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https://www.readbyqxmd.com/read/28648830/purinergic-p2y-receptors-molecular-diversity-and-implications-for-treatment-of-cardiovascular-diseases
#1
REVIEW
Akiyuki Nishimura, Caroline Sunggip, Sayaka Oda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes...
June 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28646159/yvck-a-protein-required-for-cell-wall-integrity-and-optimal-carbon-source-utilization-binds-uridine-diphosphate-sugars
#2
Elodie Foulquier, Anne Galinier
In Bacillus subtilis, Listeria monocytogenes and in two Mycobacteria, it was previously shown that yvcK is a gene required for normal cell shape, for optimal carbon source utilization and for virulence of pathogenic bacteria. Here we report that the B. subtilis protein YvcK binds to Uridine diphosphate-sugars like Uridine diphosphate-Glucose (UDP-Glc) and Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) in vitro. Using the crystal structure of Bacillus halodurans YvcK, we identified residues involved in this interaction...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642338/cellular-distribution-and-function-of-ion-channels-involved-in-transport-processes-in-rat-tracheal-epithelium
#3
Anne Hahn, Johannes Faulhaber, Lalita Srisawang, Andreas Stortz, Johanna J Salomon, Marcus A Mall, Stephan Frings, Frank Möhrlen
Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca(2+) or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca(2+)- dependent and cAMP- dependent Cl(-) secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca(2+)-gated Cl(-) channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel, the epithelial Na(+) channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28639893/apobec-1-complementation-factor-regulates-cell-migration-and-apoptosis-through-dickkopf1-by-acting-on-its-3-untranslated-region-in-mcf7-cells
#4
Xin Yan, Qianyin Li, Dongsheng Ni, Yajun Xie, Qingling He, Qianya Wan, Yamin Liu, Zhongshi Lyu, Zhaomin Mao, Qin Zhou
A1CF (apobec-1 complementation factor) acts as a component of the apolipoprotein-B messenger RNA editing complex. Previous researches mainly focused on its post-transcriptional cytidine to uridine RNA editing. However, few study reported its role in progression of breast carcinoma cells. Wound healing assay and flow cytometry were applied to detect the migration and apoptosis; western blot, real-time polymerase chain reaction, and dual-luciferase assays were applied to investigate the potential regulation mechanism of A1CF-mediated cell migration and apoptosis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28634361/uridine-ameliorates-dextran-sulfate-sodium-dss-induced-colitis-in-mice
#5
Manish Kumar Jeengar, Dinesh Thummuri, Mattias Magnusson, V G M Naidu, Srinivas Uppugunduri
Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627229/cobicistat-versus-ritonavir-similar-pharmacokinetic-enhancers-but-some-important-differences
#6
Alice Tseng, Christine A Hughes, Janet Wu, Jason Seet, Elizabeth J Phillips
OBJECTIVE: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed. DATA SOURCES: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28622881/discovery-of-%C3%AE-d-2-deoxy-2-dichlorouridine-nucleotide-prodrugs-as-potent-inhibitors-of-hepatitis-c-virus-replication
#7
Pedro Pinho, Genadiy Kalayanov, Hans Westerlind, Åsa Rosenquist, Horst Wähling, Christian Sund, Maria Almeida, Susana Ayesa, Jan Tejbrant, Paul Targett-Adams, Anders Eneroth, Annelie Lindqvist
Discovery of sofosbuvir has radically changed hepatitis C treatment and nucleoside/tide NS5B inhibitors are now viewed as one of the key components in combination therapies with other direct-acting antiviral agents. As part of our program to identify new nucleoside inhibitors of HCV replication, we now wish to report on the discovery of β-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of HCV replication. Although, cytidine analogues have long been recognized to be metabolized to both cytidine and uridine triphosphates through the action of cytidine deaminase, uridine analogues are generally believed to produce exclusively uridine triphosphate...
May 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28621641/colistin-resistance-in-pseudomonas-aeruginosa-that-is-not-linked-to-arnb
#8
Eun Seon Chung, Ji-Young Lee, Ji-Young Rhee, Kwan Soo Ko
PURPOSE: It is known that the arnB (or pmrH) gene encoding uridine 5'-(beta-1-threo-pentapyranosyl-4-ulose diphosphate) aminotransferase plays a critical role in colistin resistance in Pseudomonas aeruginosa through the addition of 4-amino-4-deoxy-l-arabinose (l-Ara4N) to lipid A. In this study, we attempted to obtain a colistin-resistant mutant from an arnB-deleted mutant through exposure to colistin. METHODOLOGY: We constructed an arnB deletion mutant (P5ΔarnB :: nptIII) from a colistin-susceptible strain (P5) by allelic replacement mutagenesis, and colistin-resistant mutants were selected in vitro using P5 and P5ΔarnB :: nptIII...
June 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28614728/triterpenoid-saponins-and-other-glycosides-from-the-stems-and-bark-of-jaffrea-xerocarpa-and-their-biological-activity
#9
Dima Muhammad, Nathalie Lalun, Hélène Bobichon, Elisabeth Le Magrex Debar, Sophie C Gangloff, Mohammed Nour, Laurence Voutquenne-Nazabadioko
Six previously undescribed triterpenoid saponins and two previously undescribed norlupane triterpenes were isolated with five known saponins, three known lupane derivatives, 17,20-didehydro-20-deoxyjujubogenin, rutin, (±) 3α-O-β-d-glucopyranosyl-lyoniresinol, (±) 4-O-β-d-glucopyranosyl-maesopsin, three phenol glycosides, and uridine from the stems and bark of Jaffrea xerocarpa (Baill.) H. C. Hopkins & Pillon (= Basionym Alphitonia xerocarpus Baill.) (Rhamnaceae), an endemic tree of New Caledonia. The chemical structures of the purified compounds were identified by nuclear magnetic resonance and mass spectrometry...
June 11, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28611824/posttranscriptional-regulation-controls-calretinin-expression-in-malignant-pleural-mesothelioma
#10
Jelena Kresoja-Rakic, Merve Sulemani, Michaela B Kirschner, Manuel Ronner, Glen Reid, Steven Kao, Beat Schwaller, Walter Weder, Rolf A Stahel, Emanuela Felley-Bosco
Calretinin (CALB2) is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM). We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide) 3' untranslated region (3'UTR) predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE) in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3'UTR in the posttranscriptional regulation of calretinin expression in MPM...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28608671/conformational-control-of-udp-galactopyranose-mutase-inhibition
#11
Kittikhun Wangkanont, Valerie J Winton, Katrina T Forest, Laura L Kiessling
UDP-galactopyranose mutase (Glf or UGM) catalyzes the formation of uridine 5'-diphosphate-α-D-galactofuranose (UDP-Galf) from UDP-galactopyranose (UDP-Galp). The enzyme is required for the production of Galf-containing glycans. UGM is absent in mammals, but members of the Corynebacterineae suborder require UGM for cell envelope biosynthesis. The need for UGM in some pathogens has prompted the search for inhibitors that could serve as antibiotic leads. Optimizing inhibitor potency, however, has been challenging...
June 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28608332/analysis-of-the-uridylation-of-both-argonaute-bound-mirnas-and-5-cleavage-products-of-their-target-rnas-in-plants
#12
Guodong Ren, Xiaoyan Wang, Bin Yu
Uridylation (3' untemplated uridine addition) provides a mechanism to trigger the degradation of miRNAs and the 5' cleavage products (5' CP) that are produced from miRNA-directed ARGONAUTE (AGO) cleavage of target RNAs. We have recently shown that HEN1 SUPPRESSOR 1 (HESO1), a terminal uridylyltransferase, and its homolog UTP:RNA uridylyltransferase 1 (URT1) catalyze the uridylation of miRNAs and 5' CPs within the AGO complex in higher plants. In this chapter, we describe detailed protocols for analyzing 3' end uridylation of both AGO-bound miRNAs and 5' CP...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28607633/pterostilbene-4-%C3%AE-glucoside-protects-against-dss-induced-colitis-via-induction-of-tristetraprolin
#13
Yingqing Chen, Jeongmin Park, Yeonsoo Joe, Hyeok-Jun Park, Seung-Joo Jekal, Daisuke Sato, Hiroki Hamada, Hun Taeg Chung
Pterostilbene, a dimethyl ester analog of resveratrol, has anti-inflammatory and antioxidative effects and alters cell proliferation. Tristetraprolin (TTP) promotes the degradation of proinflammatory mediators via binding to adenosine and uridine- (AU-) rich elements (ARE) located in the 3'-untranslated regions of mRNAs. Here, we utilized pterostilbene 4'-β-glucoside (4-PG), a compound derived from pterostilbene, to investigate whether it has anti-inflammatory effects on dextran sulfate sodium- (DSS-) induced colitis via TTP enhancement...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28604971/-a-case-of-bw39-subtype-caused-by-562c-to-t-mutation-of-exon-7-of-%C3%AE-1-3-d-galactosyltransferase-gene
#14
Bijin Wang, Lili Shi, Lin Wang, Yanchun Liu, Ling Ma, Ruoyang Zhang
OBJECTIVE: To analyze a sample with ABO subgroup using serological and molecular methods. METHODS: The ABO phenotype of the sample was determined with a tube method, and the activity of glycosyltransferases was determined with an uridine diphosphate galactose transferring method. The ABO gene of the propositus was identified by PCR with sequence-specific primers (PCR-SSP). In addition, exons 6 and 7 of the ABO gene were cloned and sequenced. RESULTS: Neither A nor B antigen was identified in the propositus, despite that its anti-B antibody was found to be attenuated...
June 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28601222/synthesis-function-and-heterogeneity-of-snorna-guided-posttranscriptional-nucleoside-modifications-in-eukaryotic-ribosomal-rnas
#15
Anthony K Henras, Célia Plisson-Chastang, Odile Humbert, Yves Romeo, Yves Henry
Ribosomal RNAs contain numerous 2'-O-methylated nucleosides and pseudouridines. Methylation of the 2' oxygen of ribose moieties and isomerization of uridines into pseudouridines are catalyzed by C/D and H/ACA small nucleolar ribonucleoprotein particles, respectively. We review the composition, structure, and mode of action of archaeal and eukaryotic C/D and H/ACA particles. Most rRNA modifications cluster in functionally crucial regions of the rRNAs, suggesting they play important roles in translation. Some of these modifications promote global translation efficiency or modulate translation fidelity...
2017: Enzymes
https://www.readbyqxmd.com/read/28601221/posttranscriptional-rna-pseudouridylation
#16
Meemanage D De Zoysa, Yi-Tao Yu
Pseudouridine (Ψ) is the most abundant posttranscriptional modification in noncoding RNAs. Pseudouridines are often clustered in important regions of rRNAs (ribosomal RNAs), snRNAs (small nuclear RNAs), and tRNAs (transfer RNAs), contributing to RNA function. Pseudouridylation is governed by two independent mechanisms. The first involves single protein enzymes called pseudouridine synthases (PUSs) that alone recognize the substrate and catalyze the isomerization of uridine to pseudouridine (RNA-independent pseudouridylation)...
2017: Enzymes
https://www.readbyqxmd.com/read/28599486/knockout-of-kr%C3%A3-ppel-like-factor-10-suppresses-hepatic-cell-proliferation-in-a-partially-hepatectomized-mouse-model
#17
Seung-Ho Heo, Eui-Suk Jeong, Kyoung-Sun Lee, Jin-Hee Seo, Woon-Kyu Lee, Yang-Kyu Choi
The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598848/synaptic-membrane-synthesis-in-rats-depends-on-dietary-sufficiency-of-vitamin-c-vitamin-e-and-selenium-relevance-for-alzheimer-s-disease
#18
Mehmet Cansev, Mesut Turkyilmaz, John W C Sijben, Cansu Sevinc, Laus M Broersen, Nick van Wijk
Chronic consumption of a diet enriched with nutritional precursors of phospholipids, including uridine and the polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), was shown previously to enhance levels of brain phospholipids and synaptic proteins in rodents. Vitamin C, vitamin E, and selenium may directly affect the breakdown or synthesis of membrane phospholipids. The present study investigated the necessity of antioxidants for the effectiveness of supplementation with uridine plus DHA and EPA (as fish oil) in rats...
June 9, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28595015/2-chloro-2-fluoro-ribonucleotide-prodrugs-with-potent-pan-genotypic-activity-against-hepatitis-c-virus-replication-in-culture
#19
Shaoman Zhou, Sawsan Mahmoud, Peng Liu, Longhu Zhou, Maryam Ehteshami, Leda Bassit, Sijia Tao, Robert A Domaoal, Ozkan Sari, Coralie De Schutter, Sheida Amiralaei, Ahmed Khalil, Olivia Ollinger Russell, Tamara R McBrayer, Tony Whitaker, Nageh Abou-Taleb, Franck Amblard, Steven J Coats, Raymond Felix Schinazi
Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a -D-2'-Cl,2'-F-uridine phosphoramidate nucleotide 16, as a non-toxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5'-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28590418/enhancement-of-x-ray-induced-apoptosis-by-mobile-phone-like-radio-frequency-electromagnetic-fields-in-mouse-spermatocyte-derived-cells
#20
Ke-Ying Zhang, Hui Xu, Le Du, Jun-Ling Xing, Bin Zhang, Qiang-Shan Bai, Yu-Qiao Xu, Yong-Chun Zhou, Jun-Ping Zhang, Yan Zhou, Gui-Rong Ding
To explore the combined effects of environmental radio-frequency (RF) field and X-ray, mouse spermatocyte-derived (GC-1) cells were exposed to 1950 MHz RF field at specific absorption rate (SAR) of 3 W/kg for 24 h combined with or without X-ray irradiation at 6 Gy. After treatment, the cell proliferation level was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) Assay and 5-Bromo-2-deoxy Uridine (BrdU) enzyme linked immunosorbent (ELISA) Assay. The apoptosis level was detected by annexin V flow cytometry assay, transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) Assay and Caspase-3 Activity Assay...
June 7, 2017: International Journal of Environmental Research and Public Health
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