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Ninon Very, Agata Steenackers, Caroline Dubuquoy, Jeanne Vermuse, Laurent Dubuquoy, Tony Lefebvre, Ikram El Yazidi-Belkoura
The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes. O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins. Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels...
March 9, 2018: Journal of Bioenergetics and Biomembranes
Mitsunobu Nakamura, Fuyuki Ota, Tadao Takada, Kazuo Akagi, Kazushige Yamana
In this report, we describe the circularly polarized luminescence (CPL) of the RNA duplexes having one to four 2'-O-pyrene modified uridines (Upy) and the DNA duplexes having two, four, and six pyrene modified non-nucleosidic linkers (Py). Both the pyrene π-stack arrays formed on the RNA and DNA double helical structures exhibited pyrene excimer fluorescence. In the pyrene-modified RNA systems, the RNA duplex having four Upys gives CPL emission with glum value of <0.01 at 480 nm. The structure of pyrene stacks on the RNA duplex may be rigidly regulated with increase in the Upy domains, which resulted in the CPL emission...
March 9, 2018: Chirality
Femke M de Man, Andrew K L Goey, Ron H N van Schaik, Ron H J Mathijssen, Sander Bins
Since its clinical introduction in 1998, the topoisomerase I inhibitor irinotecan has been widely used in the treatment of solid tumors, including colorectal, pancreatic, and lung cancer. Irinotecan therapy is characterized by several dose-limiting toxicities and large interindividual pharmacokinetic variability. Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself. Several phase I and II enzymes, including cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A, are involved in the formation of inactive metabolites, making its metabolism prone to environmental and genetic influences...
March 8, 2018: Clinical Pharmacokinetics
Hua Fu, Jing Hu, Min Zhang, Yuerong Wang, Hongyang Zhang, Ping Hu
For enrichment and separation of cis -diol-containing compounds from biomatrix, a new type of magnetic nanoparticles named MS-48-PBSC, whichwas facilely prepared in a one-step heterogeneous reaction. The morphology results demonstrated that the MS-48-PBSC was a spherical nanomaterial containing a core of silica-coated magnetic particle with a diameter of about 200 nm, and a cover layer of mesoporous silica with a thickness of approximate 50 nm. The characterization results showed that MS-48-PBSC presented a pore size of 4...
March 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Tapaswini Nayak, Lingaraja Jena, Pranita Waghmare, Bhaskar C Harinath
Background: The Mycobacterium tuberculosis (MTB) uridine diphosphogalactofuranose (UDP)-galactopyranose mutase (UGM) is an essential flavoenzyme for mycobacterial viability and an important component of cell wall. It catalyzes the interconversion of UDP-galactopyranose into UDP-galactofuranose, a key building block for cell wall construction, essential for linking the peptidoglycan and mycolic acid cell wall layers in MTB through a 2-keto intermediate. Further, as this enzyme is not present in humans, it is an excellent therapeutic target for MTB...
January 2018: International Journal of Mycobacteriology
Uche Godfrey Okeke, Deniz Akdemir, Ismail Rabbi, Peter Kulakow, Jean-Luc Jannink
The HarvestPlus program for cassava ( Crantz) fortifies cassava with β-carotene by breeding for carotene-rich tubers (yellow cassava). However, a negative correlation between yellowness and dry matter (DM) content has been identified. We investigated the genetic control of DM in white and yellow cassava. We used regional heritability mapping (RHM) to associate DM with genomic segments in both subpopulations. Significant segments were subjected to candidate gene analysis and candidates were validated with prediction accuracies...
March 2018: Plant Genome
Martina Dvořáčková, Jiří Fajkus
Thanks to recent innovative methodologies, key cellular processes such as replication or transcription can be visualized directly in situ in intact tissues. Many studies use so-called click iT chemistry where nascent DNA can be tracked by 5-ethynyl-2'-deoxyuridine (EdU), and nascent RNA by 5-ethynyl uridine (EU). While the labeling of replicating DNA by EdU has already been well established and further exploited in plants, the use of EU to reveal nascent RNA has not been developed to such an extent. In this article, we present a protocol for labeling of nucleolar RNA transcripts using EU and show that EU effectively highlights the nucleolus...
2018: Frontiers in Plant Science
Claire Domenger, Marine Allais, Virginie François, Adrien Léger, Emilie Lecomte, Marie Montus, Laurent Servais, Thomas Voit, Philippe Moullier, Yann Audic, Caroline Le Guiner
Non-coding uridine-rich small nuclear RNAs (UsnRNAs) have emerged in recent years as effective tools for exon skipping for the treatment of Duchenne muscular dystrophy (DMD), a degenerative muscular genetic disorder. We recently showed the high capacity of a recombinant adeno-associated virus (rAAV)-U7snRNA vector to restore the reading frame of the DMD mRNA in the muscles of DMD dogs. We are now moving toward a phase I/II clinical trial with an rAAV-U7snRNA-E53, carrying an antisense sequence designed to hybridize exon 53 of the human DMD messenger...
March 2, 2018: Molecular Therapy. Nucleic Acids
Xiaogang Liu, Cailing Lin, Xiaodi Ma, Yan Tan, Jiuzhao Wang, Ming Zeng
Fruits of sweet orange ( Citrus sinensis ), a popular commercial Citrus species, contain high concentrations of flavonoids beneficial to human health. These fruits predominantly accumulate O -glycosylated flavonoids, in which the disaccharides [neohesperidose (rhamnosyl-α-1,2-glucose) or rutinose (rhamnosyl-α-1,6-glucose)] are linked to the flavonoid aglycones through the 3- or 7-hydroxyl sites. The biotransformation of the flavonoid aglycones into O -rutinosides or O -neohesperidosides in the Citrus plants usually consists of two glycosylation reactions involving a series of uridine diphosphate-sugar dependent glycosyltransferases (UGTs)...
2018: Frontiers in Plant Science
Sailendra Nath Sarma, Ammar Saleem, Jin-Yong Lee, Maki Tokumoto, Gi-Wook Hwang, Hing Man Chan, Masahiko Satoh
Cadmium (Cd) is a common environmental pollutant with known toxic effects on the kidney. Urinary metabolomics is a promising approach to study mechanism by which Cd-induced nephrotoxicity. The aim of this study was to elucidate the mechanism of Cd toxicity and to develop specific biomarkers by identifying urinary metabolic changes after a long-term of Cd exposure and with the critical concentration of Cd in the kidney. Urine samples were collected from wild-type 129/Sv mice after 67 weeks of 300 ppm Cd exposure and analyzed by ultra performance liquid chromatography connected with quadrupole time of flight mass spectrometer (UPLC-QTOF-MS) based metabolomics approach...
2018: Journal of Toxicological Sciences
Gregory F Pirrone, Rose M Mathew, Alexey A Makarov, Frank Bernardoni, Artis Klapars, Robert Hartman, John Limanto, Erik L Regalado
Impurity fate and purge studies are critical in order to establish an effective impurity control strategy for approval of the commercial filing application of new medicines. Reversed phase liquid chromatography-diode array-mass spectrometry (RPLC-DAD-MS) has traditionally been the preferred tool for impurity fate mapping. However, separation of some reaction mixtures by LC can be very problematic requiring combination LC-UV for area % analysis and a different LC-MS method for peak identification. In addition, some synthetic intermediates might be chemically susceptible to the aqueous conditions used in RPLC separations...
February 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Rachel Chen
Oligosaccharides, in either free or bound forms, play crucial roles in a wide range of biological processes. Increasing appreciation of their roles in cellular communication, interaction, pathogenesis, and prebiotic functions has stimulated tremendous interests in their synthesis. Pure and structurally defined oligosaccharides are essential for fundamental studies. On the other hand, for those with near term medical and nutraceutical applications, their large-scale synthesis is necessary. Unfortunately, oligosaccharides are notoriously difficult in their synthesis, and their enormous diverse structures leave a vast gap between what have been synthesized in laboratory and those present in various biological systems...
February 23, 2018: Applied Microbiology and Biotechnology
Joana Rocha, Milène Nitenberg, Agnès Girard-Egrot, Juliette Jouhet, Eric Maréchal, Maryse A Block, Christelle Breton
A unique feature of chloroplasts is their high content of the galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), which constitute up to 80% of their lipids. These galactolipids are synthesized in the chloroplast envelope membrane through the concerted action of galactosyltransferases, the so-called 'MGDG synthases (MGDs)' and 'DGDG synthases (DGDs),' which use uridine diphosphate (UDP)-galactose as donor. In Arabidopsis leaves, under standard conditions, the enzymes MGD1 and DGD1 provide the bulk of galactolipids, necessary for the massive expansion of thylakoid membranes...
2018: Frontiers in Plant Science
Annette Korsholm Mouritsen, Alexander Siegfried Busch, Lise Aksglaede, Ewa Rajpert-De Meyts, Anders Juul
OBJECTIVE: Only a few genetic loci are known to be associated with male pubertal events. The ability of excreting testosterone (T) and other steroids in the urine depends on sulfation and glucuronidation. One of several essential glucuronidases is encoded by the UGT2B17 gene. In a preliminary report, we found that homozygous deletion of UGT2B17 in boys was associated with lower urinary excretion of T. We hypothesized that boys with a lower glucuronidation capacity may have altered androgen action and excretion affecting pubarche, as this represents a T dependent event...
February 21, 2018: Endocrine Connections
Morgane Placet, Guillaume Arguin, Caroline M Molle, Jean-Philippe Babeu, Christine Jones, Julie C Carrier, Bernand Robaye, Sameh Geha, Francois Boudreau, Fernand-Pierre Gendron
Colorectal tumors are immersed in an array of tumor-promoting factors including extracellular nucleotides such as uridine 5'‑diphosphate (UDP). UDP is the endogenous agonist of the G protein-coupled P2Y 6 receptor (P2Y 6 R), which may contribute to the formation of a tumor-promoting microenvironment by coordinating resistance to apoptosis. Colorectal cancer (CRC) was chemically induced in P2ry6 knockout (P2ry6 -/- ) mice using azoxymethane and dextran sulfate sodium challenges. Mice were euthanatized and their tumor load determined...
February 14, 2018: Biochimica et Biophysica Acta
Jenny A Greig, Jayme M L Nordin, Christine Draper, Peter Bell, James M Wilson
Adeno-associated viral (AAV) vectors can target the liver, making them an attractive platform for gene therapy approaches that require the correction of hepatocytes. Crigler-Najjar syndrome is an autosomal recessive disorder of bilirubin metabolism that occurs when the liver's uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) enzyme activity is partially or completely absent. This syndrome is characterized by elevated bilirubin levels in the blood. We developed an AAV8 vector expressing a codon-optimized human version of UGT1A1 from a liver-specific promoter...
February 16, 2018: Human Gene Therapy
Yuichi Yokoyama, Yoshifumi Sasaki, Natsuko Terasaki, Taku Kawataki, Koji Takekawa, Yumiko Iwase, Toshinobu Shimizu, Seigo Sanoh, Shigeru Ohta
Differentiated HepaRG cells maintain liver-specific functions such as drug-metabolizing enzymes. In this study, the feasibility of HepaRG cells as a human hepatocyte model for in vitro toxicity assessment was examined using selected hepatotoxic compounds. First, basal drug-metabolizing enzyme activities (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, uridine 5'-diphospho-glucuronosyltransferase [UGT], and sulfotransferases [SULT]) were measured in HepaRG, human hepatocytes, and HepG2 cells. Enzyme activities in differentiated HepaRG cells were comparable to those in human hepatocytes and much higher than those in HepG2 cells, except for SULT activity...
February 14, 2018: Biological & Pharmaceutical Bulletin
Koji Izumi, Satoshi Inoue, Hiroki Ide, Kazutoshi Fujita, Taichi Mizushima, Guiyang Jiang, Seiji Yamaguchi, Hiroaki Fushimi, Norio Nonomura, Hiroshi Miyamoto
OBJECTIVE: To determine the expression status of uridine 5'diphospho-glucuronosyltransferase 1A, a major phase II drug metabolism enzyme, in upper urinary tract urothelial carcinoma, as well as to assess its prognostic significance. METHODS: We immunohistochemically stained for uridine 5'diphospho-glucuronosyltransferase 1A in tissue microarray consisting of 99 upper urinary tract urothelial carcinoma samples and paired non-neoplastic urothelial tissues. We also assessed the effect of uridine 5'diphospho-glucuronosyltransferase 1A knockdown on urothelial cancer cell growth...
February 14, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
Fong-Chin Huang, Ashok Giri, Melina Daniilidis, Guangxin Sun, Katja Härtl, Thomas Hoffmann, Wilfried Schwab
Glycosylation mediated by uridine diphosphate-dependent glycosyltransferase (UGT) is one of the most common reactions for the biosynthesis of small molecule glycosides. As glycosides have various biological roles we characterized UGTs from grapevine (Vitis vinifera). In silico analysis of VvUGTs that were highly expressed in leaves identified UGT92G6 which showed sequence similarity to both, monosaccharide and disaccharide glucoside forming transferases. The recombinant UGT92G6 glucosylated phenolics, among them caffeic acid, carvacrol, eugenol, and raspberry ketone, and also accepted geranyl glucoside and citronellyl glucoside...
February 10, 2018: Plant & Cell Physiology
Gokila Devi Mathialagan, Narkunaraja Shanmugam
Diabetes, a chronic metabolic disorder associated with significantly accelerated rates of inflammation. Gold nanoparticle plays a crucial role in biomedical applications. We described the development of hetero-functionalized gold nanoparticles (hfAuNPs) for targeted selective gene silencing by RNAi interference. This hfAuNPs was developed by parallelly conjugating biotinylated ARE-siRNA (siRNA to Adenosine Uridine-rich elements) and biotinylated RAGE interacting-peptide (RIP) to streptavidin coated gold nanoparticles (aAuNPs) thus forms a complex that provides biocompatibility and functionality in a physiological environment...
May 1, 2018: Journal of Nanoscience and Nanotechnology
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