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Lactate AND NAD

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https://www.readbyqxmd.com/read/29330792/evaluating-the-metabolic-impact-of-hypoxia-on-pancreatic-cancer-cells
#1
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-1-13c-lactate
#2
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan 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 in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed 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 (e...
January 12, 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
#3
Xinyao Lu, Shunli Ren, Jingzheng Lu, Hong Zong, Jian Song, Bin Zhuge
AIMS: This study aimed to strengthen the reducing equivalent regeneration 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 titer 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 titer to 19...
January 3, 2018: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29288336/cytotoxicity-of-propofol-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#4
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)...
December 29, 2017: 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
#5
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
https://www.readbyqxmd.com/read/29243436/-effect-of-neoflavonoid-latifolin-isolated-from-dalbergia-odorifera-on-acute-myocardial-ischemia-in-rats-and-its-mechanism-of-nrf2-signaling-pathway
#6
Xue-Liang Li, Lan-Ying Chen, Zi-Yi Guan, Yao Luo, Ya-Ru Cui, Rong-Hua Liu, Feng Shao, Ding-Qing Wang
The present study was designed to evaluate the cardioprotective effect of latifolin on pituitrin(Pit) or isoproterenol(ISO)-induced myocardial injury in rats, and further investigate its underlying mechanisms. Rats were administrated sublingually with pituitrin or subcutaneously with isoproterenol to induce acute myocardial ischemia in rats, and lead II electrocardiograph was recorded. In rats with isoproterenol, ELISA assay or colorimetric method was used to detect the content or activity of myocardial injury markers in serum, and the SOD activity and MDA content in myocardium were detected by colorimetric assay; histopathological examination was conducted by HE staining; the frozen section of myocardial tissues was used for DCFH-DA fluorescent staining to detect the content of ROS in myocardium; Western blot was used to detect the protein expression levels of Nrf2, Keap1, HO-1 and NQO1 in myocardium...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29236080/three-dimensional-analysis-of-the-interactions-between-hldh5-and-its-inhibitors
#7
REVIEW
Giulio Poli, Carlotta Granchi, Mohamed Aissaoui, Filippo Minutolo, Tiziano Tuccinardi
Inhibitors of human lactate dehydrogenase (hLDH5)-the enzyme responsible for the conversion of pyruvate to lactate coupled with oxidation of NADH to NAD⁺-are promising therapeutic agents against cancer because this enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. Consequently, significant efforts have been made for the identification of small-molecule hLDH5 inhibitors displaying high inhibitory potencies. X-ray structure of hLDH5 complexes as well as molecular modeling studies contribute to identify and explain the main binding modes of hLDH5 inhibitors reported in literature...
December 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29206478/lactate-is-oxidized-outside-of-the-mitochondrial-matrix-in-rodent-brain
#8
Eric A F Herbst, Mitchell A J George, Karen Brebner, Graham P Holloway, Daniel A Kane
The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine whether lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex and hippocampus (dorsal) subregions...
December 5, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
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
#9
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
#10
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...
October 23, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29178416/2d-enzyme-cascade-network-with-efficient-substrate-channeling-by-swinging-arms
#11
Yuhe R Yang, Jinglin Fu, Shaun Wootten, Xiaodong Qi, Minghui Liu, Hao Yan, Yan Liu
In living cells, compartmented or membrane-associated enzymes are often assembled into large networks for cooperatively catalyzing cascade reaction pathways essential for the cellular metabolism. Here, we report the assembly of an artificial 2D enzyme network of two cascade enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) on a wireframe DNA origami template. Swinging arms were used to facilitate the transport of redox intermediate of NAD+/NADH between enzyme pairs on the array...
November 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29156703/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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