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Lactate AND NAD

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https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#1
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523535/self-protection-against-triptolide-induced-toxicity-in-human-hepatic-cells-via-nrf2-are-nqo1-pathway
#2
Ling-Ling Zhou, Cong Zhou, Xiao-Wen Liang, Zhe Feng, Zhang-Pu Liu, Hao-Lu Wang, Xue-Ping Zhou
OBJECTIVE: To find the signaling pathway of triptolide (TP)-induced liver injury and to reveal whether NF-E2-related factor 2 (Nrf2) plays an important role in cellular self-protection. METHODS: The L-02 and HepG2 cells were cultured and treated with various concentrations of TP. The cell viability was observed, and the cell medium was collected for detecting the aspartate aminotransferase (ALT), alanine aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and L-glutathione production (GSH) levels...
May 18, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28488541/microrna-124-suppresses-proliferation-and-glycolysis-in-non-small-cell-lung-cancer-cells-by-targeting-akt-glut1-hkii
#3
Xiaojian Zhao, Caiping Lu, Weiwei Chu, Bing Zhang, Qiang Zhen, Renfeng Wang, Yaxiao Zhang, Zhe Li, Baolei Lv, Huixian Li, Jiabao Liu
Non-small cell lung cancer accounts for 85% of all types of lung cancer and is the leading cause of worldwide cancer-associated mortalities. MiR-124 is epigenetically silenced in various types of cancer and plays important roles in tumor development and progression. MiR-124 was also significantly downregulated in non-small cell lung cancer patients. Glycolysis has been considered as a feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key enzymes in the regulation of glycolysis and energy metabolism in cancer cells...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28463593/production-of-d-lactate-using-a-pyruvate-producing-escherichia-coli-strain
#4
Hironaga Akita, Nobutaka Nakashima, Tamotsu Hoshino
To generate an organism capable of producing d-lactate, NAD(+)-dependent d-lactate dehydrogenase was expressed in our pyruvate-producing strain, Escherichia coli strain LAFCPCPt-accBC-aceE. After determining the optimal culture conditions for d-lactate production, 18.4 mM d-lactate was produced from biomass-based medium without supplemental mineral or nitrogen sources. Our results show that d-lactate can be produced in simple batch fermentation processes.
May 2, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28463416/quantification-of-lactate-dehydrogenase-for-cell-viability-testing-using-cell-lines-and-primary-cultured-astrocytes
#5
Simon Kaja, Andrew J Payne, Yuliya Naumchuk, Peter Koulen
Drug discovery heavily relies on cell viability studies to assess the potential toxicity of drug candidates. L-Lactate dehydrogenase (LDH) is a cytoplasmic enzyme that catalyzes the concomitant interconversions of pyruvate to L-lactate and NADH to NAD(+) during glycolysis, and the reverse reactions during the Cori cycle. In response to cellular damage, induced by endogenous cellular mechanisms or as a result of exogenously applied insults, LDH is released from the cytoplasm into the extracellular environment...
May 2, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28413646/role-of-malate-dehydrogenase-in-facilitating-lactate-dehydrogenase-to-support-the-glycolysis-pathway-in-tumors
#6
Siavash Mansouri, Ali Shahriari, Hadi Kalantar, Taraneh Moini Zanjani, Mojtaba Haghi Karamallah
High aerobic glycolysis, as one of the hallmarks of cancer cells, requires nicotinamide adenine dinucleotide (NAD(+)) as a vital co-factor, to guarantee the flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer metabolism, is a source of NAD(+) additional to lactate dehydrogenase (LDH). The current study aimed to elucidate the kinetic parameters of MDH in human breast cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis-Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the crude extracts of human breast tumors and healthy tissue samples, which were obtained directly from the operating theatre...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28374531/from-nad-to-ni-pincer-complex-a-significant-cofactor-evolution-presented-by-lactate-racemase
#7
Ming-Jia Yu, Shi-Lu Chen
Lactate racemase (LarA), a new Ni enzyme discovered recently, catalyzes the racemization between D- and L-lactates via a novel Ni pincer cofactor (Ni-PTTMN) derived from nicotinic acid. Here, using DFT and a 200-atom active-site model, LarA is revealed to employ a modified proton-coupled hydride transfer mechanism where a hydride is transferred to a cofactor pyridine carbon from the substrate α-carbon along with a proton transfer from the substrate hydroxyl to a histidine, and then moved back from the opposite side...
April 4, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28370165/neuroprotective-effects-of-a-novel-poly-adp-ribose-polymerase-1-inhibitor-jpi-289-in-hypoxic-rat-cortical-neurons
#8
Youngchul Kim, Young Seo Kim, Min-Young Noh, Hanchang Lee, Boyoung Joe, Hyun Young Kim, Jeongmin Kim, Seung Hyun Kim, Jiseon Park
Excessive activation of Poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischemic brain injury. Therefore, PARP-1 inhibition after ischemic stroke has been attemptedin successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischemic injury in an in vitro model. The half-life of JPI-289 after Intravenous or oral administration in rats was relatively long (1...
April 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28345875/reactive-oxygen-species-synergize-to-potently-and-selectively-induce-cancer-cell-death
#9
Hyang Yeon Lee, Elizabeth I Parkinson, Carlotta Granchi, Ilaria Paterni, Dipak Panigrahy, Pankaj Seth, Filippo Minutolo, Paul J Hergenrother
A distinctive feature of cancer cells is their elevated levels of reactive oxygen species (ROS), a trait that can cause cancer cells to be more sensitive to ROS-inducing agents than normal cells. ROS take several forms, each with different reactivity and downstream consequence. Here we show that simultaneous generation of superoxide and hydrogen peroxide within cancer cells results in significant synergy, potently and selectively causing cancer cell death. In these experiments superoxide is generated using the NAD(P)H quinone oxidoreductase 1 (NQO1) substrate deoxynyboquinone (DNQ), and hydrogen peroxide is generated using the lactate dehydrogenase A (LDH-A) inhibitor NHI-Glc-2...
April 7, 2017: ACS Chemical Biology
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/28263970/cytosolic-malate-dehydrogenase-activity-helps-support-glycolysis-in-actively-proliferating-cells-and-cancer
#11
E A Hanse, C Ruan, M Kachman, D Wang, X H Lowman, A Kelekar
Increased glucose consumption is a hallmark of cancer cells. The increased consumption and subsequent metabolism of glucose during proliferation creates the need for a constant supply of NAD, a co-factor in glycolysis. Regeneration of the NAD required to support enhanced glycolysis has been attributed to the terminal glycolytic enzyme, lactate dehydrogenase (LDH). However, loss of glucose carbons to biosynthetic pathways early in glycolysis reduces the carbon supply to LDH. Thus, alternative routes for NAD regeneration must exist to support the increased glycolytic rate while allowing for the diversion of glucose to generate biomass and support proliferation...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28261868/in-vivo-assessment-of-intracellular-redox-state-in-rat-liver-using-hyperpolarized-1-13-c-alanine
#12
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...
March 5, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#13
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28159812/right-ventricular-metabolism-during-venoarterial-extracorporeal-membrane-oxygenation-in-immature-swine-heart-in-vivo
#14
Masaki Kajimoto, Dolena R Ledee, Nancy G Isern, Michael A Portman
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and, therefore, enhances functional recovery. The RV must often assume systemic ventricular pressures and function on weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown...
April 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28150419/misconceptions-regarding-basic-thermodynamics-and-enzyme-kinetics-have-led-to-erroneous-conclusions-regarding-the-metabolic-importance-of-lactate-dehydrogenase-isoenzyme-expression
#15
REVIEW
Lasse K Bak, Arne Schousboe
Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate involving the coenzyme NAD(+) . Part of the foundation for the proposed shuttling of lactate from astrocytes to neurons during brain activation is the differential distribution of LDH isoenzymes between the two cell types. In this short review, we outline the basic kinetic properties of the LDH isoenzymes expressed in neurons and astrocytes, and argue that the distribution of LDH isoenzymes does not in any way govern directional flow of lactate between the two cellular compartments...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28121062/exposure-to-15-oxygen-in-vivo-up-regulates-cardioprotective-sur2a-without-affecting-erk1-2-and-akt-a-crucial-role-for-ampk
#16
Khaja Shameem Mohammed Abdul, Sofija Jovanović, Aleksandar Jovanović
SUR2A is an 'atypical' ABC protein that forms sarcolemmal ATP-sensitive K(+) (KATP ) channels by binding to inward rectifier Kir6.2. Manipulation with SUR2A levels has been suggested to be a promising therapeutic strategy against ischaemic heart diseases and other diseases where increased heart resistance to stress is beneficial. Some years ago, it has been reported that high-altitude residents have lower mortality rates for ischaemic heart disease. The purpose of this study was to determine whether SUR2A is regulated by mild-to-severe hypoxic conditions (15% oxygen; oxygen tension equivalent to 3000 m above sea level) and elucidate the underlying mechanism...
January 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28108222/diquat-induced-cellular-pyridine-nucleotide-redox-changes-and-alteration-of-metabolic-enzyme-activities-in-colonic-carcinoma-cells
#17
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
Previously we have shown that the redox cycler menadione (MQ) induced cellular pyridine nucleotide redox imbalance that was linked to a decrease in aerobic glycolysis and perturbation of the mitochondrial respiratory activity due to the redox cycling of the compound; these processes were potentiated by low glucose. In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NAD(+)/NADH and NADP(+)/NADPH) redox homeostasis upon acute metabolic variation and exposure to the redox cycling diquat (DQ)...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28093125/hairpin-stabilized-fluorescent-silver-nanoclusters-for-quantitative-detection-of-nad-and-monitoring-nad-nadh-based-enzymatic-reactions
#18
Priyamvada Jain, Babina Chakma, Sanjukta Patra, Pranab Goswami
A set of 90 mer long ssDNA candidates, with different degrees of cytosine (C-levels) (% and clusters) was analyzed for their function as suitable Ag-nanocluster (AgNC) nucleation scaffolds. The sequence (P4) with highest C-level (42.2%) emerged as the only candidate supporting the nucleation process as evident from its intense fluorescence peak at λ660 nm. Shorter DNA subsets derived from P4 with only stable hairpin structures could support the AgNC formation. The secondary hairpin structures were confirmed by PAGE, and CD studies...
March 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#19
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28079261/effect-of-parthanatos-on-ropivacaine-induced-damage-in-sh-sy5y-cells
#20
Ting Zheng, Chun-Ying Zheng, Xiao-Chun Zheng, Ruo-Guang Zhao, Yan-Qing Chen
Ropivacaine is one of the most common but toxic local anesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and NAD(+) depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD(+) level, and Western blots were used to analyze the expression levels of PARP-1 and AIF after ropivacaine treatments with different concentrations and durations...
January 12, 2017: Clinical and Experimental Pharmacology & Physiology
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