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https://www.readbyqxmd.com/read/28334607/the-sarm1-toll-interleukin-1-receptor-domain-possesses-intrinsic-nad-cleavage-activity-that-promotes-pathological-axonal-degeneration
#1
Kow Essuman, Daniel W Summers, Yo Sasaki, Xianrong Mao, Aaron DiAntonio, Jeffrey Milbrandt
Axonal degeneration is an early and prominent feature of many neurological disorders. SARM1 is the central executioner of the axonal degeneration pathway that culminates in depletion of axonal NAD(+), yet the identity of the underlying NAD(+)-depleting enzyme(s) is unknown. Here, in a series of experiments using purified proteins from mammalian cells, bacteria, and a cell-free protein translation system, we show that the SARM1-TIR domain itself has intrinsic NADase activity-cleaving NAD(+) into ADP-ribose (ADPR), cyclic ADPR, and nicotinamide, with nicotinamide serving as a feedback inhibitor of the enzyme...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28333449/epigenetic-modulation-of-endophytic-eupenicillium-sp-lg41-by-a-histone-deacetylase-inhibitor-for-production-of-decalin-containing-compounds
#2
Gang Li, Souvik Kusari, Christopher Golz, Hartmut Laatsch, Carsten Strohmann, Michael Spiteller
An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD(+)-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-containing compounds, eupenicinicols C and D (3 and 4), along with two biosynthetically related known compounds, eujavanicol A (1) and eupenicinicol A (2). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECD calculations, as well as single-crystal X-ray diffraction...
March 23, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#3
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/28333148/salusin-%C3%AE-contributes-to-oxidative-stress-and-inflammation-in-diabetic-cardiomyopathy
#4
Ming-Xia Zhao, Bing Zhou, Li Ling, Xiao-Qing Xiong, Feng Zhang, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Salusin-β accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-β levels were increased in diabetic patients. This study was designed to determine whether salusin-β is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-β attenuates cardiac inflammation and oxidative stress in rats with DCM. H9c2 or neonatal rat cardiomyocytes were incubated with 33.3 mM of glucose to mimic the high glucose (HG) in diabetes...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28333140/metabolic-and-molecular-insights-into-an-essential-role-of-nicotinamide-phosphoribosyltransferase
#5
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/28330719/nicotinamide-mononucleotide-inhibits-jnk-activation-to-reverse-alzheimer-disease
#6
Zhiwen Yao, Wenhao Yang, Zhiqiang Gao, Peng Jia
Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice...
March 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28330104/purification-and-characterization-of-the-enzymes-involved-in-nicotinamide-adenine-dinucleotide-degradation-by-penicillium-brevicompactum-nrc-829
#7
Thanaa Hamed Ali, Dina Helmy El-Ghonemy
The present study was conducted to investigate a new pathway for the degradation of nicotinamide adenine dinucleotide (NAD) by Penicillium brevicompactum NRC 829 extracts. Enzymes involved in the hydrolysis of NAD, i.e. alkaline phosphatase, aminohydrolase and glycohydrolase were determined. Alkaline phosphatase was found to catalyse the sequential hydrolysis of two phosphate moieties of NAD molecule to nicotinamide riboside plus adenosine. Adenosine was then deaminated by aminohydrolase to inosine and ammonia...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28327357/the-ternary-complex-structure-of-d-mandelate-dehydrogenase-with-nadh-and-anilino-oxo-acetate
#8
Nayuta Furukawa, Akimasa Miyanaga, Masahiro Nakajima, Hayao Taguchi
Enterococcus faecium NAD-dependent d-mandelate dehydrogenase (D-ManDH) belongs to a ketopantoate reductase (KPR)-related D-2-hydroxyacid dehydrogenase family, and exhibits broad substrate specificity toward bulky hydrophobic 2-ketoacids, preferring C3-branched substrates. The ternary complex structure of D-ManDH with NADH and anilino(oxo)acetate (AOA) revealed that the substrate binding induces a shear motion of the N-terminal domain along the C-terminal domain, following the hinge motion induced by the NADH binding, and allows the bound NADH molecule to form favorable interactions with a 2-ketoacid substrate...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28325093/differences-in-intracellular-mobile-zinc-levels-affect-susceptibility-to-plasma-activated-medium-induced-cytotoxicity
#9
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/28324209/molecular-cloning-structural-modeling-and-the-production-of-soluble-triple-mutated-diphtheria-toxoid-k51e-g52e-e148k-co-expressed-with-molecular-chaperones-in-recombinant-escherichia-coli
#10
Naphatsamon Uthailak, Pornpimol Mahamad, Pamorn Chittavanich, Somchai Yanarojana, Wassana Wijagkanalan, Jean Petre, Watanalai Panbangred
CRM197 is a diphtheria toxin (DT) mutant (G52E) which has been used as a carrier protein for conjugate vaccines. However, it still possesses cytotoxicity toward mammalian cells. The goal of this project was to produce a non-toxic and soluble CRM197EK through introduction of triple amino acid substitutions (K51E/G52E/E148K) in Escherichia coli. The expression of CRM197EKTrxHis was optimized and co-expressed with different molecular chaperones. The soluble CRM197EKTrxHis was produced at a high concentration (97...
March 21, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28323302/vegetable-and-fruit-juice-enhances-antioxidant-capacity-and-regulates-antioxidant-gene-expression-in-rat-liver-brain-and-colon
#11
Linhong Yuan, Jinmeng Liu, Jie Zhen, Yao Xu, Shuying Chen, Nicholas Van Halm-Lutterodt, Rong Xiao
To explore the effect of fruit and vegetable (FV) juice on biomarkers of oxidative damage and antioxidant gene expression in rats, 36 adult male Wistar rats were randomly divided into control, low FV juice dosage or high FV juice dosage treatment groups. The rats were given freshly extracted FV juice or the same volume of saline water daily for five weeks. After intervention, serum and tissues specimens were collected for biomarker and gene expression measurement. FV juice intervention increased total antioxidant capacity, glutathione, vitamin C, β-carotene, total polyphenols, flavonoids levels andglutathione peroxidaseenzyme activity in rat serum or tissues (p < 0...
March 20, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28323211/metabolic-pathway-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-and-its-effects-on-cellular-energetics
#12
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/28322842/simultaneous-blockade-of-nmda-receptors-and-parp-1-activity-synergistically-alleviate-immunoexcitotoxicity-and-bioenergetics-in-3-nitropropionic-acid-intoxicated-mice-evidences-from-memantine-and-3-aminobenzamide-interventions
#13
Saravana Babu Chidambaram, Ranju Vijayan, Sathiya Sekar, Sugumar Mani, Barathidsan Rajamani, Ramakrishnan Ganapathy
Interlink between excitotoxicity and cellular bioenergetics depletion is implicated as one of the central deteriorative pathways in many neurodegenerative diseases including Huntington's disease (HD). Chronic administration of 3-nitropropionic acid (3-NP) depletes ATP and NAD(+;) and increases TNFα, IL-6 and glutamate content resulting in "immunoexcitotoxicity". Present study was designed to determine whether the combination of memantine (MN) and 3-aminobenzamide (3-AB), PARP inhibitor, can ameliorate immunoexcitotoxicity and improve bioenergetics in a better manner than individual administration against 3-NP intoxication in mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28321576/two-distinct-cinnamoyl-coa-reductases-in-selaginella-moellendorffii-offer-insight-into-the-divergence-of-ccrs-in-plants
#14
Nan Chao, Shuang Li, Ning Li, Qi Qi, Wen-Ting Jiang, Xiang-Ning Jiang, Ying Gai
Two distinct cinnamoyl-coenzyme A reductases (CCRs) from Selaginella moellendorffii were evaluated, and of these, SmCCR2-1, which has both distinct sequence motifs and catalytic properties, was clustered into a new CCR subgroup. Cinnamoyl-coenzyme A reductases (CCRs) have been reported in many land plants to have critical functions in monolignol biosynthesis. In this study, we performed a genome-wide screen and obtained two distinct SmCCRs from S. moellendorffii. Phylogenetic analysis indicated that SmCCR2 (both SmCCR2-1 and 2-2) and SmCCR3 together with PpaCCR belong to a distinct subgroup of genuine CCRs with variations in the NAD(P)H-binding motif...
March 20, 2017: Planta
https://www.readbyqxmd.com/read/28320303/substrate-specific-reduction-of-tetrazolium-salts-by-isolated-mitochondria-tissues-and-leukocytes
#15
N I Fedotcheva, E G Litvinova, M V Zakharchenko, N V Khunderyakova, R S Fadeev, V V Teplova, T A Fedotcheva, N V Beloborodova, M N Kondrashova
Tetrazolium salts are commonly used in cytochemical and biochemical studies as indicators of metabolic activity of cells. Formazans, formed by reduction of tetrazolium salts, behave as pseudo-solutions during initial incubation, which allows monitoring their optical density throughout incubation. The criteria and conditions for measuring oxidative activity of mitochondria and dehydrogenase activity in reduction of nitroblue tetrazolium (NBT) and methyl thiazolyl tetrazolium (MTT) in suspensions of isolated mitochondria, tissue homogenates, and leukocytes were investigated in this work...
February 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28318242/whole-blood-metabolomics-by-1h-nmr-spectroscopy-provides-a-new-opportunity-to-evaluate-coenzymes-and-antioxidants
#16
G A Nagana Gowda, Daniel Raftery
Conventional human blood metabolomics employs serum or plasma and provides a wealth of metabolic information therein. However, this approach lacks the ability to measure and evaluate important metabolites such as coenzymes that are present at high concentrations in red blood cells. As an important alternative to serum/plasma metabolomics, we show here that a simple 1H NMR experiment can simultaneously measure coenzymes and antioxidants in extracts of whole human blood, in addition to the nearly 70 metabolites that were shown to be quantitated in serum/plasma, recently [Anal...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28315861/the-risk-factors-for-metastasis-in-non-ampullary-duodenal-neuroendocrine-tumors-measuring-20-mm-or-less-in-diameter
#17
Waku Hatta, Tomoyuki Koike, Katsunori Iijima, Kiyotaka Asanuma, Naoki Asano, Hiroaki Musha, Yoshifumi Inomata, Toshikazu Sano, Hiroyuki Endo, Atsushi Ikehata, Toru Horii, Motoki Ohyauchi, Satoshi Yokosawa, Atsuko Kasajima, Fumiyoshi Fujishima, Hironobu Sasano, Naoki Nakaya, Tomohiro Nakamura, Tooru Shimosegawa
BACKGROUND/AIMS: The treatment strategy for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) ≤20 mm in diameter has not been established. In this study, we aimed to evaluate the detailed characteristics of NAD-NETs ≤20 mm in diameter to clarify the risk factors of subsequent metastasis. METHODS: The patients with NAD-NETs ≤20 mm in diameter who had been treated at 12 institutions between 1992 and 2013 were enrolled. Clinical records were retrieved, and histopathological findings of all cases were centrally reviewed by 2 pathologists...
March 18, 2017: Digestion
https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anemia-cells-to-glycolytic-metabolism
#18
Enrico Cappelli, Paola Cuccarolo, Giorgia Stroppiana, Maurizio Miano, Roberta Bottega, Vanessa Cossu, Paolo Degan, Silvia Ravera
Energetic metabolism plays an essential role in the differentiation of haematopoietic stem cells (HSC). In Fanconi Anaemia (FA), DNA damage is accumulated during HSC differentiation, an event that is likely associated with bone marrow failure (BMF). One of the sources of the DNA damage is altered mitochondrial metabolism and an associated increment of oxidative stress. Recently, altered mitochondrial morphology and a deficit in the energetic activity in FA cells have been reported. Considering that mitochondria are the principal site of aerobic ATP production, we investigated FA metabolism in order to understand what pathways are able to compensate for this energy deficiency...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315326/identification-of-parp14-inhibitors-using-novel-methods-for-detecting-auto-ribosylation
#19
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/28314858/identification-and-characterization-of-a-20%C3%AE-hydroxysteroid-dehydrogenase-from-the-anaerobic-gut-bacterium-butyricicoccus-desmolans-atcc-43058
#20
Saravanan Devendran, Celia Méndez-Garcia, Jason M Ridlon
Members of the gastrointestinal microbiota are known to convert glucocorticoids to androstanes, which can be subsequently converted to potent androgens by other members of the gut microbiota or host tissues. Butyricicoccus desmolans and Clostridium cadaveris has previously been reported for steroid-17,20-desmolase and 20β-hydroxysteroid dehydrogenase (20β-HSDH) activities that were responsible for androstane formation from cortisol, however the gene encoding these enzymes has yet to be reported. In this work, we identified and located a gene encoding 20β-HSDH in both B...
March 17, 2017: Journal of Lipid Research
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