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NAD AND NADH ratio

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https://www.readbyqxmd.com/read/29349500/exogenous-h2s-switches-cardiac-energy-substrate-metabolism-by-regulating-sirt3-expression-in-db-db-mice
#1
Yu Sun, Zhiliang Tian, Ning Liu, Linxue Zhang, Zhaopeng Gao, Xiaojiao Sun, Miao Yu, Jichao Wu, Fan Yang, Yajun Zhao, Huan Ren, He Chen, Dechao Zhao, Yan Wang, Shiyun Dong, Changqing Xu, Fanghao Lu, Weihua Zhang
Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD + -dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice...
January 19, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29341594/designing-flavoprotein-gfp-fusion-probes-for-analyte-specific-ratiometric-fluorescence-imaging
#2
Devin A Hudson, Jeffrey L Caplan, Colin Thorpe
The development of genetically encoded fluorescent probes for analyte-specific imaging has revolutionized our understanding of intracellular processes. Current classes of intracellular probes depend on the selection of binding domains that either undergo conformational changes on analyte binding or can be linked to thiol redox chemistry. Here we have designed novel probes by fusing a flavoenzyme, whose fluorescence is quenched on reduction by the analyte of interest, with a GFP domain to allow for rapid and specific ratiometric sensing...
January 17, 2018: Biochemistry
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
#3
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/29327656/nad-nadh-homeostasis-affects-metabolic-adaptation-to-hypoxia-and-secondary-metabolite-production-in-filamentous-fungi
#4
Motoyuki Shimizu
Filamentous fungi are used to produce fermented foods, organic acids, beneficial secondary metabolites and various enzymes. During such processes, these fungi balance cellular NAD+:NADH ratios to adapt to environmental redox stimuli. Cellular NAD(H) status in fungal cells is a trigger of changes in metabolic pathways including those of glycolysis, fermentation, and the production of organic acids, amino acids and secondary metabolites. Under hypoxic conditions, high NADH:NAD+ ratios lead to the inactivation of various dehydrogenases, and the metabolic flow involving NAD+ is down-regulated compared with normoxic conditions...
January 12, 2018: Bioscience, Biotechnology, and Biochemistry
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
#5
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
#6
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/29261292/haloacetic-acid-water-disinfection-by-products-affect-pyruvate-dehydrogenase-activity-and-disrupt-cellular-metabolism
#7
Azra Dad, Clara Hyunhee Jeong, Elizabeth D Wagner, Michael J Plewa
The disinfection of drinking water has been a major public health achievement. However, haloacetic acids (HAAs), generated as by-products of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown...
December 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29245965/the-aldehyde-group-of-gossypol-induces-mitochondrial-apoptosis-via-ros-sirt1-p53-puma-pathway-in-male-germline-stem-cell
#8
Xin He, Chongyang Wu, Yanhua Cui, Haijing Zhu, Zhiming Gao, Bo Li, Jinlian Hua, Baoyu Zhao
As a widely grown economic crop, cotton is the major oil and protein resource for human and livestock. But the highly toxic of gossypol in cottonseed severely restricts its effective utilization, consequently creating huge resource waste. Previous studies have shown the male germline stem cells were the most vulnerable cells in gossypol damages, but the mechanism was still unclear. We found gossypol induced cell viability decline resulted from apoptosis. And the increase of Caspase-9 activity in gossypol treatment hinted the mitochondrial apoptosis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29213318/targeted-redox-and-energy-cofactor-metabolomics-in-clostridium-thermocellum-and-thermoanaerobacterium-saccharolyticum
#9
Kyle Sander, Keiji G Asano, Deepak Bhandari, Gary J Van Berkel, Steven D Brown, Brian Davison, Timothy J Tschaplinski
Background: Clostridium thermocellum and Thermoanaerobacterium saccharolyticum are prominent candidate biocatalysts that, together, can enable the direct biotic conversion of lignocellulosic biomass to ethanol. The imbalance and suboptimal turnover rates of redox cofactors are currently hindering engineering efforts to achieve higher bioproductivity in both organisms. Measuring relevant intracellular cofactor concentrations will help understand redox state of these cofactors and help identify a strategy to overcome these limitations; however, metabolomic determinations of these labile metabolites have historically proved challenging...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29211728/an-open-label-non-randomized-study-of-the-pharmacokinetics-of-the-nutritional-supplement-nicotinamide-riboside-nr-and-its-effects-on-blood-nad-levels-in-healthy-volunteers
#10
Sophia E Airhart, Laura M Shireman, Linda J Risler, Gail D Anderson, G A Nagana Gowda, Daniel Raftery, Rong Tian, Danny D Shen, Kevin D O'Brien
OBJECTIVES: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium...
2017: PloS One
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
#11
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
#12
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/29189956/changes-of-mitochondrial-respiratory-function-during-odontogenic-differentiation-of-rat-dental-papilla-cells
#13
Fuping Zhang, Liulin Jiang, Yifan He, Wenguo Fan, Xiaoyan Guan, Qianyi Deng, Fang Huang, Hongwen He
Dental papilla cells (DPCs) belong to precursor cells differentiating to odontoblasts and play an important role in dentin formation and reproduction. This study aimed to explore the changes and and involvement of mitochondrial respiratory function during odontogenic differentiation. Primary DPCs were obtained from first molar dental papilla of neonatal rats and cultured in odontogenic medium for 7, 14, 21 days. DPCs, which expressed mesenchymal surface markers CD29, CD44 and CD90, had the capacity for self-renewal and multipotent differentiation...
November 30, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29184484/ketone-based-metabolic-therapy-is-increased-nad-a-primary-mechanism
#14
Marwa Elamin, David N Ruskin, Susan A Masino, Paola Sacchetti
The ketogenic diet's (KD) anticonvulsant effects have been well-documented for nearly a century, including in randomized controlled trials. Some patients become seizure-free and some remain so after diet cessation. Many recent studies have explored its expanded therapeutic potential in diverse neurological disorders, yet no mechanism(s) of action have been established. The diet's high fat, low carbohydrate composition reduces glucose utilization and promotes the production of ketone bodies. Ketone bodies are a more efficient energy source than glucose and improve mitochondrial function and biogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162105/changing-oxidoreduction-potential-to-improve-water-soluble-yellow-pigment-production-with-monascus-ruber-cgmcc-10910
#15
Tao Huang, Hailing Tan, Fangju Lu, Gong Chen, Zhenqiang Wu
BACKGROUND: Monascus pigments are widely used in the food and pharmaceutical industries due to their safety to human health. Our previous study found that glucose concentration induced extracellular oxidoreduction potential (ORP) changes could influence extracellular water-soluble yellow pigment production by Monascus ruber CGMCC 10910 in submerged fermentation. In this study, H2O2 and dithiothreitol (DTT) were used to change the oxidoreduction potential for investigating the effects of oxidative or reductive substances on Monascus yellow pigment production by Monascus ruber CGMCC 10910...
November 21, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29145079/microbial-transcript-and-metabolome-analysis-uncover-discrepant-metabolic-pathways-in-autotrophic-and-mixotrophic-anammox-consortia
#16
Ying Feng, Yunpeng Zhao, Yongzhao Guo, Sitong Liu
The ability of anammox bacteria to utilize organic matter has drawn extensive attention. However, the metabolic discrepancies between autotrophic and mixotrophic anammox consortia need to be further explored. Here, microbial transcript and metabolomic analysis were conducted for the samples harvested in the reactors and batch assays to investigate the phenotype discrepancies and intrinsic causes in autotrophic and mixotrophic anammox consortia. Results showed that metabolically active community structures did not show significant difference between autotrophic and mixotrophic anammox consortia (C/N = 0...
October 31, 2017: Water Research
https://www.readbyqxmd.com/read/29137352/maternal-high-calorie-diet-induces-mitochondrial-dysfunction-and-senescence-phenotype-in-subcutaneous-fat-of-newborn-mice
#17
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/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#18
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#19
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/29104634/endogenous-nampt-upregulation-is-associated-with-diabetic-nephropathy-inflammatory-fibrosis-through-the-nf-%C3%AE%C2%BAb-p65-and-sirt1-pathway-nmn-alleviates-diabetic-nephropathy-inflammatory-fibrosis-by-inhibiting-endogenous-nampt
#20
Ye Chen, Yuzhen Liang, Tingting Hu, Riming Wei, Congjie Cai, Ping Wang, Lingyu Wang, Wei Qiao, Leping Feng
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD(+)) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported...
November 2017: Experimental and Therapeutic Medicine
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