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NAD AND NADH ratio

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https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#1
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27896382/the-mechanism-of-improved-intracellular-organic-selenium-and-glutathione-contents-in-selenium-enriched-candida-utilis-by-acid-stress
#2
Gao-Chuan Zhang, Da-Hui Wang, Dong-Hua Wang, Gong-Yuan Wei
Batch culture of Candida utilis CCTCC M 209298 for the preparation of selenium (Se)-enriched yeast was carried out under different pH conditions, and maximal intracellular organic Se and glutathione (GSH) contents were obtained in a moderate acid stress environment (pH 3.5). In order to elucidate the physiological mechanism of improved performance of Se-enriched yeast by acid stress, assays of the key enzymes involved in GSH biosynthesis and determinations of energy supply and regeneration were performed. The results indicated that moderate acid stress increased the activity of γ-glutamylcysteine synthetase and the ratios of NADH/NAD(+) and ATP/ADP, although no significant changes in intracellular pH were observed...
November 28, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27892932/reciprocal-regulation-of-carbon-monoxide-metabolism-and-the-circadian-clock
#3
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jürchott, Sabrina Klemz, Veronika Lang, Stephan Lorenzen, Miriam Knauer, Steffi Heidenreich, Min Xu, Jürgen A Ripperger, Michael Schupp, Ralf Stanewsky, Achim Kramer
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD(+)/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters...
November 28, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27878107/imaging-the-nadh-nad-homeostasis-for-understanding-the-metabolic-response-of-mycobacterium-to-physiologically-relevant-stresses
#4
Shabir A Bhat, Iram K Iqbal, Ashwani Kumar
The NADH:NAD(+) ratio is the primary indicator of the metabolic state of bacteria. NAD(H) homeostasis is critical for Mycobacterium tuberculosis (Mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of NAD(H) remain a challenge. Genetically encoded fluorescent biosensors of the NADH:NAD(+) ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. Here we have adapted the genetically encoded biosensor Peredox for measurement of the metabolic state of Mtb in vitro and during infection of macrophage cells...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27874078/glutamate-dehydrogenase-activator-bch-stimulating-reductive-amination-prevents-high-fat-high-fructose-diet-induced-steatohepatitis-and-hyperglycemia-in-c57bl-6j-mice
#5
Seung Jin Han, Sung-E Choi, Sang-A Yi, Jong Gab Jung, Ik-Rak Jung, Maureen Shin, Seok Kang, Hyunhee Oh, Hae Jin Kim, Dae Jung Kim, Ji Eun Kwon, Cheol Soo Choi, Kwan Woo Lee, Yup Kang
Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871066/a-novel-amino-acid-and-metabolomics-signature-in-mice-overexpressing-muscle-uncoupling-protein-3
#6
Céline Aguer, Brian D Piccolo, Oliver Fiehn, Sean H Adams, Mary-Ellen Harper
Uncoupling protein 3 (UCP3) is highly selectively expressed in skeletal muscle and is known to lower mitochondrial reactive oxygen species and promote fatty acid oxidation; however, the global impact of UCP3 activity on skeletal muscle and whole-body metabolism have not been extensively studied. We utilized untargeted metabolomics to identify novel metabolites that distinguish mice overexpressing UCP3 in muscle, both at rest and after exercise regimens that challenged muscle metabolism, to potentially unmask subtle phenotypes...
November 10, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27867097/mitochondrial-remodeling-in-the-liver-following-chronic-alcohol-feeding-to-rats
#7
Derick Han, Heather S Johnson, Madhuri P Rao, Gary Martin, Harsh Sancheti, Kai H Silkwood, Carl W Decker, Kim Tho Nguyen, Joseph G Casian, Enrique Cadenas, Neil Kaplowitz
The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver...
November 17, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27824080/lycium-barbarum-polysaccharide-attenuates-high-fat-diet-induced-hepatic-steatosis-by-up-regulating-sirt1-expression-and-deacetylase-activity
#8
Li Jia, Wang Li, Jianning Li, Yan Li, Hui Song, Yansong Luan, Hui Qi, Lirong Ma, Xiaohong Lu, Yi Yang
In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD(+)/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816420/investigation-of-the-nadh-nad-ratio-in-ralstonia-eutropha-using-the-fluorescence-reporter-protein-peredox
#9
Vijay Tejwani, Franz-Josef Schmitt, Svea Wilkening, Ingo Zebger, Marius Horch, Oliver Lenz, Thomas Friedrich
Ralstonia eutropha is a hydrogen-oxidizing ("Knallgas") bacterium that can easily switch between heterotrophic and autotrophic metabolism to thrive in aerobic and anaerobic environments. Its versatile metabolism makes R. eutropha an attractive host for biotechnological applications, including H2-driven production of biodegradable polymers and hydrocarbons. H2 oxidation by R. eutropha takes place in the presence of O2 and is mediated by four hydrogenases, which represent ideal model systems for both biohydrogen production and H2 utilization...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27815040/the-addition-of-ketone-bodies-alleviates-mitochondrial-dysfunction-by-restoring-complex-i-assembly-in-a-melas-cellular-model
#10
Samuel Frey, Guillaume Geffroy, Valerie Desquiret-Dumas, Naig Gueguen, Celine Bris, Sophie Belal, Patrizia Amati-Bonneau, Arnaud Chevrollier, Magalie Barth, Daniel Henrion, Guy Lenaers, Dominique Bonneau, Pascal Reynier, Vincent Procaccio
Ketogenic Diet used to treat refractory epilepsy for almost a century may represent a treatment option for mitochondrial disorders for which effective treatments are still lacking. Mitochondrial complex I deficiencies are involved in a broad spectrum of inherited diseases including Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes syndrome leading to recurrent cerebral insults resembling strokes and associated with a severe complex I deficiency caused by mitochondrial DNA (mtDNA) mutations...
November 1, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27798266/focally-perfused-succinate-potentiates-brain-metabolism-in-head-injury-patients
#11
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)...
October 17, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27793977/acute-stimulation-of-glucose-influx-upon-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#12
Dania C Liemburg-Apers, Jori A L Wagenaars, Jan A M Smeitink, Peter H G M Willems, Werner J H Koopman
Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A stimulated Glut1-mediated glucose uptake without altering Glut1 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27790277/increased-cellular-nad-level-through-nqo1-enzymatic-action-has-protective-effects-on-bleomycin-induced-lung-fibrosis-in-mice
#13
Gi-Su Oh, Su-Bin Lee, Anjani Karna, Hyung-Jin Kim, AiHua Shen, Arpana Pandit, SeungHoon Lee, Sei-Hoon Yang, Hong-Seob So
BACKGROUND: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet...
October 2016: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27783615/thermodynamic-driving-force-of-hydrogen-on-rumen-microbial-metabolism-a-theoretical-investigation
#14
Henk J van Lingen, Caroline M Plugge, James G Fadel, Ermias Kebreab, André Bannink, Jan Dijkstra
Hydrogen is a key product of rumen fermentation and has been suggested to thermodynamically control the production of the various volatile fatty acids (VFA). Previous studies, however, have not accounted for the fact that only thermodynamic near-equilibrium conditions control the magnitude of reaction rate. Furthermore, the role of NAD, which is affected by hydrogen partial pressure (PH2), has often not been considered. The aim of this study was to quantify the control of PH2 on reaction rates of specific fermentation pathways, methanogenesis and NADH oxidation in rumen microbes...
2016: PloS One
https://www.readbyqxmd.com/read/27760881/impaired-cyclic-electron-flow-around-photosystem-i-disturbs-high-light-respiratory-metabolism
#15
Igor Florez-Sarasa, Ko Noguchi, Wagner L Araújo, Ana Garcia-Nogales, Alisdair R Fernie, Jaume Flexas, Miquel Ribas-Carbo
The cyclic electron flow around photosystem I (CEF-PSI) increases ATP/NADPH production in the chloroplast, acting as an energy balance mechanism. Higher export of reducing power from the chloroplast in CEF-PSI mutants has been correlated with higher mitochondrial alternative oxidase (AOX) capacity and protein amount under high-light (HL) conditions. However, in vivo measurements of AOX activity are still required to confirm the exact role of AOX in dissipating the excess of reductant power from the chloroplast...
December 2016: Plant Physiology
https://www.readbyqxmd.com/read/27746050/environment-dictates-dependence-on-mitochondrial-complex-i-for-nad-and-aspartate-production-and-determines-cancer-cell-sensitivity-to-metformin
#16
Dan Y Gui, Lucas B Sullivan, Alba Luengo, Aaron M Hosios, Lauren N Bush, Nadege Gitego, Shawn M Davidson, Elizaveta Freinkman, Craig J Thomas, Matthew G Vander Heiden
Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis...
November 8, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27739595/3-hydroxybutyrate-regulates-energy-metabolism-and-induces-bdnf-expression-in-cerebral-cortical-neurons
#17
Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye-Knudsen, Aiwu Cheng, Roy Cutler, Simonetta Camandola, Mark P Mattson
During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD(+) /NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain-derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons...
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27732642/replicative-senescence-in-human-fibroblasts-is-delayed-by-hydrogen-sulfide-in-a-nampt-sirt1-dependent-manner
#18
Reiko Sanokawa-Akakura, Shin Akakura, Siamak Tabibzadeh
Recent evidence suggests that hydrogen sulfide (H2S) has cytoprotective and anti-aging effects. However, the mechanisms for such properties are not fully understood. Here, we show that the expression of the main H2S producing enzyme, CBS, and production of H2S are coordinately diminished in replicative senescent adult human dermal fibroblasts. The reduced production of H2S falls within the same time-frame that the hallmarks of replicative senescence appear including accumulation of SA-β-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall...
2016: PloS One
https://www.readbyqxmd.com/read/27717568/hexadecane-degradation-of-pseudomonas-aeruginosa-ny3-promoted-by-glutaric-acid
#19
Hongyun Nie, Maiqian Nie, Ting Xiao, Yan Wang, Xiaoting Tian
For further understanding of the roles of small organic acids commonly produced during alkane degradation, glutaric acid was found to be effective for promoting hexadecane degradation by P. aeruginosa NY3. Our results demonstrated that the synchronous metabolism of glutaric acid could increase both the growth rates and hexadecane degradation ability of P. aeruginosa NY3. Glutaric acid was proved to be able to increase the ratios of the concentrations of NAD(+) and NADH inside strain NY3 cells, and subsequently accelerated cell growth rates through improving electron respiration rates...
October 4, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27706102/the-redox-status-of-cancer-cells-supports-mechanisms-behind-the-warburg-effect
#20
Jorgelindo da Veiga Moreira, Minoo Hamraz, Mohammad Abolhassani, Erwan Bigan, Sabine Pérès, Loïc Paulevé, Marcel Levy Nogueira, Jean-Marc Steyaert, Laurent Schwartz
To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study their redox (NAD, NADP) and bioenergetic (ATP, pHi) status...
October 3, 2016: Metabolites
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