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https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#1
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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/29339820/histone-variant-macroh2a1-plays-an-isoform-specific-role-in-suppressing-epithelial-mesenchymal-transition
#3
Dayle Q Hodge, Jihong Cui, Matthew J Gamble, Wenjun Guo
Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key roles in various developmental and pathological processes. Although much work has been done on signaling pathways and transcription factors regulating EMT, the epigenetic regulation of EMT remains not well understood. Histone variants have been recognized as a key group of epigenetic regulators. Among them, macroH2A1 is involved in stem cell reprogramming and cancer progression. We postulated that macroH2A1 may play a role in EMT, a process involving reprogramming of cellular states...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29338114/divergent-pathways-involving-1-3-dipolar-addition-and-n-n-bond-splitting-of-an-organic-azide-across-a-zirconium-methylidene
#4
Takashi Kurogi, Manoj V Mane, Shuai Zheng, Patrick J Carroll, Mu-Hyun Baik, Daniel J Mindiola
The zirconium methylidene (PNP)Zr=CH2 (OAr) (1) reacts with N3 Ad to give two products (PNP)Zr=NAd(OAr) (2) and (PNP)Zr(η2 -N=NAd)(N=CH2 )(OAr) (3), both resulting from a common cycloaddition intermediate (PNP)Zr(CH2 N3 Ad)(OAr) (A). Using a series of control experiments in combination with DFT calculations, it was found that 2 results from a nitrene by a carbene metathesis reaction in which N2 acts as a delivery vehicle and forms N2 CH2 as a side product. In the case of 3, N-N bond splitting of the azide at the α-position allowed the isolation of a rare example of a parent ketimide complex of zirconium...
January 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29337692/generation-of-superoxide-and-hydrogen-peroxide-by-side-reactions-of-mitochondrial-2-oxoacid-dehydrogenase-complexes-in-isolation-and-in-cells
#5
Victoria I Bunik, Martin D Brand
Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate, branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen. Studies using isolated mitochondria in media mimicking cytosol suggest that the 2-oxoacid dehydrogenase complexes contribute little to the production of superoxide or hydrogen peroxide relative to other mitochondrial sites at physiological steady-states...
June 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29337590/novel-mechanism-for-nicotinamide-phosphoribosyltransferase-inhibition-of-tnf-%C3%AE-mediated-apoptosis-in-human-lung-endothelial-cells
#6
Radu C Oita, Sara M Camp, Wenli Ma, Ermelinda Ceco, Mark Harbeck, Patrick Singleton, Joe Messana, Xiaoguang Sun, Ting Wang, Joe G N Garcia
Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular (iNAMPT) and extracellular (eNAMPT) proteins. eNAMPT is secreted into the blood and functions as a cytokine/enzyme (cytozyme) that activates NFκB signaling via ligation of the TLR4 receptor, further serving as a biomarker for inflammatory lung disorders such as the acute respiratory distress syndrome (ARDS). In contrast, iNAMPT is involved in nicotinamide mononucleotide (NMN) synthesis and has been implicated in the regulation of cellular apoptosis, although the exact mechanisms for this regulation are poorly understood...
January 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29334761/regulation-of-cancer-and-cancer-related-genes-via-nad
#7
Tanveer Sharif, Emma Martell, Cathleen Dai, Mohammad Ghassemi-Rad, Barry Kennedy, Patrick Lee, Shashi Gujar
SIGNIFICANCE: NAD+ is an essential redox cofactor in cellular metabolism and has emerged as an important regulator of a wide spectrum of disease conditions, most notably, cancers. As such, various strategies targeting NAD+ synthesis in cancers are in clinical trials. Recent Advances: Being a substrate required for the activity of various enzyme families, especially sirtuins and poly(ADP-ribose) polymerases, NAD+-mediated signaling plays an important role in gene expression, calcium release, cell cycle progression, DNA repair and cell proliferation...
January 15, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29332790/ultrasensitive-electrochemical-detection-of-poly-adp-ribose-polymerase-1-via-polyaniline-deposition
#8
Yong Liu, Jiahui Fan, Li Shangguan, Yuanjian Liu, Yuanqing Wei, Wei Wei, Songqin Liu
Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target because it is closely related to the development of tumor. So, studies on its detection and inhibitors evaluation have attracted more attention. It is interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the existence of nicotinamide adenine dinucleotide (NAD+), possess twice charge density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and multiple branched strands...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29332274/callitriche-cophocarpa-water-starwort-proteome-under-chromate-stress-evidence-for-induction-of-a-quinone-reductase
#9
Paweł Kaszycki, Aleksandra Dubicka-Lisowska, Joanna Augustynowicz, Barbara Piwowarczyk, Wojciech Wesołowski
Chromate-induced physiological stress in a water-submerged macrophyte Callitriche cophocarpa Sendtn. (water starwort) was tested at the proteomic level. The oxidative stress status of the plant treated with 1 mM Cr(VI) for 3 days revealed stimulation of peroxidases whereas catalase and superoxide dismutase activities were similar to the control levels. Employing two-dimensional electrophoresis, comparative proteomics enabled to detect five differentiating proteins subjected to identification with mass spectrometry followed by an NCBI database search...
January 13, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29332131/assessment-of-human-corneas-prior-to-transplantation-using-high-resolution-two-photon-imaging
#10
Ana Batista, Hans Georg Breunig, Aisada König, Andreas Schindele, Tobias Hager, Berthold Seitz, António Miguel Morgado, Karsten König
Purpose: The purpose of this study was to evaluate the feasibility of using two-photon imaging (TPI) to assess the condition of human corneas for transplantation. Methods: Human corneas were imaged after different storage times: short-term (STS), medium-term (MTS), and long-term (LTS) storage. A high-resolution, custom-built 5-dimensional multiphoton microscope with 12-fs pulsed laser excitation was used for image acquisition. Results: Optical discrimination between different corneal layers and sublayers based on their morphologic characteristics revealed by two-photon autofluorescence (AF) is possible...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29331223/structure-based-design-and-application-of-a-nucleotide-coenzyme-mimetic-ligand-application-to-the-affinity-purification-of-nucleotide-dependent-enzymes
#11
Marigianna Marinou, Dimitrios Platis, Farid S Ataya, Evangelia Chronopoulou, Dimitrios Vlachakis, Nikolaos E Labrou
In the present study, a structure-based approach was exploited for the in silico design of a nucleotide coenzyme mimetic ligand. The enzyme formate dehydrogenase (FDH) was employed as a model in our study. The biomimetic ligand was designed and synthesized based on a tryptamine/3-aminopropylphosphonic acid bi-substituted 1,3,5-triazine (Trz) scaffold (Tra-Trz-3APP), which potentially mimics the interactions of NAD+-FDH complex. Molecular docking studies of the biomimetic ligand predicted that it can occupy the same binding site as the natural coenzyme...
January 3, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29330792/evaluating-the-metabolic-impact-of-hypoxia-on-pancreatic-cancer-cells
#12
Divya Murthy, Enza Vernucci, Gennifer Goode, Jaime Abrego, Pankaj K Singh
Hypoxia is frequently observed in human cancers and induces global metabolic reprogramming that includes an increase in glucose uptake and glycolysis, alterations in NAD(P)H/NAD(P)+ and intracellular ATP levels, and increased utilization of glutamine as the major precursor for fatty acid synthesis. In this chapter, we describe in detail various physiological assays that have been adopted to study the metabolic shift propagated by exposure to hypoxic conditions in pancreatic cell culture model that includes glucose uptake, glutamine uptake, and lactate release by pancreatic cancer cell lines...
2018: Methods in Molecular Biology
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
#13
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/29330189/targeted-synthesis-and-characterization-of-a-gene-cluster-encoding-nad-p-h-dependent-3%C3%AE-3%C3%AE-and-12%C3%AE-hydroxysteroid-dehydrogenases-from-eggerthella-cag-298-a-gut-metagenomic-sequence
#14
Sean M Mythen, Saravanan Devendran, Celia Méndez-García, Isaac Cann, Jason M Ridlon
Gut metagenomic sequences provide a rich source of microbial genes, the majority of which are annotated by homology or unknown. Genes and gene pathways that encode enzymes catalyzing biotransformation of host bile acids are important to identify in gut metagenomic sequences due to the importance of bile acids on gut microbiome structure and host physiology. Hydroxysteroid dehydrogenases (HSDH) are pyridine nucleotide-dependent enzymes with stereo-specificity and regio-specificity for bile acid and steroid hydroxyl groups...
January 12, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29330025/the-role-of-extracellular-and-intracellular-nicotinamide-phosphoribosyl-transferase-in-cancer-diagnostic-and-therapeutic-perspectives-and-challenges
#15
REVIEW
Maria Dalamaga, Gerasimos Socrates Christodoulatos, Christos S Mantzoros
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties...
January 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29329649/hppr-encodes-the-hydroxyphenylpyruvate-reductase-required-for-the-biosynthesis-of-hydrophilic-phenolic-acids-in-salvia-miltiorrhiza
#16
Guo-Quan Wang, Jun-Feng Chen, Bo Yi, He-Xin Tan, Lei Zhang, Wan-Sheng Chen
Salvia miltiorrhiza is a medicinal plant widely used in the treatment of cardiovascular and cerebrovascular diseases. Hydrophilic phenolic acids, including rosmarinic acid (RA) and lithospermic acid B (LAB), are its primary medicinal ingredients. However, the biosynthetic pathway of RA and LAB in S. miltiorrhiza is still poorly understood. In the present study, we accomplished the isolation and characterization of a novel S. miltiorrhiza Hydroxyphenylpyruvate reductase (HPPR) gene, SmHPPR, which plays an important role in the biosynthesis of RA...
December 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29328405/liraglutide-repairs-the-infarcted-heart-the-role-of-the-sirt1-parkin-mitophagy-pathway
#17
Huiying Qiao, Haiyan Ren, He Du, Minfang Zhang, Xiaofang Xiong, Rong Lv
Liraglutide is glucagon‑like peptide‑1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post‑infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways...
January 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327656/nad-nadh-homeostasis-affects-metabolic-adaptation-to-hypoxia-and-secondary-metabolite-production-in-filamentous-fungi
#18
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/29325897/an-improved-cell-permeable-fluorogenic-substrate-as-the-basis-for-a-highly-sensitive-test-for-nad-p-h-quinone-oxidoreductase-1-nqo1-in-living-cells
#19
Simone Cuff, Ruth D Lewis, Edwin Chinje, Mohammed Jaffar, Richard Knox, Ian Weeks
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme upregulated in response to oxidative stress and in some cancers. Its upregulation by compounds has been used as an indicator of their potential anti-cancer properties. In this study we have designed, produced and tested a fluorogenic coumarin conjugate which selectively releases highly fluorescent 4-methylumbelliferone (4-MU) in the presence of NQO1. It was found that measuring 4-MU release rapidly and specifically quantitated NQO1 levels in vitro and in live cells...
January 8, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29324867/comparative-transcriptome-analysis-reveals-key-genes-potentially-related-to-soluble-sugar-and-organic-acid-accumulation-in-watermelon
#20
Lei Gao, Shengjie Zhao, Xuqiang Lu, Nan He, Hongju Zhu, Junling Dou, Wenge Liu
Soluble sugars and organic acids are important components of fruit flavor and have a strong impact on the overall organoleptic quality of watermelon (Citrullus lanatus) fruit. Several studies have analyzed the expression levels of the genes related to soluble sugar accumulation and the dynamic changes in their content during watermelon fruit development and ripening. Nevertheless, to date, there have been no reports on the organic acid content in watermelon or the genes regulating their synthesis. In this study, the soluble sugars and organic acids in watermelon were measured and a comparative transcriptome analysis was performed to identify the key genes involved in the accumulation of these substances during fruit development and ripening...
2018: PloS One
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