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Lactate AND NAD

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https://www.readbyqxmd.com/read/29156703/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#1
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154218/proteomics-of-dark-cutting-longissimus-thoracis-muscle-from-heifer-and-steer-carcasses
#2
Shahid Mahmood, Nancy Turchinsky, Francois Paradis, Walter T Dixon, Heather L Bruce
Studies have suggested that the phenomenon of dark cutting (Canada B4) beef may also be related to muscle glycolytic proteins. The objective of this study, therefore, was to analyze longissimus thoracis (LT; n=23), from Canada AA (n=8), atypical (AB4; pH<5.9, n=8) and typical (TB4; pH>5.9, n=7) B4 heifer and steer carcasses, for sarcoplasmic and myofibrillar proteins using 2-D gel electrophoresis and LC-MS/MS mass spectrometry. Results indicated that AB4 LT had intramuscular pH and lactate concentration similar to Canada AA but lower (P<0...
November 10, 2017: Meat Science
https://www.readbyqxmd.com/read/29149207/evolution-of-the-metabolome-in-response-to-selection-for-increased-immunity-in-populations-of-drosophila-melanogaster
#3
Navdeep Gogna, Rakesh Sharma, Vanika Gupta, Kavita Dorai, N G Prasad
We used NMR-based metabolomics to test two hypotheses-(i) there will be evolved differences in the metabolome of selected and control populations even under un-infected conditions and (ii) post infection, the metabolomes of the selected and control populations will respond differently. We selected replicate populations of Drosophila melanogaster for increased survivorship (I) against a gram-negative pathogen. We subjected the selected (I) and their control populations (S) to three different treatments: (1) infected with heat-killed bacteria (i), (2) sham infected (s), and (3) untreated (u)...
2017: PloS One
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
#4
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/29137352/maternal-high-calorie-diet-induces-mitochondrial-dysfunction-and-senescence-phenotype-in-subcutaneous-fat-of-newborn-mice
#5
Daniele Lettieri-Barbato, Fabiana D'Angelo, Francesca Sciarretta, Giuseppe Tatulli, Flavia Tortolici, Maria Rosa Ciriolo, Katia Aquilano
Mitochondrial dysfunction, inflammation and senescence-like features are observed in adipose depots in aging and obesity. Herein, we evaluated how maternal high calorie diet (HCD) may impact on subcutaneous adipose tissue (sAT) of the newborn mice. Adult C57BL/6J mice were randomly divided in three groups: normal calorie diet (NCD), HCD and HCD supplemented with niacin 8 weeks before mating. Mothers and pups were then sacrificed and metabolic and molecular analyses were carried out on sAT. HCD induced mitochondria dysfunction in mothers without inflammation and senescence, whereas in pups we also revealed the occurrence of senescent phenotype...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#6
Wo-Lin Hou, Jun Yin, Miriayi Alimujiang, Xue-Ying Yu, Li-Gen Ai, Yu-Qian Bao, Fang Liu, Wei-Ping Jia
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29099858/effects-of-glucose-availability-in-lactobacillus-sakei-metabolic-change-and-regulation-of-the-proteome-and-transcriptome
#7
Anette McLeod, Ellen F Mosleth, Ida Rud, Filipe Branco Dos Santos, Lars Snipen, Kristian Hovde Liland, Lars Axelsson
Effects of glucose availability were investigated in Lactobacillus sakei strains 23K and LS25 cultivated in anaerobic, glucose-limited chemostats set at high (D = 0.357 h-1) and low (D = 0.045 h-1) dilution rates. We observed for both strains a shift from homolactic towards more mixed acid fermentation when comparing high to low growth rates. However, this change was more pronounced for LS25 than for 23K, where dominating products were lactate>formate>acetate≥ethanol at both conditions. A multivariate approach was used for analyzing proteome and transcriptome data from the bacterial cultures, where the predictive power of the omics data was used for identifying features that can explain the differences in the end-product profiles...
2017: PloS One
https://www.readbyqxmd.com/read/29094331/pterostilbene-protects-against-uraemia-serum-induced-endothelial-cell-damage-via-activation-of-keap1-nrf2-ho-1-signaling
#8
Zhi-Wei Chen, Hai-Feng Miu, Hui-Ping Wang, Zhi-Niu Wu, Wen-Juan Wang, Yu-Jing Ling, Xiao-Hui Xu, Hai-Jian Sun, Xia Jiang
Chronic kidney disease causes uremia-related endothelial cell dysfunction associated with high risk for cardiovascular diseases. The vascular endothelium is permanently exposed to uraemic toxins including indoxyl sulfate, which provokes endothelial damage in subjects with end-stage renal disease. Pterostilbene (PT) is identified to be homologous derivative of resveratrol and exerts antioxidant and anti-inflammatory actions. However, the effects of PT on uraemic serum-induced endothelial cell damage have not been elucidated...
November 1, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29081884/the-neuroprotective-effects-of-sirt1-on-nmda-induced-excitotoxicity
#9
Xiaorong Yang, Peipei Si, Huaping Qin, Litian Yin, Liang-Jun Yan, Ce Zhang
Silent information regulator 1 (SIRT1), an NAD(+)-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV) in cultured cortical neurons or by overexpression of SIRT1 in SH-SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA-induced excitotoxicity...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29064158/the-natural-compound-2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-protects-against-adriamycin-induced-nephropathy-through-activating-the-nrf2-keap1-antioxidant-pathway
#10
En-Yuan Lin, Uyanga Bayarsengee, Ching-Chiung Wang, Yung-Hsiao Chiang, Chao-Wen Cheng
2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is an active compound extracted from Polygonum multiflorum Thunb. This herb and radix Polygoni Multiflori preparata have been used to treat arteriosclerosis, hyperlipidemia, hypercholesterolemia, and diabetes for thousands of years. This study aimed to investigate the protective effects of THSG in an Adriamycin (AD)-induced focal segmental glomerulosclerosis (FSGS) mouse model and the underlying mechanisms in an in vitro system. Mice were treated with THSG (2...
October 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29057578/label-free-imaging-of-redox-status-and-collagen-deposition-showing-metabolic-differences-in-the-heart
#11
Janna L Morrison, Alexandra Sorvina, Jack R T Darby, Christie A Bader, Mitchell C Lock, Mike Seed, Tim Kuchel, Sally E Plush, Douglas A Brooks
The heart has high metabolic demand to maintain function. The primary source of energy supply to support correct contractile muscle function differs between a fetus and an adult. In fetal life, ATP is primarily generated by glycolysis and lactate oxidation, whereas following birth there is a shift towards a reliance on mitochondrial metabolism and fatty acid oxidation. This change in metabolic status is an adaptation to different fuel availability, oxygenation and growth patterns. Here, we have employed two-photon excitation fluorescence microscopy to define the relationship between two critical metabolic co-factors NAD(P)H and FAD, effectively utilising a redox ratio to differentiate between the metabolic status in fetal (proliferative) and adult (quiescent/hypertrophic) hearts...
October 23, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/29043790/emissive-synthetic-cofactors-an-isomorphic-isofunctional-and-responsive-nad-analogue
#12
Alexander R Rovira, Andrea Fin, Yitzhak Tor
The synthesis, photophysics, and biochemical utility of a fluorescent NAD(+) analogue based on an isothiazolo[4,3-d]pyrimidine core (N(tz)AD(+)) are described. Enzymatic reactions, photophysically monitored in real time, show N(tz)AD(+) and N(tz)ADH to be substrates for yeast alcohol dehydrogenase and lactate dehydrogenase, respectively, with reaction rates comparable to that of the native cofactors. A drop in fluorescence is seen as N(tz)AD(+) is converted to N(tz)ADH, reflecting a complementary photophysical behavior to that of the native NAD(+)/NADH...
November 8, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29032377/microrna-210-modulates-the-cellular-energy-metabolism-shift-during-h2o2-induced-oxidative-stress-by-repressing-iscu-in-h9c2-cardiomyocytes
#13
Wei Sun, Lei Zhao, Xianjing Song, Jichang Zhang, Yue Xing, Ning Liu, Youyou Yan, Zhibo Li, Yang Lu, Junduo Wu, Longbo Li, Yanlong Xiao, Xin Tian, Tianyi Li, Yinuo Guan, Yiran Wang, Bin Liu
BACKGROUND/AIMS: The myocardial energy metabolism shift is one of the most important pathological features of ischemic heart disease (IHD). Although several microRNAs (miRs) are involved in the regulation of myocardial energy metabolism, their exact effects and underlying mechanisms remain unclear. The aim of this study was to investigate whether microRNA(miR-210) regulates the energy metabolism shift during oxidative stress in H9c2 cardiomyocytes. METHODS: Cell survival was analyzed via CCK assay...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29030620/transcriptomic-profiles-of-clostridium-ljungdahlii-during-lithotrophic-growth-with-syngas-or-h2-and-co2-compared-to-organotrophic-growth-with-fructose
#14
Muktak Aklujkar, Ching Leang, Pravin M Shrestha, Minita Shrestha, Derek R Lovley
Clostridium ljungdahlii derives energy by lithotrophic and organotrophic acetogenesis. C. ljungdahlii was grown organotrophically with fructose and also lithotrophically, either with syngas - a gas mixture containing hydrogen (H2), carbon dioxide (CO2), and carbon monoxide (CO), or with H2 and CO2. Gene expression was compared quantitatively by microarrays using RNA extracted from all three conditions. Gene expression with fructose and with H2/CO2 was compared by RNA-Seq. Upregulated genes with both syngas and H2/CO2 (compared to fructose) point to the urea cycle, uptake and degradation of peptides and amino acids, response to sulfur starvation, potentially NADPH-producing pathways involving (S)-malate and ornithine, quorum sensing, sporulation, and cell wall remodeling, suggesting a global and multicellular response to lithotrophic conditions...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025729/live-cell-imaging-of-cytosolic-nadh-nad-ratio-in-hepatocytes-and-liver-slices
#15
Ricard Masia, William J McCarty, Carolina Lahmann, Jay Luther, Raymond T Chung, Martin L Yarmush, Gary Yellen
Fatty liver disease (FLD), the most common chronic liver disease in the US, may be caused by alcohol or the metabolic syndrome. Alcohol is oxidized in the cytosol of hepatocytes by alcohol dehydrogenase (ADH), which generates NADH and increases cytosolic NADH/NAD(+) ratio. The increased ratio may be important for development of FLD, but our ability to examine this question is hindered by methodological limitations. To address this, we used the genetically-encoded fluorescent sensor Peredox to obtain dynamic, real-time measurements of cytosolic NADH/NAD(+) ratio in living hepatocytes...
October 12, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28966650/dried-rehmannia-root-protects-against-glutamate-induced-cytotoxity-to-pc12-cells-through-energy-metabolism-related-pathways
#16
Yong Liu, Lei Liu, Xi-Xiang Ying, Wen-Juan Wei, Chao Han, Yang Liu, Chun-Hui Han, Ai-Jing Leng, Jing-Yun Ma, Jing Liu
Rehmannia has been shown to be clinically effective in treating neurodegenerative diseases; however, the neuroprotective mechanisms remain unclear. In this study, we established a model of neurodegenerative disease using PC12 cytotoxic injury induced by glutamate. The cells were treated with 20 mM glutamate in the absence or presence of water extracts of dried Rehmannia root of varying concentrations (70%, 50% and 30%). The different concentrations of Rehmannia water extract significantly increased the activity of glutamate-injured cells, reduced the release of lactate dehydrogenase, inhibited apoptosis, increased the concentrations of NADH, NAD and ATP in cells, ameliorated mitochondrial membrane potential, and reduced the levels of light chain 3...
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28950656/oxamate-potentiates-taxol-chemotherapeutic-efficacy-in-experimentally-induced-solid-ehrlich-carcinoma-sec-in-mice
#17
Alaa E El-Sisi, Samia S Sokar, Sally E Abu-Risha, Sara R El-Mahrouk
Several human cancers including the breast display elevated expression of Lactate dehydrogenase-A (LDH-A), the enzyme that converts pyruvate to lactate and oxidizes NADH to NAD(+). Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate also plays roles in promoting tumor inflammation and as a signaling molecule that stimulates tumor angiogenesis. Because of its essential role in cancer metabolism, LDH-A has been considered as a potential target for combination cancer therapy...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#18
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide and then peroxide formation, which damages DNA and causes hyperactivation of poly(ADP-ribose) polymerase, resulting in extensive NAD(+)/ATP depletion...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28890689/integration-between-glycolysis-and-glutamate-glutamine-cycle-flux-may-explain-preferential-glycolytic-increase-during-brain-activation-requiring-glutamate
#19
REVIEW
Leif Hertz, Ye Chen
The 1988 observation by Fox et al. (1988) that brief intense brain activation increases glycolysis (pyruvate formation from glucose) much more than oxidative metabolism has been abundantly confirmed. Specifically glycolytic increase was unexpected because the amount of ATP it generates is much smaller than that formed by subsequent oxidative metabolism of pyruvate. The present article shows that preferential glycolysis can be explained by metabolic processes associated with activation of the glutamate-glutamine cycle...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/28871787/nmr-spectroscopy-based-metabolomics-of-drosophila-model-of-huntington-s-disease-suggests-altered-cell-energetics
#20
Virender Singh, Raj Kumar Sharma, Thamarailingam Athilingam, Pradip Sinha, Neeraj Sinha, Ashwani Kumar Thakur
Huntington's disease (HD) is a neurodegenerative disorder induced by aggregation of the pathological form of Huntingtin protein that has expanded polyglutamine (polyQ) repeats. In the Drosophila model, for instance, expression of transgenes with polyQ repeats induces HD-like pathologies, progressively correlating with the increasing lengths of these repeats. Previous studies on both animal models and clinical samples have revealed metabolite imbalances during HD progression. To further explore the physiological processes linked to metabolite imbalances during HD, we have investigated the 1D (1)H NMR spectroscopy-based metabolomics profile of Drosophila HD model...
September 26, 2017: Journal of Proteome Research
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