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NAD AND NADH ratio

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https://www.readbyqxmd.com/read/28807773/influence-of-oxidative-stress-on-the-antibacterial-activity-of-betulin-betulinic-acid-and-ursolic-acid
#1
H O B Oloyede, H O Ajiboye, M O Salawu, T O Ajiboye
Contribution of reactive oxygen species and oxidative stress in the antibacterial activities of betulin, betulinic acid and ursolic acid against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was investigated. The minimum inhibitory concentrations of betulin, betulinic acid and ursolic acid against E. coli, P. aeruginosa and S. aureus are 1024-, 256- and 1024-μg/mL; 512-, 256- and 256 μg/mL; 256-, 256- and 64 μg/mL respectively. Cell viability of betulin-, betulinic acid- and ursolic acid-treated bacteria decrease in time dependent manner...
August 11, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28805804/a-genetically-encoded-tool-for-manipulation-of-nadp-nadph-in-living-cells
#2
Valentin Cracan, Denis V Titov, Hongying Shen, Zenon Grabarek, Vamsi K Mootha
The redox coenzymes NADH and NADPH are broadly required for energy metabolism, biosynthesis and detoxification. Despite detailed knowledge of specific enzymes and pathways that utilize these coenzymes, a holistic understanding of the regulation and compartmentalization of NADH- and NADPH-dependent pathways is lacking, partly because of a lack of tools with which to investigate these processes in living cells. We have previously reported the use of the naturally occurring Lactobacillus brevis H2O-forming NADH oxidase (LbNOX) as a genetic tool for manipulation of the NAD(+)/NADH ratio in human cells...
August 7, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28803211/melatonin-protects-chondrocytes-from-impairment-induced-by-glucocorticoids-via-nad-dependent-sirt1
#3
Wei Yang, Xiaomin Kang, Na Qin, Feng Li, Xinxin Jin, Zhengmin Ma, Zhuang Qian, Shufang Wu
Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively...
August 9, 2017: Steroids
https://www.readbyqxmd.com/read/28755312/mouse-nudt13-is-a-mitochondrial-nudix-hydrolase-with-nad-p-h-pyrophosphohydrolase-activity
#4
Salama R Abdelraheim, David G Spiller, Alexander G McLennan
The mammalian NUDT13 protein possesses a sequence motif characteristic of the NADH pyrophosphohydrolase subfamily of Nudix hydrolases. Due to the persistent insolubility of the recombinant product expressed in Escherichia coli, active mouse Nudt13 was expressed in insect cells from a baculovirus vector as a histidine-tagged recombinant protein. In vitro, it efficiently hydrolysed NADH to NMNH and AMP and NADPH to NMNH and 2',5'-ADP and had a marked preference for the reduced pyridine nucleotides. Much lower activity was obtained with other nucleotide substrates tested...
July 28, 2017: Protein Journal
https://www.readbyqxmd.com/read/28754952/mycobacterial-dna-binding-protein-1-is-critical-for-long-term-survival-of-mycobacterium-smegmatis-and-simultaneously-coordinates-cellular-functions
#5
Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, Sohkichi Matsumoto
Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28741793/telomerase-enzyme-deficiency-promotes-metabolic-dysfunction-in-murine-hepatocytes-upon-dietary-stress
#6
Raquel M Alves-Paiva, Sachiko Kajigaya, Xingmin Feng, Jichun Chen, Marie Desierto, Susan Wong, Danielle M Townsley, Flávia S Donaires, Adeline Bertola, Bin Gao, Neal S Young, Rodrigo T Calado
Short telomeres and genetic telomerase defects are risk factors for some human liver diseases, ranging from non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) to cirrhosis. In murine models, telomere dysfunction has been shown to metabolically compromise hematopoietic cells, liver, and heart via the activation of the p53-PGC axis METHODS: Tert- and Terc-deficient mice were challenged with liquid high fat diet (HFD). Liver metabolic contents were analyzed by CE-TOFMS and liver fat content was confirmed by confocal and electronic microscopy RESULTS: Tert-deficient but not Terc-deficient mice develop hepatocyte injury and frank steatosis when challenged with liquid HFD...
July 25, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28736426/modulation-of-mitochondrial-membrane-potential-and-ros-generation-by-nicotinamide-in-a-manner-independent-of-sirt1-and-mitophagy
#7
Seon Beom Song, So-Young Jang, Hyun Tae Kang, Bie Wei, Un-Woo Jeoun, Gye Soon Yoon, Eun Seong Hwang
Nicotinamide (NAM) plays essential roles in physiology through facilitating NAD(+) redox homeostasis. Importantly, at high doses, it protects cells under oxidative stresses, and has shown therapeutic effectiveness in a variety of disease conditions. In our previous studies, NAM lowered reactive oxygen species (ROS) levels and extended cellular life span in primary human cells. In the treated cells, levels of NAD(+)/NADH and SIRT1 activity increased, while mitochondrial content decreased through autophagy activation...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28724915/quinolinate-phosphoribosyltransferase-is-an-antiviral-host-factor-against-hepatitis-c-virus-infection
#8
Zhilong Wang, Yanhang Gao, Chao Zhang, Haiming Hu, Dongwei Guo, Yi Xu, Qiuping Xu, Weihong Zhang, Sisi Deng, Pingyun Lv, Yan Yang, Yanhua Ding, Qingquan Li, Changjiang Weng, Xinwen Chen, Sitang Gong, Hairong Chen, Junqi Niu, Hong Tang
HCV infection can decrease NAD(+)/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O(Tg) mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715469/cofactor-engineering-improved-calb-production-in-pichia-pastoris-through-heterologous-expression-of-nadh-oxidase-and-adenylate-kinase
#9
Charumathi Jayachandran, Balakumaran Palanisamy Athiyaman, Meenakshisundaram Sankaranarayanan
The cofactor engineering strategy can relieve the metabolic stress induced by expression of recombinant protein in cellular metabolism related to cofactor and energy reactions. To study the effect of cofactor regeneration on recombinant protein expression, NADH oxidase (noxE) was engineered in P. pastoris expressing lipase B (GSCALB). Expression of noxE in P. pastoris (GSCALBNOX) increased NAD+ levels by 85% with a concomitant reduction in NADH/NAD+ ratio of 67% compared to GSCALB. The change in the redox level positively influenced the methanol uptake rate and made 34% augment in CALB activity...
2017: PloS One
https://www.readbyqxmd.com/read/28688179/resveratrol-attenuates-excessive-ethanol-exposure-induced-insulin-resistance-in-rats-via-improving-nad-nadh-ratio
#10
Gang Luo, Bingqing Huang, Xiang Qiu, Lin Xiao, Ning Wang, Qin Gao, Wei Yang, Liping Hao
SCOPE: Resveratrol has been shown to improve insulin resistance via activating the NAD(+) -dependent deacetylase SIRT1, but the effects of resveratrol on ethanol-induced insulin resistance remain unclear. This study was designed to explore the potential mechanism by which resveratrol ameliorated ethanol-induced insulin resistance, focusing on its regulations on the ratio of NAD(+) /NADH and SIRT1 expression. METHODS AND RESULTS: Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 0...
July 8, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28685427/imaging-redox-state-in-mouse-muscles-of-different-ages
#11
Lily Moon, David W Frederick, Joseph A Baur, Lin Z Li
Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD(+)) and the NAD(+)-coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD(+) falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD(+)/NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28663873/autofluorescence-imaging-captures-heterogeneous-drug-response-differences-between-2d-and-3d-breast-cancer-cultures
#12
T M Cannon, A T Shah, M C Skala
Two-photon microscopy of cellular autofluorescence intensity and lifetime (optical metabolic imaging, or OMI) is a promising tool for preclinical drug development. OMI, which exploits the endogenous fluorescence from the metabolic coenzymes NAD(P)H and FAD, is sensitive to changes in cell metabolism produced by drug treatment. Previous studies have shown that drug response, genetic expression, cell-cell communication, and cell signaling in 3D culture match those of the original in vivo tumor, but not those of 2D culture...
March 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28655753/the-thermodynamic-basis-of-glucose-stimulated-insulin-release-a-model-of-the-core-mechanism
#13
David F Wilson, Abigail T J Cember, Franz M Matschinsky
A model for glucose sensing by pancreatic β-cells is developed and compared with the available experimental data. The model brings together mathematical representations for the activities of the glucose sensor, glucokinase, and oxidative phosphorylation. Glucokinase produces glucose 6-phosphate (G-6-P) in an irreversible reaction that determines glycolytic flux. The primary products of glycolysis are NADH and pyruvate. The NADH is reoxidized and the reducing equivalents transferred to oxidative phosphorylation by the glycerol phosphate shuttle, and some of the pyruvate is oxidized by pyruvate dehydrogenase and enters the citric acid cycle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#14
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28646144/using-fractional-intensities-of-time-resolved-fluorescence-to-sensitively-quantify-nadh-nad-with-genetically-encoded-fluorescent-biosensors
#15
Mengfang Chang, Lei Li, Hanyang Hu, Qingxun Hu, Aoxue Wang, Xiaodan Cao, Xiantong Yu, Sanjun Zhang, Yuzheng Zhao, Jinquan Chen, Yi Yang, Jianhua Xu
In this paper, we propose a novel and sensitive ratiometric analysis method that uses the fractional intensities of time-resolved fluorescence of genetically encoded fluorescent NADH/NAD(+) biosensors, Peredox, SoNar, and Frex. When the conformations of the biosensors change upon NADH/NAD(+) binding, the fractional intensities (α i τ i ) have opposite changing trends. Their ratios could be exploited to quantify NADH/NAD(+) levels with a larger dynamic range and higher resolution versus commonly used fluorescence intensity and lifetime methods...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28631845/mild-metabolic-perturbations-alter-succinylation-of-mitochondrial-proteins
#16
Huanlian Chen, Hui Xu, Samuel Potash, Anatoly Starkov, Vsevolod V Belousov, Dmitry S Bilan, Travis T Denton, Gary E Gibson
Succinylation of proteins is widespread, modifies both the charge and size of the molecules, and can alter their function. For example, liver mitochondrial proteins have 1,190 unique succinylation sites representing multiple metabolic pathways. Succinylation is sensitive to both increases and decreases of the NAD(+) -dependent desuccinylase, SIRT5. Although the succinyl group for succinylation is derived from metabolism, the effects of systematic variation of metabolism on mitochondrial succinylation are not known...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28578808/real-time-monitoring-of-intracellular-redox-changes-in-methylococcus-capsulatus-bath-for-efficient-bioconversion-of-methane-to-methanol
#17
Masahito Ishikawa, Yuya Tanaka, Risa Suzuki, Kota Kimura, Kenya Tanaka, Kazuhide Kamiya, Hidehiro Ito, Souichiro Kato, Toshiaki Kamachi, Katsutoshi Hori, Shuji Nakanishi
This study aimed to develop a novel method for real-time monitoring of the intracellular redox states in a methanotroph Methylococcus capsulatus, using Peredox as a genetically encoded fluorescent sensor of the NADH:NAD(+) ratio. As expected, the fluorescence derived from the Peredox-expressing M. capsulatus transformant increased by supplementation of electron donor compounds (methane and formate), while it decreased by specifically inhibiting the methanol oxidation reaction. Electrochemical measurements confirmed that the Peredox fluorescence reliably represents the intracellular redox changes...
October 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28554565/antioxidant-mechanism-of-mitochondria-targeted-plastoquinone-skq1-is-suppressed-in-aglycemic-hepg2-cells-dependent-on-oxidative-phosphorylation
#18
Jan Ježek, Hana Engstová, Petr Ježek
Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1(+) with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28537923/aldehyde-dehydrogenase-1a1-increases-nadh-levels-and-promotes-tumor-growth-via-glutathione-dihydrolipoic-acid-dependent-nad-reduction
#19
Baiyun Wang, Xue Chen, Zixi Wang, Wei Xiong, Tao Xu, Xinyuan Zhao, Yang Cao, Yanru Guo, Lin Li, She Chen, Song Huang, Xiaodong Wang, Min Fang, Zhirong Shen
Aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD+ to NADH. We report here that ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#20
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
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