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https://www.readbyqxmd.com/read/28202678/stress-induced-o-glcnacylation-an-adaptive-process-of-injured-cells
#1
REVIEW
Marissa R Martinez, Thiago Braido Dias, Peter S Natov, Natasha E Zachara
In the 30 years, since the discovery of nucleocytoplasmic glycosylation, O-GlcNAc has been implicated in regulating cellular processes as diverse as protein folding, localization, degradation, activity, post-translational modifications, and interactions. The cell co-ordinates these molecular events, on thousands of cellular proteins, in concert with environmental and physiological cues to fine-tune epigenetics, transcription, translation, signal transduction, cell cycle, and metabolism. The cellular stress response is no exception: diverse forms of injury result in dynamic changes to the O-GlcNAc subproteome that promote survival...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28195695/o-glcnacylation-of-%C3%AE-synuclein-at-serine-87-reduces-aggregation-without-affecting-membrane-binding
#2
Yuka E Lewis, Ana Galesic, Paul M Levine, Cesar A De Leon, Natalie Lamiri, Caroline K Brennan, Matthew R Pratt
The aggregation of neurodegenerative-disease associated proteins can be affected by many factors, including a variety of posttranslational modifications. One such modification, O-GlcNAcylation, has been found on some of these aggregation prone proteins, including α-synuclein, the major protein that plays a causative role in synucleinopathies like Parkinson's disease. We previously used synthetic protein chemistry to prepare α-synuclein bearing an homogeneous O-GlcNAc modification at threonine 72 and showed that this modification inhibits protein aggregation...
February 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28178567/defective-branched-chain-amino-acid-catabolism-disrupts-glucose-metabolism-and-sensitizes-the-heart-to-ischemia-reperfusion-injury
#3
Tao Li, Zhen Zhang, Stephen C Kolwicz, Lauren Abell, Nathan D Roe, Maengjo Kim, Bo Zhou, Yang Cao, Julia Ritterhoff, Haiwei Gu, Daniel Raftery, Haipeng Sun, Rong Tian
Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28159857/glycosylation-is-a-global-target-for-androgen-control-in-prostate-cancer-cells
#4
Jennifer Munkley
Changes in glycan composition are common in cancer and can play important roles in all of the recognised hallmarks of cancer. We recently identified glycosylation as a global target for androgen control in prostate cancer cells and further defined a set of 8 glycosylation enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly up-regulated in prostate cancer tissue. These 8 enzymes are under direct control of the androgen receptor (AR) and are linked to the synthesis of important cancer-associated glycans such as sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulphate...
February 3, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28154133/proteomic-analysis-reveals-o-glcnac-modification-on-proteins-with-key-regulatory-functions-in-arabidopsis
#5
Shou-Ling Xu, Robert J Chalkley, Jason C Maynard, Wenfei Wang, Weimin Ni, Xiaoyue Jiang, Kihye Shin, Ling Cheng, Dasha Savage, Andreas F R Hühmer, Alma L Burlingame, Zhi-Yong Wang
Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. However, the proteins and sites subject to this posttranslational modification are largely unknown. Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins...
February 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28150883/analysis-of-protein-o-glcnacylation-by-mass-spectrometry
#6
Junfeng Ma, Gerald W Hart
O-linked β-D-N-acetyl glucosamine (O-GlcNAc) addition (O-GlcNAcylation), a post-translational modification of serine/threonine residues of proteins, is involved in diverse cellular metabolic and signaling pathways. Aberrant O-GlcNAcylation underlies the initiation and progression of multiple chronic diseases including diabetes, cancer, and neurodegenerative diseases. Numerous methods have been developed for the analysis of protein O-GlcNAcylation, but instead of discussing the classical biochemical techniques, this unit covers O-GlcNAc characterization by combining several enrichment methods and mass spectrometry detection techniques [including collision-induced dissociation (CID), higher energy collision dissociation (HCD), and electron transfer dissociation (ETD) mass spectrometry]...
February 2, 2017: Current Protocols in Protein Science
https://www.readbyqxmd.com/read/28143929/o-glcnac-transferase-regulates-excitatory-synapse-maturity
#7
Olof Lagerlöf, Gerald W Hart, Richard L Huganir
Experience-driven synaptic plasticity is believed to underlie adaptive behavior by rearranging the way neuronal circuits process information. We have previously discovered that O-GlcNAc transferase (OGT), an enzyme that modifies protein function by attaching β-N-acetylglucosamine (GlcNAc) to serine and threonine residues of intracellular proteins (O-GlcNAc), regulates food intake by modulating excitatory synaptic function in neurons in the hypothalamus. However, how OGT regulates excitatory synapse function is largely unknown...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28135057/the-small-molecule-2-azido-2-deoxy-glucose-is-a-metabolic-chemical-reporter-of-o-glcnac-modifications-in-mammalian-cells-revealing-an-unexpected-promiscuity-of-o-glcnac-transferase
#8
Balyn W Zaro, Anna R Batt, Kelly N Chuh, Marisol X Navarro, Matthew R Pratt
Glycans can be directly labeled using unnatural monosaccharide analogs, termed metabolic chemical reporters (MCRs). These compounds enable the secondary visualization and identification of glycoproteins by taking advantage of bioorthogonal reactions. Most widely used MCRs have azides or alkynes at the 2-N-acetyl position but are not selective for one class of glycoprotein over others. To address this limitation, we are exploring additional MCRs that have bioorthogonal functionality at other positions. Here, we report the characterization of 2-azido-2-deoxy-glucose (2AzGlc)...
January 30, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28115479/o-glcnac-transferase-is-essential-for-sensory-neuron-survival-and-maintenance
#9
Cathy Su, Thomas L Schwarz
: O-GlcNAc transferase (OGT) regulates a wide range of cellular processes through the addition of the O-GlcNAc sugar moiety to thousands of protein substrates. Its activity is affected by nutrient availability, and therefore its role has been broadly studied in metabolic tissues. OGT is enriched in the nervous system, but little is known about its importance in basic neuronal processes in vivo Here, we show that OGT is essential for sensory neuron survival and maintenance in mice. Sensory neuron-specific knockout of OGT results in behavioral hyposensitivity to thermal and mechanical stimuli accompanied by decreased epidermal innervation and cell body loss in the dorsal root ganglia...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28104396/o-glcnac-modification-of-sp1-mediates-hyperglycaemia-induced-icam-1-up-regulation-in-endothelial-cells
#10
Yuan Zhang, Yuan Qu, Tian Niu, Haiyan Wang, Kun Liu
Intracellular adhesion molecule 1 (ICAM-1) is an important inflammatory factor that causes retinal damage during diabetic retinopathy. Hyperglycaemia can increase ICAM-1 expression in endothelial cells and the ICAM-1 promoter is responsive to the transcription factor specificity protein 1 (Sp1). O-GlcNAc modification is driven by the glucose concentration and has a profound effect on Sp1 activity. In this study, we investigated the underlying mechanism through which hyperglycaemia triggers ICAM-1 expression, which is mediated by O-GlcNAc modification of Sp1 in human umbilical vein endothelial cells (HUVECs) and rat retinal capillary endothelial cells (RRCECs)...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#11
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096468/o-glcnac-expression-levels-epigenetically-regulate-colon-cancer-tumorigenesis-by-affecting-the-cancer-stem-cell-compartment-via-modulating-expression-of-transcriptional-factor-mybl1
#12
Huabei Guo, Bing Zhang, Alison V Nairn, Tamas Nagy, Kelley W Moremen, Phillip Buckhaults, Michael Pierce
To study the regulation of colorectal adenocarcinoma progression by O-GlcNAc, we have focused on the O-GlcNAc-mediated epigenetic regulation of human colon cancer stem cells (CCSC). Xenograft tumors from colon tumor cells with OGT knockdown grew significantly slower than those formed from control cells, indicating a reduced proliferation of tumor cells due to inhibition of OGT expression. Significant reduction of CCSC population was observed in the tumor cells after OGT knockdown, while tumor cells treated with O-GlcNAcase inhibitor showed an increased CCSC population, indicating that O-GlcNAc levels regulated the CCSC compartment...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28093214/the-upr-reduces-glucose-metabolism-via-ire1-signaling
#13
Judith M van der Harg, Jessica C van Heest, Fabian N Bangel, Sanne Patiwael, Jan R T van Weering, Wiep Scheper
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis...
January 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28055183/deciphering-the-functions-of-protein-o-glcnacylation-with-chemistry
#14
Matthew Worth, Hao Li, Jiaoyang Jiang
O-GlcNAcylation is the modification of serine and threonine residues with β-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. This dynamic modification is attached by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA) and is a critical regulator of various cellular processes. Furthermore, O-GlcNAcylation is dysregulated in many diseases, such as diabetes, cancer, and Alzheimer's disease. However, the precise role of this modification and its cycling enzymes (OGT and OGA) in normal and disease states remains elusive...
January 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28054006/western-blot-data-using-two-distinct-anti-o-glcnac-monoclonal-antibodies-showing-unique-glycosylation-status-on-cellular-proteins-under-2-deoxy-d-glucose-treatment
#15
Tetsuya Okuda
Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28038474/inhibition-of-aldh2-by-o-glcnacylation-contributes-to-the-hyperglycemic-exacerbation-of-myocardial-ischemia-reperfusion-injury
#16
Baoshan Liu, Jiali Wang, Minghua Li, Qiuhuan Yuan, Mengyang Xue, Feng Xu, Yuguo Chen
Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032764/discovery-of-cell-permeable-o-glcnac-transferase-inhibitors-via-tethering-in-situ-click-chemistry
#17
Yue Wang, Jingjing Zhu, Lianwen Zhang
O-GlcNAc transferase (OGT) is a key enzyme involved in dynamic O-GlcNAcylation of nuclear and cytoplasmic proteins similar to phosphorylation. Discovery of cell-permeable OGT inhibitors is significant to clarify the function and regulatory mechanism of O-GlcNAcylation. This will establish the foundation for the development of therapeutic drugs for relevant diseases. Here, we report two cell-permeable OGT inhibitors (APNT and APBT), developed from low-activity precursors (IC50 > 1 mM) via "tethering in situ click chemistry (TISCC)"...
December 29, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28017896/augmented-o-glcnac-signaling-via-glucosamine-attenuates-oxidative-stress-and-apoptosis-following-contrast-induced-acute-kidney-injury-in-rats
#18
Jiachang Hu, Rongyi Chen, Ping Jia, Yi Fang, Tongqiang Liu, Nana Song, Xialian Xu, Jun Ji, Xiaoqiang Ding
Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals. Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI. O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear. Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective...
December 23, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28008135/gfat1-phosphorylation-by-ampk-promotes-vegf-induced-angiogenesis
#19
Darya Zibrova, Franck Vandermoere, Olga Göransson, Mark Peggie, Karina V Mariño, Anne Knierim, Katrin Spengler, Cora Weigert, Benoit Viollet, Nicholas A Morrice, Kei Sakamoto, Regine Heller
Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood. Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate. GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches...
22, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27988387/insights-into-the-role-of-maladaptive-hexosamine-biosynthesis-and-o-glcnacylation-in-development-of-diabetic-cardiac-complications
#20
Cheng Xue Qin, Rochelle Sleaby, Amy J Davidoff, James R Bell, Miles J De Blasio, Leanne M Delbridge, John C Chatham, Rebecca H Ritchie
Diabetes mellitus significantly increases the risk of heart failure, independent of coronary artery disease. The mechanisms implicated in the development of diabetic heart disease, commonly termed diabetic cardiomyopathy, are complex, but much of the impact of diabetes on the heart can be attributed to impaired glucose handling. It has been shown that the maladaptive nutrient-sensing hexosamine biosynthesis pathway (HBP) contributes to diabetic complications in many non-cardiac tissues. Glucose metabolism by the HBP leads to enzymatically-regulated, O-linked attachment of a sugar moiety molecule, β-N-acetylglucosamine (O-GlcNAc), to proteins, affecting their biological activity (similar to phosphorylation)...
February 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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