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Lactate AND NAD ratio

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https://www.readbyqxmd.com/read/29751795/inhibition-of-glutamate-oxaloacetate-transaminase-1-in-cancer-cell-lines-results-in-altered-metabolism-with-increased-dependency-of-glucose
#1
Xiaoshan Zhou, Sophie Curbo, Fuqiang Li, Shuba Krishnan, Anna Karlsson
BACKGROUND: Glutamate oxaloacetate transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements. KRAS mutated cancer cells were recently shown to rely on GOT1 to support long-term cell proliferation. The aim of the present study was to address the role of GOT1 in the metabolic adaption of cancer cells. METHODS: GOT1-null and knockdown cell lines were established through CRISPR/Cas9 and shRNA techniques...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29680643/phosphorylation-of-nuclear-factor-erythroid-2-like-2-nfe2l2-in-mammary-tissue-of-holstein-cows-during-the-periparturient-period-is-associated-with-mrna-abundance-of-antioxidant-gene-networks
#2
L Q Han, Z Zhou, Y Ma, F Batistel, J S Osorio, J J Loor
Changes in the production of reactive oxygen species in the mammary gland of dairy cows during the periparturient period could lead to oxidative stress and potentially impair mammary function. Phosphorylation of the transcription factor nuclear factor erythroid 2-like 2 (NFE2L2), also known as nuclear factor-E2-related factor 2, controls mRNA abundance of genes encoding antioxidant proteins and enzymes. The hypothesis was that NFE2L2 phosphorylation status and target gene mRNA abundance in the mammary gland of dairy cows is altered around parturition...
April 18, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29672321/metabolic-plasticity-enables-circadian-adaptation-to-acute-hypoxia-in-zebrafish-cells
#3
Adolf M Sandbichler, Bianca Jansen, Bettina A Peer, Monika Paulitsch, Bernd Pelster, Margit Egg
BACKGROUND/AIMS: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. METHODS: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts...
April 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29615678/protein-bound-nad-p-h-lifetime-is-sensitive-to-multiple-fates-of-glucose-carbon
#4
Joe T Sharick, Peter F Favreau, Amani A Gillette, Sophia M Sdao, Matthew J Merrins, Melissa C Skala
While NAD(P)H fluorescence lifetime imaging (FLIM) can detect changes in flux through the TCA cycle and electron transport chain (ETC), it remains unclear whether NAD(P)H FLIM is sensitive to other potential fates of glucose. Glucose carbon can be diverted from mitochondria by the pentose phosphate pathway (via glucose 6-phosphate dehydrogenase, G6PDH), lactate production (via lactate dehydrogenase, LDH), and rejection of carbon from the TCA cycle (via pyruvate dehydrogenase kinase, PDK), all of which can be upregulated in cancer cells...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29462203/a-generic-hts-assay-for-kinase-screening-validation-for-the-isolation-of-an-engineered-malate-kinase
#5
Romain Irague, Christopher M Topham, Nelly Martineau, Audrey Baylac, Clément Auriol, Thomas Walther, Jean-Marie François, Isabelle André, Magali Remaud-Siméon
An end-point ADP/NAD+ acid/alkali assay procedure, directly applicable to library screening of any type of ATP-utilising/ADP producing enzyme activity, was implemented. Typically, ADP production is coupled to NAD+ co-enzyme formation by the conventional addition of pyruvate kinase and lactate dehydrogenase. Transformation of enzymatically generated NAD+ into a photometrically active alkali derivative product is then achieved through the successive application of acidic/alkali treatment steps. The assay was successfully miniaturized to search for malate kinase activity in a structurally-guided library of LysC aspartate kinase variants comprising 6,700 clones...
2018: PloS One
https://www.readbyqxmd.com/read/29330792/evaluating-the-metabolic-impact-of-hypoxia-on-pancreatic-cancer-cells
#6
Divya Murthy, Enza Vernucci, Gennifer Goode, Jaime Abrego, Pankaj K Singh
Hypoxia is frequently observed in human cancers and induces global metabolic reprogramming that includes an increase in glucose uptake and glycolysis, alterations in NAD(P)H/NAD(P)+ and intracellular ATP levels, and increased utilization of glutamine as the major precursor for fatty acid synthesis. In this chapter, we describe in detail various physiological assays that have been adopted to study the metabolic shift propagated by exposure to hypoxic conditions in pancreatic cell culture model that includes glucose uptake, glutamine uptake, and lactate release by pancreatic cancer cell lines...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13-c-lactate
#7
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina DiGialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan R Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials, and this study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on the cellular metabolism of prostate cancer cells. We observed a reduction in cell motility and aerobic glycolysis in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes and transporters involved in glycolysis...
March 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29297957/enhanced-1-3-propanediol-production-in-klebsiella-pneumoniae-by-a-combined-strategy-of-strengthening-the-tca-cycle-and-weakening-the-glucose-effect
#8
X Y Lu, S L Ren, J Z Lu, H Zong, J Song, B Zhuge
AIMS: This study aimed to strengthen the reducing equivalent generation in Klebsiella pneumoniae for improving 1,3-propanediol (PDO) production. METHODS AND RESULTS: Disruption of the arcA gene activated the transcription levels of the TCA cycle genes and thus increased the NADH/NAD+ ratio by 54·2%, leading to the improved PDO titre and yield per cell from 16·1 g l-1 and 4·0 g gDCW-1 to 18·8 g l-1 and 6·4 g gDCW-1 respectively. Further ldhA gene deletion eliminated lactate accumulation and promoted the PDO titre to 19·9 g l-1 ...
March 2018: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29288336/cytotoxicity-of-propofol-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Koji Kido, Hiroyuki Ito, Yudai Yamamoto, Koshi Makita, Tokujiro Uchida
PURPOSE: Propofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10)...
February 2018: Journal of Anesthesia
https://www.readbyqxmd.com/read/29200830/notoginsenoside-r1-attenuates-high-glucose-induced-endothelial-damage-in-rat-retinal-capillary-endothelial-cells-by-modulating-the-intracellular-redox-state
#10
Chunlan Fan, Yuan Qiao, Minke Tang
The aim of this study was to examine whether Notoginsenoside R1 (NR1) attenuates high glucose-induced cell damage in rat retinal capillary endothelial cells (RCECs) and to explore the mechanisms involved. The exposure of rat RCECs to high concentration of glucose (30 mM) for 72 h led to significant cytotoxicity, including decreased cell viability, reduced mitochondrial DNA copy number, increased lactate dehydrogenase release and elevated apoptosis. NR1, when present in the culture medium, markedly attenuated the high glucose-induced cytotoxicity in rat RCECs...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29190547/low-folate-stress-reprograms-cancer-stem-cell-like-potentials-and-bioenergetics-metabolism-through-activation-of-mtor-signaling-pathway-to-promote-in-vitro-invasion-and-in-vivo-tumorigenicity-of-lung-cancers
#11
Wan-Jing Chen, Rwei-Fen S Huang
Low-folate (LF) nutritional status is associated with increased risks of lung cancer. It has unexplored effects on lung cancer malignancy, a cancer stem cell (CSC) disease. We hypothesized that LF may reprogram CSC-like potential and bioenergetics metabolism to increase metastasis potential of lung cancers. Cultivation of human non-small-cell lung cancer cells (H23) in an LF medium enhanced CSC-like properties signified by increased expressions of the CSC surface marker CD44 and pluripotency markers Sox2, Oct4 and ALDH1A1, and promoted self-renewal ability of anchorage-independent oncospheroid formation...
March 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29137352/maternal-high-calorie-diet-induces-mitochondrial-dysfunction-and-senescence-phenotype-in-subcutaneous-fat-of-newborn-mice
#12
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
#13
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...
February 2018: 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
#14
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/29057578/label-free-imaging-of-redox-status-and-collagen-deposition-showing-metabolic-differences-in-the-heart
#15
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. In this study, we have employed 2-photon excitation fluorescence microscopy to define the relationship between two critical metabolic cofactors nicotinamide adenine dinucleotide(P)H and flavin adenine dinucleotide, effectively utilizing a redox ratio to differentiate between the metabolic status in fetal (proliferative) and adult (quiescent/hypertrophic) hearts...
March 2018: Journal of Biophotonics
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
#16
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/29025729/live-cell-imaging-of-cytosolic-nadh-nad-ratio-in-hepatocytes-and-liver-slices
#17
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 United States, 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...
January 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28890689/integration-between-glycolysis-and-glutamate-glutamine-cycle-flux-may-explain-preferential-glycolytic-increase-during-brain-activation-requiring-glutamate
#18
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
#19
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
https://www.readbyqxmd.com/read/28569777/the-novel-hypoxia-inducible-factor-1%C3%AE-inhibitor-idf-11774-regulates-cancer-metabolism-thereby-suppressing-tumor-growth
#20
Hyun Seung Ban, Bo-Kyung Kim, Hongsub Lee, Hwan Mook Kim, Dipesh Harmalkar, Miso Nam, Song-Kyu Park, Kiho Lee, Joon-Tae Park, Inhyub Kim, Kyeong Lee, Geum-Sook Hwang, Misun Won
HIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. We previously developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, a clinical candidate for cancer therapy. We also reported that IDF-1174 inhibited HSP70 chaperone activity and suppressed accumulation of HIF-1α. In this study, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells...
June 1, 2017: Cell Death & Disease
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