Read by QxMD icon Read

Lactate AND NAD ratio

Andrew Jm Lewis, Jack Jj 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 upon heart and liver pyruvate metabolism in rats in vivo Both oral treatment for four 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...
August 25, 2016: Diabetes
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...
June 21, 2016: Oncotarget
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
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...
2016: Oncogenesis
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
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
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
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...
March 25, 2016: Journal of Steroid Biochemistry and Molecular Biology
Rebecca Mongeon, Veena Venkatachalam, Gary Yellen
AIM: Cytosolic NADH-NAD(+) redox state is central to cellular metabolism and a valuable indicator of glucose and lactate metabolism in living cells. Here we sought to quantitatively determine NADH-NAD(+) redox in live cells and brain tissue using a fluorescence lifetime imaging of the genetically-encoded single-fluorophore biosensor Peredox. RESULTS: We show that Peredox exhibits a substantial change in its fluorescence lifetime over its sensing range of NADH-NAD(+) ratio...
October 1, 2016: Antioxidants & Redox Signaling
Long Liu, Ningzi Guan, Gexin Zhu, Jianghua Li, Hyun-Dong Shin, Guocheng Du, Jian Chen
Propionic acid (PA) is an important chemical building block widely used in the food, pharmaceutical, and chemical industries. In our previous study, a shuttle vector was developed as a useful tool for engineering Propionibacterium jensenii, and two key enzymes-glycerol dehydrogenase and malate dehydrogenase-were overexpressed to improve PA titer. Here, we aimed to improve PA production further via the pathway engineering of P. jensenii. First, the phosphoenolpyruvate carboxylase gene (ppc) from Klebsiella pneumoniae was overexpressed to access the one-step synthesis of oxaloacetate directly from phosphoenolpyruvate without pyruvate as intermediate...
2016: Scientific Reports
Manuel S Godoy, Pablo I Nikel, José G Cabrera Gomez, M Julia Pettinari
The CreBC (carbon source-responsive) two-component regulation system of Escherichia coli affects a number of functions, including intermediary carbon catabolism. The impacts of different creC mutations (a ΔcreC mutant and a mutant carrying the constitutive creC510 allele) on bacterial physiology were analyzed in glucose cultures under three oxygen availability conditions. Differences in the amounts of extracellular metabolites produced were observed in the null mutant compared to the wild-type strain and the mutant carrying creC510 and shown to be affected by oxygen availability...
January 2016: Applied and Environmental Microbiology
Ilkyun Im, Mi-Jin Jang, Seung Ju Park, Sang-Hee Lee, Jin-Ho Choi, Han-Wook Yoo, Seyun Kim, Yong-Mahn Han
A defective mitochondrial respiratory chain complex (DMRC) causes various metabolic disorders in humans. However, the pathophysiology of DMRC in the liver remains unclear. To understand DMRC pathophysiology in vitro, DMRC-induced pluripotent stem cells were generated from dermal fibroblasts of a DMRC patient who had a homoplasmic mutation (m.3398T→C) in the mitochondrion-encoded NADH dehydrogenase 1 (MTND1) gene and that differentiated into hepatocytes (DMRC hepatocytes) in vitro. DMRC hepatocytes showed abnormalities in mitochondrial characteristics, the NAD(+)/NADH ratio, the glycogen storage level, the lactate turnover rate, and AMPK activity...
December 4, 2015: Journal of Biological Chemistry
R Gary Sawers, David P Clark
Pyruvate and acetyl-CoA form the backbone of central metabolism. The nonoxidative cleavage of pyruvate to acetyl-CoA and formate by the glycyl radical enzyme pyruvate formate lyase is one of the signature reactions of mixed-acid fermentation in enterobacteria. Under these conditions, formic acid accounts for up to one-third of the carbon derived from glucose. The further metabolism of acetyl-CoA to acetate via acetyl-phosphate catalyzed by phosphotransacetylase and acetate kinase is an exemplar of substrate-level phosphorylation...
December 2004: EcoSal Plus
Nadia Messaoudi, Valérie Gautier, Julien Dairou, Mouhad Mihoub, Gaëlle Lelandais, Philippe Bouloc, Ahmed Landoulsi, Gilbert Richarme
YajL is the closest prokaryotic homologue of Parkinson's disease-associated DJ-1, a protein of undefined function involved in the oxidative stress response. We reported recently that YajL and DJ-1 protect cells against oxidative stress-induced protein aggregation by acting as covalent chaperones for the thiol proteome, including the NuoG subunit of NADH dehydrogenase 1, and that NADH dehydrogenase 1 activity is negligible in the yajL mutant. We report here that this mutant compensates for low NADH dehydrogenase activity by utilizing NADH-independent alternative dehydrogenases, including pyruvate oxidase PoxB and d-amino acid dehydrogenase DadA, and mixed acid aerobic fermentations characterized by acetate, lactate, succinate and ethanol excretion...
November 2015: Microbiology
J L Baker, A M Derr, R C Faustoferri, R G Quivey
UNLABELLED: Previous studies of the oral pathogen Streptococcus mutans have determined that this Gram-positive facultative anaerobe mounts robust responses to both acid and oxidative stresses. The water-forming NADH oxidase (Nox; encoded by nox) is thought to be critical for the regeneration of NAD(+), for use in glycolysis, and for the reduction of oxygen, thereby preventing the formation of damaging reactive oxygen species. In this study, the free NAD(+)/NADH ratio in a nox deletion strain (Δnox) was discovered to be remarkably higher than that in the parent strain, UA159, when the strains were grown in continuous culture...
December 2015: Journal of Bacteriology
J P Bitoun, Z T Wen
The NAD(+) and NADH-sensing transcriptional regulator Rex is widely conserved across gram-positive bacteria. Rex monitors cellular redox poise and controls the expression of genes/operons involved in diverse pathways including alternative fermentation, oxidative stress responses, and biofilm formation. The oral cavity undergoes frequent and drastic fluctuations in nutrient availability, pH, temperature, oxygen tension, saliva, and shear forces. The oral streptococci are major colonizers of oral mucosa and tooth surfaces and include commensals as well as opportunistic pathogens, including the primary etiological agent of dental caries, Streptococcus mutans...
April 2016: Molecular Oral Microbiology
Sebastiano Rupiani, Rosa Buonfiglio, Marcella Manerba, Lorenza Di Ianni, Marina Vettraino, Elisa Giacomini, Matteo Masetti, Federico Falchi, Giuseppina Di Stefano, Marinella Roberti, Maurizio Recanatini
Glycolysis is drastically increased in tumors and it is the main route to energy production with a minor use of oxidative phosphorylation. Among the key enzymes in the glycolytic process, LDH is emerging as one of the most interesting targets for the development of new inhibitors. In this context, in the present work, we carried out a virtual screening procedure followed by chemical modifications of the identified structures according to a "hit-to-lead" process. The effects of the new molecules were preliminary probed against purified human LDH-A...
August 28, 2015: European Journal of Medicinal Chemistry
Chang Shu, Chenchen Guo, Shuizhong Luo, Shaotong Jiang, Zhi Zheng
Respiratory-deficient mutants of Rhizopus oryzae (R. oryzae) AS 3.3461 were acquired by ultraviolet (UV) irradiation to investigate changes in intracellular NADH metabolic pathway and its influence on the fermentation characteristics of the strain. Compared with R. oryzae AS 3.3461, the intracellular ATP level of the respiratory-deficient strain UV-1 decreased by 52.7 % and the glucose utilization rate rose by 8.9 %; When incubated for 36 h, the activities of phosphofructokinase (PFK), hexokinase (HK), and pyruvate kinase (PK) in the mutant rose by 74...
August 2015: Applied Biochemistry and Biotechnology
Mitsuaki Moriyama, Yuki Fujimoto, Shizuka Rikimaru, Miharu Ushikai, Eishi Kuroda, Kenji Kawabe, Katsura Takano, Akihiro Asakawa, Akio Inui, Kazuhiro Eto, Takashi Kadowaki, David S Sinasac, Yoshiyuki Okano, Masahide Yazaki, Shu-Ichi Ikeda, Chunhua Zhang, Yuan-Zong Song, Osamu Sakamoto, Shigeo Kure, Hiroshi Mitsubuchi, Fumio Endo, Masahisa Horiuchi, Yoichi Nakamura, Ken-Ichi Yamamura, Takeyori Saheki
The mitochondrial aspartate-glutamate carrier isoform 2 (citrin) and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse has been a useful model of human citrin deficiency. One of the most prominent findings has been markedly increased hepatic glycerol 3-phosphate (G3P) following oral administration of a sucrose solution. We aimed to investigate whether this change is detectable outside of the liver, and to explore the mechanism underlying the increased hepatic G3P in these mice. We measured G3P and its metabolite glycerol in plasma and urine of the mice under various conditions...
September 2015: Biochimica et Biophysica Acta
Hyllana Catarine Dias de Medeiros, Jorgete Constantin, Emy Luiza Ishii-Iwamoto, Fábio Erminio Mingatto
Fipronil is an insecticide used to control pests in animals and plants that can causes hepatotoxicity in animals and humans, and it is hepatically metabolized to fipronil sulfone by cytochrome P-450. The present study aimed to characterize the effects of fipronil (10-50μM) on energy metabolism in isolated perfused rat livers. In fed animals, there was increased glucose and lactate release from glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis. In the livers of fasted animals, fipronil inhibited glucose and urea production from exogenous l-alanine, whereas ammonia and lactate production were increased...
July 2, 2015: Toxicology Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"