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https://www.readbyqxmd.com/read/30327117/surface-plasmon-resonance-biosensor-for-the-accurate-and-sensitive-quantification-of-o-glcnac-based-on-cleavage-by-%C3%AE-d-n-acetylglucosaminidase
#1
Li Gao, Ruihuan Zhao, Yiwen Wang, Mei Lu, Dingding Yang, Mengmei Fa, Xin Yao
Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.). However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult. In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed...
December 21, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/30305725/il-8-induced-o-glcnac-modification-via-glut3-and-gfat-regulates-cancer-stem-cell-like-properties-in-colon-and-lung-cancer-cells
#2
Masahiro Shimizu, Nobuyuki Tanaka
Interleukin-8 (IL-8) is a pro-inflammatory chemokine that is associated with induction of chemotaxis and degranulation of neutrophils. IL-8 is overexpressed in many tumors, including colon and lung cancer, and recent studies demonstrated essential roles for IL-8 in tumor progression within the tumor microenvironment. However, the molecular mechanism underlying the functions of IL-8 in tumor progression is unclear. In this study, we found that IL-8 is overexpressed in colon and lung cancer cells with cancer stem cell (CSC)-like characteristics and is required for CSC properties, including tumor-initiating abilities...
October 10, 2018: Oncogene
https://www.readbyqxmd.com/read/30298013/-o-glcnac-modification-during-pregnancy-focus-on-placental-environment
#3
Victor Vitorino Lima, Vanessa Dela Justina, Rinaldo Rodrigues Dos Passos, Gustavo Tadeu Volpato, Paula Cristina S Souto, Sebastian San Martin, Fernanda Regina Giachini
Successful placentation is a key event for fetal development, which commences following embryo implantation into the uterine wall, eliciting decidualization, placentation, and remodeling of blood vessels to provide physiological exchange between embryo-fetus and mother. Several signaling pathways are recruited to modulate such important processes and specific proteins that regulate placental function are a target for the glycosylation with O- linked β-N-acetylglucosamine ( O- GlcNAc), or O- GlcNAcylation. This is a reversible post-translational modification on nuclear and cytoplasmic proteins, mainly controlled by O- GlcNAc transferase (OGT) and O- GlcNAcase (OGA)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30296064/direct-one-step-fluorescent-labeling-of-o-glcnac-modified-proteins-in-live-cells-using-metabolic-intermediates
#4
Hong Yee Tan, Razieh Eskandari, David Shen, Yanping Zhu, Ta-Wei Liu, Lianne I Willems, Matthew G Alteen, Zarina Madden, David J Vocadlo
The modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology. Metabolic labeling strategies to monitor O-GlcNAcylation in cells has proven of great value for uncovering the molecular roles of O-GlcNAc. These strategies rely on two-step labeling procedures, which limits the scope of experiments that can be performed. Here we report on the creation of fluorescent uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore...
October 8, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/30286322/in-silico-analysis-of-pax6-protein-glycosylation-in-vertebrates
#5
Muhammet Uslupehlivan, Ecem Şener, Remziye Deveci
Pax6 is a transcription factor that involves in the formation of the eye, brain, and central nervous system in vertebrates. Due to various roles in the eye morphogenesis, Pax6 interacts with DNA and various transcription factors via post-translational modifications. Post-translational modifications of Pax6 have been studied extensively but there is a paucity of information about the glycosylation. Here, we focused on predicting the glycosylation positions of Pax6 protein in vertebrates. Also, 3D protein and glycoprotein models were generated using I-TASSER and GLYCAM servers in order to understand the effect of glycosylation on the Pax6 protein structure...
September 27, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/30285435/structure-based-evolution-of-low-nanomolar-o-glcnac-transferase-inhibitors
#6
Sara E S Martin, Zhi-Wei Tan, Harri M Itkonen, Damien Y Duveau, Joao A Paulo, John Janetzko, Paul L Boutz, Lisa Törk, Frederick A Moss, Craig J Thomas, Steven P Gygi, Michael B Lazarus, Suzanne Walker
Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans. One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function. Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity. In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development...
October 4, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/30258536/synthetic-glycopeptides-allow-for-the-quantitation-of-scarce-nonfucosylated-igg-fc-n-glycans-of-therapeutic-antibody
#7
Kazuki Hammura, Akari Ishikawa, Ravi Kumar H V, Risho Miyoshi, Yasuhiro Yokoi, Masakazu Tanaka, Hiroshi Hinou, Shin-Ichiro Nishimura
Glycans attached to the IgG Fc domain affect strongly biological activities such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of therapeutic antibodies. However, molecular mechanism in the glycoform-dependent functional modulation of the IgGs remains elusive. The present study communicates that selected reaction monitoring (SRM)-based assay of tryptic IgG Fc glycopeptides is a promising approach for the characterization of antibodies when combined with structure-defined synthetic Fc peptides having a focused N -glycoform as a calibration standard...
September 13, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/30250906/the-decisive-role-of-fumarase-responsive-signaling-to-glucose-deficiency
#8
Qiujing Yu, Ting Wang, Yuhui Jiang
Our recent study shows that AMPK normally phosphorates fumarase (FH) at Ser75 under glucose deprivation, resulting in FH-ATF2 complex formation that facilitates transcription for cell growth arrest. Meanwhile, O-GlcNAc transferase can compete with AMPK to O-GlcNAcylate FH. In tumor cells, FH is highly O-GlcNAcylated and is proinhibited from AMPK-ATF2 signaling.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30250452/nutrient-driven-o-glcnacylation-at-promoters-impacts-genome-wide-rna-pol-ii-distribution
#9
Michael W Krause, Dona C Love, Salil K Ghosh, Peng Wang, Sijung Yun, Tetsunari Fukushige, John A Hanover
Nutrient-driven O -GlcNAcylation has been linked to epigenetic regulation of gene expression in metazoans. In C. elegans, O -GlcNAc marks the promoters of over 800 developmental, metabolic, and stress-related genes; these O -GlcNAc marked genes show a strong 5', promoter-proximal bias in the distribution of RNA Polymerase II (Pol II). In response to starvation or feeding, the steady state distribution of O -GlcNAc at promoters remain nearly constant presumably due to dynamic cycling mediated by the transferase OGT-1 and the O -GlcNAcase OGA-1...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30241321/chemical-reporters-and-their-bioorthogonal-reactions-for-labeling-protein-o-glcnacylation
#10
REVIEW
Eun Ju Kim
Protein O -GlcNAcylation is a non-canonical glycosylation of nuclear, mitochondrial, and cytoplasmic proteins with the attachment of a single O -linked β- N -acetyl-glucosamine ( O -GlcNAc) moiety. Advances in labeling and identifying O -GlcNAcylated proteins have helped improve the understanding of O -GlcNAcylation at levels that range from basic molecular biology to cell signaling and gene regulation to physiology and disease. This review describes these advances in chemistry involving chemical reporters and their bioorthogonal reactions utilized for detection and construction of O -GlcNAc proteomes in a molecular mechanistic view...
September 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30237786/real-talk-the-inter-play-between-the-mtor-ampk-and-hexosamine-biosynthetic-pathways-in-cell-signaling
#11
REVIEW
Gentry K Cork, Jeffrey Thompson, Chad Slawson
O-linked N-acetylglucosamine, better known as O-GlcNAc, is a sugar post-translational modification participating in a diverse range of cell functions. Disruptions in the cycling of O-GlcNAc mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively, is a driving force for aberrant cell signaling in disease pathologies, such as diabetes, obesity, Alzheimer's disease, and cancer. Production of UDP-GlcNAc, the metabolic substrate for OGT, by the Hexosamine Biosynthetic Pathway (HBP) is controlled by the input of amino acids, fats, and nucleic acids, making O-GlcNAc a key nutrient-sensor for fluctuations in these macromolecules...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30231545/effects-of-acute-cold-stress-on-liver-o-glcnacylation-and-glycometabolism-in-mice
#12
Ruizhi Yao, Yuying Yang, Shuai Lian, Hongzhao Shi, Peng Liu, Yang Liu, Huanmin Yang, Shize Li
Protein O -linked β- N -acetylglucosamine glycosylation ( O -GlcNAcylation) regulates many biological processes. Studies have shown that O -GlcNAc modification levels can increase during acute stress and suggested that this may contribute to the survival of the cell. This study investigated the possible effects of O -GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress. Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined...
September 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30224358/the-conserved-threonine-rich-region-of-the-hcf-1-pro-repeat-activates-promiscuous-ogt-udp-glcnac-glycosylation-and-proteolysis-activities
#13
Vaibhav Kapuria, Ute F Röhrig, Patrice Waridel, Fabienne Lammers, Vladimir S Borodkin, Daan M F van Aalten, Vincent Zoete, Winship Herr
O-linked N-acetylglucosamine transferase (OGT) possesses dual glycosyltransferase-protease activities. OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1). Here, we probed the relationship between these distinct glycosylation and proteolytic activities. For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region...
September 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30221662/o-glcnac-modified-snap29-inhibits-autophagy-mediated-degradation-via-the-disturbed-snap29-stx17-vamp8-complex-and-exacerbates-myocardial-injury-in-type-i-diabetic-rats
#14
Lin Huang, Ping Yuan, Peng Yu, Qiling Kong, Zixuan Xu, Xia Yan, Yang Shen, Juesheng Yang, Rong Wan, Kui Hong, Yanhua Tang, Jinzhu Hu
The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated. The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury. A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg)...
September 7, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30214079/congenital-diseases-caused-by-defective-o-glycosylation-of-notch-receptors
#15
REVIEW
Yuko Tashima, Tetsuya Okajima
The Notch signaling pathway is highly conserved and essential for animal development. It is required for cell differentiation, survival, and proliferation. Regulation of Notch signaling is a crucial process for human health. Ligands initiate a signal cascade by binding to Notch receptors expressed on a neighboring cell. Notch receptors interact with ligands through their epidermal growth factor-like repeats (EGF repeats). Most EGF repeats are modified by O -glycosylation with residues such as O -linked N -acetylglucosamine ( O -GlcNAc), O -fucose, and O -glucose...
August 2018: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/30199580/chemical-and-biochemical-strategies-to-explore-the-substrate-recognition-of-o-glcnac-cycling-enzymes
#16
Chia-Wei Hu, Matthew Worth, Hao Li, Jiaoyang Jiang
The O-linked N-acetylglucosamine (O-GlcNAc) modification is an essential component in cell regulation. A single pair of human enzymes conducts this modification dynamically on a broad variety of proteins: O-GlcNAc transferase (OGT) adds the GlcNAc residue and O-GlcNAcase (OGA) hydrolyzes it. This modification is dysregulated in many diseases, but its exact role on particular substrates remains unclear. In addition, no apparent sequence motif was found in the modified proteins and the factors controlling the substrate specificity of OGT and OGA are largely unknown...
September 10, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/30186544/remote-ischemic-preconditioning-ameliorates-acute-kidney-injury-due-to-contrast-exposure-in-rats-through-augmented-o-glcnacylation
#17
Jiachang Hu, Yimei Wang, Shuan Zhao, Jing Chen, Shi Jin, Ping Jia, Xiaoqiang Ding
Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs. O-linked β -N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions. Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective. The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/30181664/the-effects-of-o-glcnac-alteration-on-alzheimer-like-neurodegeneration-in-sk-n-sh-cells
#18
Nan Ding, Peng Peng, Yu-Jing Chu, Jing-Jing Wang, Shu-Yi Chen, Renuka Arulthas, Yan-Qiu Deng
BACKGROUND: O-GlcNAcylation is a highly dynamic post-translational modification that plays a key role in regulating phosphorylation of protein and cell survival. The proteins O-GlcNAcylation level is regulated dynamically by O-GlcNAc transferase (OGT) and β-N-acetylglucosaminidase (O-GlcNAcase, OGA). Although previous studies have suggested the role of O-GlcNAcylation in neurodegenerative diseases, the mechanism of O-GlcNAcylation in Alzheimer's disease (AD) remains unclear. METHODS: The decrease of O-GlcNAcylation by alloxan, an OGT inhibitor, and increase by NAG-thiazolines (NAG-Ae), an O-GlcNAcase inhibitor were tested to investigate the effects of O-GlcNAc alteration on AD like neurodegeneration in SK-N-SH cells...
September 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/30177911/apart-from-rhoptries-identification-of-toxoplasma-gondii-s-o-glcnacylated-proteins-reinforces-the-universality-of-the-o-glcnacome
#19
Moyira Osny Aquino-Gil, Mattis Kupferschmid, Hosam Shams-Eldin, Jörg Schmidt, Nao Yamakawa, Marlène Mortuaire, Frédéric Krzewinski, Stéphan Hardivillé, Edgar Zenteno, Christian Rolando, Fabrice Bray, Eduardo Pérez Campos, Jean-François Dubremetz, Yobana Perez-Cervera, Ralph T Schwarz, Tony Lefebvre
O -linked β-N-acetylglucosaminylation or O -GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations. The functions managed by O -GlcNAcylation are diverse and include regulation of transcription, replication, protein's fate, trafficking, and signaling. More and more evidences tend to show that deregulations in the homeostasis of O -GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies. O -GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30176726/transcriptomic-analysis-reveals-the-pathways-associated-with-resisting-and-degrading-microcystin-in-ochromonas
#20
Lu Zhang, Kai Lyu, Na Wang, Lei Gu, Yunfei Sun, Xuexia Zhu, Jun Wang, Yuan Huang, Zhou Yang
Toxic Microcystis bloom is a tough environment problem worldwide. Microcystin is highly toxic and is an easily accumulated secondary metabolite of toxic Microcystis that threatens water safety. Biodegradation of microcystin by protozoan grazing is a promising and efficient biological method, but the mechanism in this process is still unclear. The present study aimed to identify potential pathways involved in resisting and degrading microcystin in flagellates through transcriptomic analyses. A total of 999 unigenes were significantly differentially expressed between treatments with flagellates Ochromonas fed on microcystin-producing Microcystis and microcystin-free Microcystis...
October 2, 2018: Environmental Science & Technology
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