-identification-of-vitamin-c-and-cape-as-natural-products-targeting-stemness
#19
Gloria Bonuccelli, Ernestina Marianna De Francesco, Rianne de Boer, Herbert B Tanowitz, Michael P Lisanti
Here, we assembled a broad molecular "tool-kit" to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to "metabolic fractionation" by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for "stem cell activity", using the mammosphere assay (3D-spheroids)...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#20
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
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