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Lactate AND NAD

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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/29750296/hyperoside-protects-human-kidney%C3%A2-2-cells-against-oxidative-damage-induced-by-oxalic-acid
#2
Yongliang Chen, Lihong Ye, Wangjian Li, Dongzhang Li, Feng Li
The majority of renal calculi (kidney stones) are calcium stones. Oxidative damage to renal tubular epithelial cells induced by reactive oxygen species (ROS) is the predominant cause of calcium oxalate stone formation. Hyperoside (Hyp) is a flavonol glycoside extracted from medicinal plants and appears to exhibit potent antioxidant activity in various cells. The aim of the present study was to investigate the protective effect of Hyp on renal cells exposed to oxidative stress simulated by oxalic acid (OA), and to determine whether the underlying mechanism involves the nuclear factor E2‑related factor2 (Nrf2)‑antioxidative response element signaling pathway...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29688005/reversible-ph-responsive-behavior-of-ruthenium-ii-arene-complexes-with-tethered-carboxylate
#3
Francisco Martínez-Peña, Sonia Infante-Tadeo, Abraha Habtemariam, Ana M Pizarro
Five complexes of formula [Ru(η6 -C6 H5 CH2 COOH)(XY)Cl]Cl/Na (XY = ethylenediamine (1), o-phenylenediamine (2), phenanthroline (3), and oxalato (4)) and [Ru(η6 :κ1 -C6 H5 CH2 COO)(tmen)]Cl (tmen = N, N, N', N'-tetramethylethylenediamine, 5C) have been synthesized and fully characterized. Five new X-ray crystal structures ([Ru(η6 -C6 H5 CH2 COOH)(μ-Cl)Cl]2 , 1, 3, 4, and 5C·PF6 ) have been determined, which are the first examples of ruthenium(II) structures with phenylacetic acid as arene ligand. Furthermore, 5C·PF6 is the first example of a five-membered tether ring with a Ru(η6 :κ1 -arene:O) bond...
April 24, 2018: Inorganic Chemistry
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
#4
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
#5
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
#6
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/29603726/mechanisms-driving-the-lactate-switch-in-chinese-hamster-ovary-cells
#7
REVIEW
Fiona Hartley, Tracy Walker, Vicky Chung, Karl Morten
The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. This review aims to consolidate current theories surrounding the lactate switch...
March 31, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29593673/flavin-based-electron-bifurcation-ferredoxin-flavodoxin-and-anaerobic-respiration-with-protons-ech-or-nad-rnf-as-electron-acceptors-a-historical-review
#8
REVIEW
Wolfgang Buckel, Rudolf K Thauer
Flavin-based electron bifurcation is a newly discovered mechanism, by which a hydride electron pair from NAD(P)H, coenzyme F420 H2 , H2 , or formate is split by flavoproteins into one-electron with a more negative reduction potential and one with a more positive reduction potential than that of the electron pair. Via this mechanism microorganisms generate low- potential electrons for the reduction of ferredoxins (Fd) and flavodoxins (Fld). The first example was described in 2008 when it was found that the butyryl-CoA dehydrogenase-electron-transferring flavoprotein complex (Bcd-EtfAB) of Clostridium kluyveri couples the endergonic reduction of ferredoxin (E0 ' = -420 mV) with NADH (-320 mV) to the exergonic reduction of crotonyl-CoA to butyryl-CoA (-10 mV) with NADH...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29571471/persimmon-vinegar-polyphenols-protect-against-hydrogen-peroxide-induced-cellular-oxidative-stress-via-nrf2-signalling-pathway
#9
Bo Zou, Gengsheng Xiao, Yujuan Xu, Jijun Wu, Yuanshan Yu, Manqin Fu
Since polyphenols are known to exhibit antioxidative properties, we prepared and characterized persimmon vinegar polyphenols (PVP) in this study. Furthermore, we investigated the protective effect of PVP on hydrogen peroxide (H2 O2 )-induced oxidative stress in HepG2 cells and its underlying mechanisms. Our results showed that flavon-3-ols were the predominant polyphenols in PVP. Pre-treatment with PVP significantly decreased (p < 0.05) H2 O2 -induced cell damage in a dose-dependent manner, accompanied by decrease in lactate dehydrogenase (LDH) leakage, aminotransferase activities, and ROS accumulation...
July 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29568961/cytoprotective-effects-of-diosmetin-against-hydrogen-peroxide-induced-l02-cell-oxidative-damage-via-activation-of-the-nrf2-are-signaling-pathway
#10
Chunjing Wang, Yaping Liao, Shengnan Wang, Dan Wang, Nana Wu, Qingao Xu, Wanwan Jiang, Menran Qiu, Changqing Liu
Oxidative stress is considered a crucial mediator in the pathogenesis of various liver diseases. The flavone diosmetin has been reported to exhibit antioxidant activities; however, the hepatoprotective effects of diosmetin against oxidative stress, and the underlying molecular mechanisms, remain unknown. The present study aimed to investigate the potential hepatoprotective effects of diosmetin on hydrogen peroxide (H2O2)‑induced oxidative damage in L02 cells and attempted to evaluate the role of the nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response element pathway in this process...
March 15, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29541451/cancer-cell-metabolic-plasticity-allows-resistance-to-nampt-inhibition-but-invariably-induces-dependence-on-ldha
#11
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
https://www.readbyqxmd.com/read/29464059/characterization-and-metabolic-synthetic-lethal-testing-in-a-new-model-of-sdh-loss-familial-pheochromocytoma-and-paraganglioma
#12
John Smestad, Oksana Hamidi, Lin Wang, Molly Nelson Holte, Fatimah Al Khazal, Luke Erber, Yue Chen, L James Maher
Succinate dehydrogenase (SDH)-loss pheochromocytoma and paraganglioma (PPGL) are tumors driven by metabolic derangement. SDH loss leads to accumulation of intracellular succinate, which competitively inhibits dioxygenase enzymes, causing activation of pseudohypoxic signaling and hypermethylation of histones and DNA. The mechanisms by which these alterations lead to tumorigenesis are unclear, however. In an effort to fundamentally understand how SDH loss reprograms cell biology, we developed an immortalized mouse embryonic fibroblast cell line with conditional disruption of Sdhc and characterize the kinetics of Sdhc gene rearrangement, SDHC protein loss, succinate accumulation, and the resultant hypoproliferative phenotype...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29462203/a-generic-hts-assay-for-kinase-screening-validation-for-the-isolation-of-an-engineered-malate-kinase
#13
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/29404209/development-of-an-rna-interference-rnai-gene-knockdown-protocol-in-the-anaerobic-gut-fungus-pecoramyces-ruminantium-strain-c1a
#14
Shelby S Calkins, Nicole C Elledge, Katherine E Mueller, Stephen M Marek, M B Couger, Mostafa S Elshahed, Noha H Youssef
Members of the anaerobic gut fungi (AGF) reside in rumen, hindgut, and feces of ruminant and non-ruminant herbivorous mammals and reptilian herbivores. No protocols for gene insertion, deletion, silencing, or mutation are currently available for the AGF, rendering gene-targeted molecular biological manipulations unfeasible. Here, we developed and optimized an RNA interference (RNAi)-based protocol for targeted gene silencing in the anaerobic gut fungus Pecoramyces ruminantium strain C1A. Analysis of the C1A genome identified genes encoding enzymes required for RNA silencing in fungi (Dicer, Argonaute, Neurospora crassa QDE-3 homolog DNA helicase, Argonaute-interacting protein, and Neurospora crassa QIP homolog exonuclease); and the competency of C1A germinating spores for RNA uptake was confirmed using fluorescently labeled small interfering RNAs (siRNA)...
2018: PeerJ
https://www.readbyqxmd.com/read/29377633/constraint-based-modelling-captures-the-metabolic-versatility-of-desulfovibrio-vulgaris
#15
Jason J Flowers, Matthew A Richards, Nitin Baliga, Birte Meyer, David A Stahl
A refined Desulfovibrio vulgaris Hildenborough flux balance analysis (FBA) model (iJF744) was developed, incorporating 1016 reactions that include 744 genes and 951 metabolites. A draft model was first developed through automatic model reconstruction using the ModelSeed Server and then curated based on existing literature. The curated model was further refined by incorporating three recently proposed redox reactions involving the Hdr-Flx and Qmo complexes and a lactate dehydrogenase (LdhAB, DVU 3027-3028) indicated by mutation and transcript analyses to serve electron transfer reactions central to syntrophic and respiratory growth...
April 2018: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/29330792/evaluating-the-metabolic-impact-of-hypoxia-on-pancreatic-cancer-cells
#16
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
#17
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
#18
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
#19
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/29259615/silencing-of-d-lactate-dehydrogenase-impedes-glyoxalase-system-and-leads-to-methylglyoxal-accumulation-and-growth-inhibition-in-rice
#20
Baoguang An, Jie Lan, Xiaolong Deng, Silan Chen, Chao Ouyang, Huiyun Shi, Jing Yang, Yangsheng Li
D-Lactate is oxidized by two classes of D-lactate dehydrogenase (D-LDH), namely, NAD-dependent and NAD-independent D-LDHs. Little is known about the characteristics and biological functions of D-LDHs in rice. In this study, a functional NAD-independent D-LDH (LOC_Os07g06890) was identified in rice, as a result of alternative splicing events. Characterization of the expression profile, subcellular localization, and enzymatic properties of the functional OsD-LDH revealed that it is a mitochondrial cytochrome- c -dependent D-LDH with high affinity and catalytic efficiency...
2017: Frontiers in Plant Science
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