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https://www.readbyqxmd.com/read/28644902/sirt6-alters-adult-hippocampal-neurogenesis
#1
Eitan Okun, Daniel Marton, Daniel Cohen, Kathleen Griffioen, Yariv Kanfi, Tomer Illouz, Ravit Madar, Haim Y Cohen
Sirtuins are pleiotropic NAD+ dependent histone deacetylases involved in metabolism, DNA damage repair, inflammation and stress resistance. SIRT6, a member of the sirtuin family, regulates the process of normal aging and increases the lifespan of male mice over-expressing Sirt6 by 15%. Neurogenesis, the formation of new neurons within the hippocampus of adult mammals, involves several complex stages including stem cell proliferation, differentiation, migration and network integration. During aging, the number of newly generated neurons continuously declines, and this is correlated with a decline in neuronal plasticity and cognitive behavior...
2017: PloS One
https://www.readbyqxmd.com/read/28643389/combined-molecular-modelling-and-3d-qsar-study-for-understanding-the-inhibition-of-nqo1-by-heterocyclic-quinone-derivatives
#2
Claudia Lopez-Lira, Jans H Alzate-Morales, Margot Paulino, Jaime Mella-Raipán, Cristian O Salas, Ricardo A Tapia, Jorge Soto-Delgado
A combination of three-dimensional quantitative structure-activity relationship (3D-QSAR), and molecular modelling methods were used to understand the potent inhibitory NAD(P)H:quinone oxidoreductase 1 (NQO1) activity of a set of 52 heterocyclic quinones. Molecular docking results indicated that some favourable interactions of key amino acid residues at the binding site of NQO1 with these quinones, would be responsible for an improvement of the NQO1 activity of these compounds. The main interactions involved are hydrogen bond of the amino group of residue Tyr128, π-stacking interactions with Phe106 and Phe178, and electrostatic interactions with flavin adenine dinucleotide (FADH) cofactor...
June 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28642875/rapid-elimination-of-blood-alcohol-using-erythrocytes-mathematical-modeling-and-in-vitro-study
#3
Yuliya G Alexandrovich, Elena A Kosenko, Elena I Sinauridze, Sergey I Obydennyi, Igor I Kireev, Fazoil I Ataullakhanov, Yuriy G Kaminsky
Erythrocytes (RBCs) loaded with alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALD) can metabolize plasma ethanol and acetaldehyde but with low efficiency. We investigated the rate-limiting factors in ethanol oxidation by these enzymes loaded into RBCs. Mathematical modeling and in vitro experiments on human RBCs loaded simultaneously with ADH and ALD (by hypoosmotic dialysis) were performed. The simulation showed that the rate of nicotinamide-adenine dinucleotide (NAD(+)) generation in RBC glycolysis, but not the activities of the loaded enzymes, is the rate-limiting step in external ethanol oxidation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642848/mycobacterium-tuberculosis-glyceraldehyde-3-phosphate-dehydrogenase-gapdh-functions-as-a-receptor-for-human-lactoferrin
#4
Himanshu Malhotra, Anil Patidar, Vishant M Boradia, Rajender Kumar, Rakesh D Nimbalkar, Ajay Kumar, Zahid Gani, Rajbeer Kaur, Prabha Garg, Manoj Raje, Chaaya I Raje
Iron is crucial for the survival of living cells, particularly the human pathogen Mycobacterium tuberculosis (M.tb) which uses multiple strategies to acquire and store iron. M.tb synthesizes high affinity iron chelators (siderophores), these extract iron from host iron carrier proteins such as transferrin (Tf) and lactoferrin (Lf). Recent studies have revealed that M.tb may also relocate several housekeeping proteins to the cell surface for capture and internalization of host iron carrier protein transferrin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28642005/expression-purification-and-crystallization-of-type-1-isocitrate-dehydrogenase-from-trypanosoma-brucei
#5
Xinying Wang, Daniel Ken Inaoka, Tomoo Shiba, Emmanuel Oluwadare Balogun, Stefan Allmann, Yoh-Ichi Watanabe, Michael Boshart, Kiyoshi Kita, Shigeharu Harada
Isocitrate dehydrogenases (IDHs) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate. Depending on the electron acceptor and subcellular localization, these enzymes are classified as NADP(+)-dependent IDH1 in the cytosol or peroxisomes, NADP(+)-dependent IDH2 and NAD(+)-dependent IDH3 in mitochondria. Trypanosoma brucei is a protozoan parasite that causes African sleeping sickness in humans and Nagana disease in animals. Here, for the first time, a putative glycosomal T...
June 19, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28640600/horse-liver-alcohol-dehydrogenase-zinc-coordination-and-catalysis
#6
Bryce V Plapp, Baskar Raj Savarimuthu, Daniel J Ferraro, Jon K Rubach, Eric N Brown, Subramanian Ramaswamy
: During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism may involve a pentacoordinated zinc or a double displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1 and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. Apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174 and a water molecule...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28639725/targeting-nad-p-h-quinone-oxidoreductase-nqo1-in-pancreatic-cancer
#7
Anne M Lewis, Matthew Ough, Juan Du, Ming-Sound Tsao, Larry W Oberley, Joseph J Cullen
Quinone oxidoreductase (NQO1) functions as an important part of cellular antioxidant defense by detoxifying quinones, thus preventing the formation of reactive oxygen species. The aims of our study were to determine if NQO1 is elevated in pancreatic cancer specimens and pancreatic cancer cell lines and if so, would compounds previously demonstrated to redox cycle with NQO1 be effective in killing pancreatic cancer cells. Immunohistochemistry of resected pancreatic specimens demonstrated an increased immunoreactivity for NQO1 in pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) specimens versus normal human pancreas...
July 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28637419/pharmacological-inhibitors-of-nad-biosynthesis-as-potential-anticancer-agents
#8
Stephanie Lucas, Claire Soave, Gazal Nabil, Zainab Ahmed, Guohua Chen, Hossny El-Banna, Q Ping Dou, Jian Wang
BACKGROUND: Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics by targeting through inhibition of cancer metabolism. Nicotinamide adenine dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer...
June 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#9
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28635300/pyridine-dinucleotides-from-molecules-to-man
#10
Joshua P Fessel, William M Oldham
SIGNIFICANCE: Pyridine dinucleotides, NAD and NADP, were discovered over 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28634236/alternative-evolutionary-pathways-for-drug-resistant-small-colony-variant-mutants-in-staphylococcus-aureus
#11
Sha Cao, Douglas L Huseby, Gerrit Brandis, Diarmaid Hughes
Staphylococcus aureus is known to generate small colony variants (SCVs) that are resistant to aminoglycoside antibiotics and can cause persistent and recurrent infections. The SCV phenotype is unstable, and compensatory mutations lead to restored growth, usually with loss of resistance. However, the evolution of improved growth, by mechanisms that avoid loss of antibiotic resistance, is very poorly understood. By selection with serial passaging, we isolated and characterized different classes of extragenic suppressor mutations that compensate for the slow growth of small colony variants...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28631845/mild-metabolic-perturbations-alter-succinylation-of-mitochondrial-proteins
#12
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/28631789/electrolyte-effect-in-induced-charge-electroosmosis
#13
Huicheng Feng, Yi Huang, Teck Neng Wong, Fei Duan
This paper reports an interesting phenomenon that the velocity increases with increasing sodium chloride (NaCl) concentration in induced charge electroosmosis (ICEO) around a conducting cylinder measured by microparticle image velocimetry (μPIV). It is different from the widely reported velocity decay with increasing electrolyte concentration in AC electroosmosis (ACEO) [M. Z. Bazant et al., MicroTAS, 2007, 2875-2878] and induced charge electrophoresis (ICEP) of Janus particles [S. Gangwal et al., Phys. Rev...
June 20, 2017: Soft Matter
https://www.readbyqxmd.com/read/28630487/multicolor-two-photon-imaging-of-endogenous-fluorophores-in-living-tissues-by-wavelength-mixing
#14
Chiara Stringari, Lamiae Abdeladim, Guy Malkinson, Pierre Mahou, Xavier Solinas, Isabelle Lamarre, Sébastien Brizion, Jean-Baptiste Galey, Willy Supatto, Renaud Legouis, Ana-Maria Pena, Emmanuel Beaurepaire
Two-photon imaging of endogenous fluorescence can provide physiological and metabolic information from intact tissues. However, simultaneous imaging of multiple intrinsic fluorophores, such as nicotinamide adenine dinucleotide(phosphate) (NAD(P)H), flavin adenine dinucleotide (FAD) and retinoids in living systems is generally hampered by sequential multi-wavelength excitation resulting in motion artifacts. Here, we report on efficient and simultaneous multicolor two-photon excitation of endogenous fluorophores with absorption spectra spanning the 750-1040 nm range, using wavelength mixing...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630126/a-key-enzyme-of-the-nad-salvage-pathway-in-thermus-thermophilus-characterization-of-nicotinamidase-and-the-impact-of-its-gene-deletion-at-high-temperatures
#15
Hironori Taniguchi, Sathidaphorn Sungwallek, Phatcharin Chotchuang, Kenji Okano, Kohsuke Honda
Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor related to many cellular processes. This cofactor is known to be unstable, especially at high temperatures, where it chemically decomposes to nicotinamide and ADP-ribose. Bacteria, yeast, and higher organisms possess the salvage pathway for reconstructing NAD(+) from these decomposition products; however, the importance of the salvage pathway for survival is not well elucidated, except for in pathogens lacking the NAD(+)de novo synthesis pathway. Herein, we report the importance of the NAD(+) salvage pathway in the thermophilic bacterium Thermus thermophilus HB8 at high temperatures...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28630124/the-dna-repair-repertoire-of-mycobacterium-smegmatis-fena-includes-the-incision-of-dna-5-flaps-and-the-removal-of-5-adenylylated-products-of-aborted-nick-ligation
#16
Maria Loressa Uson, Shreya Ghosh, Stewart Shuman
We characterize Mycobacterium smegmatis FenA as a manganese-dependent 5' -flap endonuclease homologous to the 5' -exonuclease of DNA polymerase I. FenA incises a nicked 5' flap between the first and second nucleotides of the duplex segment to yield a 1-nucleotide gapped DNA, which is then further resected in dinucleotide steps. Initial FenA cleavage at a Y-flap or nick occurs between the first and second nucleotides of the duplex. However, when the template 3' -single-strand is eliminated to create a 5' -tailed duplex, FenA incision shifts to between the second and third nucleotides...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28630000/betaine-aldehyde-dehydrogenase-expression-during-physiological-cardiac-hypertrophy-induced-by-pregnancy
#17
Jesús Alfredo Rosas-Rodríguez, José Guadalupe Soñanez-Organis, José Arquimides Godoy-Lugo, Juan Alberto Espinoza-Salazar, Cesar Jeravy López-Jacobo, Norma Aurora Stephens-Camacho, Guadalupe González-Ochoa
Betaine Aldehyde Dehydrogenase (betaine aldehyde: NAD(P)(+) oxidoreductase, (E.C. 1.2.1.8; BADH) catalyze the irreversible oxidation of betaine aldehyde (BA) to glycine betaine (GB) and is essential for polyamine catabolism, γ-aminobutyric acid synthesis, and carnitine biosynthesis. GB is an important osmolyte that regulates the homocysteine levels, contributing to a vascular risk factor reduction. In this sense, distinct investigations describe the physiological roles of GB, but there is a lack of information about the GB novo synthesis process and regulation during cardiac hypertrophy induced by pregnancy...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629697/increase-in-furfural-tolerance-by-combinatorial-overexpression-of-nad-salvage-pathway-enzymes-in-engineered-isobutanol-producing-e-coli
#18
Hun-Suk Song, Jong-Min Jeon, Hyun-Joong Kim, Shashi Kant Bhatia, Ganesan Sathiyanarayanan, Junyoung Kim, Ju Won Hong, Yoon Gi Hong, Kwon Young Choi, Yun-Gon Kim, Wooseong Kim, Yung-Hun Yang
To reduce the furfural toxicity for biochemical production in E. coli, a new strategy was successfully applied by supplying NAD(P)H through the nicotine amide salvage pathway. To alleviate the toxicity, nicotinamide salvage pathway genes were overexpressed in recombinant, isobutanol-producing E. coli. Gene expression of pncB and nadE respectively showed increased tolerance to furfural among these pathways. The combined expression of pncB and nadE was the most effective in increasing the tolerance of the cells to toxic aldehydes...
June 1, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28629498/rodentibacter-gen-nov-including-rodentibacter-pneumotropicus-comb-nov-rodentibacter-heylii-sp-nov-rodentibacter-myodis-sp-nov-rodentibacter-ratti-sp-nov-rodentibacter-heidelbergensis-sp-nov-rodentibacter-trehalosifermentans-sp-nov-rodentibacter-rarus-sp-nov
#19
Sadhana Adhikary, Werner Nicklas, Magne Bisgaard, Ron Boot, Peter Kuhnert, Torsten Waberschek, Bent Aalbæk, Bozena Korczak, Henrik Christensen
Rodentibacter gen. nov. is proposed based on isolation and phenotypic characterization of strains, predominantly from rodents. The strains showed 86 % or higher rpoB gene sequence similarity and indicated a genus-level relationship within Pasteurellaceae. The strains compared at 16S rRNA gene sequence level showed 93.8 % or higher similarity, and their genus-level relationship within Pasteurellaceae was confirmed by phenotypic analysis. The type species Rodentibacter pneumotropicus comb. nov. is reclassified from [Pasteurella] pneumotropica with type strain NCTC 8141T (=CCUG 12398T)...
June 20, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28628905/a-ros-mediated-mitochondrial-pathway-and-nrf2-pathway-activation-are-involved-in-bde-47-induced-apoptosis-in-neuro-2a-cells
#20
Hongmei Chen, Xuexi Tang, Bin Zhou, Zhongyuan Zhou, Ningning Xu, You Wang
Our previous study showed that 2,2'-,4,4'-tetrabromodiphenyl ether (BDE-47) is cytotoxic and induces apoptosis in Neuro-2a cells. In the present study, we aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcriptional regulator of oxidative stress and apoptosis, is involved in this process. The results of toxicological experiments showed that BDE-47 decreased the cellular mitochondrial membrane potential (MMP) and increased cytochrome c release to the cytoplasm, followed by an increase in intracellular caspase-9 and caspase-3 activity, suggesting that a mitochondrial pathway was involved in the apoptotic process...
June 3, 2017: Chemosphere
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