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Lactate AND NAD ratio

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https://www.readbyqxmd.com/read/29137352/maternal-high-calorie-diet-induces-mitochondrial-dysfunction-and-senescence-phenotype-in-subcutaneous-fat-of-newborn-mice
#1
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
#2
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
#3
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
#4
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/29032377/microrna-210-modulates-the-cellular-energy-metabolism-shift-during-h2o2-induced-oxidative-stress-by-repressing-iscu-in-h9c2-cardiomyocytes
#5
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
#6
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/28890689/integration-between-glycolysis-and-glutamate-glutamine-cycle-flux-may-explain-preferential-glycolytic-increase-during-brain-activation-requiring-glutamate
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anaemia-cells-to-glycolytic-metabolism
#10
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/28261868/in-vivo-assessment-of-intracellular-redox-state-in-rat-liver-using-hyperpolarized-1-13-c-alanine
#11
Jae Mo Park, Chalermchai Khemtong, Shie-Chau Liu, Ralph E Hurd, Daniel M Spielman
PURPOSE: The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD(+) ]. In this study, we assessed the use of hyperpolarized [1-(13) C]alanine and the subsequent detection of the intracellular products of [1-(13) C]pyruvate and [1-(13) C]lactate as a useful substrate for assessing redox levels in the liver in vivo. METHODS: Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion...
May 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/27798266/focally-perfused-succinate-potentiates-brain-metabolism-in-head-injury-patients
#12
Ibrahim Jalloh, Adel Helmy, Duncan J Howe, Richard J Shannon, Peter Grice, Andrew Mason, Clare N Gallagher, Matthew G Stovell, Susan van der Heide, Michael P Murphy, John D Pickard, David K Menon, T Adrian Carpenter, Peter J Hutchinson, Keri Lh Carpenter
Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients)...
July 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27561726/assessment-of-metformin-induced-changes-in-cardiac-and-hepatic-redox-state-using-hyperpolarized-1-13c-pyruvate
#13
Andrew J M Lewis, Jack J J Miller, Chloe McCallum, Oliver J Rider, Stefan Neubauer, Lisa C Heather, Damian J Tyler
Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-(13)C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment on heart and liver pyruvate metabolism in rats in vivo. Both oral treatment for 4 weeks and a single intravenous metformin infusion significantly increased the cardiac [1-(13)C]lactate:[1-(13)C]pyruvate ratio but had no effect on the [1-(13)C]bicarbonate + (13)CO2:[1-(13)C]pyruvate ratio, an index of pyruvate dehydrogenase flux...
December 2016: Diabetes
https://www.readbyqxmd.com/read/27374086/exogenous-pyruvate-facilitates-cancer-cell-adaptation-to-hypoxia-by-serving-as-an-oxygen-surrogate
#14
Chengqian Yin, Dan He, Shuyang Chen, Xiaoling Tan, Nianli Sang
Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27267826/radon-induced-alterations-in-p53-mediated-energy-metabolism-of-malignantly-transformed-human-bronchial-epithelial-cells
#15
Xing Liu, Xu Wang, Jian Tong
Radon and its progeny were confirmed to be a category I carcinogenic agent. However, the molecular basis underlying carcinogenesis induced by radon has not been fully elucidated. Expression of p53, a key regulator in glycolysis, is known to be decreased in carcinogenesis. The aim of this investigation was to determine changes in energy metabolism mediated by p53-related metabolic pathway using radon-induced transformation of human bronchial epithelial (HBE) cells. HBE cells were exposed to radon for 20 min at a concentration of 20,000 Bq/m(3) and cultured for 3 d, and exposed again at the same concentration and duration...
2016: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/27159677/mir-186-inhibited-aerobic-glycolysis-in-gastric-cancer-via-hif-1%C3%AE-regulation
#16
L Liu, Y Wang, R Bai, K Yang, Z Tian
Deregulation of microRNAs in human malignancies has been well documented, among which microRNA-186 (miR-186) has an antiproliferative role in some carcinomas. Here we demonstrate that low expression of miR-186 facilitates aerobic glycolysis in gastric cancer. MiR-186 suppresses cell proliferation induced by hypoxia inducible factor 1 alpha (HIF-1α) in gastric cancer cell lines MKN45 and SGC7901. Cellular glycolysis, including cellular glucose uptake, lactate, ATP/ADP and NAD+/NADH ratios, are also inhibited by miR-186...
May 9, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27157912/malate-aspartate-shuttle-inhibitor-aminooxyacetic-acid-leads-to-decreased-intracellular-atp-levels-and-altered-cell-cycle-of-c6-glioma-cells-by-inhibiting-glycolysis
#17
Caixia Wang, Heyu Chen, Mingchao Zhang, Jie Zhang, Xunbin Wei, Weihai Ying
NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures...
August 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27145082/a-hidden-transhydrogen-activity-of-a-fmn-bound-diaphorase-under-anaerobic-conditions
#18
John Collins, Ting Zhang, Scott Huston, Fangfang Sun, Y-H Percival Zhang, Jinglin Fu
BACKGROUND: Redox cofactors of NADH/NADPH participate in many cellular metabolic pathways for facilitating the electron transfer from one molecule to another in redox reactions. Transhydrogenase plays an important role in linking catabolism and anabolism, regulating the ratio of NADH/NADPH in cells. The cytoplasmic transhydrogenases could be useful to engineer synthetic biochemical pathways for the production of high-value chemicals and biofuels. METHODOLOGY/PRINCIPAL FINDINGS: A transhydrogenase activity was discovered for a FMN-bound diaphorase (DI) from Geobacillus stearothermophilus under anaerobic conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27035562/nampt-protects-against-6-hydroxydopamine-induced-neurotoxicity-in-pc12-cells-through-modulating-sirt1-activity
#19
Xiao-Dong Zou, Shao-Qing Guo, Zhi-Wei Hu, Wei-Lang Li
Parkinson's disease (PD) is the second most common progressive neurodegenerative movement disorder. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate‑limiting step in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in mammals, is a substrate for NAD+‑dependent enzymes, such as sirtuin 1 (SIRT1), and contributes to cell fate decisions. However, the role of NAMPT in PD has remained to be fully elucidated. In the present study, PC12 cells were treated with the neurotoxin 6-hydroxydopamine (6‑OHDA) to establish an in vitro model of PD, following which an obvious inhibitory effect on the levels of NAMPT and NAD+ as well as the NAD+/NADH ratio was detected...
May 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27020660/mitochondrial-dysfunctions-in-7-ketocholesterol-treated-158n-oligodendrocytes-without-or-with-%C3%AE-tocopherol-impacts-on-the-cellular-profil-of-tricarboxylic-cycle-associated-organic-acids-long-chain-saturated-and-unsaturated-fatty-acids-oxysterols-cholesterol
#20
Valerio Leoni, Thomas Nury, Anne Vejux, Amira Zarrouk, Claudio Caccia, Meryam Debbabi, Agnès Fromont, Randa Sghaier, Thibault Moreau, Gérard Lizard
In multiple sclerosis (MS) a process of white matter degradation leading to demyelination is observed. Oxidative stress, inflammation, apoptosis, necrosis and/or autophagy result together into a progressive loss of oligodendrocytes. 7-ketocholesterol (7KC), found increased in the cerebrospinal fluid of MS patients, triggers a rupture of RedOx homeostasis associated with mitochondrial dysfunctions, aptoptosis and autophagy (oxiapoptophagy) in cultured murine oligodendrocytes (158N). α-tocopherol is able to mild the alterations induced by 7KC partially restoring the cellular homeostasis...
May 2017: Journal of Steroid Biochemistry and Molecular Biology
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