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https://www.readbyqxmd.com/read/28254760/personal-model-assisted-identification-of-nad-and%C3%A2-glutathione-metabolism-as-intervention-target-in-nafld
#1
Adil Mardinoglu, Elias Bjornson, Cheng Zhang, Martina Klevstig, Sanni Söderlund, Marcus Ståhlman, Martin Adiels, Antti Hakkarainen, Nina Lundbom, Murat Kilicarslan, Björn M Hallström, Jesper Lundbom, Bruno Vergès, Peter Hugh R Barrett, Gerald F Watts, Mireille J Serlie, Jens Nielsen, Mathias Uhlén, Ulf Smith, Hanns-Ulrich Marschall, Marja-Riitta Taskinen, Jan Boren
To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD(+) and glutathione (GSH) in subjects with high HS Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting...
March 2, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28246130/nicotinamide-mononucleotide-an-nad-precursor-rescues-age-associated-susceptibility-to-aki-in-a-sirtuin-1-dependent-manner
#2
Yi Guan, Su-Rong Wang, Xin-Zhong Huang, Qiong-Hong Xie, Yun-Yu Xu, Da Shang, Chuan-Ming Hao
The rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD(+) Supplementation with nicotinamide mononucleotide (NMN), an NAD(+) precursor, restored renal SIRT1 activity and NAD(+) content in 20-month-old mice and further increased both in 3-month-old mice...
February 28, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#3
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28211759/gamma-tocopherol-supplementation-ameliorated-hyper-inflammatory-response-during-the-early-cutaneous-wound-healing-in-alloxan-induced-diabetic-mice
#4
Jihyun Shin, Soo Jin Yang, Yunsook Lim
Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT)...
March 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28163307/role-of-nad-and-mitochondrial-sirtuins-in-cardiac-and-renal-diseases
#5
REVIEW
Kathleen A Hershberger, Angelical S Martin, Matthew D Hirschey
The coenzyme nicotinamide adenine dinucleotide (NAD(+)) has key roles in the regulation of redox status and energy metabolism. NAD(+) depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD(+) repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD(+) enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD(+) functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes...
February 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28146411/neuroprotective-effect-of-halophyte-salicornia-herbacea-l-is-mediated-by-activation-of-heme-oxygenase-1-in-mouse-hippocampal-ht22-cells
#6
Min Sun Kim, Ji Yeon Seo, Jisun Oh, Yu Kyung Jang, Choong Hwan Lee, Jong-Sang Kim
Salicornia herbacea L. (glasswort, tungtungmadi in Korean), a halophyte that grows in salt marshes and muddy seashores along the western coast of Korea, has been used as a seasoning vegetable and a folk medicine for intestinal ailments, nephropathy, and hepatitis. As the salt-tolerant herb was reported to contain antioxidants, including tungtungmadic acid, quercetin, and chlorogenic acid, we hypothesized that the ethanolic extract of S. herbacea L. (SH extract) enriched with antioxidative compounds will have neuroprotective activity...
February 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#7
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28089880/a-combined-approach-for-enhancing-the-stability-of-recombinant-cis-dihydrodiol-naphthalene-dehydrogenase-from-pseudomonas-putida-g7-allowed-for-the-structural-and-kinetic-characterization-of-the-enzyme
#8
Débora Maria Abrantes Costa, Mariana Amalia Figueiredo Costa, Samuel Leite Guimarães, Juliana Barbosa Coitinho, Stefanya Velásquez Gómez, Tiago Antônio da Silva Brandão, Ronaldo Alves Pinto Nagem
The second enzyme of the naphthalene degradation pathway in Pseudomonas putida G7 is NahB, a dehydrogenase that converts cis-1,2-dihydroxy-1,2-dihydronaphthalene to 1,2-dihydroxynaphthalene. We report the cloning, optimization of expression, purification, kinetic studies and preliminary structural characterization of the recombinant NahB. The nahB gene was cloned into a T7 expression vector and the enzyme was overexpressed in Escherichia coli Rosetta (DE3) as an N-terminal hexa-histidine-tagged protein (6xHis-NahB)...
January 9, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#9
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/28035366/inhibitory-effects-of-alpha-lipoic-acid-on-oxidative-stress-in-the-rostral-ventrolateral-medulla-in-rats-with-salt-induced-hypertension
#10
Yu-Peng Huang, Hong-Yan Jin, Hui-Ping Yu
Oxidative stress in the rostral ventrolateral medulla (RVLM) plays an important role in the pathophysiology of hypertension. Alpha‑lipoic acid (ALA) is widely recognized for its potent superoxide inhibitory properties, and it can safely penetrate deep into the brain. The aim of this study was to explore whether ALA supplementation attenuates hypertensive responses and cardiac hypertrophy by decreasing the NAD(P)H oxidase (NOX)-derived overproduction of reactive oxygen species (ROS) in the mitochondria in the RVLM, and thus attenuating the development of salt‑induced hypertension...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28011627/enhancing-nad-salvage-metabolism-is-neuroprotective-in-a-pink1-model-of-parkinson-s-disease
#11
Susann Lehmann, Samantha H Y Loh, L Miguel Martins
Familial forms of Parkinson's disease (PD) caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is essential for both generating energy in mitochondria and nuclear DNA repair through NAD(+)-consuming poly(ADP-ribose) polymerases (PARPs). We found alterations in NAD(+) salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD(+) precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration...
February 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28003588/effectiveness-of-medium-chain-triglyceride-oil-therapy-in-two-japanese-citrin-deficient-siblings-evaluation-using-oral-glucose-tolerance-tests
#12
Hiroki Otsuka, Hideo Sasai, Elsayed Abdelkreem, Norio Kawamoto, Minako Kawamoto, Toshiya Kamiya, Yasuo Tanimoto, Atsuo Kikuchi, Shigeo Kure, Chikahiko Numakura, Kiyoshi Hayasaka, Toshiyuki Fukao
Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD(+) ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28000862/sirt1%C3%A2-mediated-regulation-of-oxidative-stress-induced-by-pseudomonas-aeruginosa-lipopolysaccharides-in-human-alveolar-epithelial-cells
#13
Xiaoli Liu, Tuo Yang, Tieying Sun, Kuiqing Shao
Sirtuin1 (SIRT1) is an NAD+‑dependent deacetylase that exhibits multiple biological functions, including cell differentiation inhibition, transcription regulation, cell cycle regulation and anti‑apoptosis. Lipopolysaccharides (LPS) are crucial virulence factors produced by Pseudomonas aeruginosa and serve an important role in adjusting the interactions between the host and the pathogen. However, the effect of SIRT1 in the regulation of LPS‑induced A459 human alveolar epithelial cells (AECs) oxidative stress remains unclear...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27979136/simultaneous-quantitation-of-nicotinamide-riboside-nicotinamide-mononucleotide-and-nicotinamide-adenine-dinucleotide-in-milk-by-a-novel-enzyme-coupled-assay
#14
Simone Ummarino, Massimo Mozzon, Federica Zamporlini, Adolfo Amici, Francesca Mazzola, Giuseppe Orsomando, Silverio Ruggieri, Nadia Raffaelli
Nicotinamide riboside, the most recently discovered form of vitamin B3, and its phosphorylated form nicotinamide mononucleotide, have been shown to be potent supplements boosting intracellular nicotinamide adenine dinucleotide (NAD) levels, thus preventing or ameliorating metabolic and mitochondrial diseases in mouse models. Here we report for the first time on the simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and NAD in milk by means of a fluorometric, enzyme-coupled assay...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27911769/reductive-carboxylation-is-a-major-metabolic-pathway-in-the-retinal-pigment-epithelium
#15
Jianhai Du, Aya Yanagida, Kaitlen Knight, Abbi L Engel, Anh Huan Vo, Connor Jankowski, Martin Sadilek, Van Thi Bao Tran, Megan A Manson, Aravind Ramakrishnan, James B Hurley, Jennifer R Chao
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using (13)C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#16
Xingxing Jian, Ningchuan Li, Cheng Zhang, Qiang Hua
BACKGROUND: Succinic acid is a valuable product due to its wide-ranging utilities. To improve succinate production and reduce by-products formation, Escherichia coli NZN111 was constructed by insertional inactivation of lactate dehydrogenase (LDH) and pyruvate formate lyase (PFL) encoded by the genes ldhA and pflB, respectively. However, this double-deletion mutant is incapable of anaerobically growing on glucose in rich or minimal medium even with acetate supplementation. A widespread hold view is that the inactivation of NADH-dependent LDH limits the regeneration of NAD(+) and consequently disables proper growth under anaerobic conditions...
2016: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/27878891/cloning-and-characterization-of-the-glutamate-dehydrogenase-gene-in-streptococcus-bovis
#17
Tasuke Ando, Yoko Sugawara, Ryohei Nishio, Miho Murakami, Emiko Isogai, Hiroshi Yoneyama
Streptococcus bovis, an etiologic agent of rumen acidosis in cattle, is a rumen bacterium that can grow in a chemically defined medium containing ammonia as a sole source of nitrogen. To understand its ability to assimilate inorganic ammonia, we focused on the function of glutamate dehydrogenase. In order to identify the gene encoding this enzyme, we first amplified an internal region of the gene by using degenerate primers corresponding to hexameric family I and NAD(P)(+) binding motifs. Subsequently, inverse PCR was used to identify the whole gene, comprising an open reading frame of 1350 bp that encodes 449 amino acid residues that appear to have the substrate binding site of glutamate dehydrogenase observed in other organisms...
November 23, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/27826689/%C3%AE-hydroxybutyrate-in-the-brain-one-molecule-multiple-mechanisms
#18
REVIEW
Lavanya B Achanta, Caroline D Rae
β-Hydroxybutyrate (βOHB), a ketone body, is oxidised as a brain fuel. Although its contribution to energy metabolism in the healthy brain is minimal, it is an interesting metabolite which is not only oxidised but also has other direct and collateral effects which make it a molecule of interest for therapeutic purposes. In brain βOHB can be produced in astrocytes from oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types although uptake across the blood brain barrier is a metabolic control point...
January 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27809334/nicotinamide-adenine-dinucleotide-biosynthesis-promotes-liver-regeneration
#19
Sarmistha Mukherjee, Karthikeyani Chellappa, Andrea Moffitt, Joan Ndungu, Ryan W Dellinger, James G Davis, Beamon Agarwal, Joseph A Baur
The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27807756/the-yeast-scheffersomyces-amazonensis-is-an-efficient-xylitol-producer
#20
Raquel M Cadete, Monaliza A Melo-Cheab, Adriana L Viana, Evelyn S Oliveira, César Fonseca, Carlos A Rosa
This study assessed the efficiency of Scheffersomyces amazonensis UFMG-CM-Y493(T), cultured in xylose-supplemented medium (YPX) and rice hull hydrolysate (RHH), to convert xylose to xylitol under moderate and severe oxygen limitation. The highest xylitol yields of 0.75 and 1.04 g g(-1) in YPX and RHH, respectively, were obtained under severe oxygen limitation. However, volumetric productivity in RHH was ninefold decrease than that in YPX medium. The xylose reductase (XR) and xylitol dehydrogenase (XDH) activities in the YPX cultures were strictly dependent on NADPH and NAD(+) respectively, and were approximately 10% higher under severe oxygen limitation than under moderate oxygen limitation...
December 2016: World Journal of Microbiology & Biotechnology
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